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1. Protective effects of degraded Bletilla striata polysaccharides against UVB-induced oxidative stress in skin.

Author

Chen H, Lin C, Wu Y, Wang B, Kui M, Xu J, Ma H, Li J, Zeng J, Gao W, and Chen K

Subjects
Animals, Mice, Orchidaceae chemistry, Melanins metabolism, Reactive Oxygen Species metabolism, Humans, Molecular Weight, Cell Proliferation drug effects, Oxidative Stress drug effects, Ultraviolet Rays adverse effects, Polysaccharides pharmacology, Polysaccharides chemistry, Skin drug effects, Skin metabolism, Skin radiation effects, Antioxidants pharmacology, Antioxidants chemistry
Abstract

The Bletilla striata polysaccharides (BSP) extracted through alkali-assisted method exhibit significant antioxidant activity, but its bioaccessibility was inadequate due to its tightly filamentous reticulation structure and high molecular weight. The anti-photoaging and anti-melanogenesis effects of degraded BSP (DBSPs) against UVB-induced oxidative stress on the skin were investigated. The molecular weights of the DBSPs were reduced to 153.94 kDa, 66.96 kDa, and 15.54 kDa from an initial value of 298.82 kDa. The degradation treatment altered the branched chain structure of the DBSPs, while the backbone structure, triple-helix structure, and crystallinity remained. DBSPs with a lower molecular weight exhibit better in vitro antioxidant activity. DBSPs did not show cytotoxicity to HSF cells but inhibited B16F10 cell proliferation. The addition of DBSPs protected HSF and B16F10 cells from oxidative stress and reduced ROS levels, B16F10 melanin content, and B16F10 tyrosinase activity after UVB damage, but DBSP-10 particles were slightly less effective due to aggregation. In contrast, DBSP-5 demonstrated effectiveness in reducing MDA levels in cells stressed by oxidative stress, increased total antioxidant capacity, and inhibited melanogenesis in B16F10, suggesting that DBSP-5 has potential as a topical therapeutic agent for the treatment of skin diseases associated with oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Published
2024
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2. Antioxidant properties and neuroprotective effects of isocampneoside II on hydrogen peroxide-induced oxidative injury in PC12 cells.

Author

Si CL, Shen T, Jiang YY, Wu L, Yu GJ, Ren XD, Xu GH, and Hu WC

Subjects
Animals, Apoptosis Regulatory Proteins biosynthesis, Apoptosis Regulatory Proteins genetics, Apoptosis Regulatory Proteins metabolism, Cell Survival drug effects, Chelating Agents pharmacology, Gene Expression Regulation drug effects, Hydrogen Peroxide antagonists & inhibitors, Hydrogen Peroxide toxicity, Nerve Tissue Proteins biosynthesis, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Neurons enzymology, Neurons metabolism, Oxidants antagonists & inhibitors, Oxidants toxicity, Oxidation-Reduction, Oxidoreductases metabolism, PC12 Cells, Rats, Reactive Oxygen Species antagonists & inhibitors, Reactive Oxygen Species metabolism, Antioxidants pharmacology, Apoptosis drug effects, Caffeic Acids pharmacology, Disaccharides pharmacology, Glycosides pharmacology, Lipid Peroxidation drug effects, Neurons drug effects, Neuroprotective Agents pharmacology, Oxidative Stress drug effects
Abstract

Oxidative stress has been considered as a major cause of cell damage in various neurodegenerative disorders. One of the reasonable strategies for delaying the disease's progression is to prevent reactive oxygen species (ROS) mediated cellular injury by dietary or pharmaceutical augmentation of free radical scavengers. Isocampneoside II (ICD) is an active phenylethanoid glycoside isolated from the medicinal hardwood genus Paulownia. This study was designed to explore free radical scavenging potential of ICD in different in vitro systems and its protective role in hydrogen peroxide (H₂O₂)-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma (PC12) cells. The results showed ICD eliminated approximately 80.75% superoxide radical at the concentration of 0.1mg/ml and inhibited metal chelating by 22.07% at 8 mg/ml. Additionally, ICD showed a strong ability on reducing power and provided protection against oxidative protein damage induced by hydroxyl radicals. Pretreatment of PC12 cells with ICD prior to H₂O₂ exposure elevated cell viability, enhanced activity of superoxide dismutase and catalase, and decreased levels of malondialdehyde and intracellular ROS. Furthermore, ICD inhibited cell apoptosis and Bax/Bcl-2 ratio induced by H₂O₂. These findings suggested ICD may be considered as a potential antioxidant agent and should encourage for further research in neurodegenerative diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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3. Relationship between Physical Activity, Oxidative Stress, and Total Plasma Antioxidant Capacity in Spanish Children from the GENOBOX Study

