106 results on '"Nury, T"'
Search Results
2. Protective effects of bezafibrate against elaidic acid-induced accumulation of lipid droplets in monocytic cells
- Author
-
Haj Ahmed, S., Kharroubi, W., Zarrouk, A., Brahmi, F., Nury, T., Lizard, G., and Hammami, M.
- Published
- 2017
- Full Text
- View/download PDF
3. Dual effect of docosahexaenoic acid (attenuation or amplification) on C22:0-, C24:0-, and C26:0-Induced mitochondrial dysfunctions and oxidative stress on human neuronal SK-N-BE cells
- Author
-
Zarrouk, A., Nury, T., Riedinger, J. M., Rouaud, O., Hammami, M., and Lizard, Gérard
- Published
- 2015
- Full Text
- View/download PDF
4. Attenuation of 7-ketocholesterol- and 7β-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases
- Author
-
Nury, T., primary, Yammine, A., additional, Ghzaiel, I., additional, Sassi, K., additional, Zarrouk, A., additional, Brahmi, F., additional, Samadi, M., additional, Rup-Jacques, S., additional, Vervandier-Fasseur, D., additional, Pais de Barros, J.P., additional, Bergas, V., additional, Ghosh, S., additional, Majeed, M., additional, Pande, A., additional, Atanasov, A., additional, Hammami, S., additional, Hammami, M., additional, Mackrill, J., additional, Nasser, B., additional, Andreoletti, P., additional, Cherkaoui-Malki, M., additional, Vejux, A., additional, and Lizard, G., additional
- Published
- 2021
- Full Text
- View/download PDF
5. Induction of a non-apoptotic mode of cell death associated with autophagic characteristics with steroidal maleic anhydrides and 7β-hydroxycholesterol on glioma cells
- Author
-
Sassi, K., primary, Nury, T., additional, Zarrouk, A., additional, Sghaier, R., additional, Khalafi-Nezhad, A., additional, Vejux, A., additional, Samadi, M., additional, Aissa-Fennira, F. Ben, additional, and Lizard, G., additional
- Published
- 2019
- Full Text
- View/download PDF
6. Cellular interactions of functionalized superparamagnetic iron oxide nanoparticles on oligodendrocytes without detrimental side effects: Cell death induction, oxidative stress and inflammation
- Author
-
Sruthi, S., primary, Maurizi, L., additional, Nury, T., additional, Sallem, F., additional, Boudon, J., additional, Riedinger, J.M., additional, Millot, N., additional, Bouyer, F., additional, and Lizard, G., additional
- Published
- 2018
- Full Text
- View/download PDF
7. Evaluation of two human dental pulp stem cell cryopreservation methods
- Author
-
Juan C, Munévar, Nicole, Gutiérrez, Nury T, Jiménez, and Gloria I, Lafaurie
- Subjects
Adult ,Cryopreservation ,Young Adult ,Adolescent ,Stem Cells ,Humans ,Cell Differentiation ,Dental Pulp - Abstract
Dental pulp is a promising source of mesenchymal stem cells for use in cell therapy and regenerative medicine. Methods for storing stem cells with minimum compromise of cell viability, differentiation capacity and function should be developed for clinical and research applications. The aim of this study was to evaluate whether human dental pulp stem cells (hDPSCs) isolated and cryopreserved for 1, 7 and 30 days maintain viability and expression of specific stem cell markers. Human dental pulp stem cells were isolated from 23 healthy patients aged 18 to 31 years. Dental pulp was enzymatically dissociated, and CD105+ cells were separated using the Miltenyi™ system. The hDPSCs were cryopreserved using the Kamath and Papaccio methods. Post-cryopreservation viability was measured by flow cytometry (7AAD) and by the expression of the phenotype markers CD105+/ CD73+, CD34-/CD45-. The Papaccio method showed greater cell viability for cells that had been frozen for 30 days (59.5%) than the Kamath method (56.2%), while the Kamath method provided better results for 1 day (65.5%) and 7 days (56%). Post-cryopreservation expression of the markers CD105+/CD34- was greater after 1 and 7 days with the Kamath method and CD105+/CD45- were expressed after all 3 cryopreservation times. There was greater expression of CD73+ in the hDPSCs after 1 and 7 days with the Kamath method, and after 30 days with the Papaccio method. These results suggest that hDPSCs express mesenchymal stem cell markers after cryopreservation. However, cryopreservation time may affect marker expression, probably by altering the spatialconfiguration of cell membrane proteins or by compromising cells at a certain level of differentiation.
- Published
- 2015
8. Evaluation of two human dental pulp stem cell cryopreservation methods
- Author
-
Munévar Niño, Juan Carlos, Gutiérrez, Nicole, Jiménez, Nury T., Lafaurie, Gloria Ines, Lafaurie, Gloria Ines [0000-0003-3986-0625], and Munévar Niño, Juan Carlos [0000-0002-8482-2962]
- Subjects
Cryopreservation ,Dental pulp ,Criopreservación ,Medicina regenerativa ,Phenotype ,Regenerative medicine ,Mesenchymal stem cells ,Pulpa dental ,Células troncales mesenquimales ,Fenotipo ,Viabilidad celular ,Cell viabilit - Abstract
La pulpa dental es una fuente promisoria de celulas madre mesenquimales para ser utilizadas en terapia celular y medicina regenerativa. El desarrollo de metodos que permitan almacenar las celulas madre con minimo compromiso de la viabilidad celular, capacidad de diferenciacion y funcion es necesario para aplicaciones clinicas e investigacion. El objetivo de este estudio fue evaluar si las celulas troncales de pulpa dental humana (hDPSCs) aisladas y criopreservadas durante 1, 7 y 30 dias conservan la viabilidad y expresion de marcadores especificos de celulas troncales pos crio-preservacion. Para esto, las hDPSCs se aislaron de 23 pacientes sanos entre 18 y 31 anos. La pulpa dental se disocio enzimaticamente, y las celulas CD105+ se separaron mediante el sistema Miltenyi™. Posteriormente, las hDPSCs se criopreservaron utilizando el metodo de Kamath y de Papaccio, se evaluo la viabilidad pos crio-preservacion por citometria de flujo (7AAD) y la expresion de marcadores CD105+/ CD73+, CD34-/CD45-. El metodo de Papaccio, mostro mayor viabilidad celular a los 30 dias (59,5%) comparado con el metodo de Kamath, a 1 dia (65,5%) y 7 dias (56%) respectivamente. Se observo mayor expresion de los marcadores CD105+/CD34- a 1 y 7 dias pos-criopreservacion con el metodo Kamath y CD105+/CD45- a los 3 tiempos de criopreservacion. CD73+ presento mayor expresion en las hDPSCs a las 24 horas y 7 dias con el metodo de Kamath, y al mes con el metodo Papaccio. Estos resultados sugieren que las hDPSCs expresan marca - dores de celulas troncales mesenquimales postcriopreservacion. Sin embargo el tiempo de criopreservacion podria modificar la expresion de los marcadores probablemente por alterar Dental pulp is a promising source of mesenchymal stem cells for use in cell therapy and regenerative medicine. Methods for storing stem cells with minimum compromise of cell viability, differentiation capacity and function should be developed for clinical and research applications. The aim of this study was to evaluate whether human dental pulp stem cells (hDPSCs) isolated and cryopreserved for 1, 7 and 30 days maintain viability and expression of specific stem cell markers. Human dental pulp stem cells were isolated from 23 healthy patients aged 18 to 31 years. Dental pulp was enzymatically dissociated, and CD105+ cells were separated using the Miltenyi™ system. The hDPSCs were cryopreserved using the Kamath and Papaccio methods. Post-cryopreservation viability was measured by flow cytometry (7AAD) and by the expression of the phenotype markers CD105+/ CD73+, CD34-/CD45-. The Papaccio method showed greater cell viability for cells that had been frozen for 30 days (59.5%) than the Kamath method (56.2%), while the Kamath method provided better results for 1 day (65.5%) and 7 days (56%). Post-cryopreservation expression of the markers CD105+/CD34- was greater after 1 and 7 days with the Kamath method and CD105+/CD45- were expressed after all 3 cryopreservation times. There was greater expression of CD73+ in the hDPSCs after 1 and 7 days with the Kamath method, and after 30 days with the Papaccio method. These results suggest that hDPSCs express mesenchymal stem cell markers after cryopreservation. However, cryopreservation time may affect marker expression, probably by altering the spatialconfiguration of cell membrane proteins or by compromising cells at a certain level of differentiation.
- Published
- 2015
9. Dual effect of docosahexaenoic acid (attenuation or amplification) on C22:0-, C24:0-, and C26:0-Induced mitochondrial dysfunctions and oxidative stress on human neuronal SK-N-BE cells
- Author
-
Zarrouk, A., primary, Nury, T., additional, Riedinger, J. M., additional, Rouaud, O., additional, Hammami, M., additional, and Lizard, Gérard, additional
- Published
- 2014
- Full Text
- View/download PDF
10. Brain peroxisomes
- Author
-
Trompier, D., primary, Vejux, A., additional, Zarrouk, A., additional, Gondcaille, C., additional, Geillon, F., additional, Nury, T., additional, Savary, S., additional, and Lizard, G., additional
- Published
- 2014
- Full Text
- View/download PDF
11. Determination of heavy metal content and lipid profiles in mussel extracts from two sites on the moroccan atlantic coast and evaluation of their biological activities on MIN6 pancreatic cells
- Author
-
Boumhras, M., primary, Ouafik, S., additional, Nury, T., additional, Gresti, J., additional, Athias, A., additional, Ragot, K., additional, Nasser, B., additional, Cherkaoui-Malki, M., additional, and Lizard, G., additional
- Published
- 2013
- Full Text
- View/download PDF
12. Evidence of oxidative stress in very long chain fatty acid – Treated oligodendrocytes and potentialization of ROS production using RNA interference-directed knockdown of ABCD1 and ACOX1 peroxisomal proteins
- Author
-
Baarine, M., primary, Andréoletti, P., additional, Athias, A., additional, Nury, T., additional, Zarrouk, A., additional, Ragot, K., additional, Vejux, A., additional, Riedinger, J.-M., additional, Kattan, Z., additional, Bessede, G., additional, Trompier, D., additional, Savary, S., additional, Cherkaoui-Malki, M., additional, and Lizard, G., additional
- Published
- 2012
- Full Text
- View/download PDF
13. Determination of heavy metal content and lipid profiles in mussel extracts from two sites on the moroccan atlantic coast and evaluation of their biological activities on MIN6 pancreatic cells.
- Author
-
Boumhras, M., Ouafik, S., Nury, T., Gresti, J., Athias, A., Ragot, K., Nasser, B., Cherkaoui‐Malki, M., and Lizard, G.
