title: Induction of oxiapoptophagy, a mixed mode of cell death associated with oxidative stress, apoptosis and autophagy, on 7-ketocholesterol-treated 158N murine oligodendrocytes: impairment by α-tocopherol.
abstract: 7-Ketocholesterol (7KC) has been suggested to induce a complex mode of cell death on monocytic cells: oxiapoptophagy (OXIdation, APOPTOsis, and autoPHAGY) (Monier et al. (2003) [12]). The aim of the present study, realized on 158N murine oligodendrocytes, was to bring new evidence on this mixed form of cell death. On 158N cells, 7KC induces an overproduction of reactive oxygen species (ROS) revealed by dihydroethidium staining, a loss of transmembrane mitochondrial potential measured with DiOC6(3), caspase-3 activation, and condensation and/or fragmentation of the nuclei which are typical criteria of oxidative stress and apoptosis. Moreover, 7KC enhances cytoplamic membrane permeability to propidium iodide, and induces acidic vesicular organelle formation evaluated with acridine orange. In addition, 7KC promotes conversion of microtubule-associated protein light chain 3 (LC3-I) to LC3-II which is characteristic of autophagy. These different side effects were impaired by α-tocopherol. Altogether, our data demonstrate that oxiapoptophagy including ROS overproduction, apoptosis and autophagy could be a particular type of cell death activated by 7KC which can be inhibited by α-tocopherol.
authors.affiliation: Equipe 'Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique' EA 7270/Université de Bourgogne/INSERM, Dijon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nury
authors.affiliation: Equipe 'Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique' EA 7270/Université de Bourgogne/INSERM, Dijon, France; Université de Monastir, Faculté de Médecine, LR12ES05-Lab-NAFS, Monastir, Tunisia.
authors.forename: Amira
authors.initials: A
authors.lastname: Zarrouk
authors.affiliation: Equipe 'Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique' EA 7270/Université de Bourgogne/INSERM, Dijon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vejux
authors.affiliation: Equipe 'Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique' EA 7270/Université de Bourgogne/INSERM, Dijon, France.
authors.forename: Margaux
authors.initials: M
authors.lastname: Doria
authors.affiliation: Centre de Lutte Contre le Cancer GF Leclerc, Laboratoire de Biologie Médicale, Dijon, France.
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Riedinger
authors.affiliation: UFR Sciences et Techniques EA3922/SFR IBCT FED 4234, Université de Franche-Comté, Besançon, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Delage-Mourroux
authors.affiliation: Equipe 'Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique' EA 7270/Université de Bourgogne/INSERM, Dijon, France. Electronic address: gerard.lizard@u-bourgogne.fr.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lizard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007653:Ketocholesterols / Q000494:pharmacology*; D051379:Mice; D008858:Microscopy, Phase-Contrast / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D007653:Ketocholesterols; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D024502:alpha-Tocopherol; C003001:7-ketocholesterol
keywords: 158N cells; 7-Ketocholesterol; Apoptosis; Autophagy; Oxiapoptophagy; Oxidative stress; α-Tocopherol