Author

María D. Mesa, Rosaura Leis, Augusto Anguita-Ruiz, Azahara I. Rupérez, Concepción M. Aguilera, Luis A. Moreno, Angel Gil, Francisco Jesus Llorente-Cantarero, Francisco Javier Aguilar-Gómez, Gloria Bueno, Rocío Vázquez-Cobela, Mercedes Gil-Campos, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, [Llorente-Cantarero,FJ] Department of Specific Didactics, Faculty of Education, Maimónides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Llorente-Cantarero,FJ, Leis,R, Bueno,G, Anguita-Ruiz,A, Vázquez-Cobela,R, Moreno,LA, Gil,A, Aguilera,CM, Gil-Campos,M] CIBEROBN, (Physiopathology of Obesity and Nutrition) Institute of Health Carlos III (ISCIII), Madrid, Spain. [Aguilar-Gomez FJ, Gil-Campos,M] Metabolism and Investigation Unit, Reina Sofía University Hospital, Maimónides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Leis,R, Vázquez-Cobela,R] Unit of Investigation in Nutrition, Growth and Human Development of Galicia, Pediatric Department, University of Santiago de Compostela, Clinic University Hospital of Santiago, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain. [Bueno,G] Pediatric Endocrinology Unit, Clinic University Hospital Lozano Blesa, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain. [Bueno,G, Rupérez,AI, Moreno,LA] GENUD Research Group, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Zaragoza, Spain. [Anguita-Ruiz,A, Mesa,MA, Aguilera,CM] Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology 'José Mataix', Center of Biomedical Research, University of Granada, Armilla, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] Instituto de Investigación Biosanitaria ibs Granada, 18014 Granada, Spain., This research was funded by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI11/02042, PI11/02059, PI11/01425, and PI16/00871, PI16/01301, PI16/01205) and RETIC (Redes temáticas de investigación cooperativa) (Red SAMID RD12/0026/0015). The authors also acknowledge Instituto de Salud Carlos III for personal funding of A.A.R: Contratos i-PFIS: doctorados IIS-empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016 (IFI17/00048). Á.G. was funded by the Research Plan of the Vice-Rectorate of Research and Transfer of the University of Granada, Spain This paper will be included in F.J.A. doctorate, under the 'Biomedicine Program' at the University of Córdoba, Spain.

Subjects
Antioxidant, Isoprostane, 8-hydroxy-2′-deoxyguanosine, Physiology, medicine.medical_treatment, Clinical Biochemistry, Physical fitness, physical activity, medicine.disease_cause, Biochemistry, Acelerometría, chemistry.chemical_compound, 0302 clinical medicine, Accelerometry, oxidative stress, 030212 general & internal medicine, Isoprostane F2α, Plasma total antioxidant capacity, Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings], Health Care::Health Care Economics and Organizations::Organizations::International Agencies::United Nations::World Health Organization [Medical Subject Headings], Total plasma, plasma total antioxidant capacity, Estrés oxidativo, Ejercicio físico, isoprostane F2, Antioxidant capacity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Titrimetry::Colorimetry [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme Techniques::Enzyme-Linked Immunosorbent Assay [Medical Subject Headings], 8-Hidroxi-2'-Desoxicoguanosina, medicine.medical_specialty, Physical activity, Article, 03 medical and health sciences, Internal medicine, isoprostane F2α, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Protective Agents::Antioxidants [Medical Subject Headings], medicine, accelerometry, Pysical activity, Molecular Biology, Redox homeostasis, business.industry, lcsh:RM1-950, 030229 sport sciences, Cell Biology, 8-hydroxy-20-deoxyguanosine, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Physical Fitness [Medical Subject Headings], lcsh:Therapeutics. Pharmacology, chemistry, Oxidative stress, business
Abstract

