title: 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.
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 α- and γ-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 α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-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, α-and γ-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 β-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.
authors.affiliation: Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, University Bourgogne Franche-Comté, 21000 Dijon, France. debbabi.meryam55@gmail.com.|Lab-NAFS 'Nutrition-Functional Food & Vascular Health', University Monastir, LR12ES05, 5000 Monastir, Tunisia. debbabi.meryam55@gmail.com.
authors.forename: Meryam
authors.initials: M
authors.lastname: Debbabi
authors.affiliation: Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, University Bourgogne Franche-Comté, 21000 Dijon, France. thomas.nury@u-bourgogne.fr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nury
authors.affiliation: Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, University Bourgogne Franche-Comté, 21000 Dijon, France. zarroukamira@gmail.com.|Lab-NAFS 'Nutrition-Functional Food & Vascular Health', University Monastir, LR12ES05, 5000 Monastir, Tunisia. zarroukamira@gmail.com.|Faculty of Medicine, University Sousse, 4000 Sousse, Tunisia. zarroukamira@gmail.com.
authors.forename: Amira
authors.initials: A
authors.lastname: Zarrouk
authors.affiliation: Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, University Bourgogne Franche-Comté, 21000 Dijon, France. nadia.mekahli@yahoo.fr.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mekahli
authors.affiliation: Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, University Bourgogne Franche-Comté, 21000 Dijon, France. bezzinemaryem@yahoo.fr.|Laboratory 'Venoms & Therapeutic Biomolecules', Pasteur Institute, University Tunis El Manar, 1000 Tunis, Tunisia. bezzinemaryem@yahoo.fr.
authors.forename: Maryem
authors.initials: M
authors.lastname: Bezine
authors.affiliation: Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, University Bourgogne Franche-Comté, 21000 Dijon, France. sg.randa@yahoo.fr.|Faculty of Medicine, University Sousse, 4000 Sousse, Tunisia. sg.randa@yahoo.fr.
authors.forename: Randa
authors.initials: R
authors.lastname: Sghaier
authors.affiliation: Eye & Nutrition Research Group, CSGA, UMR 1324 INRA, 6265 CNRS, University Bourgogne Franche-Comté, 21000 Dijon, France. stephane.gregoire@dijon.inra.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Grégoire
authors.affiliation: Eye & Nutrition Research Group, CSGA, UMR 1324 INRA, 6265 CNRS, University Bourgogne Franche-Comté, 21000 Dijon, France. lucie.martine@dijon.inra.fr.
authors.forename: Lucy
authors.initials: L
authors.lastname: Martine
authors.affiliation: Kirial International/Laboratoires Spiral, 21560 Couternon, France. p.guyondet.spiral@orange.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Durand
authors.affiliation: Kirial International/Laboratoires Spiral, 21560 Couternon, France. camusprost@hotmail.fr.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Camus
authors.affiliation: Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, University Bourgogne Franche-Comté, 21000 Dijon, France. anne.vejux@u-bourgogne.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Vejux
authors.affiliation: Société Nopal Nutra, 21000 Dijon, France. aymen.jabrane@nopalnutra.com.
authors.forename: Aymen
authors.initials: A
authors.lastname: Jabrane
authors.affiliation: Eye & Nutrition Research Group, CSGA, UMR 1324 INRA, 6265 CNRS, University Bourgogne Franche-Comté, 21000 Dijon, France. lionel.bretillon@dijon.inra.fr.
authors.forename: Lionel
authors.initials: L
authors.lastname: Bretillon
authors.affiliation: Kirial International/Laboratoires Spiral, 21560 Couternon, France. michelprost.spiral@wanadoo.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Prost
authors.affiliation: Department of Neurology, University Hospital of Dijon, 21000 Dijon, France. thibault.moreau@chu-dijon.fr.
authors.forename: Thibault
authors.initials: T
authors.lastname: Moreau
authors.affiliation: Department of Neurology, University Hospital Sahloul, 4000 Sousse, Tunisia. sofien.benammou@rns.tn.
authors.forename: Sofien Ben
authors.initials: SB
authors.lastname: Ammou
authors.affiliation: Lab-NAFS 'Nutrition-Functional Food & Vascular Health', University Monastir, LR12ES05, 5000 Monastir, Tunisia. mohamed.hammami@fmm.rnu.tn.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hammami
authors.affiliation: Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, University Bourgogne Franche-Comté, 21000 Dijon, France. gerard.lizard@u-bourgogne.fr.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lizard
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D007653:Ketocholesterols / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D019301:Oleic Acid / Q000494:pharmacology*; D000069463:Olive Oil / Q000494:pharmacology*; D020675:Peroxisomes / Q000187:drug effects* / Q000473:pathology; D024502:alpha-Tocopherol / Q000494:pharmacology*; D024504:gamma-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D007653:Ketocholesterols; D000069463:Olive Oil; D019301:Oleic Acid; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol; C003001:7-ketocholesterol
keywords: Trolox; mitochondria; murine microglial BV-2 cells; oleic acid; peroxisome; α-tocopherol; γ-tocopherol