Author: "Régulations cellulaires: lipidoses et atherosclerose" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Régulations cellulaires: lipidoses et atherosclerose"' showing total 68 results

Start Over Author "Régulations cellulaires: lipidoses et atherosclerose"

68 results on '"Régulations cellulaires: lipidoses et atherosclerose"'

1. Opuntiaspp.: Characterization and Benefits in Chronic Diseases

Author: María del Socorro Santos Díaz, Anne Nègre-Salvayre, Françoise Guéraud, Ana P. Barba de la Rosa, Cécile Héliès-Toussaint, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Facultad de Ciencias Químicas, Universidad de Concepción [Chile], Instituto Potosino de Investigación Cientifica y Tecnológica (IPICYT), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées, This work was funded by the INSERM, INRA, University of Toulouse and by the bilateral French/Mexican ANR (French National Research Agency)/CONACYT (National Council of Science and Technology of Mexico) project BIOPUNTIA (ANR-2010-INTB-1702), U 1048, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Régulations cellulaires: lipidoses et atherosclerose.
Subjects: opuntia, 0301 basic medicine, Aging, Mediterranean diet, [SDV]Life Sciences [q-bio], Review Article, human health, Biochemistry, chronic diseases, propriété biologique, pyrrolizidine alkaloids, 03 medical and health sciences, 0404 agricultural biotechnology, Biological property, Botany, Cladodes, medicine, prickly pear, lcsh:QH573-671, drug plant, Carotenoid, ComputingMilieux_MISCELLANEOUS, Economic potential, alcaloide, 2. Zero hunger, chemistry.chemical_classification, PEAR, 030109 nutrition & dietetics, biology, Traditional medicine, lcsh:Cytology, maladie chronique, santé humaine, 04 agricultural and veterinary sciences, Cell Biology, General Medicine, biology.organism_classification, medicine.disease, 040401 food science, Obesity, 3. Good health, plante médicinale, Phytochemical, chemistry, propriété médicinale, opuntia ficus indica, composé phytochimique, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Opuntiaspecies have been used for centuries as food resources and in traditional folk medicine for their nutritional properties and their benefit in chronic diseases, particularly diabetes, obesity, cardiovascular diseases, and cancer. These plants are largely distributed in America, Africa, and the Mediterranean basin.Opuntiaspp. have great economic potential because they grow in arid and desert areas, andO. ficus-indica, the domesticatedO. species, is used as a nutritional and pharmaceutical agent in various dietary and value-added products. Though differences in the phytochemical composition exist between wild and domesticated (O. ficus-indica)Opuntiaspp., allOpuntiavegetatives (pear, roots, cladodes, seeds, and juice) exhibit beneficial properties mainly resulting from their high content in antioxidants (flavonoids, ascorbate), pigments (carotenoids, betalains), and phenolic acids. Other phytochemical components (biopeptides, soluble fibers) have been characterized and contribute to the medicinal properties ofOpuntiaspp. The biological properties ofOpuntiaspp. have been investigated on cellular and animal models and in clinical trials in humans, allowing characterization and clarification of the protective effect ofOpuntia-enriched diets in chronic diseases. This review is an update on the phytochemical composition and biological properties ofOpuntiaspp. and their potential interest in medicine.
Published: 2017

2. Modification of endothelial nitric oxide synthase by 4-oxo-2(E)-nonenal(ONE) in preeclamptic placentas

Author: Christophe Vayssière, Olivier Parant, Paul Guerby, Koji Uchida, Frédéric Rodriguez, Anne Nègre-Salvayre, Takahiro Shibata, Oriane Tasta, Robert Salvayre, Audrey Swiader, Frédéric Pont, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Mise en Forme des Matériaux (CEMEF), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS), Département d'échographie et de Médecine fœtale, SIHCUS-CMCO, Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences-Nagoya University, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Nagoya University, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-PSL Research University (PSL)-MINES ParisTech - École nationale supérieure des mines de Paris, Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Régulations cellulaires: lipidoses et atherosclerose., Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Placenta, Cell Culture Techniques, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, medicine.disease_cause, Biochemistry, Lipid peroxidation, chemistry.chemical_compound, 0302 clinical medicine, Pre-Eclampsia, Enos, Pregnancy, Tandem Mass Spectrometry, Acrolein, ComputingMilieux_MISCELLANEOUS, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 3. Good health, Trophoblasts, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], embryonic structures, Female, [CHIM.CHEM]Chemical Sciences/Cheminformatics, Adult, Nitric Oxide Synthase Type III, Cell Survival, Protein Carbonyl Content, Oxidative phosphorylation, Nitric Oxide, Preeclampsia, 4-Hydroxynonenal, Nitric oxide, Andrology, 03 medical and health sciences, Physiology (medical), medicine, Humans, Aldehydes, medicine.disease, biology.organism_classification, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Oxidative Stress, 030104 developmental biology, chemistry, Lipid Peroxidation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], 030217 neurology & neurosurgery, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Chromatography, Liquid
Abstract: Preeclampsia (PE) is a leading cause of pregnancy complications, affecting 3-7% of pregnant women worldwide. The pathophysiology of preeclampsia involves a redox imbalance, oxidative stress and a reduced nitric oxide (NO) bioavailability. The molecular and cellular mechanisms leading to the dysfunction of the placental endothelial NO synthase (eNOS) are not clarified. This study was designed to investigate whether aldehydes generated by lipid peroxidation products (LPP), may contribute to placental eNOS dysfunction in PE. The analysis of placentas from PE-affected patients and normal pregnancies, showed a significant increase in protein carbonyl content, indicative of oxidative stress-induced protein modification, as shown by the accumulation of acrolein, 4-hydroxynonenal (HNE), and 4-oxo-2(E)-nonenal (ONE) adducts in PE placentas. In contrast, the levels of these LPP-adducts were low in placentas from normal pregnancies. Immunofluorescence and confocal experiments pointed out a colocalization of eNOS with ONE-Lys adducts, whereas eNOS was not modified in normal placentas. LC-MS/MS analysis of recombinant eNOS preincubated with ONE, allowed to identify several ONE-modified Lys-containing peptides, confirming that eNOS may undergo post-translational modification by LPP. The preincubation of HTR-8/SVneo human trophoblasts (HTR8) with ONE, resulted in ONE-Lys modification of eNOS and a reduced generation of NO. ONE inhibited the migration of HTR8 trophoblasts in the wound closure model, and this was partly restored by the NO donor, NOC-18, which confirmed the important role of NO in the invasive potential of trophoblasts. In conclusion, placental eNOS is modified by ONE in PE placentas, which emphasizes the sensitivity of this protein to oxidative stress in the disturbed redox environment of preeclamptic pregnancies.
Published: 2019

3. A thioredoxin-mimetic peptide exerts potent anti-inflammatory, antioxidant, and atheroprotective effects in ApoE2.Ki mice fed high fat diet

Author: Khadija El Hadri, Dominique Couchie, Sonia Karabina, Anne Nègre-Salvayre, Mustapha Rouis, Fanny Canesi, Véronique Mateo, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vieillissement Cellulaire Intégré et Inflammation (VCII), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Negre-Salvayre, Anne, Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Dieu-Nosjean, Marie-Caroline, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Régulations cellulaires: lipidoses et atherosclerose.
Subjects: 0301 basic medicine, Apolipoprotein E, Mice, Knockout, ApoE, Physiology, [SDV]Life Sciences [q-bio], Anti-Inflammatory Agents, 030204 cardiovascular system & hematology, medicine.disease_cause, Antioxidants, Thioredoxins, 0302 clinical medicine, Aorta, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Interleukin, Plaque, Atherosclerotic, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Female, Tumor necrosis factor alpha, Inflammation Mediators, medicine.symptom, Thioredoxin, Cardiology and Cardiovascular Medicine, Oligopeptides, Signal Transduction, medicine.medical_specialty, Aortic Diseases, Inflammation, Diet, High-Fat, 03 medical and health sciences, Physiology (medical), Internal medicine, medicine, Animals, Sulfhydryl Compounds, Reactive oxygen species, Monocyte, Molecular Mimicry, Atherosclerosis, Mice, Inbred C57BL, Disease Models, Animal, Oxidative Stress, 030104 developmental biology, Endocrinology, chemistry, Macrophages, Peritoneal, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Aims: Oxidative stress and inflammation play a pathogenic role in atherosclerosis. Thioredoxin-1 (Trx-1) is an anti-oxidative, anti-inflammatory protein with atheroprotective effects. However, in vivo cleavage of Trx-1 generates a truncated pro-inflammatory protein, Trx-80, which compromises the therapeutic use of Trx-1. Here we analysed whether the thioredoxin-mimetic peptide (TxMP), CB3 might exert anti-oxidative, anti-inflammatory, and atheroprotective effects in ApoE2.Ki mice.Methods and results: We synthesized a small TxMP, Ac-Cys-Pro-Cys-amide, CB3 and characterized its antioxidant and anti-inflammatory effects on cultured peritoneal murine macrophages. CB3 significantly and dose-dependently reduced the level of reactive oxygen species in lipopolysaccharides (LPS)-activated macrophages. In addition, it efficiently lowered LPS-induced inflammatory process through NF-κB inhibition, as evidenced by the reduced secretion of monocyte chemoattractant protein-1, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α by macrophages. Nevertheless, CB3 did not affect cholesterol accumulation in macrophages. A daily-administered dose of 10 µg/g body weight CB3 to ApoE2.Ki mice on high fat diet did not affect plasma of total cholesterol and triglycerides levels but significantly reduced the plasma levels of pro-inflammatory cytokines (IL-33 and TNF-α) and oxidative markers. In contrast, it significantly induced the plasma levels of anti-inflammatory proteins (adiponectin, IL-10). In addition, CB3 reduced the number of pro-inflammatory M1 macrophages in spleen and decreased the ratio of M1/M2 macrophages in atherosclerotic lesion areas. Finally, CB3 significantly reduced the surface area of aortic lesions.Conclusions: Our results clearly showed that similar to the full length Trx-1, CB3 exerts protective effects, by reducing inflammation and oxidative stress in macrophages and in ApoE2.Ki mice. The atheroprotective effect of CB3 opens promising therapeutic approaches for treatment of atherosclerosis.
Published: 2019

4. Small dense HDLs display potent vasorelaxing activity, reflecting their elevated content of sphingosine-1-phosphate

Author: Anne Nègre-Salvayre, Carolane Dauteuille, Anatol Kontush, Maryam Darabi, Marie Lhomme, M. John Chapman, Patrice Thérond, S. Chantepie, Serge Monier, Robert Salvayre, Kerry-Anne Rye, Philippe Lesnik, L. Perségol, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Dyslipoproteinémies et athérosclerose : Génétique, métabolisme et thérapeutique, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Heart Research Institute, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Faculty of medicine (University of New South Wales Australia, Sydney), Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia, Laboratoire de biochimie metabolique et clinique, Université Paris Descartes - Paris 5 (UPD5), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Université Bourgogne Franche-Comté ( UBFC ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Université Paris Descartes - Paris 5 ( UPD5 ), Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Hôpital de Rangueil-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Régulations cellulaires: lipidoses et atherosclerose., and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: 0301 basic medicine, Endothelium, endothelium, Sphingosine-1-phosphate receptor, [SDV]Life Sciences [q-bio], Vasodilation, QD415-436, 030204 cardiovascular system & hematology, Pharmacology, Biochemistry, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, High-density lipoprotein, Sphingosine, nitric oxide, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Sphingosine-1-phosphate, Receptor, vasodilation, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Research Articles, ComputingMilieux_MISCELLANEOUS, Antagonist, Cell Biology, Healthy Volunteers, 030104 developmental biology, medicine.anatomical_structure, chemistry, high density lipoprotein, lipids (amino acids, peptides, and proteins), oxidized low density lipoprotein, Lysophospholipids, atherosclerosis, Lipoproteins, HDL, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IF 4.810; International audience; The functional heterogeneity of HDL is attributed to its diverse bioactive components. We evaluated whether the vasodilatory effects of HDL differed across HDL subpopulations, reflecting their distinct molecular composition. The capacity of five major HDL subfractions to counteract the inhibitory effects of oxidized LDL on acetylcholine-induced vasodilation was tested in a rabbit aortic rings model. NO production, an essential pathway in endothelium-dependent vasorelaxation, was studied in simian vacuolating virus 40-transformed murine endothelial cells (SVECs). Small dense HDL3 subfractions displayed potent vasorelaxing activity (up to +31% vs. baseline, P < 0.05); in contrast, large light HDL2 did not induce aortic-ring relaxation when compared on a total protein basis. HDL3 particles were enriched with sphingosine-1-phosphate (S1P) (up to 3-fold vs. HDL2), with the highest content in HDL3b and -3c that concomitantly revealed the strongest vasorelaxing properties. NO generation was enhanced by HDL3c in SVECs (1.5-fold, P < 0.01), a phenomenon that was blocked by the S1P receptor antagonist, VPC 23019. S1P-enriched reconstituted HDL (rHDL) was a 1.8-fold (P < 0.01) more potent vasorelaxant than control rHDL in aortic rings. Small dense HDL3 particles displayed potent protective effects against oxidative stress-associated endothelium dysfunction, potentially reflecting their elevated content of S1P that might facilitate interaction with S1P receptors and ensuing NO generation.
Published: 2018

5. Human Plasma Thioredoxin-80 Increases With Age and in ApoE −/− Mice Induces Inflammation, Angiogenesis, and Atherosclerosis

Author: Tamas Fulop, Dler Faieeq Darweesh Mahmood, Magda M. Hamza, Fanny Canesi, Amna Abderrazak, Dominique Couchie, Boris L. Vaisman, Mustapha Rouis, Alan T. Remaley, Vimala Diderot, Khadija El Hadri, Aurélie Le Page, Anne Nègre-Salvayre, Vieillissement Cellulaire Intégré et Inflammation (VCII), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vieillissement, stress, inflammation, Université Pierre et Marie Curie - Paris 6 (UPMC), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire de Gériatrie de Sherbrooke (CSSS-IUGS), National Institutes of Health [Bethesda] (NIH), Régulations cellulaires: lipidoses et atherosclerose., Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Genetically modified mouse, Angiogenesis, [SDV]Life Sciences [q-bio], Inflammasome, Inflammation, Biology, Molecular biology, Proinflammatory cytokine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Physiology (medical), medicine, Macrophage, Tumor necrosis factor alpha, Scavenger receptor, medicine.symptom, Cardiology and Cardiovascular Medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Background: Thioredoxin (TRX)-1, a ubiquitous 12-kDa protein, exerts antioxidant and anti-inflammatory effects. In contrast, the truncated form, called TRX80, produced by macrophages induces upregulation of proinflammatory cytokines. TRX80 also promotes the differentiation of mouse peritoneal and human macrophages toward a proinflammatory M1 phenotype. Methods: TRX1 and TRX80 plasma levels were determined with a specific ELISA. A disintegrin and metalloproteinase domain-containing protein (ADAM)-10, ADAM-17, and ADAM-10 activities were measured with SensoLyte 520 ADAM10 Activity Assay Kit, Fluorimetric, and InnoZyme TACE Activity Kit, respectively. Western immunoblots were performed with specific antibodies to ADAM-10 or ADAM-17. Angiogenesis study was evaluated in vitro with human microvascular endothelial cells-1 and in vivo with the Matrigel plug angiogenesis assay in mice. The expression of macrophage phenotype markers was investigated with real-time polymerase chain reaction. Phosphorylation of Akt, mechanistic target of rapamycin, and 70S6K was determined with specific antibodies. The effect of TRX80 on NLRP3 inflammasome activity was evaluated by measuring the level of interleukin-1β and -18 in the supernatants of activated macrophages with ELISA. Hearts were used for lesion surface evaluation and immunohistochemical studies, and whole descending aorta were stained with Oil Red O. For transgenic mice generation, the human scavenger receptor (SR-A) promoter/enhancer was used to drive macrophage-specific expression of human TRX80 in mice. Results: In this study, we observed a significant increase of plasma levels of TRX80 in old subjects compared with healthy young subjects. In parallel, an increase in expression and activity of ADAM-10 and ADAM-17 in old peripheral blood mononuclear cells compared with those of young subjects was observed. Furthermore, TRX80 was found to colocalize with tumor necrosis factor-α, a macrophage M1 marker, in human atherosclerotic plaque. In addition, TRX80 induced the expression of murine M1 macrophage markers through Akt2/mechanistic target of rapamycin–C1/70S6K pathway and activated the inflammasome NLRP3, leading to the release of interleukin-1β and -18, potent atherogenic cytokines. Moreover, TRX80 exerts a powerful angiogenic effect in both in vitro and in vivo mouse studies. Finally, transgenic mice that overexpress human TRX80 specifically in macrophages of apoE −/− mice have a significant increase of aortic atherosclerotic lesions. Conclusions: TRX80 showed an age-dependent increase in human plasma. In mouse models, TRX80 was associated with a proinflammatory status and increased atherosclerosis.
Published: 2017

6. Dietary cladode powder from wild type and domesticated Opuntia species reduces atherogenesis in apoE knock-out mice

Author: Michel Rossignol, María del Socorro Santos Díaz, Anne Nègre-Salvayre, Sandra Garoby-Salom, Ana P. Barba de la Rosa, Françoise Guéraud, Caroline Camaré, Robert Salvayre, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto Potosino de Investigación Cientifica y Tecnológica (IPICYT), Université McGill, Facultad de Ciencias Químicas, Universidad de Concepción [Chile], Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Régulations cellulaires: lipidoses et atherosclerose., Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), McGill University = Université McGill [Montréal, Canada], INSERM, University Toulouse 3, and bilateral French/Mexican ANR (French National Research Agency)/CONACYT (National council of Science and Technology of Mexico) project BIOPUNTIA [ANR-2010-INTB-1702]
Subjects: 0301 basic medicine, Male, Antioxidant, Physiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Inflammation, Biology, Biochemistry, LDL, 03 medical and health sciences, chemistry.chemical_compound, Mice, Apolipoproteins E, Lipid oxidation, Oxidation, medicine, Extracellular, Animals, Foam cells, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Mice, Knockout, Reactive oxygen species, Cell adhesion molecule, Superoxide, Wild type, Opuntia, General Medicine, Atherosclerosis, Cell biology, apoE(-/-) mice, 030104 developmental biology, chemistry, medicine.symptom, Powders, Adhesion molecules, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Dietary intake of Opuntia species may prevent the development of cardiovascular diseases. The present study was designed to characterize the biological antioxidant and anti-inflammatory properties of Opuntia species and to investigate whether Opuntia cladodes prevent the development of atherosclerosis in vivo, in apoE(-)KO mice. The effects of the two Opuntia species, the wild Opuntia streptacantha and the domesticated Opuntia ficus-indica, were tested on the generation of intra- and extracellular reactive oxygen species (ROS) production and kinetics of the LDL oxidation by murine CRL2181 endothelial cells and on the subsequent inflammatory signaling leading to the adhesion of monocytes on the activated endothelium and the formation of foam cells. Opuntia species blocked the extracellular ROS (superoxide anion) generation and LDL oxidation by CRL2181, as well as the intracellular ROS rise and signaling evoked by the oxidized LDL, including the nuclear translocation of the transcription factor NF kappa B, the expression of ICAM-1 and VCAM-1 adhesion molecules, and the adhesion of monocytes to CRL2181. In vivo, Opuntia significantly reduced the formation of atherosclerotic lesions and the accumulation of 4-hydroxynonenal adducts in the vascular wall of apoE-KO mice, indicating that Opuntia cladodes prevent lipid oxidation in the vascular wall. In conclusion, wild and domesticated Opuntia species exhibit antioxidant, anti-inflammatory, and antiatherogenic properties which emphasize their nutritional benefit for preventing cardiovascular diseases.
Published: 2016

