title: Induction of oxiapoptophagy on 158N murine oligodendrocytes treated by 7-ketocholesterol-, 7β-hydroxycholesterol-, or 24(S)-hydroxycholesterol: Protective effects of α-tocopherol and docosahexaenoic acid (DHA; C22:6 n-3).
abstract: In demyelinating or non-demyelinating neurodegenerative diseases, increased levels of 7-ketocholesterol (7KC), 7β-hydroxycholesterol (7β-OHC) and 24(S)-hydroxycholesterol (24S-OHC) can be observed in brain lesions. In 158N murine oligodendrocytes, 7KC triggers a complex mode of cell death defined as oxiapoptophagy, involving simultaneous oxidative stress, apoptosis and autophagy. In these cells, 7KC as well as 7β-OHC and 24S-OHC induce a decrease of cell proliferation evaluated by phase contrast microscopy, an alteration of mitochondrial activity quantified with the MTT test, an overproduction of reactive oxygen species revealed by staining with dihydroethidium and dihydrorhodamine 123, caspase-3 activation, PARP degradation, reduced expression of Bcl-2, and condensation and/or fragmentation of the nuclei which are typical criteria of oxidative stress and apoptosis. Moreover, 7KC, 7β-OHC and 24S-OHC promote conversion of microtubule-associated protein light chain 3 (LC3-I) to LC3-II which is a characteristic of autophagy. Consequently, 7β-OHC and 24S-OHC, similarly to 7KC, can be considered as potent inducers of oxiapoptophagy. Furthermore, the different cytotoxic effects associated with 7KC, 7β-OHC and 24S-OHC-induced oxiapoptophagy are attenuated by vitamin E (VitE, α-tocopherol) and DHA which enhances VitE protective effects. In 158N murine oligodendrocytes, our data support the concept that oxiapoptophagy, which can be inhibited by VitE and DHA, could be a particular mode of cell death elicited by cytotoxic oxysterols.
authors: Team 'Biochemistry of Peroxisome, Inflammation and Lipid Metabolism' EA 7270/University of Bourgogne-Franche Comté/INSERM, Dijon, France.
authors: Thomas
authors: T
authors: Nury
authors: Team 'Biochemistry of Peroxisome, Inflammation and Lipid Metabolism' EA 7270/University of Bourgogne-Franche Comté/INSERM, Dijon, France; University of Monastir, Faculty of Medicine, LR12ES05, Lab-NAFS 'Nutrition - Functional Food & Vascular Health', Monastir, Tunisia; Department of Physiology, University College Cork, BioSciences Institute, Cork, Ireland; School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
authors: Amira
authors: A
authors: Zarrouk
authors: Department of Physiology, University College Cork, BioSciences Institute, Cork, Ireland.
authors: John J
authors: JJ
authors: Mackrill
authors: LCPMC-A2, ICPM, Département de Chimie, Université de Lorraine, Metz, France.
authors: Mohammad
authors: M
authors: Samadi
authors: SPIRAL/KIRIAL Company, Couternon, France.
authors: Philippe
authors: P
authors: Durand
authors: Centre de Lutte Contre le Cancer GF Leclerc, Laboratoire de Biologie Médicale, Dijon, France.
authors: Jean-Marc
authors: JM
authors: Riedinger
authors: Team 'Biochemistry of Peroxisome, Inflammation and Lipid Metabolism' EA 7270/University of Bourgogne-Franche Comté/INSERM, Dijon, France.
authors: Margaux
authors: M
authors: Doria
authors: Team 'Biochemistry of Peroxisome, Inflammation and Lipid Metabolism' EA 7270/University of Bourgogne-Franche Comté/INSERM, Dijon, France.
authors: Anne
authors: A
authors: Vejux
authors: Centre de Recherche INSERM U866 - 'Lipids, Nutrition, Cancer', Dijon, France.
authors: Emeric
authors: E
authors: Limagne
authors: Centre de Recherche INSERM U866 - 'Lipids, Nutrition, Cancer', Dijon, France.
authors: Dominique
authors: D
authors: Delmas
authors: SPIRAL/KIRIAL Company, Couternon, France.
authors: Michel
authors: M
authors: Prost
authors: CHU de Dijon, Service de Neurologie, Dijon, France.
authors: Thibault
authors: T
authors: Moreau
authors: University of Monastir, Faculty of Medicine, LR12ES05, Lab-NAFS 'Nutrition - Functional Food & Vascular Health', Monastir, Tunisia.
authors: Mohamed
authors: M
authors: Hammami
authors: UFR Sciences et Techniques EA3922/SFR IBCT FED 4234, University of Bourgogne-Franche Comté, Besançon, France.
authors: Régis
authors: R
authors: Delage-Mourroux
authors: School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
authors: Nora M
authors: NM
authors: O'Brien
authors: Team 'Biochemistry of Peroxisome, Inflammation and Lipid Metabolism' EA 7270/University of Bourgogne-Franche Comté/INSERM, Dijon, France. Electronic address: gerard.lizard@u-bourgogne.fr.
authors: Gérard
authors: G
authors: Lizard
mesh_terms: D000818:Animals; D000838:Anions; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007653:Ketocholesterols / Q000494:pharmacology*; D051379:Mice; D008858:Microscopy, Phase-Contrast; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000838:Anions; D015415:Biomarkers; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D020011:Protective Agents; D013481:Superoxides; D004281:Docosahexaenoic Acids; C044563:24-hydroxycholesterol; C011724:cholest-5-en-3 beta,7 alpha-diol; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol; C003001:7-ketocholesterol
keywords: 24(S)-hydroxycholesterol; 7-Ketocholesterol; 7β-Hydroxycholesterol; Docosahexaenoic acid; Oxiapoptophagy; α-Tocopherol