- Subjects
HEAVY metals ,LYSOSOMES ,ORGANELLES ,FATTY acids ,PHOSPHOLIPIDS - Abstract
Mussels may concentrate pollutants, with possibly significant side effects on human health. Therefore, mussels (Mytilus galloprovincialis) from two sites of the Moroccan Atlantic coast (Jorf Lasfar [JL], an industrial site, and Oualidia [OL], a vegetable-growing area), were subjected to biochemical analyses to quantify the presence of heavy metals (Cd, Cr, and Pb) and to establish the lipid profile: fatty acid, cholesterol, oxysterol, phytosterol and phospholipid content. In addition, mussel lipid extracts known to accumulate numerous toxic components were tested on murine pancreatic β-cells (MIN6), and their biological activities were measured with various flow cytometric and biochemical methods to determine their impacts on cell death induction, organelle dysfunctions (mitochondria, lysosomes, and peroxisomes), oxidative stress and insulin secretion. The characteristics of JL and OL lipid extracts were compared with those of commercially available mussels from Spain (SP) used for human consumption. OL and JL contained heavy metals, high amounts of phospholipids, and high levels of oxysterols; the [(unsaturated fatty acids)/(saturated fatty acids)] ratio, which can be considered a sign of environmental stress leading to lipid peroxidation, was low. On MIN6 cells, JL and OL lipid extracts were able to trigger cell death. This event was associated with overproduction of H
2 O2 , increased catalase activity, a decreased GSH level, lipid peroxidation and stimulation of insulin secretion. These effects were not observed with SP lipid extracts. These data suggest that some components from OL and JL lipid extracts might predispose to pancreatic dysfunctions. Epidemiological studies would be needed to assess the global risk on human health and the metabolic disease incidence in a context of regular seafood consumption from the OL and JL areas. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1245-1261, 2014. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
14. Impact of C24:0 on actin-microtubule interaction in human neuronal SK-N-BE cells: evaluation by FRET confocal spectral imaging microscopy after dual staining with rhodamine-phalloidin and tubulin tracker green
- Author
-
Zarrouk A, Nury T, Dauphin A, Frère P, Jm, Riedinger, Cm, Bachelet, Frédérique Frouin, Moreau T, Hammami M, Kahn E, and Lizard G
15. Protective effects of milk thistle (Sylibum marianum) seed oil and α-tocopherol against 7β-hydroxycholesterol-induced peroxisomal alterations in murine C2C12 myoblasts: Nutritional insights associated with the concept of pexotherapy
- Author
-
Imen Ghzaiel, Amira Zarrouk, Soukaina Essadek, Lucy Martine, Souha Hammouda, Aline Yammine, Mohamed Ksila, Thomas Nury, Wiem Meddeb, Mounia Tahri Joutey, Wafa Mihoubi, Claudio Caccia, Valerio Leoni, Mohammad Samadi, Niyazi Acar, Pierre Andreoletti, Sonia Hammami, Taoufik Ghrairi, Anne Vejux, Mohamed Hammami, Gérard Lizard, Ghzaiel, I, Zarrouk, A, Essadek, S, Martine, L, Hammouda, S, Yammine, A, Ksila, M, Nury, T, Meddeb, W, Tahri Joutey, M, Mihoubi, W, Caccia, C, Leoni, V, Samadi, M, Acar, N, Andreoletti, P, Hammami, S, Ghrairi, T, Vejux, A, Hammami, M, and Lizard, G
- Subjects
Pharmacology ,Flavonoids ,Sarcopenia ,Organic Chemistry ,Clinical Biochemistry ,alpha-Tocopherol ,7β-hydroxycholesterol ,Milk thistle seed oil ,Peroxisome ,Biochemistry ,Antioxidants ,Hydroxycholesterols ,Myoblasts ,Mice ,Endocrinology ,Animals ,Humans ,Milk Thistle ,Plant Oils ,Pexotherapy ,RNA, Messenger ,C2C12 myoblast ,Reactive Oxygen Species ,Molecular Biology - Abstract
Peroxisomes play an important role in regulating cell metabolism and RedOx homeostasis. Peroxisomal dysfunctions favor oxidative stress and cell death. The ability of 7β-hydroxycholesterol (7β-OHC; 50 μM, 24 h), known to be increased in patients with age-related diseases such as sarcopenia, to trigger oxidative stress, mitochondrial and peroxisomal dysfunction was studied in murine C2C12 myoblasts. The capacity of milk thistle seed oil (MTSO, 100 μg/mL) as well as α-tocopherol (400 µM; reference cytoprotective agent) to counteract the toxic effects of 7β-OHC, mainly at the peroxisomal level were evaluated. The impacts of 7β-OHC, in the presence or absence of MTSO or α-tocopherol, were studied with complementary methods: measurement of cell density and viability, quantification of reactive oxygen species (ROS) production and transmembrane mitochondrial potential (ΔΨm), evaluation of peroxisomal mass as well as topographic, morphologic and functional peroxisomal changes. Our results indicate that 7β-OHC induces a loss of cell viability and a decrease of cell adhesion associated with ROS overproduction, alterations of mitochondrial ultrastructure, a drop of ΔΨm, and several peroxisomal modifications. In the presence of 7β-OHC, comparatively to untreated cells, important quantitative and qualitative peroxisomal modifications were also identified: a) a reduced number of peroxisomes with abnormal sizes and shapes, mainly localized in cytoplasmic vacuoles, were observed; b) the peroxisomal mass was decreased as indicated by lower protein and mRNA levels of the peroxisomal ABCD3 transporter; c) lower mRNA level of Pex5 involved in peroxisomal biogenesis as well as higher mRNA levels of Pex13 and Pex14, involved in peroxisomal biogenesis and/or pexophagy, was found; d) lower levels of ACOX1 and MFP2 enzymes, implicated in peroxisomal β-oxidation, were detected; e) higher levels of very-long-chain fatty acids, which are substrates of peroxisomal β-oxidation, were found. These different cytotoxic effects were strongly attenuated by MTSO, in the same range of order as with α-tocopherol. These findings underline the interest of MTSO and α-tocopherol in the prevention of peroxisomal damages (pexotherapy).
- Published
- 2022
16. Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7β-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes
- Author
-
Gérard Lizard, Ahmed Salhedine Masmoudi, Valerio Leoni, Randa Sghaier, Mohammad Samadi, Anne Vejux, Boubker Nasser, Thomas Nury, John J. Mackrill, Thibault Moreau, Nora M. O'Brien, Amira Zarrouk, Mustapha Cherkaoui-Malki, Ilham Badreddine, Claudio Caccia, Sghaier, R, Zarrouk, A, Nury, T, Badreddine, I, O'Brien, N, Mackrill, J, Vejux, A, Samadi, M, Nasser, B, Caccia, C, Leoni, V, Moreau, T, Cherkaoui-Malki, M, Salhedine Masmoudi, A, and Lizard, G
- Subjects
0301 basic medicine ,alpha-Tocopherol ,Apoptosis ,Mitochondrion ,medicine.disease_cause ,Biochemistry ,Antioxidants ,Lipid peroxidation ,Mice ,chemistry.chemical_compound ,Biotin ,polycyclic compounds ,158N oligodendrocyte ,Membrane Potential, Mitochondrial ,Caspase 3 ,Chemistry ,Fatty Acids ,7β-hydroxycholesterol ,General Medicine ,Catalase ,Mitochondria ,Cell biology ,Oligodendroglia ,lipids (amino acids, peptides, and proteins) ,Oxidation-Reduction ,Programmed cell death ,oxiapoptophagy ,Cell Line ,03 medical and health sciences ,Autophagy ,Cell Adhesion ,medicine ,Animals ,oxidative stre ,Glutathione Peroxidase ,030102 biochemistry & molecular biology ,Superoxide Dismutase ,Lipid metabolism ,Lipid Metabolism ,apoptosi ,Hydroxycholesterols ,Oxidative Stress ,030104 developmental biology ,Gene Expression Regulation ,Lipid Peroxidation ,sense organs ,Reactive Oxygen Species ,Oxidative stress - Abstract
Mitochondrial dysfunction and oxidative stress are involved in neurodegenerative diseases associated with an enhancement of lipid peroxidation products such as 7β-hydroxycholesterol (7β-OHC). It is, therefore, important to study the ability of 7β-OHC to trigger mitochondrial defects, oxidative stress, metabolic dysfunctions and cell death, which are hallmarks of neurodegeneration, and to identify cytoprotective molecules. The effects of biotin were evaluated on 158N murine oligodendrocytes, which are myelin synthesizing cells, exposed to 7β-OHC (50 µM) with or without biotin (10 and 100 nM) or α-tocopherol (positive control of cytoprotection). The effects of biotin on 7β-OHC activities were determined using different criteria: cell adhesion; plasma membrane integrity; redox status. The impact on mitochondria was characterized by the measurement of transmembrane mitochondrial potential (ΔΨm), reactive oxygen species (ROS) overproduction, mitochondrial mass, quantification of cardiolipins and organic acids. Sterols and fatty acids were also quantified. Cell death (apoptosis, autophagy) was characterized by the enumeration of apoptotic cells, caspase-3 activation, identification of autophagic vesicles, and activation of LC3-I into LC3-II. Biotin attenuates 7β-OHC-induced cytotoxicity: loss of cell adhesion was reduced; antioxidant activities were normalized. ROS overproduction, protein and lipid oxidation products were decreased. Biotin partially restores mitochondrial functions: attenuation of the loss of ΔΨm; reduced levels of mitochondrial O2•− overproduction; normalization of cardiolipins and organic acid levels. Biotin also normalizes cholesterol and fatty acid synthesis, and prevents apoptosis and autophagy (oxiapoptophagy). Our data support that biotin, which prevents oligodendrocytes damages, could be useful in the treatment of neurodegeneration and demyelination.
- Published
- 2019
17. Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy
- Author
-
Imen Ghzaiel, Gérard Lizard, Anne Vejux, Amira Zarrouk, Karine Charrière, Valerio Leoni, Vincent Schneider, Thibault Moreau, Thomas Nury, Randa Sghaier, Vejux, A, Ghzaiel, I, Nury, T, Schneider, V, Charriere, K, Sghaier, R, Zarrouk, A, Leoni, V, Moreau, T, and Lizard, G
- Subjects
0301 basic medicine ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Multiple Sclerosis ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Central nervous system ,Disease ,Bioinformatics ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Oxysterol ,0302 clinical medicine ,Endocrinology ,Immune system ,Cerebrospinal fluid ,Medicine ,Humans ,Multiple sclerosi ,Molecular Biology ,MED/05 - PATOLOGIA CLINICA ,Myelin Sheath ,Autoimmune disease ,medicine.diagnostic_test ,business.industry ,Cholesterol ,Multiple sclerosis ,Fatty Acids ,Magnetic resonance imaging ,Biomarker ,Cell Biology ,Oxysterols ,medicine.disease ,BIO/10 - BIOCHIMICA ,Lipids ,Phospholipid ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Blood-Brain Barrier ,030220 oncology & carcinogenesis ,Immunoglobulin G ,Molecular Medicine ,business ,Biomarkers - Abstract
Multiple sclerosis is an autoimmune disease that affects the central nervous system. Dysfunction of the immune system leads to lesions that cause motor, sensory, cognitive, visual and/or sphincter disturbances. In the long term, these disorders can progress towards an irreversible handicap. The diagnosis takes time because there are no specific criteria to diagnose multiple sclerosis. To realize the diagnosis, a combination of clinical, biological, and radiological arguments is therefore required. Hence, there is a need to identify multiple sclerosis biomarkers. Some biomarkers target immunity through the detection of oligoclonal bands, the measurement of the IgG index and cytokines. During the physiopathological process, the blood-brain barrier can be broken, and this event can be identified by measuring metalloproteinase activity and diffusion of gadolinium in the brain by magnetic resonance imaging. Markers of demyelination and of astrocyte and microglial activity may also be of interest as well as markers of neuronal damage and mitochondrial status. The measurement of different lipids in the plasma and cerebrospinal fluid can also provide suitable information. These different lipids include fatty acids, fatty acid peroxidation products, phospholipids as well as oxidized derivatives of cholesterol (oxysterols). Oxysterols could constitute new biomarkers providing information on the form of multiple sclerosis, the outcome of the disease and the answer to treatment.