7. Comparative shotgun proteomic analysis of wild and domesticated Opuntia spp. species shows a metabolic adaptation through domestication

Author: Antonio Reyes-Agüero, Anne Nègre-Salvayre, Ana P. Barba de la Rosa, Michel Rossignol, Carole Pichereaux, Françoise Guéraud, Odile Schiltz, Eric E. Hernández-Domínguez, María del Socorro Santos-Díaz, Marizel Astello-García, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Instituto Potosino de Investigación Cientifica y Tecnológica (IPICYT), Facultad de Ciencias Químicas, Universidad de Concepción [Chile], Instituto de Investigación en Zonas Desérticas, Universidad Autonoma de San Luis Potosi [México] (UASLP), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), ilateral Mexico-France Project Collaboration 'Biopuntia' grant no. 142873, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université McGill, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University = Université McGill [Montréal, Canada], Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Fédération de Recherche en Biologie de Toulouse (FR BT), ProdInra, Archive Ouverte, Universidad de Concepción - University of Concepcion [Chile], and Régulations cellulaires: lipidoses et atherosclerose.
Subjects: Proteomics, 0106 biological sciences, 0301 basic medicine, opuntia, Acclimatization, [SDV]Life Sciences [q-bio], Shotgun analysis, Biophysics, Shotgun, 01 natural sciences, Biochemistry, Domestication, 03 medical and health sciences, hplc ms ms, Botany, Cladodes, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, carbohydrate metabolism, LC-MS/MS, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, biology, 1C-metabolism, métabolisme glucidique, 15. Life on land, biology.organism_classification, Adaptation, Physiological, Arid, [SDV] Life Sciences [q-bio], Metabolism, 030104 developmental biology, Opuntia spp, Fruit, Proteome, Species richness, RNA-seq, 010606 plant biology & botany
Abstract: The Opuntia genus is widely distributed in America, but the highest richness of wild species are found in Mexico, as well as the most domesticated Opuntia ficus-indica, which is the most domesticated species and an important crop in agricultural economies of arid and semiarid areas worldwide. During domestication process, the Opuntia morphological characteristics were favored, such as less and smaller spines in cladodes and less seeds in fruits, but changes at molecular level are almost unknown. To obtain more insights about the Opuntia molecular changes through domestication, a shotgun proteomic analysis and database-dependent searches by homology was carried out. > 1000 protein species were identified and by using a label-free quantitation method, the Opuntia proteomes were compared in order to identify differentially accumulated proteins among wild and domesticated species. Most of the changes were observed in glucose, secondary, and 1C metabolism, which correlate with the observed protein, fiber and phenolic compounds accumulation in Opuntia cladodes. Regulatory proteins, ribosomal proteins, and proteins related with response to stress were also observed in differential accumulation. These results provide new valuable data that will help to the understanding of the molecular changes of Opuntia species through domestication. Biological significance Opuntia species are well adapted to dry and warm conditions in arid and semiarid regions worldwide, and they are highly productive plants showing considerable promises as an alternative food source. However, there is a gap regarding Opuntia molecular mechanisms that enable them to grow in extreme environmental conditions and how the domestication processes has changed them. In the present study, a shotgun analysis was carried out to characterize the proteomes of five Opuntia species selected by its domestication degree. Our results will help to a better understanding of proteomic features underlying the selection and specialization under evolution and domestication of Opuntia and will provide a platform for basic biology research and gene discovery.
Published: 2016

8. Longitudinal Analysis of Gene Expression in Porcine Skeletal Muscle After Post-Injection Local Injury

Author: Pierre-Louis Toutain, François Hatey, Pierre J. Ferré, Magali SanCristobal, Agnès Bonnet, Gwenola Tosser-Klopp, Laurence Liaubet, Didier Concordet, Emmanuelle Uro-Coste, Hervé P. Lefebvre, Physiologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Génétique Cellulaire (LGC), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), and Régulations cellulaires: lipidoses et atherosclerose.
Subjects: Male, Pathology, Time Factors, MESH: Thymosin, Swine, [SDV]Life Sciences [q-bio], Muscle Proteins, MESH: Collagen Type I, Pharmaceutical Science, Post injection, MESH: Down-Regulation, MESH: Collagen, MESH: Fibronectins, Gene expression, MESH: Up-Regulation, Osteonectin, MESH: Animals, Pharmacology (medical), MESH: Swine, Oligonucleotide Array Sequence Analysis, MESH: Muscle, Skeletal, 0303 health sciences, 030302 biochemistry & molecular biology, MESH: Injections, Intramuscular, Pathophysiology, Up-Regulation, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Matrix Metalloproteinase 2, Molecular Medicine, Collagen, MESH: Osteonectin, Intramuscular injection, MESH: ras Proteins, Biotechnology, medicine.medical_specialty, Down-Regulation, Biology, Injections, Intramuscular, Collagen Type I, MESH: Gene Expression Profiling, MESH: Muscle Proteins, 03 medical and health sciences, medicine, Animals, Muscle, Skeletal, Pathological, 030304 developmental biology, Pharmacology, Gene Expression Profiling, MESH: Time Factors, Organic Chemistry, Skeletal muscle, MESH: Male, Fibronectins, Collagen Type I, alpha 1 Chain, Thymosin, MESH: Matrix Metalloproteinase 2, Gene expression profiling, MESH: Oligonucleotide Array Sequence Analysis, Time course, ras Proteins
Abstract: International audience; PURPOSE: The purpose of this study is to describe the time course of gene expression in a skeletal muscle local injury induced by an intramuscular (IM) injection, and to compare the dynamics of gene expression with pathological events. MATERIALS AND METHODS: Ten piglets received 4 IM injections of propylene glycol in the longissimus dorsi muscles 6 h, 2, 7, and 21 days before euthanasia, where control and injected muscle sites were sampled for RNA isolation and microscopic examination. The hybridization of nylon cDNA microarrays was carried out with radioactive probes obtained from the muscle RNA. RESULTS: 153 genes were found under- or over-expressed at least once among the investigated time-conditions. The eight most discriminant genes were also identified: Two genes (GTP-binding protein RAD and Ankyrin repeat domain protein) were over-expressed at 6 h and six genes between 2 and 21 days (Osteonectin, Fibronectin, Matrix metalloproteinase-2, Collagen alpha 1(I) chain, Collagen alpha 2(I) chain, and Thymosin beta-4). Necrosis, inflammation and regeneration were observed through both the dynamics of gene expression profiles and through the microscopic examinations. CONCLUSION: Our data demonstrate that several pathways are involved in post-injection muscle injury, and that necrosis, inflammation and regeneration are not sequential but occur in parallel.
Published: 2007

9. Antiatherogenic and antitumoral properties of Opuntia cladodes: inhibition of low density lipoprotein oxidation by vascular cells, and protection against the cytotoxicity of lipid oxidation product 4-hydroxynonenal in a colorectal cancer cellular model

Author: Corinne Bernis, María del Socorro Santos Díaz, Julia Keller, Françoise Guéraud, Caroline Camaré, Robert Salvayre, Ana P. Barba de la Rosa, Marizel Astello-García, Anne Nègre-Salvayre, Michel Rossignol, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto Potosino de Investigación Cientifica y Tecnológica (IPICYT), Université McGill, Régulations cellulaires: lipidoses et atherosclerose., IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Régulations cellulaires: lipidoses et atherosclerose, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), McGill University = Université McGill [Montréal, Canada], Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and ANR Blanc International, projet BIOPUNTIA (ANR-2010-INTB-1702)
Subjects: Antioxidant, Physiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Biology, medicine.disease_cause, foam cell, Biochemistry, 4-Hydroxynonenal, Lipid peroxidation, chemistry.chemical_compound, Lipid oxidation, Endothelial cell, Oxidation, medicine, Animals, Anticarcinogenic Agents, ComputingMilieux_MISCELLANEOUS, Foam cell, Aldehydes, Toxicity, Plant Extracts, Low-density lipoprotein, Endothelial Cells, Opuntia, General Medicine, Opuntia megacantha, biology.organism_classification, Colorectal cancer, 4-hydroxynonenal, 3. Good health, Lipoproteins, LDL, Mice, Inbred C57BL, chemistry, Endothelium, Vascular, Lipid Peroxidation, Colorectal Neoplasms, Oxidation-Reduction, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Opuntia species have been used for thousands of years as a folk medicine in the treatment of diseases. However, the components and protective mechanisms are still unclear. We make the hypothesis that Opuntia species may protect the development of oxidative stress-associated diseases, such as atherosclerosis or colon cancer, via their antioxidant properties. We investigated the protective effect of Opuntia cladode powder against the oxidation of low-density lipoprotein (LDL) evoked by vascular endothelial cells, an important risk factor for atherosclerosis development, and the toxicity of 4-hydroxynonenal (a major lipid peroxidation product) on normal (Apc +/+) and preneoplastic (Apc min/+) immortalized epithelial colon cells. Various Opuntia species classified according to their degree of domestication, from the wildest (Opuntia streptacantha, Opuntia hyptiacantha, Opuntia megacantha), medium (Opuntia albicarpa), to the most domesticated (Opuntia ficus-indica) were tested. Cladode powders prepared from these Opuntia species significantly inhibited LDL oxidation induced by incubation with murine endothelial cells and the subsequent foam cell formation of RAW 264.7 murine macrophages and cytotoxicity on murine endothelial cells. Moreover, Opuntia cladode powder blocked the promotion of colon cancer development on an in vitro model of colonocytes. It may be noted that the phenolic acid and flavonoids content, the antioxidant capacity, and the protective effect were relatively similar in all the cladode powders from wild (O. streptacantha) and domesticated Opuntia. Altogether, these data confirm the therapeutic potential of Opuntia cladodes in diseases associated with oxidative stress.
Published: 2015

10. Escherichia coli Morphological Changes and Lipid A Removal Induced by Reduced Pressure Nitrogen Afterglow Exposure

Author: Sarah Cousty, Anne Nègre-Salvayre, Hayat Zerrouki, Virginie Rizzati, Jean Philippe Sarrette, Corinne Bernis, Toxicologie Alimentaire (UTA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, LAboratoire PLasma et Conversion d'Energie (LAPLACE), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), and Régulations cellulaires: lipidoses et atherosclerose.
Subjects: Gram-negative bacteria, Nitrogen, Ultraviolet Rays, Science, [SDV]Life Sciences [q-bio], Population, chemistry.chemical_element, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.disease_cause, Lipid A, Mice, Escherichia coli, medicine, Animals, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, education, Aorta, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Inflammation, education.field_of_study, Multidisciplinary, biology, [SPI.PLASMA]Engineering Sciences [physics]/Plasmas, NF-kappa B, Endothelial Cells, Sterilization, Sterilization (microbiology), biology.organism_classification, 6. Clean water, Anti-Bacterial Agents, Afterglow, Atmospheric Pressure, chemistry, Biochemistry, Biophysics, Medicine, Oxidation-Reduction, Bacteria, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract: Lipid A is a major hydrophobic component of lipopolysaccharides (endotoxin) present in the membrane of most Gram-negative bacteria, and the major responsible for the bioactivity and toxicity of the endotoxin. Previous studies have demonstrated that the late afterglow region of flowing post-discharges at reduced pressure (1-20 Torr) can be used for the sterilization of surfaces and of the reusable medical instrumentation. In the present paper, we show that the antibacterial activity of a pure nitrogen afterglow can essentially be attributed to the large concentrations of nitrogen atoms present in the treatment area and not to the UV radiation of the afterglow. In parallel, the time variation of the inactivation efficiency quantified by the log reduction of the initial Escherichia coli (E. coli) population is correlated with morphologic changes observed on the bacteria by scanning electron microscopy (SEM) for increasing afterglow exposure times. The effect of the afterglow exposure is also studied on pure lipid A and on lipid A extracted from exposed E. coli bacteria. We report that more than 60% of lipid A (pure or bacteria-extracted) are lost with the used operating conditions (nitrogen flow QN2 = 1 standard liter per minute (slpm), pressure p = 5 Torr, microwave injected power PMW = 200 W, exposure time: 40 minutes). The afterglow exposure also results in a reduction of the lipid A proinflammatory activity, assessed by the net decrease of the redox-sensitive NFκB transcription factor nuclear translocation in murine aortic endothelial cells stimulated with control vs afterglow-treated (pure and extracted) lipid A. Altogether these results point out the ability of reduced pressure nitrogen afterglows to neutralize the cytotoxic components in Gram-negative bacteria.
Published: 2015

11. Small, Dense High-Density Lipoprotein-3 Particles Are Enriched in Negatively Charged Phospholipids

Author: Camont, Laurent, Lhomme, Marie, Rached, Fabiana, Le Goff, Wilfried, Nègre-Salvayre, Anne, Salvayre, Robert, Calzada, Catherine, Lagarde, Michel, Chapman, M. John, Kontush, Anatol, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de recherche Pau Droit Public (PDP), Université de Pau et des Pays de l'Adour (UPPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Régulations cellulaires: lipidoses et atherosclerose., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2013

12. Protein Disulfide Isomerase Modification and Inhibition Contribute to ER Stress and Apoptosis Induced by Oxidized Low Density Lipoproteins

Author: Corinne Bernis, Pauline Larroque-Cardoso, Carole Muller, Françoise Guéraud, Elodie Mucher, Cécile Vindis, Nathalie Augé, Caroline Camaré, Jan Bandemer, Anne Nègre-Salvayre, Robert Salvayre, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, INSERM, Universite of Toulouse, Fondation pour la Recherche Medicale [DCV2007040927], ANR Blanc SVSE1 'CARINA', Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Simon, Marie Francoise, and Régulations cellulaires: lipidoses et atherosclerose.
Subjects: MESH: Oxidation-Reduction, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, MESH: Lipoproteins, LDL, Physiology, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Apoptosis, ATHEROGENESIS, Endoplasmic Reticulum, medicine.disease_cause, Biochemistry, MESH: Dose-Response Relationship, Drug, Lipid peroxidation, chemistry.chemical_compound, 0302 clinical medicine, MESH: Structure-Activity Relationship, ATHEROSCLEROTIC LESIONS, ENDOPLASMIC-RETICULUM STRESS, Protein disulfide-isomerase, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, General Environmental Science, 0303 health sciences, OXIDATIVE MODIFICATION, MESH: Oxidative Stress, biology, U937 Cells, Cell biology, [SDV] Life Sciences [q-bio], Lipoproteins, LDL, 030220 oncology & carcinogenesis, POTENTIAL ROLE, SURVIVAL, lipids (amino acids, peptides, and proteins), Oxidation-Reduction, MESH: Cells, Cultured, inorganic chemicals, Protein Disulfide-Isomerases, MESH: U937 Cells, Structure-Activity Relationship, 03 medical and health sciences, INFLAMMATION, MESH: Endoplasmic Reticulum, medicine, Humans, MESH: Protein Disulfide-Isomerases, LIPID-PEROXIDATION PRODUCTS, Molecular Biology, 030304 developmental biology, MESH: Humans, Dose-Response Relationship, Drug, Endoplasmic reticulum, MESH: Apoptosis, Cell Biology, nervous system diseases, body regions, Oxidative Stress, chemistry, CELL-DEATH, Chaperone (protein), Unfolded protein response, biology.protein, General Earth and Planetary Sciences, Pyridoxamine, LDL-INDUCED APOPTOSIS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Oxidative stress
Abstract: Aims: Protein disulfide isomerase (PDI) is an abundant endoplasmic reticulum (ER)-resident chaperone and oxidoreductase that catalyzes formation and rearrangement (isomerization) of disulfide bonds, thereby participating in protein folding. PDI modification by nitrosative stress is known to increase protein misfolding, ER stress, and neuronal apoptosis. As LDL oxidation and ER stress may play a role in atherogenesis, this work was designed to investigate whether PDI was inactivated by oxLDLs, thereby participating in oxLDL-induced ER stress and apoptosis. Results: Preincubation of human endothelial HMEC-1 and of macrophagic U937 cells with toxic concentration of oxLDLs induced PDI inhibition and modification, as assessed by 4-HNE-PDI adducts formation. PDI inhibition by bacitracin potentiated ER stress (increased mRNA expression of CHOP and sXBP1) and apoptosis induced by oxLDLs. In contrast, increased PDI activity by overexpression of an active wild-type PDI was associated with reduced oxLDL-induced ER stress and toxicity, whereas the overexpression of a mutant inactive form was not protective. These effects on PDI were mimicked by exogenous 4-HNE and prevented by the carbonyl-scavengers N-acetylcysteine and pyridoxamine, which reduced CHOP expression and toxicity by oxLDLs. Interestingly, 4-HNE-modified PDI was detected in the lipid-rich areas of human advanced atherosclerotic lesions. Innovation and Conclusions: PDI modification by oxLDLs or by reactive carbonyls inhibits its enzymatic activity and potentiates both ER stress and apoptosis by oxLDLs. PDI modification by lipid peroxidation products in atherosclerotic lesions suggests that a loss of function of PDI may occur in vivo, and may contribute to local ER stress, apoptosis, and plaque progression. Antioxid. Redox Signal. 18, 731-742.
Published: 2013

13. Synthesis and antioxidant activity evaluation of a syringic hydrazones family

Author: Benaissa Bouguerne, Michel Baltas, Hubert Duran, Robert Salvayre, Corinne Bernis, Nadji Belkheiri, Florence Bedos-Belval, Anne Nègre-Salvayre, Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Régulations cellulaires: lipidoses et atherosclerose, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, and Régulations cellulaires: lipidoses et atherosclerose.
Subjects: Antioxidant, DPPH, medicine.medical_treatment, Protein Carbonyl Content, [SDV]Life Sciences [q-bio], Trolox equivalent antioxidant capacity, 010402 general chemistry, 01 natural sciences, Medicinal chemistry, Syringaldehyde, Antioxidants, chemistry.chemical_compound, Picrates, Superoxides, [CHIM] Chemical Sciences, Drug Discovery, medicine, TBARS, Organic chemistry, [CHIM]Chemical Sciences, Humans, Lipoprotein oxidation, Benzothiazoles, ComputingMilieux_MISCELLANEOUS, Pharmacology, ABTS, 010405 organic chemistry, Chemistry, Organic Chemistry, Biphenyl Compounds, Carbonyl stress, Hydrazones, Endothelial Cells, General Medicine, Free Radical Scavengers, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Atherosclerosis, 0104 chemical sciences, Lipoproteins, LDL, Thiazoles, Oxidative stress, Sulfonic Acids, LDL oxidation, Syringic hydrazones, Oxidation-Reduction, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; A novel series of hydrazones derived from syringaldehyde and their antioxidant properties have been explored. Several employed methods such as scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(+)) radical cation expressed as Trolox equivalent antioxidant capacity (TEAC), inhibition of superoxide anion (O(2)(-)) generation and of human cell-mediated low-density lipoprotein oxidation (monitored by the formation of TBARS) exhibited their potent antioxidant properties. The carbonyl scavenger efficacy was also evaluated by measuring the ability to decrease the protein carbonyl content in cells challenged with oxidized LDL. In this report, we discuss about the synthesis of hydrazones and their dual biological role, antioxidant and carbonyl scavenger for further application in atherosclerosis.
Published: 2010