The World Health Organization has recommended performing at least 60 min a day of moderate-to-vigorous physical activity (MVPA) and reducing sedentarism in children and adolescents to offer significant health benefits and mitigate health risks. Physical fitness and sports practice seem to improve oxidative stress (OS) status during childhood. However, to our knowledge, there are no data regarding the influence of objectively-measured physical activity (PA) and sedentarism on OS status in children and adolescents. The present study aimed to evaluate the influence of moderate and vigorous PA and sedentarism on OS and plasma total antioxidant capacity (TAC) in a selected Spanish population of 216 children and adolescents from the GENOBOX study. PA (light, moderate, and vigorous) and sedentarism (i.e., sedentary time (ST)) were measured by accelerometry. A Physical Activity-Sedentarism Score (PASS) was developed integrating moderate and vigorous PA and ST levels. Urinary 8-hydroxy-20-deoxyguanosine (8-OHdG) and isoprostane F2 (F2-IsoPs), as markers of OS, were determined by ELISA; and TAC was estimated by colorimetry using an antioxidant kit. A higher PASS was associated with lower plasma TAC and urinary 8-OHdG and F2-IsoPs, showing a better redox profile. Reduced OS markers (8-OHdG and F2-IsoPs) in children with higher PASS may diminish the need of maintaining high concentrations of antioxidants in plasma during rest to achieve redox homeostasis., Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI11/02042 PI11/02059 PI11/01425 PI16/00871 PI16/01301 PI16/01205, RETIC (Redes temáticas de investigación cooperativa) Red SAMID RD12/0026/0015, Instituto de Salud Carlos III European Commission IFI17/00048, Research Plan of the Vice-Rectorate of Research and Transfer of the University of Granada, Spain

Published
2021

4. The coming age of flavonoids in the treatment of diabetic complications

Author

Gema Marín-Royo, Carmen Gomez-Guerrero, Lucas Opazo-Ríos, Luna Jimenez-Castilla, Jesús Egido, Teresa Caro-Ordieres, Juan Antonio Moreno, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD), [Caro-Ordieres,T] Research Discovery and Innovation Department, FAES FARMA, S.A, Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country, Leioa (Bizkaia), Spain. [Marín-Royo,G, Opazo-Ríos,L, Jiménez-Castilla,L, Gómez-Guerrero,C, Egido,J] Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autonoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain. [Moreno,JA] Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain. [Moreno,JA] Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Moreno,JA] Hospital Universitario Reina Sofía, Córdoba, Spain., and This paper was not funded. The authors work has been supported by FEDER-ISCIII Funds (PI17/00130, PI17/01495), Spanish Ministry of Economy and Competitiveness (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN) and Spanish Society of Atherosclerosis (SEA). TCO is an employee of FAES Pharma. The authors (except JAM) have an ongoing research project in common with FAES Pharma on Flavonoids in diabetic complications under the auspices of the joint-RETOS Collaborations Project 2017 (RTC-2017-6089-1), program supported by Spanish Ministry of Economy and Competitiveness. No other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Subjects
medicine.medical_specialty, Microvascular complications, Nefropatías Diabéticas, Medicina, Terapéutica, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics [Medical Subject Headings], lcsh:Medicine, Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic Nephropathies [Medical Subject Headings], Review, Diabetic nephropathy, Therapeutics, Controlled studies, Chemicals and Drugs::Heterocyclic Compounds::Pyrans::Benzopyrans::Chromones::Flavonoids [Medical Subject Headings], Unmet needs, 03 medical and health sciences, Diabetes mellitus, 0302 clinical medicine, medicine, Flavonoides, Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings], Intensive care medicine, Diseases::Cardiovascular Diseases [Medical Subject Headings], Beneficial effects, Enfermedades Cardiovasculares, 030304 developmental biology, Flavonoids, Inflammation, 0303 health sciences, Inflamación, Diseases::Endocrine System Diseases::Diabetes Mellitus [Medical Subject Headings], business.industry, lcsh:R, Diabetes, General Medicine, medicine.disease, Cardiovascular disease, Clinical trial, Clinical research, Tolerability, Oxidative stress, 030220 oncology & carcinogenesis, business, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings], Estrés Oxidativo
Abstract