- Published
- 2021
18. Dimethyl fumarate and monomethyl fumarate attenuate oxidative stress and mitochondrial alterations leading to oxiapoptophagy in 158N murine oligodendrocytes treated with 7β-hydroxycholesterol
- Author
-
Amira Zarrouk, Gérard Lizard, Thibault Moreau, Khalifa Limem, Ahmed Masmoudi, Jean-Paul Pais de Barros, Thomas Nury, Mohammad Samadi, Anne Vejux, Claudio Caccia, Valerio Leoni, Randa Sghaier, Ameur Cherif, John J. Mackrill, Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Biochimie, Faculté de Médecine de Sousse, 4002 Sousse, Tunisia, Faculté de médecine de Sousse [Ibn EL Jazzar], Univ. Monastir, LR12ES05, Lab-NAFS 'Nutrition - Functional Food & Vascular Health', Monastir, Tunisia., Laboratoire Biotechnologie et Valorisation des Bio-Géo Ressources [Tunisie] (LR11ES31 (BVBGR)), Université de la Manouba [Tunisie] (UMA), Hospital of Varese, Milan, Italy, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Université de Bourgogne (UB), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes (LCP-A2MC), Université de Lorraine (UL), Biosciences Institute (BSI), University College Cork (UCC), Sghaier, R, Nury, T, Leoni, V, Caccia, C, Pais De Barros, J, Cherif, A, Vejux, A, Moreau, T, Limem, K, Samadi, M, Mackrill, J, Masmoudi, A, Lizard, G, Zarrouk, A, and CCSD, Accord Elsevier
- Subjects
Endocrinology, Diabetes and Metabolism ,[SDV]Life Sciences [q-bio] ,Clinical Biochemistry ,monomethyl fumarate ,Mitochondrion ,medicine.disease_cause ,Biochemistry ,Lipid peroxidation ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Fumarates ,peroxisome ,chemistry.chemical_classification ,0303 health sciences ,biology ,Dimethyl fumarate ,Chemistry ,Succinate dehydrogenase ,7β-hydroxycholesterol ,apoptosis ,Malondialdehyde ,3. Good health ,[SDV] Life Sciences [q-bio] ,mitochondria ,Oligodendroglia ,lipid profile ,Cholesterol ,Neuroprotective Agents ,Molecular Medicine ,autophagy ,158N cell ,oxiapoptophagy ,Cell Line ,Superoxide dismutase ,03 medical and health sciences ,medicine ,Animals ,Molecular Biology ,030304 developmental biology ,Reactive oxygen species ,oxidative58 stress ,Maleates ,Apoptosi ,Cell Biology ,Molecular biology ,Hydroxycholesterols ,158N cells ,Oxidative Stress ,biology.protein ,Oxidative stre ,Lipid Peroxidation ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
International audience; Oxidative stress and mitochondrial dysfunction contribute to the pathogenesis of neurodegenerative diseases and favor lipid peroxidation, leading to increased levels of 7β-hydroxycholesterol (7β-OHC) which induces oxiapoptophagy (OXIdative stress, APOPTOsis, autoPHAGY). The cytoprotective effects of dimethylfumarate (DMF), used in the treatment of relapsing remitting multiple sclerosis and of monomethylfumarate (MMF), its main metabolite, were evaluated on murine oligodendrocytes 158 N exposed to 7β-OHC (50 μM, 24 h) with or without DMF or MMF (25 μM). The activity of 7β-OHC in the presence or absence DMF or MMF was evaluated on several parameters: cell adhesion; plasma membrane integrity measured with propidium iodide (PI), trypan blue and fluoresceine diacetate (FDA) assays; LDH activity; antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)); generation of lipid peroxidation products (malondialdehyde (MDA), conjugated dienes (CDs)) and protein oxidation products (carbonylated proteins (CPs)); reactive oxygen species (ROS) overproduction conducted with DHE and DHR123. The effect on mitochondria was determined with complementary criteria: measurement of succinate dehydrogenase activity, evaluation of mitochondrial potential (ΔΨm) and mitochondrial superoxide anions (O2●−) production using DiOC6(3) and MitoSOX, respectively; quantification of mitochondrial mass with Mitotracker Red, and of cardiolipins and organic acids. The effects on mitochondrial and peroxisomal ultrastructure were determined by transmission electron microscopy. Intracellular sterol and fatty acid profiles were determined. Apoptosis and autophagy were characterized by staining with Hoechst 33,342, Giemsa and acridine orange, and with antibodies raised against caspase-3 and LC3. DMF and MMF attenuate 7β-OHC-induced cytotoxicity: cell growth inhibition; decreased cell viability; mitochondrial dysfunction (decrease of succinate dehydrogenase activity, loss of ΔΨm, increase of mitochondrial O2●− production, alteration of the tricarboxilic acid (TCA) cycle, and cardiolipins content); oxidative stress induction (ROS overproduction, alteration of GPx, CAT, and SOD activities, increased levels of MDA, CDs, and CPs); changes in fatty acid and cholesterol metabolism; and cell death induction (caspase-3 cleavage, activation of LC3-I in LC3-II). Ultrastructural alterations of mitochondria and peroxisomes were prevented. These results demonstrate that DMF and MMF prevent major dysfunctions associated with neurodegenerative diseases: oxidative stress, mitochondrial dysfunction, apoptosis and autophagy.
- Published
- 2019
19. 7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19
- Author
-
Amira Zarrouk, Mohamed Ksila, Thomas Nury, Khouloud Sassi, Mohammad Samadi, Gérard Lizard, Balkiss Bouhaouala-Zahar, Anne Vejux, Valerio Leoni, Mohamed Hammami, Sonia Hammami, Imen Ghzaiel, Taoufik Ghrairi, John J. Mackrill, Ghzaiel, I, Sassi, K, Zarrouk, A, Nury, T, Ksila, M, Leoni, V, Bouhaouala-Zahar, B, Hammami, S, Hammami, M, Mackrill, J, Samadi, M, Ghrairi, T, Vejux, A, and Lizard, G
- Subjects
0301 basic medicine ,Programmed cell death ,Oxysterol ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Viral diseases ,Disease ,Antiviral Agents ,Biochemistry ,Article ,Alveolar cells ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,medicine ,Animals ,Humans ,Adjuvant therapies ,Ketocholesterols ,Molecular Biology ,ComputingMethodologies_COMPUTERGRAPHICS ,SARS-CoV-2 ,Cholesterol ,business.industry ,Autophagy ,COVID-19 ,Oxysterols ,Cell Biology ,Adjuvant therapie ,7-Ketocholesterol ,Pathophysiology ,COVID-19 Drug Treatment ,Viral disease ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,Immunology ,Molecular Medicine ,business ,Biomarkers - Abstract
Graphical abstract, 7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients.
- Published
- 2021
20. Mitochondrial dysfunctions in 7-ketocholesterol-treated 158N oligodendrocytes without or with α-tocopherol: Impacts on the cellular profil of tricarboxylic cycle-associated organic acids, long chain saturated and unsaturated fatty acids, oxysterols, cholesterol and cholesterol precursors
- Author
-
Agnès Fromont, Anne Vejux, Amira Zarrouk, Valerio Leoni, Meryam Debbabi, Gérard Lizard, Randa Sghaier, Thomas Nury, Claudio Caccia, Thibault Moreau, Leoni, V, Nury, T, Vejux, A, Zarrouk, A, Caccia, C, Debbabi, M, Fromont, A, Sghaier, R, Moreau, T, and Lizard, G
- Subjects
0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,158N murine oligodendrocyte ,alpha-Tocopherol ,Clinical Biochemistry ,Cellular homeostasis ,Mitochondrion ,medicine.disease_cause ,Biochemistry ,Mass Spectrometry ,Lipid peroxidation ,Mice ,chemistry.chemical_compound ,Adenosine Triphosphate ,Endocrinology ,Ketocholesterols ,Membrane Potential, Mitochondrial ,chemistry.chemical_classification ,Oxysterols ,Flow Cytometry ,Lipids ,Mitochondria ,Lipid profile ,Oligodendroglia ,Cholesterol ,Fatty Acids, Unsaturated ,Molecular Medicine ,Oxidation-Reduction ,Programmed cell death ,Multiple Sclerosis ,Citric Acid Cycle ,Oxidative phosphorylation ,Biology ,α-Tocopherol ,03 medical and health sciences ,medicine ,Animals ,Molecular Biology ,Cell Nucleus ,Inflammation ,Reactive oxygen species ,L-Lactate Dehydrogenase ,Cell Biology ,NAD ,7-Ketocholesterol ,Citric acid cycle ,Oxidative Stress ,030104 developmental biology ,chemistry ,Lipid Peroxidation ,Reactive Oxygen Species ,Oxidative stress - Abstract
In multiple sclerosis (MS) a process of white matter degradation leading to demyelination is observed. Oxidative stress, inflammation, apoptosis, necrosis and/or autophagy result together into a progressive loss of oligodendrocytes. 7-ketocholesterol (7KC), found increased in the cerebrospinal fluid of MS patients, triggers a rupture of RedOx homeostasis associated with mitochondrial dysfunctions, aptoptosis and autophagy (oxiapoptophagy) in cultured murine oligodendrocytes (158N). α-tocopherol is able to mild the alterations induced by 7KC partially restoring the cellular homeostasis. In presence of 7KC, the amount of adherent 158N cells was decreased and oxidative stress was enhanced. An increase of caspase-3 and PARP degradation (evidences of apoptosis), and an increased LC3-II/LC3-I ratio (criterion of autophagy), were detected. These events were associated with a decrease of the mitochondrial membrane potential (ΔΨm) and by a decrease of oxidative phosphorylation revealed by reduced NAD+ and ATP. The cellular lactate was higher while pyruvate, citrate, fumarate, succinate (tricarboxylic acid (TCA) cycle intermediates) were significantly reduced in exposed cells, suggesting that an impairment of mitochondrial respiratory functions could lead to an increase of lactate production and to a reduced amount of ATP and acetyl-CoA available for the anabolic pathways. The concentration of sterol precursors lathosterol, lanosterol and desmosterol were significantly reduced together with satured and unsatured long chain fatty acids (C16:0 − C18:0, structural elements of membrane phospholipids). Such reductions were milder with α-tocopherol. It is likely that the cell death induced by 7KC is associated with mitochondrial dysfunctions, including alterations of oxidative phosphorylation, which could result from lipid anabolism dysfunctions, especially on TCA cycle intermediates. A better knowledge of mitochondrial associated dysfunctions triggered by 7KC will contribute to bring new information on the demyelination processes which are linked with oxidative stress and lipid peroxidation, especially in MS.
- Published
- 2017
21. Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles
- Author
-
Claudio Caccia, Thomas Nury, Amira Namsi, Olfa Masmoudi-Kouki, Atanas G. Atanasov, Amira Sayed Khan, Valerio Leoni, Marie Christine Tonon, David Vaudry, Gérard Lizard, Jérôme Leprince, Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST), Université de Tunis El Manar (UTM), Equipe NuTox (LNC - U1231) (NUTOX), Lipides - Nutrition - Cancer [Dijon - U1231] (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-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, 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, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Foundation IRCCS Istituto Neurologico Carlo Besta, Milan Italy, Hospital of Varese, Milan, Italy, Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Poland, CASTEL, Hélène, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Namsi, A, Nury, T, Khan, A, Leprince, J, Vaudry, D, Caccia, C, Leoni, V, Atanasov, A, Tonon, M, Masmoudi-Kouki, O, and Lizard, G
- Subjects
MAPK/ERK pathway ,octadecaneuropeptide (ODN) ,[SDV]Life Sciences [q-bio] ,Pharmaceutical Science ,Mitochondrion ,cholesterol precursors ,DiOC6 ,Analytical Chemistry ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Neurotrophic factors ,N2a cell ,Drug Discovery ,peroxisome ,Protein Kinase C ,Diazepam Binding Inhibitor ,0303 health sciences ,Chemistry ,Cell Differentiation ,hemic and immune systems ,Peroxisome ,respiratory system ,Lipids ,3. Good health ,Cell biology ,[SDV] Life Sciences [q-bio] ,mitochondria ,Chemistry (miscellaneous) ,Molecular Medicine ,Signal Transduction ,octadecaneuropeptide (ODN), N2a cells ,Neurite ,Cell Survival ,MAP Kinase Signaling System ,N2a cells ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,fatty acids ,Article ,lcsh:QD241-441 ,03 medical and health sciences ,lcsh:Organic chemistry ,Cell Line, Tumor ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,medicine ,Peroxisomes ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Viability assay ,Physical and Theoretical Chemistry ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Cell damage ,neuronal differentiation ,030304 developmental biology ,Cholesterol precursor ,Rhodamines ,Organic Chemistry ,Neuropeptides ,cholesterol ,Fatty acid ,medicine.disease ,Cyclic AMP-Dependent Protein Kinases ,Peptide Fragments ,Type C Phospholipases ,030217 neurology & neurosurgery - Abstract
Neurodegenerative diseases are characterized by oxidative stress, mitochondrial damage, and death of neuronal cells. To counteract such damage and to favor neurogenesis, neurotrophic factors could be used as therapeutic agents. Octadecaneuropeptide (ODN), produced by astrocytes, is a potent neuroprotective agent. In N2a cells, we studied the ability of ODN to promote neuronal differentiation. This parameter was evaluated by phase contrast microscopy, staining with crystal violet, cresyl blue, and Sulforhodamine 101. The effect of ODN on cell viability and mitochondrial activity was determined with fluorescein diacetate and DiOC6(3), respectively. The impact of ODN on the topography of mitochondria and peroxisomes, two tightly connected organelles involved in nerve cell functions and lipid metabolism, was evaluated by transmission electron microscopy and fluorescence microscopy: detection of mitochondria with MitoTracker Red, and peroxisome with an antibody directed against the ABCD3 peroxisomal transporter. The profiles in fatty acids, cholesterol, and cholesterol precursors were determined by gas chromatography, in some cases coupled with mass spectrometry. Treatment of N2a cells with ODN (10&minus, 14 M, 48 h) induces neurite outgrowth. ODN-induced neuronal differentiation was associated with modification of topographical distribution of mitochondria and peroxisomes throughout the neurites and did not affect cell viability and mitochondrial activity. The inhibition of ODN-induced N2a differentiation with H89, U73122, chelerythrine and U0126 supports the activation of a PKA/PLC/PKC/MEK/ERK-dependent signaling pathway. Although there is no difference in fatty acid profile between control and ODN-treated cells, the level of cholesterol and some of its precursors (lanosterol, desmosterol, lathosterol) was increased in ODN-treated cells. The ability of ODN to induce neuronal differentiation without cytotoxicity reinforces the interest for this neuropeptide with neurotrophic properties to overcome nerve cell damage in major neurodegenerative diseases.
