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Published on: January 7, 2014
Copper reduces striatal protein nitration and tyrosine hydroxylase inactivation induced by MPP+ in rats
M Rubio-Osornio1, S Montes, F Pérez-Severiano
1Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, Insurgentes Sur 3877, La Fama, México, DF, C.P. 14269, Mexico.
Abstract:
Striatal administration of 1-methyl-4-phenylpyridinium (MPP(+)), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causes nigrostriatal dopaminergic pathway damage similar to that observed in Parkinson's disease. Copper acts as a prosthetic group of several antioxidant enzymes and recent data show that copper attenuated MPP(+)-evoked neurotoxicity. We evaluated the effect of copper (as a supplement) upon proteins nitration (60 kDa) and tyrosine hydroxylase (TH) inactivation induced by MPP(+) (10 microg/8 microL) injection into the rat striatum. Copper pretreatment (10 micromol/kg i.p.) prevented both MPP(+)-induced proteins nitration and TH inactivation. Copper treatment also prevented the dopamine-depleting effect of MPP(+) injection. Those results were accompanied by a significant reduction of enzymatic activity of the constitutive nitric oxide synthase (cNOS), whereas, the protein levels of the three isoforms of NOS remained unchanged. Results indicate that the effect of copper against MPP(+)-induced proteins nitration and TH inactivation in the striatum of rat may be mediated by a reduction of cNOS activity.
Insights
Copper supplementation may protect against Parkinson's disease-like neurotoxicity. Copper prevented 1-methyl-4-phenylpyridinium (MPP(+))-induced damage, including protein nitration and tyrosine hydroxylase inactivation, by reducing nitric oxide synthase activity.
Area of Science:
- Neuroscience
- Biochemistry
- Toxicology
Background:
- 1-methyl-4-phenylpyridinium (MPP(+)), a neurotoxin, induces damage to the nigrostriatal dopaminergic pathway, mimicking Parkinson's disease pathology.
- Copper, an essential element, plays a role in antioxidant enzymes and has shown potential in mitigating MPP(+)-induced neurotoxicity.
Purpose of the Study:
- To investigate the protective effects of copper supplementation against MPP(+)-induced neurotoxicity in the rat striatum.
- To evaluate the impact of copper on protein nitration, tyrosine hydroxylase (TH) inactivation, and dopamine levels following MPP(+) administration.
Main Methods:
- Rats were pretreated with copper (10 micromol/kg i.p.) before striatal injection of MPP(+) (10 microg/8 microL).
- Assessed protein nitration (60 kDa), TH inactivation, dopamine levels, and constitutive nitric oxide synthase (cNOS) activity.
- Examined protein levels of all three nitric oxide synthase (NOS) isoforms.
Main Results:
- Copper pretreatment significantly prevented MPP(+)-induced protein nitration and TH inactivation.
- Copper administration also protected against the dopamine-depleting effects of MPP(+).
- A significant reduction in cNOS enzymatic activity was observed, while NOS protein levels remained unchanged.
Conclusions:
- Copper supplementation demonstrates neuroprotective effects against MPP(+)-induced toxicity in the rat striatum.
- The protective mechanism appears to involve the reduction of cNOS activity, rather than changes in NOS protein expression.
- These findings suggest a potential therapeutic role for copper in conditions involving dopaminergic neurodegeneration.
