Copper reduction is related to impairment of cytochrome c oxidase activity in striatum in an animal model of Parkinson's disease

Copper is an essential transition metal ion for the function of key metabolic enzymes. Copper deficiency produces impairment of mitochondrial function due to a decreased of cytochrome c oxidase activity, this leads to reactive oxygen species production, which in turn triggers mitochondria-mediated a...

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Published in:Current topics in nutraceuticals research 2012-05, Vol.10 (2), p.87
Main Authors: Rojas, Patricia, Montes, Sergio, Heras-Romero, Yessica, Montes, Pedro, Rojas, Carolina
Format: Article
Language:English
Subjects:
Apoptosis
Brain
Cytochrome c
Cytochrome oxidase
Dopamine
Electron transport
Enzymes
Experiments
Free radicals
Homeostasis
Laboratory animals
Mitochondria
Mitochondrial DNA
Neurodegeneration
Neurophysiology
Neurosciences
Neurotoxicity
Oxidative stress
Parkinson's disease
Pathogenesis
Rodents
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Summary:Copper is an essential transition metal ion for the function of key metabolic enzymes. Copper deficiency produces impairment of mitochondrial function due to a decreased of cytochrome c oxidase activity, this leads to reactive oxygen species production, which in turn triggers mitochondria-mediated apoptotic neurodegeneration. Defects in mitochondrial energy production have been implicated in Parkinson's disease (PD) pathology. Reduction in complex IV (cytochrome c oxidase) activity, the terminal enzyme of the mitochondrial electron transport chain, is copper-dependent and has also been observed in PD. We studied the changes of cytochrome c oxidase activity and copper content in different brain regions in animal model of PD using 1-methyl-4-phenylpyridinium (MPP+). Male Swiss albino mice were treated with saline or MPP+ (18 µg/3 µl, intracerebroventricular). All animals were sacrificed 24 hours after MPP+ administration and different brain regions were removed. Cytochrome c oxidase activity was analyzed using a spectrophotometric technique and copper was determined by atomic absorption analysis. Dopamine levels were measured by HPLC and spontaneous locomotor activity in an activity meter. Cytochrome c oxidase activity was reduced in corpus striatum (27.5%) after MPP+ treatment. However, its activity in cerebellum, midbrain, and frontal cortex was not different from the control group (saline). Copper content decreased only in striatum (56%) and midbrain (31%) after MPP+ administration. Copper administration (CuSO4, 2.5 mg/kg, i.p.) blocked dopaminergic neurotoxicity and displayed a significant reduction (59%) in locomotor activity after MPP+ administration. Our results suggest that copper reduction is related to impairment of cytochrome c oxidase activity in striatum and other parameters in MPP+ neurotoxicity. [PUBLICATION ABSTRACT]
ISSN:1540-7535
2641-452X