14. Cytokines correlate with age in healthy volunteers, dialysis patients and kidney-transplant patients

Author: Torsten Böhler, Cindy Canivet, Dominique Durand, Anne Nègre-Salvayre, Nassim Kamar, Lionel Rostaing, Phuong Ngan Le Nguyen, Sylvain Galvani, Mogens Thomsen, Robert Salvayre, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Gambro Dialysatoren GmbH, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie, dialyse et transplantation [Hôpital de Rangueil, Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Régulations cellulaires: lipidoses et atherosclerose., CHU Toulouse [Toulouse]-Hôpital de Rangueil, and CHU Toulouse [Toulouse]
Subjects: Male, Aging, T-Lymphocytes, medicine.medical_treatment, [SDV]Life Sciences [q-bio], MESH: Interleukin-2 Receptor alpha Subunit, 030232 urology & nephrology, Lymphocyte proliferation, 030204 cardiovascular system & hematology, Biochemistry, Gastroenterology, MESH: Kidney Transplantation, 0302 clinical medicine, Immunology and Allergy, MESH: Aging, MESH: Renal Dialysis, MESH: Antigens, CD, ComputingMilieux_MISCELLANEOUS, MESH: Cytokines, MESH: Middle Aged, Hematology, Middle Aged, 3. Good health, Cytokine, Cytokines, Biomarker (medicine), Female, medicine.drug, Adult, medicine.medical_specialty, Immunology, Mycophenolic acid, Sepsis, 03 medical and health sciences, Antigens, CD, Renal Dialysis, Internal medicine, MESH: Cell Proliferation, Receptors, Transferrin, medicine, Humans, MESH: Receptors, Transferrin, Molecular Biology, Dialysis, Cell Proliferation, MESH: Humans, Tumor Necrosis Factor-alpha, business.industry, Interleukin-2 Receptor alpha Subunit, MESH: Biological Markers, MESH: Adult, MESH: Interleukin-2, medicine.disease, Kidney Transplantation, Tacrolimus, MESH: Male, Transplantation, MESH: T-Lymphocytes, MESH: Tumor Necrosis Factor-alpha, Interleukin-2, business, MESH: Female, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; T-cell functions are currently used as biomarkers for the pharmacodynamic monitoring of immunosuppressive drugs or as disease biomarkers of inflammation/sepsis and organ rejection. In order to evaluate co-factors potentially influencing the expression of the immunological biomarkers, we explored T-cell proliferation, T-cell activation (CD25 and CD71 expressions) and intra-lymphocyte cytokine production (interleukin (IL)-2 and tumor necrosis factor (TNF)-alpha) in healthy volunteers, dialysis patients and stable kidney-transplant patients treated with standard immunosuppressive therapy, i.e. tacrolimus, mycophenolic acid with or without steroids. Age was positively correlated with TNF-alpha expression in all three patient populations, and with IL-2 expression in healthy volunteers and kidney-transplant patients. Further age was correlated with inhibition of lymphocyte proliferation in healthy volunteers and with the T-cell activation marker CD25 in kidney-transplant patients. In healthy volunteers lymphocyte proliferation was higher in woman as compared to men. Other biomarkers of T-cell function were independent of the gender. In the kidney-transplant patient group a significantly lower expression of all biomarkers of T-cell functions compared to healthy volunteers and dialysis patients. In dialysis patients we found significant increased IL-2 expression compared to healthy volunteers, while the other T-cell functions were not significantly different. Further time on dialysis had no effect on the level of biomarker expression. In conclusion we found decreased T-cell functions in kidney-transplant patients compared to healthy volunteers and dialysis patients, increased IL-2 expression in dialysis patients compared to healthy volunteers and in all three populations we found a correlation of age and intra-T-lymphocyte TNF-alpha expression.
Published: 2009

15. Small, dense HDL3 particles attenuates apoptosis in endothelial cells: Pivotal role of apolipoprotein A-I

Author: Robert Salvayre, Anne Nègre-Salvayre, Kerry-Anne Rye, Martine Couturier, Patrice Thérond, Juliana A. de Souza, Cécile Vindis, Anatol Kontush, M. John Chapman, S. Chantepie, Dyslipoproteinémies et athérosclerose : Génétique, métabolisme et thérapeutique, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Heart Research Institute, Department of Biochemistry, Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Régulations cellulaires: lipidoses et atherosclerose., IFR 31 Louis Bugnard ( IFR 31 ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Apolipoprotein B, [SDV]Life Sciences [q-bio], Immunoblotting, anti-oxidative activity, Apoptosis, 030204 cardiovascular system & hematology, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sphingosine, Annexin, Humans, HDL particle heterogeneity, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, reactive oxygen species, 0303 health sciences, Apolipoprotein A-I, biology, Caspase 3, Cholesterol, Cytochrome c, Cytochromes c, Endothelial Cells, nutritional and metabolic diseases, Lipoproteins, HDL3, Articles, Cell Biology, Cytoprotection, Molecular biology, Cell biology, Lipoproteins, LDL, chemistry, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], anti-apoptotic activity, sphingosine-1-phosphate, biology.protein, Molecular Medicine, Density gradient ultracentrifugation, lipids (amino acids, peptides, and proteins), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Lysophospholipids, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, BH3 Interacting Domain Death Agonist Protein, Lipoprotein
Abstract: International audience; Abstract Plasma high-density lipoprotein (HDL) protect endothelial cells against apoptosis induced by oxidatively modified low-density lipoprotein (oxLDL). The specific component(s) of HDL implicated in such cytoprotection remain(s) to be identified. Human microvascular endothelial cells (HMEC-1) were incubated with mildly oxLDL in the presence or absence of each of five physicochemically-distinct HDL subpopulations fractionated from normolipidemic human plasma (n=7) by isopycnic density gradient ultracentrifugation. All HDL subfractions protected HMEC-1 against oxLDL-induced primary apoptosis as revealed by nucleic acid staining, annexin V binding, quantitative DNA fragmentation, inhibition of caspase-3 activity, and reduction of cytoplasmic release of cytochrome c and apoptosis-inducing factor. Small, dense HDL3c displayed twofold superior intrinsic cytoprotective activity (as determined by mitochondrial dehydrogenase activity) relative to large, light HDL2b on a per particle basis (p
Published: 2009

16. Polyoma BK virus-associated nephropathy in kidney-transplant patients: Effects of leflunomide on T-cell functions and disease outcome

Author: Torsten Böhler, Catherine Mengelle, Robert Salvayre, Nassim Kamar, Anne Nègre-Salvayre, Cindy Canivet, Lionel Rostaing, Mogens Thomsen, Peggy Gandia, Céline Guilbeau-Frugier, Sylvain Galvani, Simon, Marie Francoise, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Pharmacocinétique et de Toxicologie [CHU Toulouse], Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie, dialyse et transplantation [Hôpital de Rangueil, Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse]-Hôpital de Rangueil, Laboratoire de Pharmacocinétique et de Toxicologie clinique [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], and Régulations cellulaires: lipidoses et atherosclerose.
Subjects: Graft Rejection, Male, T-Lymphocytes, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 030230 surgery, Kidney, medicine.disease_cause, Gastroenterology, 0302 clinical medicine, Immunology and Allergy, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, Leflunomide, Nephritis, Immunosuppression, Middle Aged, 3. Good health, BK virus, Treatment Outcome, Immunosuppressive drug, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Immunology, Mycophenolic acid, 03 medical and health sciences, Antigens, CD, Internal medicine, Receptors, Transferrin, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Cell Proliferation, Pharmacology, Polyomavirus Infections, Tumor Necrosis Factor-alpha, business.industry, Interleukin-2 Receptor alpha Subunit, Isoxazoles, Mycophenolic Acid, medicine.disease, Kidney Transplantation, Tacrolimus, Transplantation, BK Virus, Interleukin-2, business, Follow-Up Studies
Abstract: International audience; BACKGROUND: In kidney-transplant recipients, leflunomide has been shown to be efficient for treating polyomavirus BK virus-associated-nephropathy (PVAN). However, it is unknown whether the beneficial effect of leflunomide is related to it having a lower immunosuppressive effect than mycophenolate mofetil (MMF), or to its anti-viral activity. The aim of this study was to assess i) T-cell functions before and after conversion from MMF to leflunomide in kidney-transplant patients with PVAN, and ii) effects of leflunomide on PVAN outcome. PATIENTS AND METHODS: Twelve patients were enrolled in this study. At PVAN diagnosis, MMF was replaced by leflunomide. Other immunosuppressive drug doses and levels were maintained unchanged. T-cell functions, i.e., intralymphocyte cytokine expression (IL-2 and TNF-alpha), T-cell activation [i.e., transferrin receptor (CD71) and interleukin (IL)-2 alpha-chain (CD25) expression], and T-cell proliferation were measured using a flow-cytometry whole-blood assay before and at one month after conversion. RESULTS: Despite a slight decrease in tacrolimus trough levels, no significant change in T-cell-function biomarkers was observed after conversion. After a follow-up of 6 (4-30) months, five patients were cleared of the virus, and decreased viral load was observed in four patients. Only one patient suffered a graft loss. No difference in immunological parameters was observed between patients who were cleared or not of BKV. CONCLUSION: Results of this pilot study suggest that the potential benefits of leflunomide to treat PVAN in kidney-transplant patients is not related to reduced immunosuppression induced by replacing MMF by leflunomide. Virological studies are required to determine the anti-BKV effect of leflunomide.
Published: 2009

17. The type 1 TNF receptor and its associated adapter protein, FAN, are required for TNFalpha-induced sickness behavior

Author: Rose Marie Bluthé, Robert Dantzer, Keith W. Kelley, Karine Palin, Thierry Levade, Françoise Moos, Robert H. McCusker, Laboratory of Integrative Immunophysiology, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System-University of Illinois System-Integrative Immunology and Behavior Program, Neurobiologie intégrative (NI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Régulations cellulaires: lipidoses et atherosclerose., Simon, Marie Francoise, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH: Signal Transduction, medicine.medical_treatment, [SDV]Life Sciences [q-bio], MOUSE, MESH: Mice, Knockout, chemistry.chemical_compound, Mice, SICKNESS BEHAVIOR, MESH: Behavior, Animal, MESH: Receptors, Tumor Necrosis Factor, Type II, MESH: Animals, Sickness behavior, Mice, Knockout, MESH: Receptors, Tumor Necrosis Factor, Type I, Behavior, Animal, Intracellular Signaling Peptides and Proteins, Signal transducing adaptor protein, CANCER, [SDV] Life Sciences [q-bio], Cytokine, Receptors, Tumor Necrosis Factor, Type I, Tumor necrosis factor alpha, TNF RECEPTOR, MESH: Exploratory Behavior, Signal transduction, MESH: Injections, Intraventricular, Sphingomyelin, Tumor necrosis factor receptor, Signal Transduction, medicine.medical_specialty, Ceramide, Biology, Article, MESH: Weight Loss, MESH: Mice, Inbred C57BL, Internal medicine, MESH: Intracellular Signaling Peptides and Proteins, Weight Loss, medicine, GENE DEFICIENCY, Animals, Receptors, Tumor Necrosis Factor, Type II, MESH: Mice, SPHINGOMYELINASE NEUTRE, Injections, Intraventricular, Pharmacology, CERAMIDE, Tumor Necrosis Factor-alpha, FAN, MESH: Male, Mice, Inbred C57BL, CYTOKINE, Endocrinology, chemistry, MESH: Tumor Necrosis Factor-alpha, Immunology, SOCIAL EXPLORATION, Exploratory Behavior, human activities
Abstract: International audience; RATIONALE: During the course of an infection, the pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha) acts in the brain to trigger development of behavioral responses, collectively termed sickness behavior. Biological activities of TNFalpha can be mediated by TNF receptor type 1 (TNF-R1) and type 2 (TNF-R2). TNFalpha activates neutral sphingomyelinase through the TNF-R1 adapter protein FAN (factor associated with neutral sphingomyelinase activation), but a behavioral role of FAN in the brain has never been reported. OBJECTIVES: We hypothesized that TNFalpha-induced sickness behavior requires TNF-R1 and that FAN is a necessary component for this response. MATERIALS AND METHODS: We determined the role of brain TNF-R1 in sickness behavior by administering an optimal amount of TNFalpha intracerebroventricularly (i.c.v., 50 ng/mouse) to wild-type (WT), TNF-R1-, TNF-R2-, and FAN-deficient mice. Sickness was assessed by decreased social exploration of a novel juvenile, induction of immobility, and loss of body weight. RESULTS: TNF-R1-deficient mice were resistant to the sickness-inducing properties of i.c.v. TNFalpha, whereas both TNF-R2-deficient and WT mice were fully responsive. Furthermore, the complete absence of TNFalpha-induced sickness behavior in FAN-deficient mice provided in vivo evidence that FAN-dependent TNF-R1 signaling is critical for this central action of TNFalpha. CONCLUSIONS: This is the first report to demonstrate that TNFalpha-induced sickness behavior is fully mediated by TNF-R1 and that the adaptor protein FAN is a necessary intracellular intermediate for sickness behavior.
Published: 2009

18. Metabolic syndrome features small, apolipoprotein A-I-poor, triglyceride-rich HDL3 particles with defective anti-apoptotic activity

Author: Juliana A. de Souza, Carlos V. Serrano, Anatol Kontush, M. John Chapman, Anne Nègre-Salvayre, S. Chantepie, Cécile Vindis, Robert Salvayre, Boris Hansel, P. Thérond, Eric Bruckert, Heart Institute, Universidade de São Paulo = University of São Paulo (USP), Dyslipoproteinémies et athérosclerose : Génétique, métabolisme et thérapeutique, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biochimie, Université Paris Descartes - Paris 5 (UPD5), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Simon, Marie Francoise, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of São Paulo (USP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of São Paulo ( USP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Régulations cellulaires: lipidoses et atherosclerose., IFR 31 Louis Bugnard ( IFR 31 ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), and CHU Pitié-Salpêtrière [APHP]
Subjects: Male, MESH: Lipoproteins, LDL, Apolipoprotein B, medicine.medical_treatment, MESH: Apolipoprotein A-I, MESH : Reactive Oxygen Species, Apoptosis, 030204 cardiovascular system & hematology, medicine.disease_cause, chemistry.chemical_compound, 0302 clinical medicine, MESH: Metabolic Syndrome X, MESH : Particle Size, MESH: Endothelial Cells, Metabolic Syndrome, 0303 health sciences, MESH: Middle Aged, MESH: Reactive Oxygen Species, Middle Aged, MESH : Triglycerides, Lipoproteins, LDL, MESH: Insulin Resistance, MESH : Cholesterol, HDL, Cholesteryl ester, lipids (amino acids, peptides, and proteins), MESH : Apolipoprotein A-I, MESH: Cholesterol, HDL, MESH : Insulin Resistance, MESH : Lipoproteins, LDL, Cardiology and Cardiovascular Medicine, MESH: Triglycerides, medicine.medical_specialty, MESH : Male, MESH : Metabolic Syndrome X, Biology, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Humans, MESH : Middle Aged, MESH: Particle Size, Particle Size, Triglycerides, 030304 developmental biology, MESH: Humans, Apolipoprotein A-I, MESH : Endothelial Cells, Insulin, MESH: Apoptosis, MESH : Humans, Cholesterol, HDL, Hypertriglyceridemia, Endothelial Cells, medicine.disease, MESH: Male, Endocrinology, chemistry, biology.protein, Insulin Resistance, Metabolic syndrome, Reactive Oxygen Species, MESH : Apoptosis, Oxidative stress, Lipoprotein
Abstract: International audience; The metabolic syndrome (MetS) phenotype is typically characterized by visceral obesity, insulin resistance, atherogenic dyslipidemia involving hypertriglyceridemia and subnormal levels of high density lipoprotein-cholesterol (HDL-C), oxidative stress and elevated cardiovascular risk. The potent antioxidative activity of small HDL3 is defective in MetS [Hansel B, et al. J Clin Endocrinol Metab 2004;89:4963-71]. We evaluated the functional capacity of small HDL3 particles from MetS subjects to protect endothelial cells from apoptosis induced by mildly oxidized low-density lipoprotein (oxLDL). MetS subjects presented an insulin-resistant obese phenotype, with hypertriglyceridemia, elevated apolipoprotein B and insulin levels, but subnormal HDL-C concentrations and chronic low grade inflammation (threefold elevation of C-reactive protein). When human microvascular endothelial cells (HMEC-1) were incubated with oxLDL (200 microg apolipoprotein B/ml) in the presence or absence of control HDL subfractions (25 microg protein/ml), small, dense HDL3b and 3c significantly inhibited cellular annexin V binding and intracellular generation of reactive oxygen species. The potent anti-apoptotic activity of small HDL3c particles was reduced (-35%; p
Published: 2008

19. Preferential sphingosine-1-phosphate enrichment and sphingomyelin depletion are key features of small dense HDL3 particles: relevance to antiapoptotic and antioxidative activities