- Published
- 2019
22. Induction of peroxisomal changes in oligodendrocytes treated with 7-ketocholesterol: Attenuation by α-tocopherol
- Author
-
Anne Vejux, Mustapha Cherkaoui-Malki, Randa Sghaier, Amira Zarrouk, Thibault Moreau, Thomas Nury, Amira Namsi, Jean-Marc Riedinger, Franck Ménétrier, Valerio Leoni, Tugba Uzun, Gérard Lizard, Khouloud Sassi, Claudio Caccia, Wiem Meddeb, Wafa Mihoubi, Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique (Bio-PeroxIL), Université de Bourgogne (UB), Université de Monastir (Université de Monastir), Université de Sousse, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Hospital of Varese, Milan, Italy, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Université de Tunis Carthage, Université de Tunis, Centre de Biotechnologie de Sfax (CBS), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Univ. Bourgogne (Dijon, France), Univ. Monastir (Tunis, Tunisia), ABASIM (Association Bourguignonne pour les Applications des Sciences de l'Information en Médecine, Dijon, France), ASSAD (Louhans, France) and the Department of Neurology (Prof. Thibault Moreau, University Hospital, Dijon, France)., Nury, T, Sghaier, R, Zarrouk, A, Ménétrier, F, Uzun, T, Leoni, V, Caccia, C, Meddeb, W, Namsi, A, Sassi, K, Mihoubi, W, Riedinger, J, Cherkaoui-Malki, M, Moreau, T, Vejux, A, and Lizard, G
- Subjects
Male ,0301 basic medicine ,zellweger's patient fibroblasts ,Apoptosis ,Mitochondrion ,Biochemistry ,Mice ,158 n cells ,peroxisome ,Zellweger Syndrome ,Ketocholesterols ,Membrane Protein ,Membrane Potential, Mitochondrial ,Chemistry ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Tocotrienols ,Fatty Acids ,General Medicine ,Peroxisome ,α-tocotrienol ,3. Good health ,Cell biology ,mitochondria ,Oligodendroglia ,158 N cell ,Fibroblast ,ACOX1 ,Human ,Programmed cell death ,Plasmalogen ,Plasmalogens ,Oxidative phosphorylation ,oxiapoptophagy ,03 medical and health sciences ,alpha-tocopherol ,Peroxisomes ,medicine ,Animals ,Humans ,7-ketocholesterol ,alpha-tocotrienol ,Zellweger syndrome ,α-tocopherol ,Dose-Response Relationship, Drug ,Animal ,Ketocholesterol ,Tocotrienol ,Membrane Proteins ,Apoptosi ,Fibroblasts ,medicine.disease ,pexophagy ,Zellweger's patient fibroblast ,030104 developmental biology ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,Fatty Acid - Abstract
This work was presented as an oral presentation at the 7th ENOR (European Network for Oxysterol Research) Symposium ‘Oxysterols and Sterol Derivatives in Health and Disease’, September 21–22, 2017, Université catholique de Louvain, Brussels, Belgium (https://www.oxysterols.net/).; International audience; The involvement of organelles in cell death is well established especially for endoplasmic reticulum, lysosomes and mitochondria. However, the role of the peroxisome is not well known, though peroxisomal dysfunction favors a rupture of redox equilibrium. To study the role of peroxisomes in cell death, 158 N murine oligodendrocytes were treated with 7-ketocholesterol (7 KC: 25-50 mu M, 24 h). The highest concentration is known to induce oxiapoptophagy (OXIdative stress + APOPTOsis + autoPHAGY), whereas the lowest concentration does not induce cell death. In those conditions (with 7 KC: 50 mu M) morphological, topographical and functional peroxisome alterations associated with modifications of the cytoplasmic distribution of mitochondria, with mitochondrial dysfunction (loss of transmembrane mitochondrial potential, decreased level of cardiolipins) and oxidative stress were observed: presence of peroxisomes with abnormal sizes and shapes similar to those observed in Zellweger fibroblasts, lower cellular level of ABCD3, used as a marker of peroxisomal mass, measured by flow cytometry, lower mRNA and protein levels (measured by RT-qPCR and western blotting) of ABCD1 and ABCD3 (two ATP-dependent peroxisomal transporters), and of ACOX1 and MFP2 enzymes, and lower mRNA level of DHAPAT, involved in peroxisomal beta-oxidation and plasmalogen synthesis, respectively, and increased levels of very long chain fatty acids (VLCFA: C24:0, C24:1, C26:0 and C26:1, quantified by gas chromatography coupled with mass spectrometry) metabolized by peroxisomal beta-oxidation. In the presence of 7 KC (25 mu M), slight mitochondrial dysfunction and oxidative stress were found, and no induction of apoptosis was detected; however, modifications of the cytoplasmic distribution of mitochondria and clusters of mitochondria were detected. The peroxisomal alterations observed with 7 KC (25 mu M) were similar to those with 7 KC (50 mu M). In addition, data obtained by transmission electron microcopy and immunofluorescence microscopy by dual staining with antibodies raised against p62, involved in autophagy, and ABCD3, support that 7 KC (25-50 mu M) induces pexophagy. 7 KC (25-50 mu M)-induced side effects were attenuated by alpha-tocopherol but not by alpha-tocotrienol, whereas the anti-oxidant properties of these molecules determined with the FRAP assay were in the same range. These data provide evidences that 7 KC, at concentrations inducing or not cell death, triggers morphological, topographical and functional peroxisomal alterations associated with minor or major mitochondrial changes.
- Published
- 2018
23. In Vitro Evaluation of the Effects of 7-Ketocholesterol and 7β-Hydroxycholesterol on the Peroxisomal Status: Prevention of Peroxisomal Damages and Concept of Pexotherapy.
- Author
-
Ghzaiel I, Maaloul S, Ksila M, Namsi A, Yammine A, Debbabi M, Badreddine A, Meddeb W, Pires V, Nury T, Ménétrier F, Avoscan L, Zarrouk A, Baarine M, Masmoudi-Kouki O, Ghrairi T, Abdellaoui R, Nasser B, Hammami S, Hammami M, Samadi M, Vejux A, and Lizard G
- Subjects
- Humans, Animals, Mice, Ketocholesterols metabolism, Apoptosis, Mitochondria metabolism
- Abstract
7-Ketocholesterol and 7β-hydroxycholesterol are most often derived from the autoxidation of cholesterol. Their quantities are often increased in the body fluids and/or diseased organs of patients with age-related diseases such as cardiovascular diseases, Alzheimer's disease, age-related macular degeneration, and sarcopenia which are frequently associated with a rupture of RedOx homeostasis leading to a high oxidative stress contributing to cell and tissue damages. On murine cells from the central nervous system (158N oligodendrocytes, microglial BV-2 cells, and neuronal N2a cells) as well as on C2C12 murine myoblasts, these two oxysterols can induce a mode of cell death which is associated with qualitative, quantitative, and functional modifications of the peroxisome. These changes can be revealed by fluorescence microscopy (apotome, confocal microscopy), transmission electron microscopy, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and gas chromatography-coupled with mass spectrometry (GC-MS). Noteworthy, several natural molecules, including ω3 fatty acids, polyphenols, and α-tocopherol, as well as several Mediterranean oils [argan and olive oils, Milk-thistle (Sylibum marianum) and Pistacia lenticus seed oils], have cytoprotective properties and attenuate 7-ketocholesterol- and 7β-hydroxycholesterol-induced peroxisomal modifications. These observations led to the concept of pexotherapy., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
- Published
- 2024
- Full Text
- View/download PDF
24. Oxiapoptophagy in Age-Related Diseases. Comment on Ouyang et al. 7-Ketocholesterol Induces Oxiapoptophagy and Inhibits Osteogenic Differentiation in MC3T3-E1 Cells. Cells 2022, 11 , 2882.
- Author
-
Ghzaiel I, Nury T, Zarrouk A, Vejux A, and Lizard G
- Subjects
- Cell Differentiation, Longevity, Osteogenesis, Ketocholesterols
- Abstract
Due to the increase in life span and life expectancy, which can, however, be more or less pronounced depending on the economic, social and cultural context [...].
- Published
- 2022
- Full Text
- View/download PDF
25. Cytoprotective activities of representative nutrients from the Mediterranean diet and of Mediterranean oils against 7-ketocholesterol- and 7β-hydroxycholesterol-induced cytotoxicity: Application to age-related diseases and civilization diseases.
- Author
-
Rezig L, Ghzaiel I, Ksila M, Yammine A, Nury T, Zarrouk A, Samadi M, Chouaibi M, Vejux A, and Lizard G
- Subjects
- Aging, Civilization, Fatty Acids, Humans, Hydroxycholesterols pharmacology, Ketocholesterols pharmacology, Nutrients, Oils, Olive Oil, Polyphenols, Tocopherols, Diabetes Mellitus, Type 2, Diet, Mediterranean
- Abstract
7-ketocholesterol and 7β-hydroxycholesterol are two oxysterols mainly formed by the autoxidation of cholesterol. These two molecules are interconvertible via specific enzymes. These two oxysterols are often observed at increased amounts in biological fluids as well as tissues and organs affected during age-related diseases and in diseases of civilization such as cardiovascular, neurodegenerative, and ocular diseases as well as type 2 diabetes and metabolic syndrome. Noteworthy, 7-ketocholesterol and 7β-hydroxycholesterol induce oxidative stress and inflammation, which are frequently observed in patients with age-related and civilization diseases. For this reason, the involvement of these two oxysterols in the pathophysiology of these diseases is widely suspected. In addition, the toxicity of these oxysterols can lead to death by oxiapoptophagy characterized by oxidative stress, apoptosis induction and autophagy criteria. To prevent, or even treat, certain age-related or civilization diseases associated with increased levels of 7-ketocholesterol and 7β-hydroxycholesterol, the identification of molecules or mixtures of molecules attenuating or inhibiting the toxic effects of these oxysterols allows to consider new treatments. In this context, many nutrients present in significant amounts in the Mediterranean diet, especially tocopherols, fatty acids, and polyphenols, have shown cytoprotective activities as well as several Mediterranean oils (argan and olive oils, milk thistle seed oil, and pistacia lentiscus seed oil). Consequently, a nutraceutical approach, rich in nutrients present in the Mediterranean diet, could thus make it possible to counteract certain age-related and civilization diseases associated with increased levels of 7-ketocholesterol and 7β-hydroxycholesterol., 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 © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
26. Cytotoxic and Antioxidant Activities of Imine Analogs of Trans-Resveratrol towards Murine Neuronal N2a Cells.
- Author
-
Ksila M, Vejux A, Prost-Camus E, Durand P, Ghzaiel I, Nury T, Duprey D, Meziane S, Masmoudi-Kouki O, Latruffe N, Ghrairi T, Prost M, Lizard G, and Vervandier-Fasseur D
- Subjects
- Animals, Antioxidants chemistry, Antioxidants pharmacology, Imines pharmacology, Mice, Resveratrol pharmacology, Antineoplastic Agents chemistry, Stilbenes chemistry, Stilbenes pharmacology
- Abstract
Trans -resveratrol is a natural polyphenol showing numerous biological properties, especially anti-tumoral and antioxidant activity. Among numerous resveratrol derivatives, aza-stilbenes, which bear an imine bound, show interesting biological activities. In the present study, we synthesized a series of imine analogs of trans -resveratrol (seven aza-stilbenes) following an easy and low-cost procedure of green chemistry. The toxicity of synthesized aza-stilbenes, which is currently unknown, was evaluated on murine neuronal N2a cells, comparatively to trans -resveratrol, by considering: cell density evaluated by staining with sulforhodamine 101; esterase activity, which is a criteria of cell viability, by staining with fluorescein diacetate; and transmembrane mitochondrial potential, which is known to decrease during cell death, by staining with DiOC
6 (3) using flow cytometry. In addition, the antioxidant activity was quantified with the KRL (Kit Radicaux Libres) assay, the DPPH (2,2'-diphenyl-1-picrylhydrazyl radical) assay and the FRAP (ferric reducing antioxidant power) assay. The PAOT (Pouvoir Antioxidant Total) score was also used. The aza-stilbenes provide different cytotoxic and antioxidant activities, which are either higher or lower than those of trans -resveratrol. Based on their cytotoxic and antioxidant characteristics, all synthesized aza-stilbenes are distinguished from trans -resveratrol.- Published
- 2022
- Full Text
- View/download PDF
27. Protective effects of milk thistle (Sylibum marianum) seed oil and α-tocopherol against 7β-hydroxycholesterol-induced peroxisomal alterations in murine C2C12 myoblasts: Nutritional insights associated with the concept of pexotherapy.