Diabetes mellitus (DM), and its micro and macrovascular complications, is one of the biggest challenges for world public health. Despite overall improvement in prevention, diagnosis and treatment, its incidence is expected to continue increasing over the next years. Nowadays, finding therapies to prevent or retard the progression of diabetic complications remains an unmet need due to the complexity of mechanisms involved, which include inflammation, oxidative stress and angiogenesis, among others. Flavonoids are natural antioxidant compounds that have been shown to possess anti-diabetic properties. Moreover, increasing scientific evidence has demonstrated their potential anti-inflammatory and anti-oxidant effects. Consequently, the use of these compounds as anti-diabetic drugs has generated growing interest, as is reflected in the numerous in vitro and in vivo studies related to this field. Therefore, the aim of this review is to assess the recent pre-clinical and clinical research about the potential effect of flavonoids in the amelioration of diabetic complications. In brief, we provide updated information concerning the discrepancy between the numerous experimental studies supporting the eficacy of flavonoids on diabetic complications and the lack of appropriate and well-designed clinical trials. Due to the well-described beneficial effects on different mechanisms involved in diabetic complications, the excellent tolerability and low cost, future randomized controlled studies with compounds that have adequate bioavailability should be evaluated as add-on therapy on well-established anti-diabetic drugs, This paper was not funded. The authors work has been supported by FEDER-ISCIII Funds (PI17/00130, PI17/01495), Spanish Ministry of Economy and Competitiveness (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN) and Spanish Society of Atherosclerosis (SEA). TCO is an employee of FAES Pharma. The authors (except JAM) have an ongoing research project in common with FAES Pharma on Flavonoids in diabetic complications under the auspices of the joint-RETOS Collaborations Project 2017 (RTC-2017-6089-1), program supported by Spanish Ministry of Economy and Competitiveness.

Published
2020

5. Cellular Senescence: Defining a Path Forward

Author

John M. Sedivy, Paul D. Robbins, Cleo L. Bishop, Vassilis G. Gorgoulis, Konstantinos Vougas, Konstantinos Evangelou, Valery Krizhanovsky, Dorothy C. Bennett, Eiji Hara, Diana Jurk, Gerardo Ferbeyre, Judith Campisi, Masashi Narita, Laura J. Niedernhofer, Manuel Serrano, Clemens A. Schmitt, Peter D. Adams, Oliver Bischof, Andrea Alimonti, Marco Demaria, Jesús Gil, Daohong Zhou, Manuel Collado, Thomas von Zglinicki, Andrea B. Maier, João F. Passos, Institut Pasteur [Paris], National and Kapodistrian University of Athens (NKUA), University of Manchester [Manchester], Biomedical Research Foundation of the Academy of Athens (BRFAA), Institute of Cancer Sciences [Glasgow, UK] (CR-UK Beatson Institute), University of Glasgow, Sanford Burnham Prebys Medical Discovery Institute, Oncology Institute of Southern Switzerland (IOSI), Università della Svizzera italiana = University of Italian Switzerland (USI), Universita degli Studi di Padova, Veneto Institute of Molecular Medicine [Padova, Italy] (VIMM), University of London [London], Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Bart's and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Buck Institute for Research on Aging, Universidade de Santiago de Compostela [Spain] (USC ), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université de Montréal (UdeM), MRC London Institute of Medical Sciences (LMC), Imperial College London, Research Institute for Microbial Diseases [Osaka, Japan] (RIMD), Osaka University [Osaka], Department of Molecular Cell Biology [Rehovot], Weizmann Institute of Science [Rehovot, Israël], Robert and Arlene Kogod Center on Aging [Rochester, MN, USA], Mayo Clinic, Vrije Universiteit Amsterdam [Amsterdam] (VU), University of Melbourne, University of Cambridge [UK] (CAM), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Kepler University Hospital, Brown University, Newcastle University [Newcastle], University of Florida [Gainesville] (UF), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Institució Catalana de Recerca i Estudis Avançats (ICREA), University of Groningen [Groningen], European Research Institute for the Biology of Ageing [Groningen] (ERIBA), University Medical Center Groningen [Groningen] (UMCG), M.D. is funded by the Dutch Cancer Foundation, Netherlands (grant ID 10989). V.G., K.E., and K.V. were financially supported by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grants agreement no. 722729 (SYNTRAIN), the Welfare Foundation for Social & Cultural Sciences (KIKPE), Greece, the KIKPE Foundation, Athens, Greece, Pentagon Biotechnology, UK, DeepMed IO, UK, grant no. 775 from the Hellenic Foundation for Research and Innovation (HFRI), and NKUA-SARG grants 70/3/9816, 70/3/12128, and 70/3/15603. M.S.: is funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and 'laCaixa' Foundation., We would like to thank Nikolaos Kastrinakis, Panagiotis V.S. Vasileiou, Gkikas Magiorkinis, Eleni Fitsiou, and Michela Borghesan for their valuable support to this work. We apologize in advance that, for reason of space, we have omitted the citations of relevant papers and reviews., National and Kapodistrian University of Athens = University of Athens (NKUA | UoA), Organisation Nucléaire et Oncogenèse - Nuclear Organization and Oncogenesis, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], University of Santiago de Compostela [Spain] (USC), Centre de recherche du Chum [Montréal] (CRCHUM), Université de Montréal [Montréal], Research Institute for Microbial Diseases, Weizmann Institute of Science, University of Minnesota [Twin Cities], Max Delbrück Center for Molecular Medicine [Berlin], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, University of Florida [Gainesville], University of Barcelona, Università degli Studi di Padova = University of Padua (Unipd), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Narita, Masashi [0000-0001-7764-577X], and Apollo - University of Cambridge Repository

