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Rubio-Osornio M, Montes S, Perez-Severiano F, Aguilera P, Floriano-Sanchez E, Monroy-Noyola A, Rubio C, Rios C: Copper reduces striatal protein nitration and tyrosine hydroxylase inactivation induced by MPP+ in rats. Neurochem Int. 2009 Jun;54(7):447-51. Epub 2009 Feb 6.
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. |
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