title: Attenuation of 7-ketocholesterol-induced overproduction of reactive oxygen species, apoptosis, and autophagy by dimethyl fumarate on 158N murine oligodendrocytes.
abstract: Mitochondrial dysfunctions and oxidative stress are involved in several non demyelinating or demyelinating neurodegenerative diseases. Some of them, including multiple sclerosis (MS), are associated with lipid peroxidation processes leading to increased levels of 7-ketocholesterol (7KC). So, the eventual protective effect of dimethylfumarate (DMF), which is used for the treatment of MS, was evaluated on 7KC-treated oligodendrocytes, which are myelin synthesizing cells. To this end, murine oligodendrocytes 158N were exposed to 7KC (25, 50μM) for 24h without or with DMF (1, 25, 50μM). The biological activities of DMF associated or not with 7KC were evaluated by phase contrast microscopy, crystal violet and MTT tests. The impact on transmembrane mitochondrial potential (ΔYm), O2-and H2O2production, apoptosis and autophagy was measured by microscopical and flow cytometric methods by staining with DiOC6(3), dihydroethidine and dihydrorhodamine 123, Hoechst 33342, and by Western blotting with the use of specific antibodies raised against uncleaved and cleaved caspase-3 and PARP, and LC3-I/II. DMF attenuates the different effects of 7KC, namely: cell growth inhibition and/or loss of cell adhesion, decrease of ΔΨm, O2-and H2O2overproduction, PARP and caspase-3 cleavage, nuclear condensation and fragmentation, and activation of LC3-I into LC3-II. The ability of DMF to attenuate 7KC-induced reactive oxygen species overproduction, apoptosis, and autophagy on oligodendrocytes reinforces the interest for this molecule for the treatment of MS or other demyelinating diseases.
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France; Univ. Monastir, Faculty of Medicine, LR12ES05, Lab-NAFS 'Nutrition-Functional Food & Vascular Health', Monastir, & Univ. Sousse, Faculty of Medicine, Sousse, Tunisia.
authors.forename: Amira
authors.initials: A
authors.lastname: Zarrouk
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nury
authors.affiliation: Univ. Hassan 1(er), Laboratoire de Biochimie et Neuroscience, Faculté de Sciences et Techniques, Settat, Morocco.
authors.forename: El-Mostafa
authors.initials: EM
authors.lastname: Karym
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vejux
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France; Univ. Monastir, Faculty of Medicine, LR12ES05, Lab-NAFS 'Nutrition-Functional Food & Vascular Health', Monastir, & Univ. Sousse, Faculty of Medicine, Sousse, Tunisia.
authors.forename: Randa
authors.initials: R
authors.lastname: Sghaier
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gondcaille
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Andreoletti
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France.
authors.forename: Doriane
authors.initials: D
authors.lastname: Trompier
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Savary
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Cherkaoui-Malki
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France; Univ. Monastir, Faculty of Medicine, LR12ES05, Lab-NAFS 'Nutrition-Functional Food & Vascular Health', Monastir, & Univ. Sousse, Faculty of Medicine, Sousse, Tunisia.
authors.forename: Meryam
authors.initials: M
authors.lastname: Debbabi
authors.affiliation: Department of Neurology, Univ. Hospital/Univ. Bourgogne Franche Comté, Dijon, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Fromont
authors.affiliation: Centre de Lutte Contre le Cancer GF Leclerc, Lab. Biologie Médicale, Dijon, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Riedinger
authors.affiliation: Department of Neurology, Univ. Hospital/Univ. Bourgogne Franche Comté, Dijon, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Moreau
authors.affiliation: 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/Univ. Bourgogne Franche Comté/INSERM, Dijon, France. Electronic address: gerard.lizard@u-bourgogne.fr.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lizard
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001343:Autophagy; D002467:Cell Nucleus / Q000378:metabolism; D000069462:Dimethyl Fumarate / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000378:metabolism; D005434:Flow Cytometry; D007653:Ketocholesterols / Q000494:pharmacology*; D015227:Lipid Peroxidation; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008858:Microscopy, Phase-Contrast; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D007653:Ketocholesterols; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D004281:Docosahexaenoic Acids; D000069462:Dimethyl Fumarate; C003001:7-ketocholesterol
keywords: 158N cells; 7-Ketocholesterol; Apoptosis; Autophagy; Dimethyl fumarate; Oxiapoptophagy; Oxidative stress