Author: Martine Couturier, Amal Zerrad, Patrice Thérond, Anatol Kontush, M. John Chapman, Juliana A. de Souza, S. Chantepie, Anne Nègre-Salvayre, Dyslipoproteinémies et athérosclerose : Génétique, métabolisme et thérapeutique, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de biochimie, Université Paris Descartes - Paris 5 (UPD5), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Pitié-Salpêtrière [APHP], Université Paris Descartes - Paris 5 ( UPD5 ), Régulations cellulaires: lipidoses et atherosclerose., IFR 31 Louis Bugnard ( IFR 31 ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: MESH : Oxidative Stress, MESH: Oxidation-Reduction, MESH: Lipoproteins, HDL3, MESH : Dyslipidemias, Apoptosis, MESH : Cholesterol, LDL, 030204 cardiovascular system & hematology, MESH: Sphingomyelins, Antioxidants, chemistry.chemical_compound, 0302 clinical medicine, Reference Values, Sphingosine, MESH : Particle Size, MESH : Sphingosine, 0303 health sciences, MESH: Oxidative Stress, MESH: Reference Values, Lipoproteins, HDL3, Sphingomyelins, Biochemistry, MESH : Cholesterol, HDL, MESH : Antioxidants, lipids (amino acids, peptides, and proteins), Cholesterol Esters, MESH : Sensitivity and Specificity, MESH: Sphingosine, MESH: Cholesterol, HDL, Cardiology and Cardiovascular Medicine, Sphingomyelin, Oxidation-Reduction, MESH: Cholesterol, LDL, MESH : Sphingomyelins, MESH: Enzyme Activation, MESH : Cholesterol Esters, MESH: Probability, MESH : Probability, Phospholipid, MESH : Reference Values, Sensitivity and Specificity, MESH: Lysophospholipids, 03 medical and health sciences, Enzyme activator, Humans, Sphingosine-1-phosphate, MESH: Particle Size, Particle Size, Dyslipidemias, Probability, 030304 developmental biology, MESH : Oxidation-Reduction, MESH: Humans, Cholesterol, MESH: Apoptosis, Cholesterol, HDL, MESH : Humans, MESH: Antioxidants, MESH: Dyslipidemias, Cholesterol, LDL, Key features, Sphingolipid, MESH: Sensitivity and Specificity, Enzyme Activation, Oxidative Stress, chemistry, MESH : Lipoproteins, HDL3, MESH : Lysophospholipids, MESH: Cholesterol Esters, Molecular Profile, Lysophospholipids, MESH : Enzyme Activation, MESH : Apoptosis
Abstract: Objective— The purpose of this study was to define heterogeneity in the molecular profile of lipids, including sphingomyelin and sphingosine-1-phosphate, among physicochemically-defined HDL subpopulations and potential relevance to antiatherogenic biological activities of dense HDL3. Methods and Results— The molecular profile of lipids (cholesteryl esters, phospholipids, sphingomyelin, and sphingosine-1-phosphate) in physicochemically-defined normolipidemic HDL subpopulations was determined by high-performance liquid chromatography and gas chromatography. As HDL particle size and molecular weight decreased with increment in density, molar lipid content diminished concomitantly. On a % basis, sphingomyelin abundance diminished in parallel with progressive increase in HDL density from HDL2b (12.8%) to HDL3c (6.2%; P P r =0.73, P r =0.58, P Conclusions— An elevated sphingosine-1-phosphate/sphingomyelin ratio is an integral feature of small dense HDL3, reflecting enrichment in sphingosine-1-phosphate, a key antiapoptotic molecule, and depletion of sphingomyelin, a structural lipid with negative impact on surface fluidity and LCAT activity. These findings further distinguish the structure and antiatherogenic activities of small, dense HDL.
Published: 2007

20. Daunorubicin- and Mitoxantrone-Triggered Phosphatidylcholine Hydrolysis: Implication in Drug-Induced Ceramide Generation and Apoptosis

Author: Thierry Levade, Jean-Pierre Jaffrézou, Guy Laurent, Ali Bettaieb, Anne Quillet-Mary, V Mansat-De Mas, Isabelle Plo, Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Régulations cellulaires: lipidoses et atherosclerose.
Subjects: Bridged-Ring Compounds, Programmed cell death, Ceramide, Daunorubicin, Apoptosis, DNA Fragmentation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Ceramides, Diglycerides, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Thiocarbamates, Tumor Cells, Cultured, medicine, Humans, Protein Kinase C, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Diacylglycerol kinase, Pharmacology, 0303 health sciences, Phospholipase C, Phosphorylcholine, Hydrolysis, Thiones, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Lipid signaling, Norbornanes, 3. Good health, chemistry, Biochemistry, 030220 oncology & carcinogenesis, Phosphatidylcholines, Molecular Medicine, lipids (amino acids, peptides, and proteins), Mitoxantrone, medicine.drug
Abstract: Several studies have suggested that diacylglycerol can affect the induction of apoptosis induced by toxicants and ceramide. The present study demonstrates that clinically relevant concentrations of the chemotherapeutic drugs daunorubicin and mitoxantrone (0.2-1 microM) transiently stimulated concurrently with sphingomyelin-derived ceramide generation and diacylglycerol and phosphorylcholine production within 4 to 10 min via phospholipase C hydrolysis of phosphatidylcholine. Pretreatment of cells with the xanthogenate compound D609, a potent inhibitor of phosphatidylcholine-phospholipase C, led to significant inhibition of drug triggered diacylglycerol and phosphorylcholine production and to a sustained increase in ceramide levels for a period up to 2 h. Moreover, D609 pretreatment induced both cell death and ceramide generation at daunorubicin and mitoxantrone concentrations previously shown to be ineffective (i.e., 0.1 microM). These results underline the importance of diacylglycerol in the regulation of programmed cell death and strongly argue for a balance between apoptotic (ceramide) and survival (diacylglycerol) signal transducers.
Published: 1999

21. A gain-of-function RAC2 mutation is associated with bone-marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency

Author: Chantal, Lagresle-Peyrou, Aurélien, Olichon, Hanem, Sadek, Philippe, Roche, Claudine, Tardy, Cindy, Da Silva, Alexandrine, Garrigue, Alain, Fischer, Despina, Moshous, Yves, Collette, Capucine, Picard, Jean Laurent, Casanova, Isabelle, André, Marina, Cavazzana, Human Lymphohematopoiesis Laboratory (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Bidaut, Ghislain, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM] Life Sciences [q-bio]/Immunology, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Hematopoietic Stem Cell, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Bone Marrow Failure Disorders, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Bone Marrow Failure, Article, Immunodeficiencies, rac GTP-Binding Proteins, Hematopoiesis, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Bone Marrow, Gain of Function Mutation, Mutation, Leukemic Stem Cell, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Severe Combined Immunodeficiency, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: International audience; Severe combined immunodeficiencies (SCIDs) constitute a heterogeneous group of life-threatening genetic disorders that typically present in the first year of life. They are defined by the absence of autologous T cells and the presence of an intrinsic or extrinsic defect in the B-cell compartment. In three newborns presenting with frequent infections and profound leukopenia, we identified a private, heterozygous mutation in the RAC2 gene (p.G12R). This mutation was de novo in the index case, who had been cured by hematopoietic stem cell transplantation but had transmitted the mutation to her sick daughter. Biochemical assays showed that the mutation was associated with a gain of function. The results of in vitro differentiation assays showed that RAC2 is essential for the survival and differentiation of hematopoietic stem/progenitor cells. Therefore, screening for RAC2 gain-of-function mutations should be considered in patients with a SCID phenotype and who lack a molecular diagnosis.
Published: 2020

22. Iron gene expression profile in atherogenic Mox macrophages

Author: Liliana Marques, François Canonne-Hergaux, Anne Nègre-Salvayre, Luciana Costa, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Departamento da Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Universidade de Lisboa (ULISBOA), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Instituto Nacional de Saúde Doutor Ricardo Jorge [Lisboa], University of Lisbon, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR 31 Louis Bugnard (IFR 31), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]
Subjects: 0301 basic medicine, HMOX1, Macrophage, [SDV]Life Sciences [q-bio], Proinflammatory Stimuli, Ferroportin, 030204 cardiovascular system & hematology, Bioinformatics, 0302 clinical medicine, lipid metabolism, cytokine proinflammatoire, Cation Transport Proteins, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Proinflammatory stimuli, education.field_of_study, biology, Chemistry, Acetylation, Iron metabolism, Up-Regulation, Lipoproteins, LDL, Molecular Medicine, lipids (amino acids, peptides, and proteins), HAMP, Iron Metabolism, Determinantes Imunológicos em Doenças Crónicas, Oxidized LDL, expression génique, Iron, Population, macrophage humain, Proinflammatory cytokine, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Downregulation and upregulation, Hepcidin, Animals, Humans, atherogénèse, métabolisme du fer, education, Molecular Biology, métabolisme lipidique, Macrophages, Membrane Proteins, Mox, Atherosclerosis, Molecular biology, Mice, Inbred C57BL, 030104 developmental biology, LDL receptor, gene expression, biology.protein, Transcriptome, Heme Oxygenase-1, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Rationale The role of macrophage iron in the physiopathology of atherosclerosis is an open question that needs to be clarified. In atherosclerotic lesions, recruited macrophages are submitted to cytokines and oxidized lipids which influence their phenotype. An important phenotypic population driven by oxidized phospholipids is the Mox macrophages which present unique biological properties but their iron phenotype is not well described. Objective To investigate the effect of Mox polarization by oxidized LDL (oxLDL) on macrophage iron metabolism in the absence or presence of proinflammatory stimuli. Methods Bone marrow-derived macrophages were treated with different sources of LDL and/or LPS/IFNγ (M1 activator). Expression of ferroportin (Slc40a1, alias Fpn), heme oxygenase-1 (Hmox1), H- and L-ferritin (Fth1 and Ftl1), hepcidin (Hamp), ceruloplasmin (Cp) and interleukine-6 (Il6) was followed by quantitative PCR. FPN and HMOX1 protein expression was analyzed by immunofluorescence and in-cell-Western blotting. Results Mox macrophages expressed increased Hmox1 and Fth1 levels with basal FPN protein levels despite the significant increase of Fpn mRNA. Upregulation of Hmox1 and Fpn mRNA was specific to LDL oxidative modification and mediated by NRF2. The downregulation of both Cp isoforms and the upregulation of Hamp expression observed in Mox macrophages suggest that FPN mediated iron export could be compromised. Simultaneous exposure to oxLDL and LPS/IFNγ leads to a mixed Mox/M1 phenotype that is closer to M1. Conclusion A microenvironment rich in oxLDL and proinflammatory cytokines could promote macrophage iron retention and lipid accumulation profiles, a specific cell phenotype that likely contributes to lesion development and plaque instability in atherosclerosis.
Published: 2016

23. nSMase2 (Type 2-Neutral Sphingomyelinase) Deficiency or Inhibition by GW4869 Reduces Inflammation and Atherosclerosis in Apoe −/− Mice

Author: Nancy Geoffre, Anne Nègre-Salvayre, Agnès Coste, Emeline Recazens, Marie-Hélène Grazide, Paul Alayrac, Myriam Rouahi, Audrey Swiader, Tom Lallemand, Robert Salvayre, Nathalie Augé, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Inst Malad Metabol & Cardiovasc, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U1048 (I2CM), Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD)
Subjects: Male, 0301 basic medicine, Mice, Knockout, ApoE, NF-E2-Related Factor 2, [SDV]Life Sciences [q-bio], Anti-Inflammatory Agents, Aortic Diseases, Sphingomyelinase deficiency, Inflammation, Disease, Benzylidene Compounds, Mice, 03 medical and health sciences, medicine, Animals, Enzyme Inhibitors, Aorta, ComputingMilieux_MISCELLANEOUS, Aniline Compounds, sphingolipids, Apoe mice, Basic Sciences, business.industry, Endothelial Cells, Atherosclerosis, Sphingolipid, Plaque, Atherosclerotic, macrophages, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, RAW 264.7 Cells, Sphingomyelin Phosphodiesterase, 030104 developmental biology, Immunology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Macrophages, Peritoneal, Inflammation Mediators, medicine.symptom, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract: Supplemental Digital Content is available in the text., Objective— Atherosclerosis is a chronic multifactorial and inflammatory disease of large and medium arteries and the leading cause of cardiovascular diseases worldwide. The aim of this study was to investigate whether and how the nSMase2 (type 2-neutral sphingomyelinase), a key enzyme of sphingolipid metabolism, may contribute to the development of atherosclerotic lesions. Approach and Results— The role of nSMase2 in atherosclerosis was investigated in Apoe−/−;Smpd3fro/fro mice, mutant for nSMase2, and in Apoe−/−;Smpd3+/+ mice intraperitoneally injected with GW4869, a pharmacological nSMase2 inhibitor. The defect or inhibition of nSMase2 resulted in a reduction of atherosclerotic lesions and a decrease in macrophage infiltration and lipid deposition, although cholesterolemia remained unchanged. nSMase2 inhibition decreased the inflammatory response of murine endothelial cells to oxLDL (oxidized low-density lipoprotein), as assessed by the significant reduction of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1) mRNA expressions and macrophage recruitment. Likewise, in RAW264.7 or in macrophages isolated from Apoe−/−/Smpd3fro/fro or Apoe−/−/Smpd3+/+ mice stimulated by lipopolysaccharides, nSMase2 inhibition resulted in a decrease in the expression of inflammatory molecules. Mechanistically, the anti-inflammatory response resulting from nSMase2 inhibition involves Nrf2 (nuclear factor [erythroid-derived 2]-like 2 or NF-E2–related factor-2) activation in both endothelial cells and macrophages, as assessed by the lack of protective effect of GW4869 in endothelial cells silenced for Nrf2 by small interfering RNAs, and in lipopolysaccharide-stimulated macrophages issued from Nrf2-KO mice. Conclusions— The genetic deficiency or inhibition of nSMase2 strongly decreases the development of atherosclerotic lesions in Apoe−/− mice, by reducing inflammatory responses through a mechanism involving the Nrf2 pathway. Inhibitors of nSMase2 may, therefore, constitute a novel approach to slow down atherosclerosis progression.
Published: 2018

24. Synthesis and biological evaluation of diarylheptanoids as potential antioxidant and anti-inflammatory agents

Author: Anne Nègre-Salvayre, Florence Bedos-Belval, Corinne Vanucci-Bacqué, Michel Baltas, Kelly Maurent, Nathalie Augé, Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Bedos-Belval, Florence, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Lipopolysaccharides, 0301 basic medicine, Antioxidant, Lipopolysaccharide, medicine.medical_treatment, Pharmacology, medicine.disease_cause, 01 natural sciences, Antioxidants, Mice, chemistry.chemical_compound, Drug Discovery, [CHIM] Chemical Sciences, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Molecular Structure, Anti-Inflammatory Agents, Non-Steroidal, Diarylheptanoid, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Macrocycle, Cell Survival, medicine.drug_class, Anti-inflammatory, Proinflammatory cytokine, Structure-Activity Relationship, 03 medical and health sciences, Anti-inflammatory activity, Diarylheptanoids, medicine, Animals, [CHIM]Chemical Sciences, Reactive oxygen species, Dose-Response Relationship, Drug, 010405 organic chemistry, Macrophages, Organic Chemistry, 0104 chemical sciences, RAW 264.7 Cells, 030104 developmental biology, chemistry, Reactive Oxygen Species, Oxidative stress
Abstract: International audience; Reactive oxygen species (ROS) are key signaling molecules and their overproduction plays an important role in the inflammation process, the secretion of inflammatory cytokines such as IL-1β and IL-6 and the progression of inflammatory disorders. Decreasing oxidative stress represents a promising challenge in the design of antioxidant and anti-inflammatory agents. In the present study, a series of new diarylheptanoids containing allylic alcohol, amide, hydantoin or triazole fragments were synthesized and fully characterized. We evaluated the ability of these agents to block the production of intracellular ROS and the subsequent inflammatory events exerted by lipopolysaccharide (LPS) on murine macrophage RAW 264.7. Five diarylheptanoids were found to exhibit the dual required properties.
Published: 2018

25. Hyaluronan synthase-2 upregulation protects smpd3-deficient fibroblasts against cell death induced by nutrient deprivation, but not against apoptosis evoked by oxidized LDL

Author: Anne Nègre-Salvayre, Elodie Mucher, Robert Salvayre, Myriam Rouahi, Sandra Garoby-Salom, Nathalie Augé, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: HA, hyaluronan, [SDV]Life Sciences [q-bio], Clinical Biochemistry, HSP72 Heat-Shock Proteins, Apoptosis, Biochemistry, Hsp72, LDL, low density lipoprotein, chemistry.chemical_compound, Mice, Glucuronosyltransferase, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, lcsh:R5-920, Cell biology, Lipoproteins, LDL, nSMase2, neutral sphingomyelinase type 2, Sphingomyelin Phosphodiesterase, Neutral sphingomyelinase-2, Toxicity, Sphingomyelin, lcsh:Medicine (General), Research Paper, Signal Transduction, Transcriptional Activation, Oxidized LDL, Programmed cell death, Ceramide, medicine.medical_specialty, Biology, Hyaluronan Synthase 2, Downregulation and upregulation, Internal medicine, medicine, Animals, HAS2, hyaluronan synthase 2, Hyaluronan synthase-2, Organic Chemistry, Nutrient starvation, Hydrogen Peroxide, Fibroblasts, Sphingolipid, Endocrinology, chemistry, Gene Expression Regulation, lcsh:Biology (General), Hyaluronan Synthases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The neutral type 2 sphingomyelinase (nSMase2) hydrolyzes sphingomyelin and generates ceramide, a major bioactive sphingolipid mediator, involved in growth arrest and apoptosis. The role of nSMase2 in apoptosis is debated, and apparently contradictory results have been observed on fibroblasts isolated from nSMase2-deficient fragilitas ossium (homozygous fro/fro) mice. These mice exhibit a severe neonatal dysplasia, a lack of long bone mineralization and delayed apoptosis patterns of hypertrophic chondrocytes in the growth plate. We hypothesized that apoptosis induced by nutrient deprivation, which mimics the environmental modifications of the growth plate, requires nSMase2 activation. In this study, we have compared the resistance of fro/fro fibroblasts to different death inducers (oxidized LDL, hydrogen peroxide and nutrient starvation). The data show that nSMase2-deficient fro/fro cells resist to apoptosis evoked by nutrient starvation (fetal calf serum/glucose/pyruvate-free DMEM), whereas wt fibroblasts die after 48 h incubation in this medium. In contrast, oxidized LDL and hydrogen peroxide are similarly toxic to fro/fro and wt fibroblasts, indicating that nSMase2 is not involved in the mechanism of toxicity evoked by these agents. Interestingly, wt fibroblasts treated with the SMase inhibitor GW4869 were more resistant to starvation-induced apoptosis. The resistance of fro/fro cells to starvation-induced apoptosis is associated with an increased expression of hyaluronan synthase 2 (HAS2) mRNAs and protein, which is inhibited by ceramide. In wt fibroblasts, this HAS2 rise and its protective effect did not occur, but exogenously added HA exhibited a protective effect against starvation-induced apoptosis. The protective mechanism of HAS2 involves an increased expression of the heat-shock protein Hsp72, a chaperone with antiapoptotic activity. Taken together, these results highlight the role of nSMase2 in apoptosis evoked by nutrient starvation that could contribute to the delayed apoptosis of hypertrophic chondrocytes in the growth plate, and emphasize the antiapoptotic properties of HAS2., Graphical abstract Nutrient starvation triggers apoptosis in wt fibroblasts, but not in fro/fro fibroblasts (in which nSMase2 is inactive). The resistance to nutrient deprivation-induced cell death in fro/fro cells is mediated by an increased expression of HAS2 and HA secretion and from the subsequent expression of the heat-shock protein Hsp72 that acts as a chaperone and anti-apoptotic protein. HAS2 is not protective against apoptosis evoked by oxLDL and H2O2, and fro/fro fibroblasts are not resistant to these agents., Highlights • Apoptosis evoked by oxidized LDL and H2O2 is comparable in fro/fro and wt fibroblasts. • fro/fro fibroblasts resist to apoptosis evoked by nutrient starvation. • HAS2 increased expression protects fro/fro fibroblasts against apoptosis. • HAS2 regulates the expression of the antiapoptotic heat-shock protein HsP72.
Published: 2015