Subjects
Senescence, EXPRESSION, Aging, Cell cycle checkpoint, [SDV]Life Sciences [q-bio], Cell, DNA-DAMAGE RESPONSE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mitochondrion, Biology, General Biochemistry, Genetics and Molecular Biology, CHROMATIN LANDSCAPE, 03 medical and health sciences, 0302 clinical medicine, MITOCHONDRIA, ONCOGENE-INDUCED SENESCENCE, medicine, Humans, OXIDATIVE STRESS, Senolytic, Cellular Senescence, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, P53, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Genetic Diseases, Inborn, DARK SIDE, Cell Cycle Checkpoints, 06 Biological Sciences, CANCER, Chromatin, medicine.anatomical_structure, Gene Expression Regulation, CELLS, Developmental biology, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology
Abstract

International audience; Cellular senescence is a cell state implicated in various physiological processes and a wide spectrum of age-related diseases. Recently, interest in therapeutically targeting senescence to improve healthy aging and age-related disease, otherwise known as senotherapy, has been growing rapidly. Thus, the accurate detection of senescent cells, especially in vivo, is essential. Here, we present a consensus from the International Cell Senescence Association (ICSA), defining and discussing key cellular and molecular features of senescence and offering recommendations on how to use them as biomarkers. We also present a resource tool to facilitate the identification of genes linked with senescence, SeneQuest (available at http://Senequest.net). Lastly, we propose an algorithm to accurately assess and quantify senescence, both in cultured cells and in vivo.

Published
2019
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6. Structure and function of theLeptospira interrogansperoxide stress regulator (PerR), an atypical PerR devoid of a structural metal-binding site

Author

Patrick Weber, Nadia Benaroudj, Frederick Saul, Sarah Dubrac, Annie Landier, Bénédicte Beaudeau, Raléb Taher, Mounira Kebouchi, Ahmed Haouz, Mathieu Picardeau, Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris], Cristallographie (Plateforme) - Crystallography (Platform), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Biologie des Bactéries pathogènes à Gram-positif, This work was supported by the Institut Pasteur and Agence National de la Recherche Grant ANR-08-MIE-018., M. K., R. T., A. L., B. B., and P. W. performed experiments. F. S., A. H., S. D., M. P., and N. B. conceived, performed, and analyzed experiments. N. B. conceived and coordinated the study and wrote the paper. All authors approved the final version of the manuscript.We acknowledge SOLEIL for provision of synchrotron radiation facilities, and we thank the staff of beamline PROXIMA 1 for assistance. We are grateful to Gerald Murray and Ben Adler for providing the perR mutant. We thank Gouzel Karimova, Isabelle Michaud-Soret, and Victor Duarte for critically reading the manuscript and for helpful discussions., ANR-08-MIEN-0018,LEPTOVIR,Les leptospires : de la génétique à la pathogénèse(2008), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Signal Transduction, 0301 basic medicine, MESH: Leptospira interrogans, [SDV]Life Sciences [q-bio], Mutant, Regulatory site, Metal Binding Site, Cell Cycle Proteins, spirochaetes, Biochemistry, Peroxide, chemistry.chemical_compound, Metalloprotein, oxidative stress, structural biology, spirochetes, MESH: Bacterial Proteins, Leptospira, chemistry.chemical_classification, biology, Chemistry, régulation transcriptionnelle, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, transcription regulation, Leptospira interrogans, Protein Binding, Signal Transduction, Repressor, Mitosis, PerR, reactive oxygen species (ROS), Microbiology, 03 medical and health sciences, MESH: Cell Cycle Proteins, Bacterial Proteins, métalloprotéine, MESH: Protein Binding, microbiologie, Molecular Biology, Binding Sites, metalloprotein, stress oxydatif, Cell Biology, MESH: Mitosis, biology.organism_classification, 030104 developmental biology, MESH: Binding Sites, Structural biology
Abstract

