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Chromaffin cell death induced by 6‐hydroxydopamine is independent of mitochondrial swelling and caspase activation
Author(s) -
Galindo María F.,
Jordán Joaquín,
GonzálezGarcía Carmen,
Ceña Valentín
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01592.x
Subject(s) - hydroxydopamine , catalase , reactive oxygen species , ascorbic acid , programmed cell death , chemistry , mitochondrion , mitochondrial permeability transition pore , oxidative stress , biochemistry , chromaffin cell , toxicity , apoptosis , biology , endocrinology , dopamine , catecholamine , adrenal medulla , dopaminergic , food science , organic chemistry
Abstract Our results provide evidence that 6‐hydroxydopamine induced, after auto‐oxidation, toxic levels of hydrogen peroxide (H 2 O 2 ) 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.