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Copper increases the ability of 6‐hydroxydopamine to generate oxidative stress and the ability of ascorbate and glutathione to potentiate this effect: potential implications in Parkinson's disease
Author(s) -
CrucesSande Antón,
MéndezÁlvarez Estefanía,
SotoOtero Ramón
Publication year - 2017
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 - 10.1111/jnc.14019
Subject(s) - lipid peroxidation , glutathione , chemistry , hydroxydopamine , oxidative stress , autoxidation , biochemistry , dopaminergic , neurotoxin , antioxidant , ascorbic acid , biophysics , dopamine , endocrinology , biology , enzyme , food science
Copper is an essential metal for the function of many proteins related to important cellular reactions and also involved in the synaptic transmission. Although there are several mechanisms involved in copper homeostasis, a dysregulation in this process can result in serious neurological consequences, including degeneration of dopaminergic neurons. 6‐Hydroxydopamine is a dopaminergic neurotoxin mainly used in experimental models of Parkinson's disease, whose neurotoxicity has been related to its ability to generate free radicals. In this study, we examined the effects induced by copper on 6‐ OHDA autoxidation. Our data show that both Cu + and Cu 2+ caused an increase in • OH production by 6‐ OHDA autoxidation, which was accompanied by an increase in the rate of both p ‐quinone formation and H 2 O 2 accumulation. The presence of ascorbate greatly enhanced this process by establishing a redox cycle which regenerates 6‐ OHDA from its p ‐quinone. However, the presence of glutathione did not change significantly the copper‐induced effects. We observed that copper is able to potentiate the ability of 6‐ OHDA to cause both lipid peroxidation and protein oxidation, with the latter including a reduction in free‐thiol content and an increase in carbonyl content. Ascorbate also increases the lipid peroxidation induced by the action of copper and 6‐ OHDA . Glutathione protects against the copper‐induced lipid peroxidation, but does not reduce its potential to oxidize free thiols. These results clearly demonstrate the potential of copper to increase the capacity of 6‐ OHDA to generate oxidative stress and the ability of ascorbate to enhance this potential, which may contribute to the destruction of dopaminergic neurons.