- Author
-
Ghzaiel I, Zarrouk A, Essadek S, Martine L, Hammouda S, Yammine A, Ksila M, Nury T, Meddeb W, Tahri Joutey M, Mihoubi W, Caccia C, Leoni V, Samadi M, Acar N, Andreoletti P, Hammami S, Ghrairi T, Vejux A, Hammami M, and Lizard G
- Subjects
- Animals, Antioxidants pharmacology, Flavonoids, Humans, Hydroxycholesterols, Mice, Myoblasts metabolism, Plant Oils, RNA, Messenger, Reactive Oxygen Species metabolism, Silybum marianum metabolism, alpha-Tocopherol pharmacology
- Abstract
Peroxisomes play an important role in regulating cell metabolism and RedOx homeostasis. Peroxisomal dysfunctions favor oxidative stress and cell death. The ability of 7β-hydroxycholesterol (7β-OHC; 50 μM, 24 h), known to be increased in patients with age-related diseases such as sarcopenia, to trigger oxidative stress, mitochondrial and peroxisomal dysfunction was studied in murine C2C12 myoblasts. The capacity of milk thistle seed oil (MTSO, 100 μg/mL) as well as α-tocopherol (400 µM; reference cytoprotective agent) to counteract the toxic effects of 7β-OHC, mainly at the peroxisomal level were evaluated. The impacts of 7β-OHC, in the presence or absence of MTSO or α-tocopherol, were studied with complementary methods: measurement of cell density and viability, quantification of reactive oxygen species (ROS) production and transmembrane mitochondrial potential (ΔΨm), evaluation of peroxisomal mass as well as topographic, morphologic and functional peroxisomal changes. Our results indicate that 7β-OHC induces a loss of cell viability and a decrease of cell adhesion associated with ROS overproduction, alterations of mitochondrial ultrastructure, a drop of ΔΨm, and several peroxisomal modifications. In the presence of 7β-OHC, comparatively to untreated cells, important quantitative and qualitative peroxisomal modifications were also identified: a) a reduced number of peroxisomes with abnormal sizes and shapes, mainly localized in cytoplasmic vacuoles, were observed; b) the peroxisomal mass was decreased as indicated by lower protein and mRNA levels of the peroxisomal ABCD3 transporter; c) lower mRNA level of Pex5 involved in peroxisomal biogenesis as well as higher mRNA levels of Pex13 and Pex14, involved in peroxisomal biogenesis and/or pexophagy, was found; d) lower levels of ACOX1 and MFP2 enzymes, implicated in peroxisomal β-oxidation, were detected; e) higher levels of very-long-chain fatty acids, which are substrates of peroxisomal β-oxidation, were found. These different cytotoxic effects were strongly attenuated by MTSO, in the same range of order as with α-tocopherol. These findings underline the interest of MTSO and α-tocopherol in the prevention of peroxisomal damages (pexotherapy)., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2022
- Full Text
- View/download PDF
28. Saffron ( Crocus sativus L.): A Source of Nutrients for Health and for the Treatment of Neuropsychiatric and Age-Related Diseases.
- Author
-
El Midaoui A, Ghzaiel I, Vervandier-Fasseur D, Ksila M, Zarrouk A, Nury T, Khallouki F, El Hessni A, Ibrahimi SO, Latruffe N, Couture R, Kharoubi O, Brahmi F, Hammami S, Masmoudi-Kouki O, Hammami M, Ghrairi T, Vejux A, and Lizard G
- Subjects
- Aging, Humans, Nutrients, Plant Extracts chemistry, Plant Extracts pharmacology, Plant Extracts therapeutic use, Crocus chemistry, Plants, Medicinal
- Abstract
Saffron ( Crocus sativus L.) is a medicinal plant, originally cultivated in the East and Middle East, and later in some Mediterranean countries. Saffron is obtained from the stigmas of the plant. Currently, the use of saffron is undergoing a revival. The medicinal virtues of saffron, its culinary use and its high added value have led to the clarification of its phytochemical profile and its biological and therapeutic characteristics. Saffron is rich in carotenoids and terpenes. The major products of saffron are crocins and crocetin (carotenoids) deriving from zeaxanthin, pirocrocin and safranal, which give it its taste and aroma, respectively. Saffron and its major compounds have powerful antioxidant and anti-inflammatory properties in vitro and in vivo. Anti-tumor properties have also been described. The goal of this review is to present the beneficial effects of saffron and its main constituent molecules on neuropsychiatric diseases (depression, anxiety and schizophrenia) as well as on the most frequent age-related diseases (cardiovascular, ocular and neurodegenerative diseases, as well as sarcopenia). Overall, the phytochemical profile of saffron confers many beneficial virtues on human health and, in particular, on the prevention of age-related diseases, which is a major asset reinforcing the interest for this medicinal plant.
- Published
- 2022
- Full Text
- View/download PDF
29. Profiles of Fatty Acids, Polyphenols, Sterols, and Tocopherols and Scavenging Property of Mediterranean Oils: New Sources of Dietary Nutrients for the Prevention of Age-related Diseases.
- Author
-
Rezig L, Martine L, Nury T, Msaada K, Mahfoudhi N, Ghzaiel I, Prost-Camus E, Durand P, Midaoui AE, Acar N, Latruffe N, Vejux A, and Lizard G
- Subjects
- Fatty Acids analysis, Nutrients analysis, Plant Oils chemistry, Polyphenols analysis, Quercetin, Sterols analysis, Phytosterols, Tocopherols analysis
- Abstract
The present study provides the fatty acid, tocopherol, phytosterol, and polyphenol profiles of some Mediterranean oils extracted from pumpkin, melon, and black cumin seed oils and those of dietary argan seed oil. Gas chromatography analysis revealed that oleic and linoleic acids were the most abundant fatty acids. Argan and melon seed oils exhibited the highest levels of oleic acid (47.32±0.02%) and linoleic acid (58.35±0.26%), respectively. In terms of tocopherols, melon seed oil showed the highest amount (652.1±3.26 mg/kg) with a predominance of γ-tocopherol (633.1±18.81 mg/kg). The phytosterol content varied between 2237.00±37.55 µg/g for argan oil to 6995.55±224.01 µg/g for melon seed oil. High Performance Liquid Chromatography analysis also revealed the presence of several polyphenols: vanillin (0.59 mg equivalents Quercetin/100 g) for melon seed oil, and p-hydroxycinnamic acid (0.04 mg equivalents Quercetin/100 g), coumarine (0.05 mg equivalents Quercetin/100 g), and thymoquinone (1.2 mg equivalents Quercetin/100 g) for black cumin seed oil. The "Kit Radicaux Libres" (KRL) assay used to evaluate the scavenging properties of the oils showed that black cumin seed oil was the most efficient. On the light of the richness of all Mediterranean oil samples in bioactive compounds, the seed oils studied can be considered as important sources of nutrients endowed with cytoprotective properties which benefits in preventing age-related diseases which are characterized by an enhanced oxidative stress.
- Published
- 2022
- Full Text
- View/download PDF
30. Antioxidant Properties and Cytoprotective Effect of Pistacia lentiscus L. Seed Oil against 7β-Hydroxycholesterol-Induced Toxicity in C2C12 Myoblasts: Reduction in Oxidative Stress, Mitochondrial and Peroxisomal Dysfunctions and Attenuation of Cell Death.
- Author
-
Ghzaiel I, Zarrouk A, Nury T, Libergoli M, Florio F, Hammouda S, Ménétrier F, Avoscan L, Yammine A, Samadi M, Latruffe N, Biressi S, Levy D, Bydlowski SP, Hammami S, Vejux A, Hammami M, and Lizard G
- Abstract
Aging is characterized by a progressive increase in oxidative stress, which favors lipid peroxidation and the formation of cholesterol oxide derivatives, including 7β-hydroxycholesterol (7β-OHC). This oxysterol, which is known to trigger oxidative stress, inflammation, and cell death, could contribute to the aging process and age-related diseases, such as sarcopenia. Identifying molecules or mixtures of molecules preventing the toxicity of 7β-OHC is therefore an important issue. This study consists of determining the chemical composition of Tunisian Pistacia lentiscus L. seed oil (PLSO) used in the Tunisian diet and evaluating its ability to counteract the cytotoxic effects induced by 7β-OHC in murine C2C12 myoblasts. The effects of 7β-OHC (50 µM; 24 h), associated or not with PLSO, were studied on cell viability, oxidative stress, and on mitochondrial and peroxisomal damages induction. α-Tocopherol (400 µM) was used as the positive control for cytoprotection. Our data show that PLSO is rich in bioactive compounds; it contains polyunsaturated fatty acids, and several nutrients with antioxidant properties: phytosterols, α-tocopherol, carotenoids, flavonoids, and phenolic compounds. When associated with PLSO (100 µg/mL), the 7β-OHC-induced cytotoxic effects were strongly attenuated. The cytoprotection was in the range of those observed with α-tocopherol. This cytoprotective effect was characterized by prevention of cell death and organelle dysfunction (restoration of cell adhesion, cell viability, and plasma membrane integrity; prevention of mitochondrial and peroxisomal damage) and attenuation of oxidative stress (reduction in reactive oxygen species overproduction in whole cells and at the mitochondrial level; decrease in lipid and protein oxidation products formation; and normalization of antioxidant enzyme activities: glutathione peroxidase (GPx) and superoxide dismutase (SOD)). These results provide evidence that PLSO has similar antioxidant properties than α-tocopherol used at high concentration and contains a mixture of molecules capable to attenuate 7β-OHC-induced cytotoxic effects in C2C12 myoblasts. These data reinforce the interest in edible oils associated with the Mediterranean diet, such as PLSO, in the prevention of age-related diseases, such as sarcopenia.
- Published
- 2021
- Full Text
- View/download PDF
31. 7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19.
- Author
-
Ghzaiel I, Sassi K, Zarrouk A, Nury T, Ksila M, Leoni V, Bouhaouala-Zahar B, Hammami S, Hammami M, Mackrill JJ, Samadi M, Ghrairi T, Vejux A, and Lizard G
- Subjects
- Animals, Biomarkers blood, COVID-19 blood, Humans, Ketocholesterols metabolism, COVID-19 Drug Treatment, Antiviral Agents pharmacology, COVID-19 etiology, Ketocholesterols blood
- Abstract
7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
32. Oxiapoptophagy: A type of cell death induced by some oxysterols.
- Author
-
Nury T, Zarrouk A, Yammine A, Mackrill JJ, Vejux A, and Lizard G
- Subjects
- Apoptosis, Autophagy, Cell Death, Mitochondria, Oxysterols
- Abstract
Oxysterols are oxidized forms of cholesterol generated from cholesterol by auto-oxidation, enzymatic processes, or both. Some of them (7-ketocholesterol, 7β-hydroxycholesterol and 24(S)-hydroxycholesterol), when used at cytotoxic concentrations on different cell types from different species (mesenchymal bone marrow cells, monocytic cells and nerve cells), induce a type of cell death associated with OXIdative stress and several characteristics of APOPTOsis and autoPHAGY, defined as oxiapoptophagy. Oxidative stress is associated with overproduction of ROS, increased antioxidant enzyme activities, lipid peroxidation and protein carbonylation. Apoptosis is associated with activation of the mitochondrial pathway, opening of the mitochondrial permeability pore, loss of mitochondrial membrane potential, caspase-3 activation, PARP degradation, nuclear condensation and/or fragmentation. Autophagy is characterized by autophagic vacuoles revealed by monodansylcadaverine staining and transmission electron microscopy, plus increased ratio of LC-3II/LC-3I. In addition, morphological, topographical and functional changes of the peroxisome are observed. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc., (© 2020 The British Pharmacological Society.)
- Published
- 2021
- Full Text
- View/download PDF
33. Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy.
- Author
-
Vejux A, Ghzaiel I, Nury T, Schneider V, Charrière K, Sghaier R, Zarrouk A, Leoni V, Moreau T, and Lizard G
- Subjects
- Biomarkers metabolism, Blood-Brain Barrier physiopathology, Fatty Acids metabolism, Humans, Immunoglobulin G blood, Lipids blood, Lipids cerebrospinal fluid, Multiple Sclerosis therapy, Myelin Sheath metabolism, Biomarkers analysis, Lipids analysis, Multiple Sclerosis physiopathology, Oxysterols metabolism
- Abstract
Multiple sclerosis is an autoimmune disease that affects the central nervous system. Dysfunction of the immune system leads to lesions that cause motor, sensory, cognitive, visual and/or sphincter disturbances. In the long term, these disorders can progress towards an irreversible handicap. The diagnosis takes time because there are no specific criteria to diagnose multiple sclerosis. To realize the diagnosis, a combination of clinical, biological, and radiological arguments is therefore required. Hence, there is a need to identify multiple sclerosis biomarkers. Some biomarkers target immunity through the detection of oligoclonal bands, the measurement of the IgG index and cytokines. During the physiopathological process, the blood-brain barrier can be broken, and this event can be identified by measuring metalloproteinase activity and diffusion of gadolinium in the brain by magnetic resonance imaging. Markers of demyelination and of astrocyte and microglial activity may also be of interest as well as markers of neuronal damage and mitochondrial status. The measurement of different lipids in the plasma and cerebrospinal fluid can also provide suitable information. These different lipids include fatty acids, fatty acid peroxidation products, phospholipids as well as oxidized derivatives of cholesterol (oxysterols). Oxysterols could constitute new biomarkers providing information on the form of multiple sclerosis, the outcome of the disease and the answer to treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
34. Cholesterol Derivatives as Promising Anticancer Agents in Glioblastoma Metabolic Therapy
- Author
-
Sassi K, Nury T, Samadi M, Fennira FBA, Vejux A, Lizard G, and Debinski W
- Abstract
Malignant brain tumors are among the most devastating types of cancer. Glioblastoma is the most common and serious form of brain cancer. Most glioblastomas are surgically unresectable and are typically diagnosed at an advanced stage. The high level of resistance to chemotherapy, radiotherapy and immunotherapy makes glioblastoma one of the most difficult cancers to treat. In brain tumors, the challenges of targeted therapy also include the blood-brain barrier, which often contributes to treatment failure. Therefore, developments of new treatment strategies are required. Metabolic treatments could be an alternative to conventional therapies. Metabolic approaches aim at suppressing glioblastoma tumorigenicity leading to glioblastoma cell death. Since cholesterol metabolism is deregulated in these tumors, this is a promising potential target for therapy. As glioblastoma cells draw on cholesterol from the central nervous system to survive, their growth is theoretically unlimited. Targeting the metabolism of cholesterol by different strategies using, among others, targets of LXRs (Liver X Receptors) or toxic cholesterol analogues could potentially oppose the growth of glial tumors. This chapter discusses the potential of targeting cholesterol metabolism using cholesterol derivatives as a pharmacological alternative to current therapeutic strategy., (Copyright: The Authors.)