26. Proatherogenic effects of 4-hydroxynonenal

Author: Mélanie Pucelle, Robert Salvayre, Myriam Rouahi, Sandra Garoby-Salom, Anne Nègre-Salvayre, Audrey Swiader, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, NF-E2-Related Factor 2, [SDV]Life Sciences [q-bio], Inflammation, medicine.disease_cause, Biochemistry, 4-Hydroxynonenal, 03 medical and health sciences, chemistry.chemical_compound, Growth factor receptor, Physiology (medical), medicine, Animals, Humans, Scavenger receptor, Aorta, ComputingMilieux_MISCELLANEOUS, Apolipoproteins B, Aldehydes, biology, Neovascularization, Pathologic, Chemistry, Macrophages, NF-kappa B, NF-κB, Atherosclerosis, Cell biology, Lipoproteins, LDL, 030104 developmental biology, Gene Expression Regulation, LDL receptor, biology.protein, Endothelium, Vascular, Lipid Peroxidation, medicine.symptom, Platelet-derived growth factor receptor, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract: 4-hydroxy-2-nonenal (HNE) is a α,β-unsaturated hydroxyalkenal generated by peroxidation of n-6 polyunsaturated fatty acid. This reactive carbonyl compound exhibits a huge number of biological properties that result mainly from the formation of HNE-adducts on free amino groups and thiol groups in proteins. In the vascular system, HNE adduct accumulation progressively leads to cellular dysfunction and tissue damages that are involved in the progression of atherosclerosis and related diseases. HNE contributes to the atherogenicity of oxidized LDL, by forming HNE-apoB adducts that deviate the LDL metabolism to the scavenger receptor pathway of macrophagic cells, and lead to the formation of foam cells. HNE activates transcription factors (Nrf2, NF-kappaB) that (dys)regulate various cellular responses ranging from hormetic and survival signaling at very low concentrations, to inflammatory and apoptotic effects at higher concentrations. Among a variety of cellular targets, HNE can modify signaling proteins involved in atherosclerotic plaque remodeling, particularly growth factor receptors (PDGFR, EGFR), cell cycle proteins, mitochondrial and endoplasmic reticulum components or extracellular matrix proteins, which progressively alters smooth muscle cell proliferation, angiogenesis and induces apoptosis. HNE adducts accumulate in the lipidic necrotic core of advanced atherosclerotic lesions, and may locally contribute to macrophage and smooth muscle cell apoptosis, which may induce plaque destabilization and rupture, thereby increasing the risk of athero-thrombotic events.
Published: 2017

27. Angiogenesis in the atherosclerotic plaque

Author: Anne Nègre-Salvayre, Robert Salvayre, Mélanie Pucelle, Caroline Camaré, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3)
Subjects: Apolipoprotein E, SMC, smooth muscle cell, nNOS, neuronal nitric oxide synthase, RTKs, receptor tyrosine kinase, Review Article, Matrix metalloproteinase, Fibroblast growth factor, Biochemistry, 0302 clinical medicine, ERK, extracellular signal-regulated kinase, RCT, reverse cholesterol transport, Medicine, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, ApoE, apolipoprotein E, ICAM-1, InterCellular Adhesion Molecule-1, Neovascularization, Pathologic, NADPH, H+, nicotinamide adenine dinucleotide phosphate, VCAM-1, Vascular Cell Adhesion Molecule-1, ABCG1, ATP-binding cassette sub-family G member 1, Plaque, Atherosclerotic, ECM, extracellular matrix, 3. Good health, S1PR, S1P receptors, FAK, focal adhesion kinase, S1P, sphingosine 1-phosphate, iNOS, inducible nitric oxide synthase, Disease Progression, lcsh:Medicine (General), ADMA, assymetric methylarginine, PI3K, phosphoinositide 3 kinase, Spns2, S1P carry spinster homolog 2, Hypercholesterolemia, PHD, prolyl hydroxylase, 03 medical and health sciences, TGF-β, transforming growth factor-β, PKC, protein kinase C, PUFA, polyunsaturated fatty acid, Humans, FGF, basic fibroblast growth factor, NRP-1, neuropilin-1, EGF, epidermal growth factor, NO, nitric oxide, SRC, Sarcoma tyrosine kinase, Cholesterol, TIMPs, Tissue Inhibitor of Metalloproteinases, Flt-1, fms-like tyrosine kinase-1, HDL, high density lipopoprotein, 030104 developmental biology, chemistry, NF-kB, nuclear factor kappaB, Immunology, FGFR, FGF receptor, Angiogenesis, PDGFR, PDGF receptor, 0301 basic medicine, [SDV]Life Sciences [q-bio], AC, adenylate cyclase, Clinical Biochemistry, Angiogenesis Inhibitors, 030204 cardiovascular system & hematology, PDGF, platelet-derived growth factor, LDLs, low density lipoproteins, TGFβR, TGF-β receptor, Neovascularization, chemistry.chemical_compound, HUVEC, human umbilical vein endothelial cell, ROCK, Rho associated protein kinase, LOX, lipoxygenase, nSMase2, neutral sphingomyelinase-2, APOE, human ApoE gene, Clinical Trials as Topic, lcsh:R5-920, SK1, sphingosine kinase −1, eNOS, endothelial nitric oxide synthase, VEGF, vascular endothelial growth factor, VEGF, MMP, matrix metalloproteinase, H2O2, hydrogen peroxide, Dll4, Delta-like-4, EGFR, EGF receptor, medicine.symptom, TLR, Toll-like receptor, Inflammation, HIF, Hypoxia inducible factor, ARNT, aryl hydrocarbon nuclear translocator, PLC, phospholipase C, ROS, reactive oxygen species, Animals, CPT1A, carnitine palmityl transferase, VCAM-1, PAI-1, plasminogen activator inhibitor 1, PPAR, peroxisome proliferator activated receptor, VEGFR, VEGF receptor, AIBP, ApoA-I binding protein, business.industry, TK, tyrosine kinase, Organic Chemistry, Apoe, animal ApoE gene, Atherosclerosis, ApoE−/− mice, homozygous ApoE-deficient mice, HSP, heparan sulfate proteoglycans, COX, cyclooxygenase, Oxidative Stress, lcsh:Biology (General), Cancer research, business, MAPK, mitogen activated protein kinase
Abstract: Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations., Graphical abstract fx1, Highlights • Intimal neovascularization in plaque growth and destabilization. • Role of classical and specific angiogenic factors in atherosclerotic angiogenesis. • Inflammation and oxidative stress promote angiogenesis and plaque destabilization. • Angiogenesis promote intraplaque hemorrhages, afflux of blood cells and lipids. • Anti-angiogenic therapy for atherosclerotic angiogenesis.
Published: 2017

28. Dual signaling evoked by oxidized LDLs in vascular cells

Author: Gianna Ferretti, Nathalie Augé, Anne Nègre-Salvayre, Caroline Camaré, Titziana Bacchetti, Robert Salvayre, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), and Université Toulouse III - Paul Sabatier (UT3)
Subjects: 0301 basic medicine, Ceramide, CD36, [SDV]Life Sciences [q-bio], Apoptosis, Inflammation, medicine.disease_cause, Biochemistry, 4-Hydroxynonenal, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, Physiology (medical), Autophagy, medicine, Humans, Scavenger receptor, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Reactive oxygen species, biology, Chemistry, Macrophages, Atherosclerosis, Cell biology, Lipoproteins, LDL, Oxidative Stress, 030104 developmental biology, biology.protein, lipids (amino acids, peptides, and proteins), Lipid Peroxidation, medicine.symptom, Reactive Oxygen Species, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract: The oxidative theory of atherosclerosis relies on the modification of low density lipoproteins (LDLs) in the vascular wall by reactive oxygen species. Modified LDLs, such as oxidized LDLs, are thought to participate in the formation of early atherosclerotic lesions (accumulation of foam cells and fatty streaks), whereas their role in advanced lesions and atherothrombotic events is more debated, because antioxidant supplementation failed to prevent coronary disease events and mortality in intervention randomized trials. As oxidized LDLs and oxidized lipids are present in atherosclerotic lesions and are able to trigger cell signaling on cultured vascular cells and macrophages, it has been proposed that they could play a role in atherogenesis and atherosclerotic vascular remodeling. Oxidized LDLs exhibit dual biological effects, which are dependent on extent of lipid peroxidation, nature of oxidized lipids (oxidized phospholipids, oxysterols, malondialdehyde, α,β-unsaturated hydroxyalkenals), concentration of oxidized LDLs and uptake by scavenger receptors (e.g. CD36, LOX-1, SRA) that signal through different transduction pathways. Moderate concentrations of mildly oxidized LDLs are proinflammatory and trigger cell migration and proliferation, whereas higher concentrations induce cell growth arrest and apoptosis. The balance between survival and apoptotic responses evoked by oxidized LDLs depends on cellular systems that regulate the cell fate, such as ceramide/sphingosine-1-phosphate rheostat, endoplasmic reticulum stress, autophagy and expression of pro/antiapoptotic proteins. In vivo, the intimal concentration of oxidized LDLs depends on the influx (hypercholesterolemia, endothelial permeability), residence time and lipid composition of LDLs, oxidative stress intensity, induction of defense mechanisms (antioxidant systems, heat shock proteins). As a consequence, the local cellular responses to oxidized LDLs may stimulate inflammatory or anti-inflammatory pathways, angiogenic or antiangiogenic responses, survival or apoptosis, thereby contributing to plaque growth, instability, complication (intraplaque hemorrhage, proteolysis, calcification, apoptosis) and rupture. Finally, these dual properties suggest that oxLDLs could be implicated at each step of atherosclerosis development, from early fatty streaks to advanced lesions, depending on the nature and concentration of their oxidized lipid content.
Published: 2017

29. 4-Hydroxynonenal Contributes to Angiogenesis through a Redox-Dependent Sphingolipid Pathway: Prevention by Hydralazine Derivatives

Author: Anne Nègre-Salvayre, Mélanie Pucelle, Caroline Camaré, Corinne Bernis, Corinne Vanucci-Bacqué, Robert Salvayre, Michel Baltas, Nathalie Augé, Florence Bedos-Belval, Audrey Swiader, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), arroyo, anne-marie, Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Aging, Angiogenesis, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Biochemistry, Neovascularization, chemistry.chemical_compound, 0302 clinical medicine, Hydralazine Derivatives, [CHIM] Chemical Sciences, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Neovascularization, Pathologic, lcsh:Cytology, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Hydralazine, Cell biology, Phosphotransferases (Alcohol Group Acceptor), Sphingomyelin Phosphodiesterase, lipids (amino acids, peptides, and proteins), medicine.symptom, Sphingomyelin, Oxidation-Reduction, Signal Transduction, Research Article, Article Subject, Biology, 4-Hydroxynonenal, Cell Line, 03 medical and health sciences, Lipid oxidation, medicine, Humans, [CHIM]Chemical Sciences, lcsh:QH573-671, Reactive oxygen species, Aldehydes, Sphingolipids, Sphingosine, Endothelial Cells, Cell Biology, Redox-Dependent Sphingolipid Pathway, Sphingolipid, 030104 developmental biology, chemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The neovascularization of atherosclerotic lesions is involved in plaque development and may contribute to intraplaque hemorrhage and plaque fragilization and rupture. Among the various proangiogenic agents involved in the neovascularization process, proatherogenic oxidized LDLs (oxLDLs) contribute to the formation of tubesviathe generation of sphingosine 1-phosphate (S1P), a major mitogenic and proangiogenic sphingolipid mediator. In this study, we investigated whether 4-hydroxynonenal (4-HNE), an aldehydic lipid oxidation product abundantly present in oxLDLs, contributes to their proangiogenic properties. Immunofluorescence analysis of human atherosclerotic lesions from carotid endarterectomy showed the colocalization of HNE-adducts with CD31, a marker of endothelial cells, suggesting a close relationship between 4-HNE and neovessel formation. In vitro, low 4-HNE concentration (0.5–1 µM) elicited the formation of tubes by human microvascular endothelial cells (HMEC-1), whereas higher concentrations were not angiogenic. The formation of tubes by 4-HNE involved the generation of reactive oxygen species and the activation of the sphingolipid pathway, namely, the neutral type 2 sphingomyelinase and sphingosine kinase-1 (nSMase2/SK-1) pathway, indicating a role for S1P in the angiogenic signaling of 4-HNE. Carbonyl scavengers hydralazine and bisvanillyl-hydralazone inhibited the nSMase2/SK1 pathway activation and the formation of tubes on Matrigel® evoked by 4-HNE. Altogether, these results emphasize the role of 4-HNE in the angiogenic effect of oxLDLs and point out the potential interest of pharmacological carbonyl scavengers to prevent the neovascularization process.
Published: 2017

30. Synthesis and evaluation of antioxidant phenolic diaryl hydrazones as potent antiangiogenic agents in atherosclerosis

Author: Chantal Carayon, Corinne Vanucci-Bacqué, Michel Baltas, Florence Bedos-Belval, Corinne Bernis, Caroline Camaré, Anne Nègre-Salvayre, Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Spectrometry, Mass, Electrospray Ionization, Antioxidant, Angiogenesis, medicine.medical_treatment, Proton Magnetic Resonance Spectroscopy, Clinical Biochemistry, Pharmaceutical Science, Angiogenesis Inhibitors, Polyphenol Hydrazone, 030204 cardiovascular system & hematology, Biochemistry, Antioxidants, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Drug Discovery, medicine, TBARS, Humans, [CHIM]Chemical Sciences, Lipoprotein oxidation, Carbon-13 Magnetic Resonance Spectroscopy, Molecular Biology, Biphenyl derivatives, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Reactive oxygen species, Matrigel, Organic Chemistry, Hydrazones, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Atherosclerosis, 3. Good health, Lipoproteins, LDL, 030104 developmental biology, chemistry, Polyphenol, Molecular Medicine, Reactive Oxygen Species, Intracellular
Abstract: International audience; A series of bis-hydrazones derived from diaryl and diaryl ether hydroxybenzaldehyde frames 1 and 2 have been synthesized as potential antioxidant and antiangiogenic agents, two properties required to limit atherogenesis and cardiovascular events. These compounds were evaluated for their ability to neutralize free radical formation, to block endothelial cell-induced low-density lipoprotein oxidation (monitored by the formation of TBARS), an essential step in atherogenesis, and subsequent toxicity, to prevent angiogenesis evoked by low oxidized LDL concentration (monitored by the formation of capillary tubes on Matrigel) and to inhibit intracellular ROS increase involved in the angiogenic signaling. A structure/activity study has been carried out and finally allowed to select the phenolic diaryl ether hydralazine derivative 2a, sharing all these protective properties, as a promising hit for further development.
Published: 2016

31. The neutral sphingomyelinase-2 is involved in angiogenic signaling triggered by oxidized LDL

Author: Robert Salvayre, Bertrand Saint-Lebes, Anne Nègre-Salvayre, Caroline Camaré, Marie-Hélène Grazide, Mélanie Pucelle, Nathalie Augé, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Institut de médecine moléculaire de Rangueil (I2MR), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Transcriptional Activation, Ceramide, Angiogenesis, [SDV]Life Sciences [q-bio], Sphingosine kinase, Apoptosis, 030204 cardiovascular system & hematology, Ceramides, Biochemistry, Benzylidene Compounds, p38 Mitogen-Activated Protein Kinases, Muscle, Smooth, Vascular, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Sphingosine, Physiology (medical), Animals, Humans, ComputingMilieux_MISCELLANEOUS, Sprouting angiogenesis, Matrigel, NADPH oxidase, Aniline Compounds, biology, Neovascularization, Pathologic, Endothelial Cells, NADPH Oxidases, Cell biology, Lipoproteins, LDL, Chorioallantoic membrane, Oxidative Stress, Phosphotransferases (Alcohol Group Acceptor), 030104 developmental biology, Sphingomyelin Phosphodiesterase, chemistry, biology.protein, Lysophospholipids, Reactive Oxygen Species, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Capillaries of the external part of the normal arterial wall constitute the vasa vasorum network. In atherosclerotic lesions, neovascularization occurs in areas of intimal hyperplasia where it may promote plaque expansion, and intraplaque hemorrhage. Oxidized LDL that are present in atherosclerotic areas activate various angiogenic signaling pathways, including reactive oxygen species and the sphingosine kinase/sphingosine-1-phosphate pathway. We aimed to investigate whether oxidized LDL-induced angiogenesis requires neutral sphingomyelinase-2 activation and the neutral sphingomyelinase-2/sphingosine kinase-1 pathway. The role of neutral sphingomyelinase-2 in angiogenic signaling was investigated in Human Microvascular Endothelial Cells (HMEC-1) forming capillary tube on Matrigel and in vivo in the Matrigel plug assay in C57BL/6 mice and in the chicken chorioallantoic membrane model. Low concentration of human oxidized LDL elicits HMEC-1 capillary tube formation and neutral sphingomyelinase-2 activation, which were blocked by neutral sphingomyelinase-2 inhibitors, GW4869 and specific siRNA. This angiogenic effect was mimicked by low concentration of C6-Ceramide and was inhibited by sphingosine kinase-1 inhibitors. Upstream of neutral sphingomyelinase-2, oxidized LDL-induced activation required LOX-1, reactive oxygen species generation by NADPH oxidase and p38-MAPK activation. Inhibition of sphingosine kinase-1 blocked the angiogenic response and triggered HMEC-1 apoptosis. Low concentration of oxidized LDL was angiogenic in vivo, both in the Matrigel plug assay in mice and in the chorioallantoic membrane model, and was blocked by GW4869. In conclusion, low oxLDL concentration triggers sprouting angiogenesis that involves ROS-induced activation of the neutral sphingomyelinase-2/sphingosine kinase-1 pathway, and is effectively inhibited by GW4869.
Published: 2016

