1. Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells
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Sofien Ben Ammou, Anne Vejux, Meryam Debbabi, Stéphane Grégoire, Philippe Durand, Nadia Mekahli, Emmanuelle Camus, Lionel Bretillon, Amira Zarrouk, Maryem Bezine, Lucy Martine, Aymen Jabrane, Gérard Lizard, Mohamed Hammami, Thibault Moreau, Randa Sghaier, Michel Prost, Thomas Nury, Lizard, Gérard, Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique (Bio-PeroxIL), Université de Bourgogne (UB), Université de Monastir - University of Monastir (UM), Faculté de médecine de Sousse [Ibn EL Jazzar], Université Tunis El Manar (UTM), Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), OEil, nutrition et signalisation cellulaire [CSGA], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Recherche Appliquée Spiral [Bourgogne] (LARA SPIRAL), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Universitaire Sahloul (CHU Sahloul), Université de Bourgogne (Dijon, France), Université de Monastir (Monastir, Tunisia), Université El Manar (Tunis, Tunisia), ASSAD (Louhans, France), Nopal Nutra (Dijon, France), and Departments of Neurology (University Hospital, Dijon, France) and (University Hospital, Sousse, Tunisia)., Université de Tunis El Manar (UTM), 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)-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), Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique ( Bio-PeroxIL ), Université de Bourgogne ( UB ), Nutrition, Aliments Fonctionnels et Santé Vasculaire, Université de Monastir ( UM ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Recherche Appliquée Spiral [Bourgogne] ( LARA SPIRAL ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), and University Hospital of Sahloul
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0301 basic medicine ,Antioxidant ,Organes des sens ,medicine.medical_treatment ,Trolox ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,alpha-Tocopherol ,MESH: Antioxidants/pharmacology ,MESH: Peroxisomes/drug effects ,Antioxidants ,biochimie métabolique ,lcsh:Chemistry ,Lipid peroxidation ,Mice ,chemistry.chemical_compound ,peroxisome ,MESH: Animals ,lcsh:QH301-705.5 ,Ketocholesterols ,Spectroscopy ,Membrane Potential, Mitochondrial ,α-tocopherol ,γ-tocopherol ,oleic acid ,mitochondria ,murine microglial BV-2 cells ,peroxydation lipidique ,Neurodegeneration ,General Medicine ,Peroxisome ,3. Good health ,Computer Science Applications ,MESH: Membrane Potential, Mitochondrial/drug effects ,Biochemistry ,[ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,MESH: Microglia/metabolism ,Alimentation et Nutrition ,Microglia ,MESH: Mitochondria/pathology ,MESH: Mitochondria/drug effects ,acide oléique ,Programmed cell death ,MESH: gamma-Tocopherol/pharmacology ,Sensory Organs ,Médecine humaine et pathologie ,Biology ,Article ,Catalysis ,Cell Line ,Inorganic Chemistry ,03 medical and health sciences ,MESH: Oleic Acid/pharmacology ,Peroxisomes ,medicine ,Animals ,Food and Nutrition ,Propidium iodide ,Physical and Theoretical Chemistry ,Olive Oil ,Molecular Biology ,MESH: Mice ,MESH: Peroxisomes/pathology ,maladie neurodégénérative ,MESH: Microglia/drug effects ,gamma-Tocopherol ,MESH: Ketocholesterols/pharmacology ,Organic Chemistry ,Neurosciences ,gène mitochondrial ,medicine.disease ,MESH: Olive Oil/pharmacology ,MESH: Cell Line ,Oleic acid ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,Neurons and Cognition ,Human health and pathology ,MESH: alpha-Tocopherol/pharmacology - Abstract
Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of alpha- and gamma-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only alpha-, and gamma-tocopherol, and Trolox had antioxidant properties. However, only alpha-tocopherol, gamma-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, alpha-and gamma-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal beta-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.
- Published
- 2016
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