- Published
- 2021
- Full Text
- View/download PDF
35. Evidence of a non-apoptotic mode of cell death in microglial BV-2 cells exposed to different concentrations of zinc oxide nanoparticles.
- Author
-
Sruthi S, Nury T, Millot N, and Lizard G
- Subjects
- Animals, Apoptosis, Cell Death, Cell Survival, Mice, Oxidative Stress, Reactive Oxygen Species, Metal Nanoparticles toxicity, Nanoparticles, Zinc Oxide toxicity
- Abstract
Zinc oxide nanoparticles (ZnO NPs) possess huge application potential. However, the toxicity of ZnO NPs is a great cause of concern. Indeed, ZnO NPs have been found to cause neurotoxicity. As microglial dysfunctions have been linked to the neurotoxic potential of NPs, the physico-chemical properties of ZnO NPs were determined and their cytotoxic effects were characterised on murine microglial BV-2 cells. In-house prepared and meticulously characterised ZnO NPs exhibited narrow size distribution with an average size of around 20 nm and a zeta potential at physiological pH around 24 mV. ZnO NPs did not exhibit aggregation in the cell culture medium. When microglial BV-2 cells were exposed for 6 and 24 h to ZnO NPs (5, 10, 20, 40, and 80 μg/mL), several cell damages were observed. Cellular accumulation of NPs in microglial BV-2 cells was associated with cell growth inhibition and cell death induction, measured by the trypan blue exclusion and MTT assays. Mitochondrial dysfunction and lysosomal alteration were associated with increased plasma membrane permeability measured by staining with DiOC
6 (3), acridine orange, and propidium iodide, respectively. In addition, an accumulation of reactive oxygen species (ROS) was detected after staining with dihydroethidium and dihydrorhodamine 123. No apoptotic features were present: no cells with condensed and/or fragmented nuclei (Hoechst staining) characteristic of apoptotic cells, absence of subG1 cells, absence of caspase-3 cleavage, and PARP fragmentation. With ZnO NPs (80 μg/mL), with the annexin V/propidium iodide (PI) assay, few apoptotic cells (annexin V+/PI- cells) were detected whereas (annexin V+/PI+ cells) evocating necrotic cells were mainly identified. No modification of the cells in the different phases of the cell cycle was found. Altogether, our data show that ZnO NPs induce a non-apoptotic mode of cell death associated with an accumulation of ROS, mitochondrial, and lysosomal dysfunction and plasma membrane damages in microglial BV-2 cells.Graphical abstract.- Published
- 2021
- Full Text
- View/download PDF
36. Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases.
- Author
-
Yammine A, Zarrouk A, Nury T, Vejux A, Latruffe N, Vervandier-Fasseur D, Samadi M, Mackrill JJ, Greige-Gerges H, Auezova L, and Lizard G
- Subjects
- Animals, Apigenin pharmacology, Cell Line, Dose-Response Relationship, Drug, Humans, Mice, Mitochondria drug effects, Mitochondria metabolism, Neurodegenerative Diseases etiology, Neurodegenerative Diseases metabolism, Peroxisomes, Quercetin pharmacology, Reactive Oxygen Species metabolism, Resveratrol pharmacology, Apoptosis drug effects, Autophagy drug effects, Ketocholesterols adverse effects, Neurons drug effects, Neurons metabolism, Oxidative Stress drug effects, Polyphenols pharmacology
- Abstract
The Mediterranean diet is associated with health benefits due to bioactive compounds such as polyphenols. The biological activities of three polyphenols (quercetin (QCT), resveratrol (RSV), apigenin (API)) were evaluated in mouse neuronal N2a cells in the presence of 7-ketocholesterol (7KC), a major cholesterol oxidation product increased in patients with age-related diseases, including neurodegenerative disorders. In N2a cells, 7KC (50 µM; 48 h) induces cytotoxic effects characterized by an induction of cell death. When associated with RSV, QCT and API (3.125; 6.25 µM), 7KC-induced toxicity was reduced. The ability of QCT, RSV and API to prevent 7KC-induced oxidative stress was characterized by a decrease in reactive oxygen species (ROS) production in whole cells and at the mitochondrial level; by an attenuation of the increase in the level and activity of catalase; by attenuating the decrease in the expression, level and activity of glutathione peroxidase 1 (GPx1); by normalizing the expression, level and activity of superoxide dismutases 1 and 2 (SOD1, SOD2); and by reducing the decrease in the expression of nuclear erythroid 2-like factor 2 (Nrf2) which regulates antioxidant genes. QCT, RSV and API also prevented mitochondrial dysfunction in 7KC-treated cells by counteracting the loss of mitochondrial membrane potential (ΨΔm) and attenuating the decreased gene expression and/or protein level of AMP-activated protein kinase α (AMPKα), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) implicated in mitochondrial biogenesis. At the peroxisomal level, QCT, RSV and API prevented the impact of 7KC by counteracting the decrease in ATP binding cassette subfamily D member (ABCD)3 (a peroxisomal mass marker) at the protein and mRNA levels, as well as the decreased expresssion of genes associated with peroxisomal biogenesis ( Pex13 , Pex14 ) and peroxisomal β-oxidation ( Abcd1 , Acox1 , Mfp2 , Thiolase A ). The 7KC-induced decrease in ABCD1 and multifunctional enzyme type 2 (MFP2), two proteins involved in peroxisomal β-oxidation, was also attenuated by RSV, QCT and API. 7KC-induced cell death, which has characteristics of apoptosis (cells with fragmented and/or condensed nuclei; cleaved caspase-3; Poly(ADP-ribose) polymerase (PARP) fragmentation) and autophagy (cells with monodansyl cadaverine positive vacuoles; activation of microtubule associated protein 1 light chain 3-I (LC3-I) to LC3-II, was also strongly attenuated by RSV, QCT and API. Thus, in N2a cells, 7KC induces a mode of cell death by oxiapoptophagy, including criteria of OXIdative stress, APOPTOsis and autoPHAGY, associated with mitochondrial and peroxisomal dysfunction, which is counteracted by RSV, QCT, and API reinforcing the interest for these polyphenols in prevention of diseases associated with increased 7KC levels.
- Published
- 2020
- Full Text
- View/download PDF
37. Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells.
- Author
-
Yammine A, Nury T, Vejux A, Latruffe N, Vervandier-Fasseur D, Samadi M, Greige-Gerges H, Auezova L, and Lizard G
- Subjects
- Animals, Cell Death drug effects, Cell Line, Tumor, Ketocholesterols pharmacology, Mice, Mitochondria pathology, Neurons pathology, Diet, Mediterranean, Fatty Acids, Omega-3 pharmacology, Ketocholesterols adverse effects, Mitochondria metabolism, Neurons metabolism, Polyphenols pharmacology, Reactive Oxygen Species metabolism
- Abstract
The brain, which is a cholesterol-rich organ, can be subject to oxidative stress in a variety of pathophysiological conditions, age-related diseases and some rare pathologies. This can lead to the formation of 7-ketocholesterol (7KC), a toxic derivative of cholesterol mainly produced by auto-oxidation. So, preventing the neuronal toxicity of 7KC is an important issue to avoid brain damage. As there are numerous data in favor of the prevention of neurodegeneration by the Mediterranean diet, this study aimed to evaluate the potential of a series of polyphenols (resveratrol, RSV; quercetin, QCT; and apigenin, API) as well as ω3 and ω9 unsaturated fatty acids (α-linolenic acid, ALA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA, and oleic acid, OA) widely present in this diet, to prevent 7KC (50 µM)-induced dysfunction of N2a neuronal cells. When polyphenols and fatty acids were used at non-toxic concentrations (polyphenols: ≤6.25 µM; fatty acids: ≤25 µM) as defined by the fluorescein diacetate assay, they greatly reduce 7KC-induced toxicity. The cytoprotective effects observed with polyphenols and fatty acids were comparable to those of α-tocopherol (400 µM) used as a reference. These polyphenols and fatty acids attenuate the overproduction of reactive oxygen species and the 7KC-induced drop in mitochondrial transmembrane potential (ΔΨm) measured by flow cytometry after dihydroethidium and DiOC
6 (3) staining, respectively. Moreover, the studied polyphenols and fatty acids reduced plasma membrane permeability considered as a criterion for cell death measured by flow cytometry after propidium iodide staining. Our data show that polyphenols (RSV, QCT and API) as well as ω3 and ω9 unsaturated fatty acids (ALA, EPA, DHA and OA) are potent cytoprotective agents against 7KC-induced neurotoxicity in N2a cells. Their cytoprotective effects could partly explain the benefits of the Mediterranean diet on human health, particularly in the prevention of neurodegenerative diseases.- Published
- 2020
- Full Text
- View/download PDF
38. Lipids Nutrients in Parkinson and Alzheimer's Diseases: Cell Death and Cytoprotection.
- Author
-
Nury T, Lizard G, and Vejux A
- Subjects
- Apoptosis drug effects, Cytoprotection, Fatty Acids administration & dosage, Fatty Acids pharmacology, Fish Oils administration & dosage, Fish Oils pharmacology, Humans, Lipids pharmacology, Nutrients pharmacology, Oxidative Stress drug effects, Plant Oils administration & dosage, Plant Oils pharmacology, Alzheimer Disease prevention & control, Lipids administration & dosage, Nutrients administration & dosage, Parkinson Disease prevention & control
- Abstract
Neurodegenerative diseases, particularly Parkinson's and Alzheimer's, have common features: protein accumulation, cell death with mitochondrial involvement and oxidative stress. Patients are treated to cure the symptoms, but the treatments do not target the causes; so, the disease is not stopped. It is interesting to look at the side of nutrition which could help prevent the first signs of the disease or slow its progression in addition to existing therapeutic strategies. Lipids, whether in the form of vegetable or animal oils or in the form of fatty acids, could be incorporated into diets with the aim of preventing neurodegenerative diseases. These different lipids can inhibit the cytotoxicity induced during the pathology, whether at the level of mitochondria, oxidative stress or apoptosis and inflammation. The conclusions of the various studies cited are oriented towards the preventive use of oils or fatty acids. The future of these lipids that can be used in therapy/prevention will undoubtedly involve a better delivery to the body and to the brain by utilizing lipid encapsulation.
- Published
- 2020
- Full Text
- View/download PDF
39. 7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity.