32. Oxidized Low-Density Lipoproteins Trigger Endoplasmic Reticulum Stress in Vascular Cells

Author: Sanson, Marie, Augé, Nathalie, Vindis, Cécile, Muller, Carole, Bando, Yoshio, Thiers, Jean-Claude, Marachet, Marie-Agn&#232, s, Žarković, Kamelija, Sawa, Yoshiki, Salvayre, Robert, N&#232, gre-Salvayre, Anne, Simon, Marie Francoise, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Anatomy, Asahikawa Medical College, Département de biologie vasculaire, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Division of Pathology, University of Zagreb, Department of Surgery, Osaka University [Osaka], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], and University of Osaka
Subjects: MESH: Lipoproteins, LDL, Physiology, [SDV]Life Sciences [q-bio], Apoptosis, Endoplasmic Reticulum, MESH: Atherosclerosis, 0302 clinical medicine, MESH: Endothelial Cells, MESH: Proteins, Enzyme Inhibitors, MESH: Stress, Physiological, Endoplasmic Reticulum Chaperone BiP, Ketocholesterols, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Kinase, MESH: Ketocholesterols, Free Radical Scavengers, Cell biology, Lipoproteins, LDL, [SDV] Life Sciences [q-bio], Biochemistry, MESH: Enzyme Inhibitors, 030220 oncology & carcinogenesis, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, MESH: Oxygen, XBP1, KDEL, Cysteine Proteinase Inhibitors, In Vitro Techniques, MESH: Cysteine Proteinase Inhibitors, 03 medical and health sciences, MESH: Acetylcysteine, ER stress, apoptosis, ORP150, oxidized LDL, atherosclerosis, Lipid oxidation, Stress, Physiological, MESH: Endoplasmic Reticulum, Humans, HSP70 Heat-Shock Proteins, 030304 developmental biology, Aldehydes, MESH: Humans, ATF6, MESH: Apoptosis, Endoplasmic reticulum, JNK Mitogen-Activated Protein Kinases, MESH: Biological Markers, Endothelial Cells, Proteins, MESH: JNK Mitogen-Activated Protein Kinases, Atherosclerosis, Acetylcysteine, Oxygen, Chaperone (protein), MESH: Free Radical Scavengers, biology.protein, Unfolded protein response, MESH: Aldehydes, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Oxidized low-density lipoproteins (oxLDLs) trigger various biological responses potentially involved in atherogenesis. Disturbing endoplasmic reticulum (ER) function results in ER stress and unfolded protein response, which tends to restore ER homeostasis but switches to apoptosis when ER stress is prolonged. We aimed to investigate whether ER stress is induced by oxLDLs and can be prevented by the ER-associated chaperone ORP150 (150-kDa oxygen-regulated protein). oxLDLs and the lipid oxidation products 7-ketocholesterol and 4-hydroxynonenal induce ER stress in human endothelial cells (HMEC-1), characterized by the activation of ER stress sensors (phosphorylation of Ire1α and PERK, nuclear translocation of ATF6) and of their subsequent pathways (eukaryotic initiation factor 2α phosphorylation, expression of XBP1/spliced XBP1, CHOP, and KDEL chaperones GRP78, GRP94, ORP150). ER stress was inhibited by the antioxidant N -acetylcysteine. In advanced atherosclerotic lesions, phospho-Ire1α, KDEL, and ORP150 staining were localized in lipid-rich areas with 4-hydroxynonenal adducts and CD68-positive macrophagic cells. By comparison, staining for 4-hydroxynonenal, phospho-Ire1α, KDEL, and ORP were faint and more diffuse in intimal hyperplasia. ER stress takes part in the apoptotic effect of oxLDLs, through the Ire1α/c-Jun N-terminal kinase pathway, as assessed by the protective effect of specific small interfering RNAs and c-Jun N-terminal kinase inhibitor. Forced expression of the chaperone ORP150 reduced both oxLDL-induced ER stress and apoptosis. ER stress markers and ORP150 chaperone are expressed in areas containing oxLDLs in atherosclerotic lesions and are induced by oxLDLs and oxidized lipids in cultured cells. The forced expression of ORP150 highlights its new protective role against oxLDL-induced ER stress and subsequent apoptosis.
Published: 2009

33. Critical Role for Sphingosine Kinase-1 in Regulating Survival of Neuroblastoma Cells Exposed to Amyloid-β Peptide

Author: Marie-Lise Maddelein, Virginie Garcia, Dimitri Pchejetski, Leyre Brizuela, Marie-Bernadette Delisle, Marie-Françoise Altié, A. Gomez-Brouchet, Olivier Cuvillier, Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie et de biologie structurale (IPBS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Biologie du Fruit, Institut National de la Recherche Agronomique (INRA), and Institut des Maladies Métaboliques et Cardiovasculaires (I2MC)
Subjects: Programmed cell death, Ceramide, Cell Survival, Amyloid beta, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.medical_treatment, MESH: Insulin-Like Growth Factor I, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Line, Transforming Growth Factor beta1, MESH: Transforming Growth Factor beta1, Neuroblastoma, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Humans, Gene silencing, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Insulin-Like Growth Factor I, MESH: Peptide Fragments, 030304 developmental biology, Pharmacology, 0303 health sciences, MESH: Humans, Amyloid beta-Peptides, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, Sphingosine, Growth factor, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Neuroblastoma, MESH: Phosphotransferases (Alcohol Group Acceptor), MESH: Amyloid beta-Peptides, Peptide Fragments, MESH: Cell Line, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Cell biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Phosphotransferases (Alcohol Group Acceptor), MESH: Cell Survival, Sphingosine kinase 1, chemistry, Cell culture, biology.protein, Molecular Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 030217 neurology & neurosurgery
Abstract: International audience; We examined the role of sphingosine kinase-1 (SphK1), a critical regulator of the ceramide/sphingosine 1-phosphate (S1P) biostat, in the regulation of death and survival of SH-SY5Y neuroblastoma cells in response to amyloid beta (Abeta) peptide (25-35). Upon incubation with Abeta, SH-SY5Y cells displayed a marked down-regulation of SphK1 activity coupled with an increase in the ceramide/S1P ratio followed by cell death. This mechanism was redox-sensitive; N-acetylcysteine totally abrogated the down-regulation of SphK1 activity and strongly inhibited Abeta-induced cell death. SphK1 overexpression impaired the cytotoxicity of Abeta, whereas SphK1 silencing by RNA interference mimicked Abeta-induced cell death, thereby establishing a critical role for SphK1. We further demonstrated that SphK1 could mediate the well established cytoprotective action of insulin-like growth factor (IGF-I) against Abeta toxicity. A dominant-negative form of SphK1 or its pharmacological inhibition not only abrogated IGF-I-triggered stimulation of SphK1 but also hampered IGF-I protective effect. Similarly to IGF-I, the neuroprotective action of TGF-beta1 was also dependent on SphK1 activity; activation of SphK1 as well as cell survival were impeded by a dominant-negative form of SphK1. Taken together, these results provide the first illustration of SphK1 role as a critical regulator of death and survival of Abeta-treated cells.
Published: 2007

34. Elastin aging and lipid oxidation products in human aorta

Author: Kamelija Zarkovic, Robert Salvayre, Pauline Larroque-Cardoso, Anne Nègre-Salvayre, Mellanie Pucelle, Georg Waeg, Neven Zarkovic, Department of Neuropathology, University of Zagreb-Clinical Hospital Center Zagreb, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Institute of Molecular Biosciences, University of Graz, Rudjer Boskovic Institute, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Karl-Franzens-Universität [Graz, Autriche], and Rudjer Boskovic Institute [Zagreb]
Subjects: Male, Aging, [SDV]Life Sciences [q-bio], Clinical Biochemistry, MMPs, matrix metalloproteases, medicine.disease_cause, Biochemistry, Extracellular matrix, Lipid peroxidation, chemistry.chemical_compound, lcsh:QH301-705.5, Aorta, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, lcsh:R5-920, biology, Middle Aged, Malondialdehyde, 3. Good health, Cell biology, ECM, extracellular matrix, medicine.anatomical_structure, Smooth muscle cells, 4-hydroxynonenal, Elastin, Atherosclerosis, cardiovascular system, Fatty Acids, Unsaturated, Female, SMC, smooth muscle cells, Autopsy, lcsh:Medicine (General), Oxidation-Reduction, ALEs, advanced lipoxidation end products, Biotechnology, Research Paper, Adult, 4-Hydroxynonenal, Lipid oxidation, Adventitia, 4-HNE, 4-hydroxynonenal, medicine, Humans, Aged, Aldehydes, Organic Chemistry, AGEs, advanced glycation End Products, Oxidative Stress, chemistry, lcsh:Biology (General), biology.protein, Lipid Peroxidation, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Vascular aging is associated with structural and functional modifications of the arteries, and by an increase in arterial wall thickening in the intima and the media, mainly resulting from structural modifications of the extracellular matrix (ECM) components. Among the factors known to accumulate with aging, advanced lipid peroxidation end products (ALEs) are a hallmark of oxidative stress-associated diseases such as atherosclerosis. Aldehydes generated from the peroxidation of polyunsaturated fatty acids (PUFA), (4-hydroxynonenal, malondialdehyde, acrolein), form adducts on cellular proteins, leading to a progressive protein dysfunction with consequences in the pathophysiology of vascular aging. The contribution of these aldehydes to ECM modification is not known. This study was carried out to investigate whether aldehyde-adducts are detected in the intima and media in human aorta, whether their level is increased in vascular aging, and whether elastin fibers are a target of aldehyde-adduct formation. Immunohistological and confocal immunofluorescence studies indicate that 4-HNE-histidine-adducts accumulate in an age-related manner in the intima, media and adventitia layers of human aortas, and are mainly expressed in smooth muscle cells. In contrast, even if the structure of elastin fiber is strongly altered in the aged vessels, our results show that elastin is not or very poorly modified by 4-HNE. These data indicate a complex role for lipid peroxidation and in particular for 4-HNE in elastin homeostasis, in the vascular wall remodeling during aging and atherosclerosis development., Graphical abstract, Highlights • Elastin alteration, degradation, and loss in aged arteries. • Increased lipid oxidation products (4-HNE) accumulation on cells and ECM in the intima and adventitia, and at a lesser extent in the media of aged patients. • No modification of elastin by 4-HNE in human vessels. • Abundant 4-HNE-protein adducts in aortic smooth muscle cells.
Published: 2015

35. Oxidized LDL-induced angiogenesis involves sphingosine 1-phosphate: prevention by anti-S1P antibody

Author: Camare, Caroline, Trayssac, Magali, Garmy-Susini, Barbara, Mucher, Elodie, Sabbadini, Roger, Salvayre, Robert, Nègre-Salvayre, Anne, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie, PRES Université de Toulouse, Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Lpath Inc., Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2015

36. Regulation of Autophagy by Sphingosine Kinase 1 and Its Role in Cell Survival during Nutrient Starvation

Author: Grégory Lavieu, Stéphane Carpentier, Joëlle Botti, Giusy Sala, Riccardo Ghidoni, Thierry Levade, Patrice Codogno, Francesca Scarlatti, Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Biochemistry and Molecular Biology, San Paolo Medical School, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Codogno, Patrice
Subjects: MESH: Ubiquitin-Activating Enzymes, Apoptosis, Ubiquitin-Activating Enzymes, Autophagy-Related Protein 7, Biochemistry, chemistry.chemical_compound, MESH: RNA, Small Interfering, Enzyme Inhibitors, RNA, Small Interfering, 2. Zero hunger, 0303 health sciences, biology, Hydrolysis, TOR Serine-Threonine Kinases, 030302 biochemistry & molecular biology, Cell biology, Phosphotransferases (Alcohol Group Acceptor), MESH: Cell Survival, Sphingosine kinase 1, MESH: Enzyme Inhibitors, Protein kinase B signaling, MESH: Phospholipase D, Beclin-1, Female, RNA Interference, MESH: Membrane Proteins, MESH: Hydrolysis, Programmed cell death, Ceramide, MESH: Adenine, MESH: Cell Line, Tumor, Cell Survival, Blotting, Western, Green Fluorescent Proteins, MESH: RNA Interference, Lactosylceramides, Breast Neoplasms, MESH: Starvation, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Ceramides, 03 medical and health sciences, MESH: Green Fluorescent Proteins, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Autophagy, Phospholipase D, Humans, MESH: Autophagy, MESH: Blotting, Western, MESH: Lactosylceramides, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Protein Kinases, Molecular Biology, Protein kinase B, 030304 developmental biology, MESH: Humans, Sphingosine, MESH: Apoptosis Regulatory Proteins, Adenine, MESH: Apoptosis, Membrane Proteins, Cell Biology, MESH: Phosphotransferases (Alcohol Group Acceptor), MESH: Ceramides, Sphingolipid, chemistry, Starvation, Cancer research, biology.protein, Apoptosis Regulatory Proteins, Protein Kinases, MESH: Female, MESH: Breast Neoplasms
Abstract: The sphingolipid ceramide induces macroautophagy (here called autophagy) and cell death with autophagic features in cancer cells. Here we show that overexpression of sphingosine kinase 1 (SK1), an enzyme responsible for the production of sphingosine 1-phosphate (S1P), in MCF-7 cells stimulates autophagy by increasing the formation of LC3-positive autophagosomes and the rate of proteolysis sensitive to the autophagy inhibitor 3-methyladenine. Autophagy was blocked in the presence of dimethylsphingosine, an inhibitor of SK activity, and in cells expressing a catalytically inactive form of SK1. In SK1(wt)-overexpressing cells, however, autophagy was not sensitive to fumonisin B1, an inhibitor of ceramide synthase. In contrast to ceramide-induced autophagy, SK1(S1P)-induced autophagy is characterized by (i) the inhibition of mammalian target of rapamycin signaling independently of the Akt/protein kinase B signaling arm and (ii) the lack of robust accumulation of the autophagy protein Beclin 1. In addition, nutrient starvation induced both the stimulation of autophagy and SK activity. Knocking down the expression of the autophagy protein Atg7 or that of SK1 by siRNA abolished starvation-induced autophagy and increased cell death with apoptotic hallmarks. In conclusion, these results show that SK1(S1P)-induced autophagy protects cells from death with apoptotic features during nutrient starvation.
Published: 2006

37. Annexin II-dependent actin remodelling evoked by hydrogen peroxide requires the metalloproteinase/sphingolipid pathway

Author: Christelle Coatrieux, Anne Nègre-Salvayre, Aude Savary, Robert Salvayre, Christel Cinq-Frais, Romina D'Angelo, Corinne Bernis, Nathalie Augé, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3)
Subjects: [SDV]Life Sciences [q-bio], Clinical Biochemistry, SMC, smooth muscle cell, Matrix metalloproteinase, Biochemistry, p38 Mitogen-Activated Protein Kinases, mef, mouse embryonic fibroblast, AnxA2, annexin 2, Mice, Phosphorylation, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, Annexin A2, Metalloproteinase, lcsh:R5-920, Cell biology, Smooth muscle cells, H2O2, hydrogen peroxide, MMP, matrix metalloproteinases, Matrix Metalloproteinase 2, wt, wild type, Signal transduction, lcsh:Medicine (General), Proto-oncogene tyrosine-protein kinase Src, Signal Transduction, Research Paper, Myocytes, Smooth Muscle, macromolecular substances, Biology, ROS, reactive oxygen species, nSMase, neutral sphingomyelinase, fro, fragilitas ossium, Animals, Humans, nSMase2, type 2 neutral sphingomyelinase, Actin, Cell Proliferation, Sphingolipids, Organic Chemistry, mFbl, mouse fibroblast, Actin remodeling, Hydrogen Peroxide, Fibroblasts, Actins, Oxidative Stress, lcsh:Biology (General), Vasculo-proliferative diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Actin remodeling is a dynamic process associated with cell shape modification occurring during cell cycle and proliferation. Oxidative stress plays a role in actin reorganization via various systems including p38MAPK. Beside, the mitogenic response evoked by hydrogen peroxide (H2O2) in fibroblasts and smooth muscle cells (SMC) involves the metalloproteinase (MMPs)/sphingomyelinase 2 (nSMase2) signaling pathway. The aim of this work was to investigate whether this system plays a role in actin remodeling induced by H2O2. Low H2O2 dose (5 µM) rapidly triggered a signaling cascade leading to nSMase2 activation, src and annexin 2 (AnxA2) phosphorylation, and actin remodeling, in fibroblasts and SMC. These events were blocked by pharmacological inhibitors of MMPs (Ro28-2653) and p38MAPK (SB203580), and were lacking in MMP2−/− and in nSMase2-mutant (fro) fibroblasts. Likewise, H2O2 was unable to induce actin remodeling in fro and MMP2−/− fibroblasts or in cells pretreated with p38MAPK, or MMP inhibitors. Finally we show that nSMase2 activation by H2O2, depends on MMP2 and p38MAPK, and is required for the src-dependent phosphorylation of AnxA2, and actin remodeling. Taken together, these findings indicate for the first time that AnxA2 phosphorylation and actin remodeling evoked by oxidative stress depend on the sphingolipid pathway, via MMP2 and p38MAPK., Graphical abstract Schematic diagram of the signaling pathway triggered by low H2O2 concentration, leading to actin remodeling and cell proliferation. H2O2 (5 μM) activates MMP2 which leads to p38MAPK activation. P38MAPK activates nSMase2 which generates ceramide that activates src kinase. Src phosphorylates AnxA2 which leads to ERK1/2 phosphorylation involved in actin remodeling and cell proliferation., Highlights • Low concentration of H2O2 activates matrix metalloproteinases MMP-2. • MMP-2 activates p38MAPK, type 2 neutral sphingomyelinase. • This signaling pathway induces annexin II phosphorylation via src. • This pathway is involved in actin remodeling due to H2O2 stimulation.
Published: 2014

38. Synthesis, antioxidant and cytoprotective evaluation of potential antiatherogenic phenolic hydrazones. A structure–activity relationship insight

Author: Florence Bedos-Belval, Chantal Carayon, Corinne Vanucci-Bacqué, Corinne Bernis, Anne Nègre-Salvayre, Michel Baltas, Caroline Camaré, Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Antioxidant, DPPH, Cell Survival, Ultraviolet Rays, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Pharmaceutical Science, Hydrazone, Protective Agents, 01 natural sciences, Biochemistry, Antioxidants, 03 medical and health sciences, chemistry.chemical_compound, Mice, Structure-Activity Relationship, Phenols, Superoxides, Phenolic antioxidants, Drug Discovery, medicine, TBARS, Structure–activity relationship, Organic chemistry, Animals, [CHIM]Chemical Sciences, MTT assay, Lipoprotein oxidation, Arylhydrazones, Molecular Biology, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, 010405 organic chemistry, Superoxide, Organic Chemistry, Hydrazones, Endothelial Cells, Atherosclerosis, 0104 chemical sciences, Lipoproteins, LDL, chemistry, Oxidative stress, Molecular Medicine, LDL oxidation, Oxidation-Reduction
Abstract: International audience; A novel series of hydrazones derived from substituted benzaldehydes have been synthesized as potential antiatherogenic agents. Several methods were used for exploring their antioxidant and cytoprotective properties, such as their scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, the inhibition of superoxide anion (O2radical dot−) generation and the measurement of cell-induced low-density lipoprotein oxidation (monitored by the formation of TBARS). The cytoprotective efficacy was also evaluated by measuring the cell viability (monitored by the MTT assay) in the presence of cytotoxic oxidized LDL. In this report, we discuss the relationship between the chemical structure of phenolic hydrazones and their antioxidant and cytoprotective activities, for subsequent application as antiatherogenic agents. This SAR study confirms that the phenolic frame is not the only prerequisite for antioxidant activity and N-methylbenzothiazole hydrazone moiety magnifies the dual required properties in two most interesting derivatives.
Published: 2014

39. 4-Hydroxynonenal impairs transforming growth factor-β1-induced elastin synthesis via epidermal growth factor receptor activation in human and murine fibroblasts