International audience; Peroxide sensing is essential for bacterial survival during aerobic metabolism and host infection. Peroxide stress regulators (PerRs) are homodimeric transcriptional repressors with each monomer typically containing both structural and regulatory metal-binding sites. PerR binding to gene promoters is controlled by the presence of iron in the regulatory site, and iron-catalyzed oxidation of PerR by H2O2 leads to the dissociation of PerR from DNA. In addition to a regulatory metal, most PerRs require a structural metal for proper dimeric assembly. We present here a structural and functional characterization of the PerR from the pathogenic spirochete Leptospira interrogans, a rare example of PerR lacking a structural metal-binding site. In vivo studies showed that the leptospiral PerR belongs to the peroxide stimulon in pathogenic species and is involved in controlling resistance to peroxide. Moreover, a perR mutant had decreased fitness in other host-related stress conditions, including at 37 °C or in the presence of superoxide anion. In vitro, leptospiral PerR could bind to the perR promoter region in a metal-dependent manner. The crystal structure of the leptospiral PerR revealed an asymmetric homodimer, with one monomer displaying complete regulatory metal coordination in the characteristic caliper-like DNA-binding conformation and the second monomer exhibiting disrupted regulatory metal coordination in an open non-DNA-binding conformation. This structure showed that leptospiral PerR assembles into a dimer in which a metal-induced conformational switch can occur independently in the two monomers. Our study demonstrates that structural metal binding is not compulsory for PerR dimeric assembly and for regulating peroxide stress.

Published
2018

7. Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review

Author

Taha Najar, Manef Abdrabbah, Abdeljelil Ghram, Moncef Ben Mrad, Imen Belhadj Slimen, Hajer Dabbebi, Preparatory Institute for Scientific and Technical Studies [La Marsa] (IPEST), Université de Carthage - University of Carthage, Institut National Agronomique de Tunis (INAT), Ministère de l'Enseignement Supérieur et de Recherche Scientifique [Tunisie], Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), and The authors thank Gillian Murphy, Emeritus Professor in the Department of Oncology at the University of Cambridge, for her assistance and help with English editing of this paper.

Subjects
Cancer Research, Antioxidant, MESH: Oxidative Stress, Physiology, Cellular respiration, medicine.medical_treatment, Apoptosis, Oxidative phosphorylation, Mitochondrion, Biology, medicine.disease_cause, reactive oxygen species (ROS), DNA, Mitochondrial, MESH: Lipid Peroxidation, heat stress, Electron Transport, Physiology (medical), medicine, Humans, MESH: Electron Transport, chemistry.chemical_classification, MESH: DNA Damage, Reactive oxygen species, MESH: Humans, MESH: Apoptosis, MESH: DNA, Mitochondrial, Metabolism, MESH: Heat-Shock Response, mitochondria, Oxidative Stress, chemistry, Biochemistry, MESH: Reactive Oxygen Species/metabolism, Lipid Peroxidation, Reactive Oxygen Species, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Heat-Shock Response, DNA Damage
Abstract

International audience; In recent years there has been enormous interest in researching oxidative stress. Reactive oxygen species (ROS) are derived from the metabolism of oxygen as by-products of cell respiration, and are continuously produced in all aerobic organisms. Oxidative stress occurs as a consequence of an imbalance between ROS production and the available antioxidant defence against them. Nowadays, a variety of diseases and degenerative processes such as cancer, Alzheimer’s and autoimmune diseases are mediated by oxidative stress. Heat stress was suggested to be an environmental factor responsible for stimulating ROS production because of similarities in responses observed following heat stress compared with that occurring following exposure to oxidative stress. This manuscript describes the main mitochondrial sources of ROS and the antioxidant defences involved to prevent oxidative damage in all the mitochondrial compartments. It also deals with discussions concerning the cytotoxic effect of heat stress, mitochondrial heat-induced alterations, as well as heat shock protein (HSP) expression as a defence mechanism.