- Author
-
Vejux A, Abed-Vieillard D, Hajji K, Zarrouk A, Mackrill JJ, Ghosh S, Nury T, Yammine A, Zaibi M, Mihoubi W, Bouchab H, Nasser B, Grosjean Y, and Lizard G
- Subjects
- Animals, Cardiovascular Diseases chemically induced, Cardiovascular Diseases metabolism, Cataract chemically induced, Cataract metabolism, Cell Death drug effects, Cell Line, Cell Line, Tumor, Cells, Cultured, Humans, Hydroxycholesterols chemistry, Hydroxycholesterols metabolism, Inflammatory Bowel Diseases chemically induced, Inflammatory Bowel Diseases metabolism, Ketocholesterols chemistry, Ketocholesterols metabolism, Neurodegenerative Diseases chemically induced, Neurodegenerative Diseases metabolism, Organelles metabolism, Disease Models, Animal, Hydroxycholesterols toxicity, Ketocholesterols toxicity, Organelles drug effects
- Abstract
Oxysterols are molecules derived by the oxidation of cholesterol and can be formed either by auto-oxidation, enzymatically or by both processes. Among the oxysterols formed by auto-oxidation, 7-ketocholesterol and 7β-hydroxycholesterol are the main forms generated. These oxysterols, formed endogenously and brought in large quantities by certain foods, have major cytotoxic properties. They are powerful inducers of oxidative stress, inducing dysfunction of organelles (mitochondria, lysosomes and peroxisomes) that can cause cell death. These molecules are often identified in increased amounts in common pathological states such as cardiovascular diseases, certain eye conditions, neurodegenerative disorders and inflammatory bowel diseases. To oppose the cytotoxic effects of these molecules, it is important to know their biological activities and the signaling pathways they affect. Numerous cell models of the vascular wall, eye, brain, and digestive tract have been used. Currently, to counter the cytotoxic effects of 7-ketocholesterol and 7β-hydroxycholesterol, natural molecules and oils, often associated with the Mediterranean diet, as well as synthetic molecules, have proved effective in vitro. Bioremediation approaches and the use of functionalized nanoparticles are also promising. At the moment, invertebrate and vertebrate models are mainly used to evaluate the metabolism and the toxicity of 7-ketocholesterol and 7β-hydroxycholesterol. The most frequently used models are mice, rats and rabbits. In order to cope with the difficulty of transferring the results obtained in animals to humans, the development of in vitro alternative methods such as organ/body-on-a-chip based on microfluidic technology are hopeful integrative approaches., 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 © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
40. Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model.
- Author
-
Nury T, Doria M, Lizard G, and Vejux A
- Subjects
- Animals, Cell Line, Cell Survival drug effects, Membrane Potential, Mitochondrial drug effects, Mice, Mitochondria metabolism, Models, Animal, Oligodendroglia drug effects, Oligodendroglia metabolism, Oxidative Stress drug effects, Reactive Oxygen Species metabolism, Docosahexaenoic Acids pharmacology, Fatty Acids analysis, Mitochondria drug effects, Oligodendroglia cytology
- Abstract
In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to have health benefits, to inhibit the cytotoxic effects of very long-chain fatty acids (C24:0, C26:0), which can contribute to the development of some neurodegenerative diseases. The effect of DHA (50 µM) on very long-chain fatty acid-induced toxicity was studied by several complementary methods: phase contrast microscopy to evaluate cell viability and morphology, the MTT test to monitor the impact on mitochondrial function, propidium iodide staining to study plasma membrane integrity, and DHE staining to measure oxidative stress. A Western blot assay was used to assess autophagy through modification of LC3 protein. The various experiments were carried out on the cellular model of 158N murine oligodendrocytes. In 158N cells, our data establish that DHA is able to inhibit all tested cytotoxic effects induced by very long-chain fatty acids.
- Published
- 2020
- Full Text
- View/download PDF
41. 7-Ketocholesterol- and 7β-Hydroxycholesterol-Induced Peroxisomal Disorders in Glial, Microglial and Neuronal Cells: Potential Role in Neurodegeneration : 7-ketocholesterol and 7β-hydroxycholesterol-Induced Peroxisomal Disorders and Neurodegeneration.
- Author
-
Nury T, Yammine A, Menetrier F, Zarrouk A, Vejux A, and Lizard G
- Subjects
- Humans, Neurodegenerative Diseases pathology, Peroxisomal Disorders pathology, Hydroxycholesterols metabolism, Ketocholesterols metabolism, Microglia metabolism, Neurodegenerative Diseases metabolism, Neuroglia metabolism, Neurons metabolism, Peroxisomal Disorders metabolism
- Abstract
Peroxisomopathies are qualitative or quantitative deficiencies in peroxisomes which lead to increases in the level of very-long-chain fatty acids (VLCFA) and can be associated with more or less pronounced dysfunction of central nervous system cells: glial and microglial cells. Currently, in frequent neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS), peroxisomal dysfunction is also suspected due to an increase in VLCFA, which can be associated with a decrease of plasmalogens, in these patients. Moreover, in patients suffering from peroxisomopathies, such as X-linked adrenoleukodystrophy (X-ALD), AD, or MS, the increase in oxidative stress observed leads to the formation of cytotoxic oxysterols: 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7β-OHC). These observations led to the demonstration that 7KC and 7β-OHC alter the biogenesis and activity of peroxisomes in glial and microglial cells. In X-ALD, AD, and MS, it is suggested that 7KC and 7β-OHC affecting the peroxisome, and which also induce mitochondrial dysfunctions, oxidative stress, and inflammation, could promote neurodegeneration. Consequently, the study of oxisome in peroxisomopathies, AD and MS, could help to better understand the pathophysiology of these diseases to identify therapeutic targets for effective treatments.
- Published
- 2020
- Full Text
- View/download PDF
42. Potential Involvement of Peroxisome in Multiple Sclerosis and Alzheimer's Disease : Peroxisome and Neurodegeneration.
- Author
-
Zarrouk A, Nury T, El Hajj HI, Gondcaille C, Andreoletti P, Moreau T, Cherkaoui-Malki M, Berger J, Hammami M, Lizard G, and Vejux A
- Subjects
- Humans, Oxidative Stress, Alzheimer Disease metabolism, Alzheimer Disease pathology, Multiple Sclerosis metabolism, Multiple Sclerosis pathology, Peroxisomes metabolism, Peroxisomes pathology
- Abstract
Peroxisomopathies are rare diseases due to dysfunctions of the peroxisome in which this organelle is either absent or with impaired activities. These diseases, at the exception of type I hyperoxaluria and acatalasaemia, affect the central and peripheral nervous system. Due to the significant impact of peroxisomal abnormalities on the functioning of nerve cells, this has led to an interest in peroxisome in common neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis. In these diseases, a role of the peroxisome is suspected on the basis of the fatty acid and phospholipid profile in the biological fluids and the brains of patients. It is also speculated that peroxisomal dysfunctions could contribute to oxidative stress and mitochondrial alterations which are recognized as major players in the development of neurodegenerative diseases. Based on clinical and in vitro studies, the data obtained support a potential role of peroxisome in Alzheimer's disease and multiple sclerosis.
- Published
- 2020
- Full Text
- View/download PDF
43. Dimethyl fumarate and monomethyl fumarate attenuate oxidative stress and mitochondrial alterations leading to oxiapoptophagy in 158N murine oligodendrocytes treated with 7β-hydroxycholesterol.
- Author
-
Sghaier R, Nury T, Leoni V, Caccia C, Pais De Barros JP, Cherif A, Vejux A, Moreau T, Limem K, Samadi M, Mackrill JJ, Masmoudi AS, Lizard G, and Zarrouk A
- Subjects
- Animals, Apoptosis drug effects, Autophagy drug effects, Cell Line, Cholesterol metabolism, Hydroxycholesterols pharmacology, Lipid Peroxidation drug effects, Mice, Mitochondria metabolism, Mitochondria physiology, Mitochondria ultrastructure, Oligodendroglia drug effects, Oligodendroglia metabolism, Oxidative Stress drug effects, Dimethyl Fumarate pharmacology, Fumarates pharmacology, Maleates pharmacology, Mitochondria drug effects, Neuroprotective Agents pharmacology
- Abstract
Oxidative stress and mitochondrial dysfunction contribute to the pathogenesis of neurodegenerative diseases and favor lipid peroxidation, leading to increased levels of 7β-hydroxycholesterol (7β-OHC) which induces oxiapoptophagy (OXIdative stress, APOPTOsis, autoPHAGY). The cytoprotective effects of dimethylfumarate (DMF), used in the treatment of relapsing remitting multiple sclerosis and of monomethylfumarate (MMF), its main metabolite, were evaluated on murine oligodendrocytes 158 N exposed to 7β-OHC (50 μM, 24 h) with or without DMF or MMF (25 μM). The activity of 7β-OHC in the presence or absence DMF or MMF was evaluated on several parameters: cell adhesion; plasma membrane integrity measured with propidium iodide (PI), trypan blue and fluoresceine diacetate (FDA) assays; LDH activity; antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)); generation of lipid peroxidation products (malondialdehyde (MDA), conjugated dienes (CDs)) and protein oxidation products (carbonylated proteins (CPs)); reactive oxygen species (ROS) overproduction conducted with DHE and DHR123. The effect on mitochondria was determined with complementary criteria: measurement of succinate dehydrogenase activity, evaluation of mitochondrial potential (ΔΨm) and mitochondrial superoxide anions (O
2 ●- ) production using DiOC6 (3) and MitoSOX, respectively; quantification of mitochondrial mass with Mitotracker Red, and of cardiolipins and organic acids. The effects on mitochondrial and peroxisomal ultrastructure were determined by transmission electron microscopy. Intracellular sterol and fatty acid profiles were determined. Apoptosis and autophagy were characterized by staining with Hoechst 33,342, Giemsa and acridine orange, and with antibodies raised against caspase-3 and LC3. DMF and MMF attenuate 7β-OHC-induced cytotoxicity: cell growth inhibition; decreased cell viability; mitochondrial dysfunction (decrease of succinate dehydrogenase activity, loss of ΔΨm, increase of mitochondrial O2 ●- production, alteration of the tricarboxilic acid (TCA) cycle, and cardiolipins content); oxidative stress induction (ROS overproduction, alteration of GPx, CAT, and SOD activities, increased levels of MDA, CDs, and CPs); changes in fatty acid and cholesterol metabolism; and cell death induction (caspase-3 cleavage, activation of LC3-I in LC3-II). Ultrastructural alterations of mitochondria and peroxisomes were prevented. These results demonstrate that DMF and MMF prevent major dysfunctions associated with neurodegenerative diseases: oxidative stress, mitochondrial dysfunction, apoptosis and autophagy., (Copyright © 2019. Published by Elsevier Ltd.)- Published
- 2019
- Full Text
- View/download PDF
44. Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles.
- Author
-
Namsi A, Nury T, Khan AS, Leprince J, Vaudry D, Caccia C, Leoni V, Atanasov AG, Tonon MC, Masmoudi-Kouki O, and Lizard G
- Subjects
- Animals, Cell Line, Tumor, Cell Survival drug effects, MAP Kinase Signaling System drug effects, Mice, Mitochondria drug effects, Mitochondria ultrastructure, Peroxisomes drug effects, Peroxisomes ultrastructure, Rhodamines chemistry, Rhodamines metabolism, Signal Transduction drug effects, Cell Differentiation drug effects, Cyclic AMP-Dependent Protein Kinases metabolism, Diazepam Binding Inhibitor pharmacology, Lipids chemistry, Mitochondria metabolism, Neuropeptides pharmacology, Peptide Fragments pharmacology, Peroxisomes metabolism, Protein Kinase C metabolism, Type C Phospholipases metabolism
- Abstract
Neurodegenerative diseases are characterized by oxidative stress, mitochondrial damage, and death of neuronal cells. To counteract such damage and to favor neurogenesis, neurotrophic factors could be used as therapeutic agents. Octadecaneuropeptide (ODN), produced by astrocytes, is a potent neuroprotective agent. In N2a cells, we studied the ability of ODN to promote neuronal differentiation. This parameter was evaluated by phase contrast microscopy, staining with crystal violet, cresyl blue, and Sulforhodamine 101. The effect of ODN on cell viability and mitochondrial activity was determined with fluorescein diacetate and DiOC
6 (3), respectively. The impact of ODN on the topography of mitochondria and peroxisomes, two tightly connected organelles involved in nerve cell functions and lipid metabolism, was evaluated by transmission electron microscopy and fluorescence microscopy: detection of mitochondria with MitoTracker Red, and peroxisome with an antibody directed against the ABCD3 peroxisomal transporter. The profiles in fatty acids, cholesterol, and cholesterol precursors were determined by gas chromatography, in some cases coupled with mass spectrometry. Treatment of N2a cells with ODN (10-14 M, 48 h) induces neurite outgrowth. ODN-induced neuronal differentiation was associated with modification of topographical distribution of mitochondria and peroxisomes throughout the neurites and did not affect cell viability and mitochondrial activity. The inhibition of ODN-induced N2a differentiation with H89, U73122, chelerythrine and U0126 supports the activation of a PKA/PLC/PKC/MEK/ERK-dependent signaling pathway. Although there is no difference in fatty acid profile between control and ODN-treated cells, the level of cholesterol and some of its precursors (lanosterol, desmosterol, lathosterol) was increased in ODN-treated cells. The ability of ODN to induce neuronal differentiation without cytotoxicity reinforces the interest for this neuropeptide with neurotrophic properties to overcome nerve cell damage in major neurodegenerative diseases., Competing Interests: The authors declare that there are no conflicts of interest that could be prejudicial to the impartiality of the research reported.- Published
- 2019
- Full Text
- View/download PDF
45. Protective function of autophagy during VLCFA-induced cytotoxicity in a neurodegenerative cell model.
- Author
-
Doria M, Nury T, Delmas D, Moreau T, Lizard G, and Vejux A
- Subjects
- Animals, Cell Death, Cells, Cultured, Humans, Mice, Mice, Inbred BALB C, Oxidative Stress, Reactive Oxygen Species metabolism, Autophagy physiology, Brain pathology, Fatty Acids metabolism, Fibroblasts physiology, Neurodegenerative Diseases metabolism, Neurons physiology, Oligodendroglia physiology
- Abstract
In recent years, a particular interest has focused on the accumulation of fatty acids with very long chains (VLCFA) in the occurrence of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis or dementia. Indeed, it seems increasingly clear that this accumulation of VLCFA in the central nervous system is accompanied by a progressive demyelination resulting in death of neuronal cells. Nevertheless, molecular mechanisms by which VLCFA result in toxicity remain unclear. This study highlights for the first time in 3 different cellular models (oligodendrocytes 158 N, primary mouse brain culture, and patient fibroblasts) the types of cell death involved where VLCFA-induced ROS production leads to autophagy. The autophagic process protects the cell from this VLCFA-induced toxicity. Thus, autophagy in addition to oxidative stress can offer new therapeutic approaches., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
- Full Text
- View/download PDF
46. Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7β-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes.