Author: Pauline Larroque-Cardoso, Anne-Marie Schmitt, Elodie Mucher, Marie-Hélène Grazide, Robert Salvayre, Gwendal Josse, Florence Nadal-Wolbold, Anne Nègre-Salvayre, Kamelija Zarkovic, Negre-Salvayre, Anne, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Pierre Fabre Dermo-Cosmétique, Pierre Fabre Applied Skin Research Centre, Department of Neuropathology, University of Zagreb-Clinical Hospital Center Zagreb, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Division of Pathology, KBC Zagreb-Clinical Hospital Centre, and Centre de Recherche Pierre Fabre
Subjects: Adult, MAPK/ERK pathway, Aging, [SDV]Life Sciences [q-bio], Primary Cell Culture, Smad2 Protein, SMAD, Biochemistry, Transforming Growth Factor beta1, Mice, Lipid oxidation, Physiology (medical), Animals, Humans, Smad3 Protein, Aorta, ComputingMilieux_MISCELLANEOUS, Cell Line, Transformed, Flavonoids, Homeodomain Proteins, Mitogen-Activated Protein Kinase 1, Aldehydes, Mitogen-Activated Protein Kinase 3, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Tropoelastin, biology, Chemistry, 4-Hydroxynonenal, TGF-β1, EGF receptor, Fibroblasts, Free radicals, Tyrphostins, Molecular biology, Elastin, Cell biology, ErbB Receptors, Repressor Proteins, [SDV] Life Sciences [q-bio], Protein Transport, Gene Expression Regulation, Quinazolines, biology.protein, Phosphorylation, Lipid Peroxidation, Signal transduction, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction, Transforming growth factor
Abstract: International audience; Elastin is a long-lived protein and a key component of connective tissues. The tissular elastin content decreases during chronological aging, and the mechanisms underlying its slow repair are not known. Lipid oxidation products that accumulate in aged tissues may generate protein dysfunction. We hypothesized that 4-hydroxynonenal (4-HNE), a highly reactive α,β-aldehydic product generated from polyunsaturated fatty acid peroxidation, could contribute to inhibiting elastin repair by antagonizing the elastogenic signaling of transforming growth factor-β1 (TGF-β1) in skin fibroblasts. We report that a low 4-HNE concentration (2µmol/L) inhibits the upregulation of tropoelastin expression stimulated by TGF-β1 in human and murine fibroblasts. The study of signaling pathways potentially involved in the regulation of elastin expression showed that 4-HNE did not block the phosphorylation of Smad3, an early step of TGF-β1 signaling, but inhibited the nuclear translocation of Smad2. Concomitantly, 4-HNE modified and stimulated the phosphorylation of the epidermal growth factor receptor (EGFR) and subsequently ERK1/2 activation, leading to the phosphorylation/stabilization of the Smad transcriptional corepressor TGIF, which antagonizes TGF-β1 signaling. Inhibitors of EGFR (AG1478) and MEK/ERK (PD98059), and EGFR-specific siRNAs, reversed the inhibitory effect of 4-HNE on TGF-β1-induced nuclear translocation of Smad2 and tropoelastin synthesis. In vivo studies on aortas from aged C57BL/6 mice showed that EGFR is modified by 4-HNE, in correlation with an increased 4-HNE-adduct accumulation and decreased elastin content. Altogether, these data suggest that 4-HNE inhibits the elastogenic activity of TGF-β1, by modifying and activating the EGFR/ERK/TGIF pathway, which may contribute to altering elastin repair in chronological aging and oxidative stress-associated aging processes.
Published: 2014

40. Alteration of plasmalemmal caveolae mimics endothelial dysfunction observed in atheromatous rabbit aorta

Author: Marie-José Fouque, Marc Poirot, Francis Bayard, Jacques Rami, Dominique Caillaud, Benoit Darblade, Jean-François Arnal, Jean-Claude Thiers, Endocrinologie et communication cellulaire, Institut Louis Bugnard-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physiologie, Faculté de médecine Rangueil, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Poirot, Marc, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Arteriosclerosis, Physiology, MESH: Muscle Contraction, Cell Culture Techniques, MESH: Aortic Diseases, MESH: Rabbits, Aorta, Thoracic, chemistry.chemical_compound, Caveolae, MESH: Filipin, MESH: Animals, Endothelial dysfunction, beta-Cyclodextrins, MESH: Hypercholesterolemia, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 2-Hydroxypropyl-beta-cyclodextrin, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Nitric oxide synthase, medicine.anatomical_structure, Biochemistry, MESH: Research Suppo, Rabbits, MESH: Endothelium, Vascular, Cardiology and Cardiovascular Medicine, Muscle Contraction, medicine.medical_specialty, Endothelium, MESH: Aorta, Thoracic, Hypercholesterolemia, Aortic Diseases, MESH: Microscopy, Electron, Biology, Nitric Oxide, Filipin, Nitric oxide, MESH: Cyclodextrins, Physiology (medical), Internal medicine, medicine, Animals, Cyclodextrins, MESH: Cell Culture Techniques, Cell Membrane, Fatty streak, medicine.disease, MESH: Male, Microscopy, Electron, Endocrinology, MESH: Arteriosclerosis, chemistry, MESH: Nitric Oxide, biology.protein, Endothelium, Vascular, Soluble guanylyl cyclase, MESH: Cell Membrane
Abstract: OBJECTIVE: In endothelial cells, nitric oxide (NO) is produced by the endothelial isoform of nitric oxide synthase (eNOS), which is localized in the cholesterol-rich plasmalemmal microdomains involved in signal transduction, known as caveolae. The present study was undertaken to evaluate the effect of hypercholesterolemia and fatty streak formation on the endothelial caveolae and on endothelial function, and attempted to determine to what extent the caveolae were involved in endothelium-derived NO production. METHODS AND RESULTS: We first studied the effect of atheroma on endothelial NO production. Fatty streak infiltrated aorta of cholesterol-fed New Zealand White rabbits demonstrated an impairment of acetylcholine-induced relaxation and nearly normal calcium ionophore A23187-induced maximal relaxation. The abundance of caveolae in the endothelium covering the fatty streak, as well as their 'grape-like' clustering, appeared to be decreased. We therefore investigated the effect, on endothelial NO production, of the cholesterol-binding agents 2-hydroxypropyl-beta-cyclodextrin (hp-beta-CD) and filipin, known to alter caveolae structure and/or function. Treatment with either hp-beta-CD (2%) or filipin (4 microg/ml) did not affect contraction to phenylephrine or relaxant responses to A23187 or to the NO donor sodium nitroprusside. In contrast, both treatments impaired acetylcholine-induced relaxation. Cultured bovine aortic endothelial cells (BAEC) similarly treated with hp-beta-CD demonstrated a 50% decrease of total cellular cholesterol and a decreased abundance of caveolae as well as their 'grape-like' clustering. Cholesterol depletion decreased the bradykinin-induced transient peak of free intracellular calcium and subsequent receptor-stimulated NO production (assessed using reporter cells rich in soluble guanylyl cyclase), whereas that elicited by A23187 remained unaltered. CONCLUSION: Fatty streak deposit is associated with a decrease in caveolae 'transductosomes' abundance which appears to represent a novel mechanism of endothelial dysfunction.
Published: 2001

41. A signaling cascade mediated by ceramide, src and PDGFRβ coordinates the activation of the redox-sensitive neutral sphingomyelinase-2 and sphingosine kinase-1

Author: Yusuf A. Hannun, Nathalie Augé, Christelle Coatrieux, Anne Nègre-Salvayre, Christel Cinq-Frais, Marie-Hélène Grazide, Robert Salvayre, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medicine, State University of New York (SUNY)-State University of New York (SUNY), and Simon, Marie Francoise
Subjects: Ceramide, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, medicine.disease_cause, Ceramides, Cell Line, Receptor, Platelet-Derived Growth Factor beta, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Sphingosine, medicine, Animals, Humans, Sphingosine-1-phosphate, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Dose-Response Relationship, Drug, Cell Biology, Hydrogen Peroxide, Oxidants, Sphingolipid, Mice, Mutant Strains, Cell biology, Enzyme Activation, Oxidative Stress, Phosphotransferases (Alcohol Group Acceptor), Sphingomyelin Phosphodiesterase, src-Family Kinases, chemistry, Sphingosine kinase 1, biology.protein, Signal transduction, Lysophospholipids, 030217 neurology & neurosurgery, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Proto-oncogene tyrosine-protein kinase Src, Signal Transduction
Abstract: International audience; Stress-inducing agents, including oxidative stress, generate the sphingolipid mediators ceramide (Cer) and sphingosine-1-phosphate (S1P) that are involved in stress-induced cellular responses. The two redox-sensitive neutral sphingomyelinase-2 (nSMase2) and sphingosine kinase-1 (SK1) participate in transducing stress signaling to ceramide and S1P, respectively; however, whether these key enzymes are coordinately regulated is not known. We investigated whether a signaling link coordinates nSMase2 and SK1 activation by H2O2. In mesenchymal cells, H2O2 elicits a dose-dependent biphasic effect, mitogenic at low concentration (5μM), and anti-proliferative and toxic at high concentration (100μM). Low H2O2 concentration triggered activation of nSMase2 and SK1 through a nSMase2/Cer-dependent signaling pathway that acted upstream of activation of SK1. Further results implicated src and the trans-activation of PDGFRβ, as supported by the blocking effect of specific siRNAs, pharmacological inhibitors, and genetically deficient cells for nSMase2, src and SK1. The H2O2-induced src/PDGFRβ/SK1 signaling cascade was impaired in nSMase2-deficient fro/fro cells and was rescued by exogenous C2Cer that activated src/PDGFRβ/SK1. Thus, the results define a nSMase2/SK1 signaling pathway implicated in the mitogenic response to low oxidative stress. On the other hand, high oxidative stress induced inhibition of SK1. The results also showed that the toxicity of high H2O2 concentration was comparable in control and nSMase2-deficient cells. Taken together the results identify a tightly coordinated nSMase2/SK1 pathway that mediates the mitogenic effects of H2O2 and may sense the degree of oxidative stress.
Published: 2013

42. Correction: SNP Array Analysis Reveals Novel Genomic Abnormalities Including Copy Neutral Loss of Heterozygosity in Anaplastic Oligodendrogliomas

Author: Idbaih, Ahmed, Ducray, François, Dehais, Caroline, Courdy, Célia, Carpentier, Catherine, De Bernard, Simon, Uro-Coste, Emmanuelle, Mokhtari, Karima, Jouvet, Anne, Honnorat, Jérôme, Chinot, Olivier, Ramirez, Carole, Beauchesne, Patrick, Benouaich-Amiel, Alexandra, Godard, Joël, Eimer, Sandrine, PARKER, Fabrice, Lechapt-Zalcman, Emmanuelle, Colin, Philippe, Loussouarn, Delphine, Faillot, Thierry, Dam-Hieu, Phong, Elouadhani-Hamdi, Selma, Bauchet, Luc, Langlois, Olivier, Le Guerinel, Caroline, Fontaine, Denys, Vauléon, Elodie, Menei, Philippe, Fotso, Marie Janette Motsuo, Desenclos, Christine, Verrelle, Pierre, Ghiringhelli, François, Noel, Georges, Labrousse, François, Carpentier, Antoine, Dhermain, Frédéric, Delattre, Jean-Yves, Figarella-Branger, Dominique, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre d'Economie de l'Université Paris Nord (CEPN), Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Informatique (DI), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Neuro-oncologie et neuro-inflammation, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurooncologie, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Rangueil, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Laboratoire d'Histologie et de Pathologie moléculaire des tumeurs, Université Bordeaux Segalen - Bordeaux 2-EA 2406, Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Espaces Humains et Interactions Culturelles (EHIC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut Sciences de l'Homme et de la Société (IR SHS UNILIM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Université Clermont Auvergne (UCA), Service de pathologie, Service de neurochirurgie, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Études Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Pasteur [Nice] (CHU), Service de Biologie, CRLCC Eugène Marquis (CRLCC), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital Nord - Amiens, Institut Curie, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Paul Strauss, CRLCC Paul Strauss, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), CHU Pitié-Salpêtrière [APHP], Service de pathologie et neuropathologie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), AltraBio [Lyon], Brain Dynamics and Cognition Team (U1028 Inserm - UMR5292 CNRS), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), French Reference Centre for Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Brain Dynamics and Cognition (DYCOG), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Curie [Paris], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon
Subjects: 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary, 030220 oncology & carcinogenesis, lcsh:R, lcsh:Medicine, Correction, [CHIM]Chemical Sciences, lcsh:Q, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, lcsh:Science, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2013

43. Impact of endografting on the thoracic aortic anatomy: comparative analysis of the aortic geometry before and after the endograft implantation

Author: Ramiro Moreno, Marco Midulla, Hervé Rousseau, Stéphan Haulon, Jean Pierre Pruvo, Franc Nicoud, Anne Nègre-Salvayre, Cardiovascular and Interventional Radiology, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Montpelliérain Alexander Grothendieck (IMAG), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Services de neuroradiologie [Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Radiologie [Rangueil / Larrey], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), ALARA Expertise, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Chirurgie vasculaire
Subjects: Male, Future studies, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], Implantation Site, Geometry, Aorta, Thoracic, 030204 cardiovascular system & hematology, 030218 nuclear medicine & medical imaging, ultrasound imaging, 0302 clinical medicine, Segmentation, Stent graft, Thoracic aorta, ComputingMilieux_MISCELLANEOUS, RISK, Aged, 80 and over, TEVAR, Ultrasound, Endovascular Procedures, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Anatomy, Middle Aged, 3. Good health, ARCH, vector low imaging, Treatment Outcome, Cardiothoracic surgery, PLACEMENT, Radiographic Image Interpretation, Computer-Assisted, Female, Stents, Radiology, color Doppler, Cardiology and Cardiovascular Medicine, False Aneurysms, Adult, medicine.medical_specialty, Aortic Diseases, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Imaging data, 03 medical and health sciences, Blood Vessel Prosthesis Implantation, Imaging, Three-Dimensional, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.artery, ENDOLEAK FORMATION, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Radiology, Nuclear Medicine and imaging, ANEURYSMS, regularized least-squares, Aged, REPAIR, Aorta, intracardiac low imaging, business.industry, SIMULATIONS, Surgery, STENT-GRAFTS, business, Tomography, X-Ray Computed, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Although the widespread acceptance of thoracic endovascular aortic repair (TEVAR) as a first-line treatment option for a multitude of thoracic aortic diseases, little is known about the consequences of the device implantation on the native aortic anatomy. We propose a comparative analysis of the pre- and postoperative geometry on a clinical series of patients and discuss the potential clinical implications CT pre- and postoperative acquisitions of 30 consecutive patients treated by TEVAR for different pathologies (20 thoracic aortic aneurysms, 6 false aneurysms, 3 penetrating ulcers, 1 traumatic rupture) were used to model the vascular geometry. Pre- and postoperative geometries were compared for each patient by pairing and matching the 3D models. An implantation site was identified, and focal differences were detected and described. Segmentation of the data sets was successfully performed for all 30 subjects. Geometry differences between the pre- and postoperative meshes were depicted in 23 patients (76 %). Modifications at the upper implantation site were detected in 14 patients (47 %), and among them, the implantation site involved the arch (Z0-3) in 11 (78 %). Modeling the vascular geometry on the basis of imaging data offers an effective tool to perform patient-specific analysis of the vascular geometry before and after the treatment. Future studies will evaluate the consequences of these changes on the aortic function.
Published: 2012

44. Mechanisms of human smooth muscle cell proliferation and transplant vasculopathy induced by HLA class I antibodies: in vitro and in vivo studies.: Antibody-induced transplant vasculopathy

Author: Anne Nègre-Salvayre, Mogens Thomsen, Magali Trayssac, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, M. T. was funded by a Ph.D. fellowship from Ministère de l'Enseignement Supérieur et de la Recherche. This work was also supported by INSERM (Institut National de la Santé Et de la Recherche Médicale), Agence de la Biomédecine and University Paul Sabatier Toulouse III., Service de biochimie, PRES Université de Toulouse, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3)
Subjects: Graft Rejection, Isoantigens, Vascular smooth muscle, medicine.drug_class, [SDV]Life Sciences [q-bio], Myocytes, Smooth Muscle, Immunology, Vasculopathy, Human leukocyte antigen, Monoclonal antibody, Antibodies, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, In vivo, medicine, Animals, Humans, Immunology and Allergy, Myocyte, Vascular Diseases, Mesenteric arteries, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, 030304 developmental biology, 0303 health sciences, biology, Histocompatibility Antigens Class I, Antibodies, Monoclonal, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, In vitro, Signaling, 3. Good health, Animal models, Disease Models, Animal, medicine.anatomical_structure, Smooth muscle cells, biology.protein, Antibody, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; Vascular smooth muscle cells (SMC) play an important role in the pathophysiology of transplant vasculopathy (TV), a major cause of late death in patients receiving an organ transplant. In this review we describe the proliferative effect in vitro and in vivo of HLA class I antibodies on human SMC. We have developed an experimental model using segments of human mesenteric arteries transplanted in the position of the infrarenal aorta in immunodeficient mice (SCID/beige). Weekly injections of transplanted mice with a monoclonal antibody towards HLA class I provoked typical lesions of TV after 6 weeks in the human graft while transplanted mice receiving an irrelevant antibody did not develop any significant lesion. In vitro, the anti-HLA antibodies were mitogenic to SMC and we showed that they activate a stress-induced signaling pathway implicating matrix metalloproteinases (MMP) and neutral sphingomyelinase 2 (nSMase-2). The proliferative effect of anti-HLA antibodies could be blocked by pharmacological inhibitors or by siRNA. Administration of pharmacological inhibitors diminished the development of TV in grafted mice injected with anti-HLA antibodies demonstrating an important role of the MMP/nSMase-2 pathway in antibody-induced TV. This observation opens new perspectives for the management of TV in clinical settings.
Published: 2012

45. Haemodynamic imaging of thoracic stent-grafts by computational fluid dynamics (CFD): presentation of a patient-specific method combining magnetic resonance imaging and numerical simulations

