title: Chromaffin cell death induced by 6-hydroxydopamine is independent of mitochondrial swelling and caspase activation.
abstract: Our results provide evidence that 6-hydroxydopamine induced, after auto-oxidation, toxic levels of hydrogen peroxide (H2O2) that caused bovine chromaffin cell toxicity and death. 6-Hydroxydopamine (6-OHDA) treatment markedly reduced, in a dose-response fashion, chromaffin cell viability. Cell death was accompanied by cell shrinkage, nuclear condensation and DNA degradation. Under our experimental conditions, 6-OHDA auto-oxidation formed quinones and reactive oxygen species (ROS) that mainly contributed to 6-OHDA-induced cytotoxicity in bovine chromaffin cells. Accordingly, different antioxidants, including catalase, vitamin E, Mn(IIItetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) or ascorbic acid, provided protection against 6-OHDA-induced toxicity. Further evidence that 6-OHDA induces oxidative stress is provided by the fact that this compound decreased total mitochondrial reduced NAD(P)H levels. Our results also suggest that mitochondrial swelling and caspase activation do not play a direct role in 6-OHDA-induced death in bovine chromaffin cells.
authors.affiliation: Centro Regional de Investigaciones Biomédicas y Dpto. de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Avda. España, s/n, 02071 Albacete, Spain.
authors.forename: María F
authors.initials: MF
authors.lastname: Galindo
authors.forename: Joaquín
authors.initials: J
authors.lastname: Jordán
authors.forename: Carmen
authors.initials: C
authors.lastname: González-García
authors.forename: Valentín
authors.initials: V
authors.lastname: Ceña
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D016627:Oxidopamine / Q000378:metabolism / Q000633:toxicity*; D011809:Quinones / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D011809:Quinones; D017382:Reactive Oxygen Species; D009243:NAD; D009249:NADP; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D020169:Caspases