- Author
-
Sghaier R, Zarrouk A, Nury T, Badreddine I, O'Brien N, Mackrill JJ, Vejux A, Samadi M, Nasser B, Caccia C, Leoni V, Moreau T, Cherkaoui-Malki M, Salhedine Masmoudi A, and Lizard G
- Subjects
- Animals, Apoptosis drug effects, Apoptosis genetics, Autophagy drug effects, Caspase 3 genetics, Caspase 3 metabolism, Catalase genetics, Catalase metabolism, Cell Adhesion drug effects, Cell Line, Fatty Acids biosynthesis, Gene Expression Regulation, Glutathione Peroxidase genetics, Glutathione Peroxidase metabolism, Hydroxycholesterols pharmacology, Lipid Metabolism genetics, Lipid Peroxidation drug effects, Membrane Potential, Mitochondrial drug effects, Mice, Mitochondria metabolism, Oligodendroglia cytology, Oligodendroglia drug effects, Oligodendroglia metabolism, Oxidation-Reduction, Oxidative Stress drug effects, Reactive Oxygen Species antagonists & inhibitors, Reactive Oxygen Species metabolism, Superoxide Dismutase genetics, Superoxide Dismutase metabolism, Antioxidants pharmacology, Biotin pharmacology, Hydroxycholesterols antagonists & inhibitors, Lipid Metabolism drug effects, Mitochondria drug effects, alpha-Tocopherol pharmacology
- Abstract
Mitochondrial dysfunction and oxidative stress are involved in neurodegenerative diseases associated with an enhancement of lipid peroxidation products such as 7β-hydroxycholesterol (7β-OHC). It is, therefore, important to study the ability of 7β-OHC to trigger mitochondrial defects, oxidative stress, metabolic dysfunctions and cell death, which are hallmarks of neurodegeneration, and to identify cytoprotective molecules. The effects of biotin were evaluated on 158N murine oligodendrocytes, which are myelin synthesizing cells, exposed to 7β-OHC (50 µM) with or without biotin (10 and 100 nM) or α-tocopherol (positive control of cytoprotection). The effects of biotin on 7β-OHC activities were determined using different criteria: cell adhesion; plasma membrane integrity; redox status. The impact on mitochondria was characterized by the measurement of transmembrane mitochondrial potential (ΔΨm), reactive oxygen species (ROS) overproduction, mitochondrial mass, quantification of cardiolipins and organic acids. Sterols and fatty acids were also quantified. Cell death (apoptosis, autophagy) was characterized by the enumeration of apoptotic cells, caspase-3 activation, identification of autophagic vesicles, and activation of LC3-I into LC3-II. Biotin attenuates 7β-OHC-induced cytotoxicity: loss of cell adhesion was reduced; antioxidant activities were normalized. ROS overproduction, protein and lipid oxidation products were decreased. Biotin partially restores mitochondrial functions: attenuation of the loss of ΔΨm; reduced levels of mitochondrial O
2 •- overproduction; normalization of cardiolipins and organic acid levels. Biotin also normalizes cholesterol and fatty acid synthesis, and prevents apoptosis and autophagy (oxiapoptophagy). Our data support that biotin, which prevents oligodendrocytes damages, could be useful in the treatment of neurodegeneration and demyelination.- Published
- 2019
- Full Text
- View/download PDF
47. Elaboration of Trans-Resveratrol Derivative-Loaded Superparamagnetic Iron Oxide Nanoparticles for Glioma Treatment.
- Author
-
Sallem F, Haji R, Vervandier-Fasseur D, Nury T, Maurizi L, Boudon J, Lizard G, and Millot N
- Abstract
In this work, new nanohybrids based on superparamagnetic iron oxide nanoparticles (SPIONs) were elaborated and discussed for the first time as nanovectors of a derivative molecule of trans-resveratrol (RSV), a natural antioxidant molecule, which can be useful for brain disease treatment. The derivative molecule was chemically synthesized (4'-hydroxy-4-(3-aminopropoxy) trans-stilbene: HAPtS) and then grafted onto SPIONs surface using an organosilane coupling agent, which is 3-chloropropyltriethoxysilane (CPTES) and based on nucleophilic substitution reactions. The amount of HAPtS loaded onto SPIONs surface was estimated by thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS) analyses at 116 µmol·g
-1 SPIONs. The synthesized HAPtS molecule, as well as the associated nanohybrids, were fully characterized by transmission electron microscopy (TEM), XPS, TGA, infrared (IR) and UV-visible spectroscopies, dynamic light scattering (DLS), and zeta potential measurements. The in vitro biological assessment of the synthesized nanohybrid's efficiency was carried out on C6 glioma cells and showed that the nanovector SPIONs-CPTES-HAPtS do not affect the mitochondrial metabolism (MTT test), but damage the plasma membrane (FDA test), which could contribute to limiting the proliferation of cancerous cells (clonogenic test) at a HAPtS concentration of 50 µM. These nanoparticles have a potential cytotoxic effect that could be used to eliminate cancer cells., Competing Interests: The authors declare no conflict of interest.- Published
- 2019
- Full Text
- View/download PDF
48. Polydopamine Modified Superparamagnetic Iron Oxide Nanoparticles as Multifunctional Nanocarrier for Targeted Prostate Cancer Treatment.
- Author
-
Singh N, Sallem F, Mirjolet C, Nury T, Sahoo SK, Millot N, and Kumar R
- Abstract
Polydopamine (pDA)-modified iron oxide core-shell nanoparticles (IONPs) are developed and designed as nanovectors of drugs. Reactive quinone of pDA enhances the binding efficiency of various biomolecules for targeted delivery. Glutathione disulfide (GSSG), an abundant thiol species in the cytoplasm, was immobilized on the pDA-IONP surface. It serves as a cellular trigger to release the drug from the nanoparticles providing an efficient platform for the drug delivery system. Additionally, GSSG on the surface was further modified to form S-nitrosoglutathione that can act as nitric oxide (NO) donors. These NPs were fully characterized using a transmission electronic microscopy (TEM), thermogravimetric analysis (TGA), dynamic light scattering (DLS), zeta potential, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) and UV-vis spectroscopies. Doxorubicin (DOX) and docetaxel (DTX) are two anticancer drugs, which were loaded onto nanoparticles with respective loading efficiencies of 243 and 223 µmol/g of IONPs, calculated using TGA measurements. DOX release study, using UV-vis spectroscopy, showed a pH responsive behavior, making the elaborated nanocarrier a potential drug delivery system. (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium (MTS) and apoptosis assays were performed on PC3 cell lines to evaluate the efficiency of the developed nanocarriers. These nanoparticles thus can prove their worth in cancer treatment on account of their easy access to the site and release of drug in response to changes to internal parameters such as pH, chemicals, etc., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
- Full Text
- View/download PDF
49. Prevention of 7-ketocholesterol-induced side effects by natural compounds.
- Author
-
Brahmi F, Vejux A, Sghaier R, Zarrouk A, Nury T, Meddeb W, Rezig L, Namsi A, Sassi K, Yammine A, Badreddine I, Vervandier-Fasseur D, Madani K, Boulekbache-Makhlouf L, Nasser B, and Lizard G
- Subjects
- Antioxidants pharmacology, Fatty Acids pharmacology, Humans, Inflammation prevention & control, Oxidation-Reduction, Oxidative Stress, Polyphenols pharmacology, Tocopherols pharmacology, Ketocholesterols adverse effects, Noncommunicable Diseases prevention & control
- Abstract
Cholesterol oxidation products, also named oxysterols, can be formed either by cholesterol auto-oxidation, enzymatically or both. Among these oxysterols, 7-ketocholesterol (7KC) is mainly formed during radical attacks that take place on the carbon 7 of cholesterol. As increased levels of 7KC have been found in the tissues, plasma and/or cerebrospinal fluid of patients with major diseases, especially age-related diseases (cardiovascular diseases, eye diseases, neurodegenerative diseases), some cancers, and chronic inflammatory diseases, it is suspected that 7KC, could contribute to their development. Since 7KC, provided by the diet or endogenously formed, is not or little efficiently metabolized, except in hepatic cells, its cellular accumulation can trigger numerous side effects including oxidative stress, inflammation and cell death. To counteract 7KC-induced side effects, it is necessary to characterize the metabolic pathways activated by this oxysterol to identify potential targets for cytoprotection and geroprotection. Currently, several natural compounds (tocopherols, fatty acids, polyphenols, etc) or mixtures of compounds (oils) used in traditional medicine are able to inhibit the deleterious effects of 7KC. The different molecules identified could be valued in different ways (functional foods, recombinant molecules, theranostic) to prevent or treat diseases associated with 7KC.
- Published
- 2019
- Full Text
- View/download PDF
50. Profile of Fatty Acids, Tocopherols, Phytosterols and Polyphenols in Mediterranean Oils (Argan Oils, Olive Oils, Milk Thistle Seed Oils and Nigella Seed Oil) and Evaluation of their Antioxidant and Cytoprotective Activities.
- Author
-
Zarrouk A, Martine L, Grégoire S, Nury T, Meddeb W, Camus E, Badreddine A, Durand P, Namsi A, Yammine A, Nasser B, Mejri M, Bretillon L, Mackrill JJ, Cherkaoui-Malki M, Hammami M, and Lizard G
- Subjects
- Animals, Antioxidants analysis, Cell Line, Humans, Mice, Silybum marianum chemistry, Nigella chemistry, Olive Oil chemistry, Seeds chemistry, Fatty Acids analysis, Phytosterols analysis, Plant Oils analysis, Polyphenols analysis, Tocopherols analysis
- Abstract
Background: The effects of vegetable oils on human health depend on their components. Therefore, their profiles of lipid nutrients and polyphenols were determined., Objective: To establish and compare the fatty acid, tocopherol, phytosterol and polyphenol profiles of Mediterranean oils: cosmetic and dietary argan oils (AO; Morocco: Agadir, Berkane); olive oils (OO; Morocco, Spain, Tunisia); milk thistle seed oils (MTSO; Tunisia: Bizerte, Sousse, Zaghouane); nigella seed oil (NSO)., Methods: The biochemical profiles were determined by gas chromatography-flame ionization, high performance liquid chromatography and gas chromatography, coupled with mass spectrometry as required. The antioxidant and cytoprotective activities were evaluated with the KRL (Kit Radicaux Libres) and the fluorescein diacetate tests on nerve cells treated with 7-ketocholesterol (7KC)., Results: The fatty acid profile revealed high linoleic acid (C18:2 n-6) content in AO, OO, MTSO and NSO. The highest levels of oleic acid (C18:1 n-9) were found in AO and OO. The tocopherol profile showed that Agadir AO contained the highest amount of α-tocopherol, also present at high level in MTSO and Tunisian OO; Berkane AO was rich in γ-tocopherol. The phytosterol profile indicated that β-sitosterol was predominant in the oils, except AO; spinasterol was only present in AO. Polyphenol profiles underlined that OO was the richest in polyphenols; hydroxytyrosol was only found in OO; few polyphenols were detected in AO. The oils studied have antioxidant activities, and all of them, except NSO, prevented 7KC-induced cell death. The antioxidant characteristics of AO were positively correlated with procatechic acid and compestanol levels., Conclusion: Based on their biochemical profiles, antioxidant and cytoprotective characteristics, AO, OO, and MTSO are potentially beneficial to human health., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.