Author: Anne Nègre-Salvayre, Marco Midulla, Hervé Rousseau, Ramiro Moreno, Franck Nicoud, Stéphan Haulon, Ming Chau, Jean-Pierre Pruvo, Adil Baali, Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), ALARA Expertise, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), IRT SystemX (IRT SystemX), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Institut de Mathématiques et de Modélisation de Montpellier (I3M), Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Departement de Neuroradiologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Chirurgie vasculaire, Service de Radiologie [Rangueil / Larrey], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Radiologie cardiovasculaire, Université Toulouse III - Paul Sabatier (UPS), Advanced Solutions Accelerator (ASA), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM), ALARA group, IRT SystemX, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Negre-Salvayre, Anne
Subjects: Male, medicine.medical_specialty, Radiography, [SDV]Life Sciences [q-bio], Hemodynamics, Aorta, Thoracic, 030204 cardiovascular system & hematology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine.artery, medicine, Thoracic aorta, Humans, Radiology, Nuclear Medicine and imaging, Computer Simulation, Neuroradiology, Aorta, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, business.industry, Ultrasound, Phase-contrast imaging, Magnetic resonance imaging, General Medicine, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], Hydrodynamics, cardiovascular system, Female, Stents, Vascular Grafting, Radiology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: In the last decade, there was been increasing interest in finding imaging techniques able to provide a functional vascular imaging of the thoracic aorta. The purpose of this paper is to present an imaging method combining magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to obtain a patient-specific haemodynamic analysis of patients treated by thoracic endovascular aortic repair (TEVAR).MRI was used to obtain boundary conditions. MR angiography (MRA) was followed by cardiac-gated cine sequences which covered the whole thoracic aorta. Phase contrast imaging provided the inlet and outlet profiles. A CFD mesh generator was used to model the arterial morphology, and wall movements were imposed according to the cine imaging. CFD runs were processed using the finite volume (FV) method assuming blood as a homogeneous Newtonian fluid.Twenty patients (14 men; mean age 62.2 years) with different aortic lesions were evaluated. Four-dimensional mapping of velocity and wall shear stress were obtained, depicting different patterns of flow (laminar, turbulent, stenosis-like) and local alterations of parietal stress in-stent and along the native aorta.A computational method using a combined approach with MRI appears feasible and seems promising to provide detailed functional analysis of thoracic aorta after stent-graft implantation.• Functional vascular imaging of the thoracic aorta offers new diagnostic opportunities • CFD can model vascular haemodynamics for clinical aortic problems • Combining CFD with MRI offers patient specific method of aortic analysis • Haemodynamic analysis of stent-grafts could improve clinical management and follow-up.
Published: 2012

46. Serotonin 5-HT2A receptor-mediated hypertrophy is negatively regulated by caveolin-3 in cardiomyoblasts and neonatal cardiomyocytes

Author: Cécile Vindis, Christelle Villeneuve, Angelo Parini, Anne Nègre-Salvayre, Jeanne Mialet-Perez, Catherine Ordener, Romina D'Angelo, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Microscopie Confocale & Cytométrie (E22 M2C), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Simon, Marie Francoise, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Male, MESH: Signal Transduction, Caveolin 3, [SDV]Life Sciences [q-bio], MESH: Myoblasts, Cardiac, MESH: Myocytes, Cardiac, TRPC1, Mice, 0302 clinical medicine, Caveolae, Myocyte, Myocytes, Cardiac, Receptor, Serotonin, 5-HT2A, MESH: Animals, MESH: Gene Silencing, MESH: Caveolin 3, Receptor, ComputingMilieux_MISCELLANEOUS, Mice, Inbred C3H, 0303 health sciences, NFAT, MESH: Gene Expression Regulation, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cell biology, Protein Transport, MESH: Caveolae, Cardiology and Cardiovascular Medicine, Myoblasts, Cardiac, Protein Binding, Signal Transduction, Serotonin, MESH: Protein Transport, MESH: Rats, Cardiomegaly, Biology, Cell Line, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Animals, MESH: Protein Binding, Gene Silencing, MESH: Mice, Inbred C3H, MESH: Mice, Molecular Biology, 5-HT receptor, 030304 developmental biology, G protein-coupled receptor, MESH: Receptor, Serotonin, 5-HT2A, MESH: Male, Rats, MESH: Cell Line, Disease Models, Animal, Gene Expression Regulation, MESH: Serotonin, MESH: Cardiomegaly, MESH: Disease Models, Animal, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The serotonin 5-HT(2A) receptor belongs to the G-protein-coupled receptors (GPCRs) superfamily and mediates the hypertrophic response to serotonin (5-HT) in cardiac myocytes. At present the regulatory mechanisms of 5-HT(2A) receptor-induced myocyte hypertrophy are not fully understood. The localization and the compartmentation of GPCRs within specialized membrane microdomains are known to modulate their signalling pathway. Therefore, we hypothesized that caveolae microdomains and caveolin-3, the predominant isoform of cardiac caveolae, might be regulators of 5-HT(2A) receptor signalling. We demonstrate that 5-HT(2A) receptors interact with caveolin-3 upon 5-HT stimulation and traffic into caveolae membrane microdomains. We provide evidence that caveolin-3 knockdown abolishes the redistribution of 5-HT(2A) receptors into caveolae and enhances 5-HT(2A) receptor-induced myocyte hypertrophic markers such as cell size, protein synthesis and ANF gene expression. Importantly, we demonstrate that caveolin-3 and caveolae structures are negative regulators of 5-HT(2A) receptor-induced nuclear factor of activated T cells (NFAT) transcriptional activation. Taken together, our data demonstrate that caveolin-3 and caveolae microdomains are important regulators of the hypertrophic response induced by 5-HT(2A) receptors. These findings thus open new insights to target heart hypertrophy under the enhanced serotonin system. This article is part of a Special Issue entitled "Local Signaling in Myocytes".
Published: 2012

47. A key role for matrix metalloproteinases and neutral sphingomyelinase-2 in transplant vasculopathy triggered by anti-HLA antibody

Author: Anne Nègre-Salvayre, Magali Trayssac, Jean-Claude Thiers, Lionel Rostaing, Sylvain Galvani, Nassim Kamar, Hans-Willi Krell, Robert Salvayre, Mogens Thomsen, Federico Sallusto, Denis Calise, Nathalie Augé, Service de biochimie, PRES Université de Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Roche Diagnostics GmbH, Service de néphrologie, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Simon, Marie Francoise, Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Néphrologie, dialyse et transplantation [Hôpital de Rangueil, Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Matrix metalloproteinase inhibitor, [SDV]Life Sciences [q-bio], MESH: Piperazines, MESH: Antibodies, Anti-Idiotypic, Constriction, Pathologic, Mice, SCID, Matrix metalloproteinase, Muscle, Smooth, Vascular, Piperazines, Organ transplantation, Mice, MESH: Matrix Metalloproteinase 14, 0302 clinical medicine, HLA Antigens, MESH: Neointima, MESH: RNA, Small Interfering, MESH: Animals, RNA, Small Interfering, MESH: Mice, SCID, MESH: HLA Antigens, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Aniline Compounds, biology, Arteries, MESH: Muscle, Smooth, Vascular, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Antibodies, Anti-Idiotypic, 3. Good health, Sphingomyelin Phosphodiesterase, MESH: Models, Animal, Models, Animal, MESH: Vascular Diseases, Matrix Metalloproteinase 2, Antibody, Cardiology and Cardiovascular Medicine, Sphingomyelin, MESH: Cells, Cultured, medicine.medical_specialty, Anti-HLA antibody, In Vitro Techniques, Matrix Metalloproteinase Inhibitors, Benzylidene Compounds, MESH: Aniline Compounds, 03 medical and health sciences, Immune system, MESH: Constriction, Pathologic, Neointima, Physiology (medical), MESH: Vascular Grafting, Matrix Metalloproteinase 14, medicine, Animals, Humans, Vascular Diseases, MESH: Mice, MESH: Arteries, 030304 developmental biology, Immunosuppressive treatment, Hyperplasia, MESH: Humans, MESH: Hyperplasia, business.industry, MESH: Matrix Metalloproteinase 2, Disease Models, Animal, Pyrimidines, MESH: Sphingomyelin Phosphodiesterase, MESH: Pyrimidines, Immunology, biology.protein, Vascular Grafting, MESH: Benzylidene Compounds, MESH: Disease Models, Animal, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: Background— Outcomes for organ transplantation are constantly improving because of advances in organ preservation, surgical techniques, immune clinical monitoring, and immunosuppressive treatment preventing acute transplant rejection. However, chronic rejection including transplant vasculopathy still limits long-term patient survival. Transplant vasculopathy is characterized by progressive neointimal hyperplasia leading to arterial stenosis and ischemic failure of the allograft. This work sought to decipher the manner in which the humoral immune response, mimicked by W6/32 anti-HLA antibody, contributes to transplant vasculopathy. Methods and Results— Studies were performed in vitro on cultured human smooth muscle cells, ex vivo on human arterial segments, and in vivo in a model consisting of human arterial segments grafted into severe combined immunodeficiency/beige mice injected weekly with anti-HLA antibodies. We report that anti-HLA antibodies are mitogenic for smooth muscle cells through a signaling mechanism implicating matrix metalloproteinases (MMPs) (membrane type 1 MMP and MMP2) and neutral sphingomyelinase-2. This mitogenic signaling and subsequent DNA synthesis are blocked in smooth muscle cells silenced for MMP2 or for neutral sphingomyelinase-2 by small interfering RNAs, in smooth muscle cells transfected with a vector coding for a dominant-negative form of membrane type 1 MMP, and after treatment by pharmacological inhibitors of MMPs (Ro28-2653) or neutral sphingomyelinase-2 (GW4869). In vivo, Ro28-2653 and GW4869 reduced the intimal thickening induced by anti-HLA antibodies in human mesenteric arteries grafted into severe combined immunodeficiency/beige mice. Conclusions— These data highlight a crucial role for MMP2 and neutral sphingomyelinase-2 in vasculopathy triggered by a humoral immune response and open new perspectives for preventing transplant vasculopathy with the use of MMP and neutral sphingomyelinase inhibitors, in addition to conventional immunosuppression.
Published: 2011

48. Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice

Author: Aurélie Waget, Matteo Serino, Jean-Claude Thiers, Gaelle Payros, Rémy Burcelin, Amélie Lacombe, Serge Luquet, Jessica Denom, Myriam Masseboeuf, Catherine Kabani, Céline Cruciani-Guglielmacci, Nicolas Marsollier, Anne Nègre-Salvayre, Christophe Magnan, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), RB is the recipient of a grant from the European Association for the Study of Diabetes (EASD) and Amylin. CM is the recipient of funding from the 'Agence Nationale de la Recherche' (France): ANR-07-PHYSIO, Simon, Marie Francoise, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Central Nervous System, Anatomy and Physiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Guanidines, Jejunum, Lipid peroxidation, chemistry.chemical_compound, Mice, 0302 clinical medicine, Endocrinology, Integrative Physiology, Glucose homeostasis, Homeostasis, Insulin, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Multidisciplinary, Intestines, medicine.anatomical_structure, Medicine, Research Article, medicine.medical_specialty, Science, Endocrine System, Biology, Neurological System, 03 medical and health sciences, Insulin resistance, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, 030304 developmental biology, Nutrition, Diabetic Endocrinology, Endocrine Physiology, medicine.disease, Vagus nerve, Oxidative Stress, Glucose, chemistry, Metabolic Disorders, Duodenum, Lipid Peroxidation, Insulin Resistance, Physiological Processes, Digestive System, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BACKGROUND: Daily variations in lipid concentrations in both gut lumen and blood are detected by specific sensors located in the gastrointestinal tract and in specialized central areas. Deregulation of the lipid sensors could be partly involved in the dysfunction of glucose homeostasis. The study aimed at comparing the effect of Medialipid (ML) overload on insulin secretion and sensitivity when administered either through the intestine or the carotid artery in mice. METHODOLOGY/PRINCIPAL FINDINGS: An indwelling intragastric or intracarotid catheter was installed in mice and ML or an isocaloric solution was infused over 24 hours. Glucose and insulin tolerance and vagus nerve activity were assessed. Some mice were treated daily for one week with the anti-lipid peroxidation agent aminoguanidine prior to the infusions and tests. The intestinal but not the intracarotid infusion of ML led to glucose and insulin intolerance when compared with controls. The intestinal ML overload induced lipid accumulation and increased lipid peroxidation as assessed by increased malondialdehyde production within both jejunum and duodenum. These effects were associated with the concomitant deregulation of vagus nerve. Administration of aminoguanidine protected against the effects of lipid overload and normalized glucose homeostasis and vagus nerve activity. CONCLUSIONS/SIGNIFICANCE: Lipid overload within the intestine led to deregulation of gastrointestinal lipid sensing that in turn impaired glucose homeostasis through changes in autonomic nervous system activity.
Published: 2011

49. Antiatherogenic Effect of Bisvanillyl-Hydralazone, a New Hydralazine Derivative with Antioxidant, Carbonyl Scavenger, and Antiapoptotic Properties

Author: Marie-Hélène Grazide, Nadji Belkheiri, Koji Uchida, Benaissa Bouguerne, Cécile Vindis, Robert Salvayre, Florence Bedos-Belval, Hubert Duran, Michel Baltas, Anne Nègre-Salvayre, Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences-Nagoya University, Université Fédérale Toulouse Midi-Pyrénées, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP)
Subjects: Male, Antioxidant, Physiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Apoptosis, 030204 cardiovascular system & hematology, medicine.disease_cause, Biochemistry, Antioxidants, Lipid peroxidation, Protein Carbonylation, chemistry.chemical_compound, Mice, 0302 clinical medicine, [CHIM] Chemical Sciences, Hydrogen peroxide, Cells, Cultured, Chemokine CCL2, ComputingMilieux_MISCELLANEOUS, General Environmental Science, Chelating Agents, chemistry.chemical_classification, Mice, Knockout, 0303 health sciences, Superoxide, Hydralazine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Plaque, Atherosclerotic, 3. Good health, Lipoproteins, LDL, lipids (amino acids, peptides, and proteins), medicine.drug, Bisvanillyl-Hydralazone, Proteasome Endopeptidase Complex, 03 medical and health sciences, medicine, Cell Adhesion, [CHIM]Chemical Sciences, Animals, Humans, Molecular Biology, 030304 developmental biology, Reactive oxygen species, Antiapoptotic Properties, Guaiacol, Endothelial Cells, Cell Biology, Atherosclerosis, Enzyme Activation, Oxidative Stress, chemistry, Hydralazine Derivative, General Earth and Planetary Sciences, Lipid Peroxidation, Reactive Oxygen Species, Carbonyl Scavenger, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Lipoprotein, Foam Cells
Abstract: International audience; Reactive oxygen species (ROS) generated within the vascular wall trigger low-density lipoprotein (LDL) oxidation, lipid peroxidation, and carbonyl stress that are involved in atherogenesis. We recently reported that the antihypertensive drug, hydralazine, exhibits carbonyl scavenger and antiatherogenic properties, but only moderate antioxidant activity, so that high concentrations are required for inhibiting LDL oxidation. We aimed to develop agents sharing both antioxidant and carbonyl scavenger properties. We have synthesized a new hydralazine derivative, the bisvanillyl-hydralazone (BVH). BVH strongly inhibited LDL oxidation induced by copper and by human endothelial cells (HMEC-1), and prevented the formation of macrophagic foam cells. BVH reduced both the extracellular generation of ROS (superoxide anion and hydrogen peroxide) induced by oxidized LDL (oxLDL), as well as intracellular oxidative stress and proteasome activation, NFkappaB activation, and oxLDL-mediated proinflammatory signaling. In parallel, BVH prevented the carbonyl stress induced by oxLDL on cellular proteins, and blocked the apoptotic cascade as assessed by the inhibition of Bid cleavage, cytochrome C release, and DEVDase activation. Lastly, BVH prevented atherogenesis and carbonyl stress in apoE(-/-) mice. In conclusion, BVH is the prototype of a new class of antioxidant and carbonyl scavenger agents designed for new therapeutical approaches in atherosclerosis.
Published: 2011

50. Pathological aspects of lipid peroxidation

Author: Giuseppe Poli, José C. E. Serrano, Giovanni E. Mann, Reinald Pamplona, János Fehér, Nathalie Augé, Victoria Ayala, Gabriella Lengyel, Werner Siems, Rainer Brenke, Shlomo Sasson, Kamelija Zarkovic, Robert Salvayre, Guy Cohen, Jordi Boada, Tilman Grune, Anne Nègre-Salvayre, Sarah J. Chapple, Richard C.M. Siow, Manuel Portero-Otin, Ingrid Wiswedel, Yael Riahi, Neven Zarkovic, Ofer Shamni, Huveyda Basaga, Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Metabolic Pathophysiology Research GroupDepartment of Basic Medical Sciences, Universitat de Lleida, Biological Sciences and Bioengineering Program, Sabanci University [Istanbul], Departament de Medicina Experimental, Hufeland Hospital, Cardiovascular Division, King‘s College London, The Hebrew University of Jerusalem (HUJ), 2nd Department of Medicine, Semmelweis University [Budapest], Institute of Biological Chemistry and Nutrition, University of Hohenheim, Department of Clinical and Biological Sciences, San Luigi Hospital-University of Turin, Department of Pharmacology, The Hebrew University of Jerusalem (HUJ)-Institute for Drug Research, Cités, Territoires, Environnement et Sociétés (CITERES), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Research Institute of Physiotherapy and Gerontology, Institute of Medical Education Bad Harzburg-KortexMed Institute of Medical Education Bad Harzburg, Department of Pathological Biochemistry, Medical Faculty of the Otto-von-Guericke-University, Department of Neuropathology, University of Zagreb-Clinical Hospital Center Zagreb, Rudjer Boskovic Institute, Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT), Rudjer Boskovic Institute [Zagreb], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Tours, Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Università degli studi di Torino = University of Turin (UNITO)-San Luigi Hospital
Subjects: Aging, [SDV]Life Sciences [q-bio], Bioinformatics, medicine.disease_cause, Biochemistry, MESH: Lipid Peroxidation, MESH: Atherosclerosis, MESH: Neurodegenerative Diseases, Lipid peroxidation, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Neoplasms, MESH: Aging, MESH: Animals, MESH: Neoplasms, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH: Oxidative Stress, Liver Diseases, Fatty liver, Neurodegenerative Diseases, General Medicine, 3. Good health, lipid peroxidation, 4-hydroxynonenal, medicine.medical_specialty, MESH: Diabetes Mellitus, MESH: Liver Diseases, oxidative stress, oxidative homeostasis, ROS, 4-Hydroxynonenal, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, liver disease, atherosclerosis, redox equilibrium, cell signalling, oxidized phospholipids, oxysterol, diabetes, 4-hydroxydodecadienal, pre-eclampsia, HELLP syndrome, IUGR, glutathione, redox signaling, Nrf2, antioxidant enzymes, foetal endothelium, renal diseases, lymphoedema, hyperglycaemia, advanced glycation end-products, cancer, Oxysterol, Biology, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Animals, Humans, 030304 developmental biology, MESH: Humans, Atherosclerosis, medicine.disease, Oxidative Stress, Endocrinology, chemistry, Ageing, Lipid Peroxidation, 030217 neurology & neurosurgery, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Lipid peroxidation (LPO) product accumulation in human tissues is a major cause of tissular and cellular dysfunction that plays a major role in ageing and most age-related and oxidative stress-related diseases. The current evidence for the implication of LPO in pathological processes is discussed in this review. New data and literature review are provided evaluating the role of LPO in the pathophysiology of ageing and classically oxidative stress-linked diseases, such as neurodegenerative diseases, diabetes and atherosclerosis (the main cause of cardiovascular complications). Striking evidences implicating LPO in foetal vascular dysfunction occurring in pre-eclampsia, in renal and liver diseases, as well as their role as cause and consequence to cancer development are addressed.
Published: 2010

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

68 results on '"Régulations cellulaires: lipidoses et atherosclerose"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources