Chromaffin cell death induced by 6-hydroxydopamine is independent of mitochondrial swelling and caspase activation.
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.
Galindo
María F
MF
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.
Jordán
Joaquín
J
González-García
Carmen
C
Ceña
Valentín
V
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
D000975:Antioxidants; D011809:Quinones; D017382:Reactive Oxygen Species; D009243:NAD; D009249:NADP; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D020169:Caspases