Published
2014

8. Peroxisome proliferator-activated receptor-α activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment

Author

Olivier Pétrault, Bernard Dupuis, Isabelle Six, Régis Bordet, Patrick Gelé, Christophe Furman, Bart Staels, Dominique Deplanque, Roméo Cecchelli, Patrick Duriez, Muriel Bouly, Didier Leys, Jean-Charles Fruchart, Stéphane Nion, Université Lille 2 - Faculté de Médecine, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs nucléaires, lipoprotéines et athérosclérose, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Réseau International des Instituts Pasteur (RIIP), Université d'Artois (UA), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), P.G. was supported by a grant from 'Conseil Régional Nord Pas de Calais et Centre Hospitalier Régional et Universitaire de Lille. ' This work was supported by grants from ' Génopole Lille Nord-Pas de Calais '(#01360124) and Institut National de la Santé et de la Recherche Médicale (CReS4CR02F)., and We thank Alexandra Tavernier-Sommerville for her assistance with the English version of this paper.

Subjects
Middle Cerebral Artery, Mouse, Nitric Oxide Synthase Type II, Receptors, Cytoplasmic and Nuclear, Peroxisome proliferator-activated receptor, medicine.disease_cause, Rats, Inbred WKY, Mice, 0302 clinical medicine, Fenofibrate, Mice, Knockout, chemistry.chemical_classification, 0303 health sciences, biology, General Neuroscience, Infarction, Middle Cerebral Artery, Cerebral Infarction, Intercellular Adhesion Molecule-1, Neuroprotection, Vasodilation, Nitric oxide synthase, Stroke, Neuroprotective Agents, Cerebrovascular Circulation, Middle cerebral artery, medicine.symptom, medicine.drug, PPAR-α, medicine.medical_specialty, Adhesion proteins, Nitric Oxide Synthase Type III, Development/Plasticity/Repair, Ischemia, Vascular Cell Adhesion Molecule-1, Mice, Transgenic, Inflammation, Time, 03 medical and health sciences, Apolipoproteins E, medicine.artery, Internal medicine, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, business.industry, Prevention, medicine.disease, Rats, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, chemistry, Oxidative stress, biology.protein, Nitric Oxide Synthase, business, 030217 neurology & neurosurgery, Transcription Factors
Abstract

International audience; The treatment of ischemic strokes is limited to the prevention of cerebrovascular risk factors and to the modulation of the coagulation cascade during the acute phase. Anew therapeutic strategy could be to preventively protect the brain against noxious biological reactions induced by cerebral ischemia such as oxidative stress and inflammation to minimize their neurological consequences. Here, we show that a peroxisome proliferator-activated receptor (PPAR-α) activator, fenofibrate, protects against cerebral injury by anti-oxidant and antiinflammatory mechanisms. A 14 d preventive treatment with fenofibrate reduces susceptibility to stroke in apolipoprotein E-deficient mice as well as decreases cerebral infarct volume in C57BL/6 wild-type mice. The neuroprotective effect of fenofibrate is completely absent in PPAR-α-deficient mice, suggesting that PPAR-α activation is involved as a mechanism of the protection against cerebral injury. Furthermore, this neuroprotective effect appears independently of any improvement in plasma lipids or glycemia and is associated with (1) an improvement in middle cerebral artery sensitivity to endothelium-dependent relaxation unrelated to an increase in nitric oxide synthase (NOS) type III expression, (2) a decrease in cerebral oxidative stress depending on the increase in numerous antioxidant enzyme activities, and (3) the prevention of ischemia-induced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in cerebral vessels without any change in NOS II expression. These data demonstrate that PPAR-α could be a new pharmacological target to preventively reduce the deleterious neurological consequences of stroke in mice and suggest that PPAR-α activators could preventively decrease the severity of stroke in humans.

Published
2003