Copper reduces striatal protein nitration and tyrosine hydroxylase inactivation induced by MPP+ in rats.
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.
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, Insurgentes Sur 3877, La Fama, México, DF, C.P. 14269, Mexico.
M
M
Rubio-Osornio
S
S
Montes
F
F
Pérez-Severiano
P
P
Aguilera
E
E
Floriano-Sánchez
A
A
Monroy-Noyola
C
C
Rubio
C
C
Ríos
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D015153:Blotting, Western; D019327:Copper Sulfate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity; D004591:Electrophoresis, Polyacrylamide Gel; D020267:MPTP Poisoning / Q000517:prevention & control*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis; D010302:Parkinson Disease, Secondary / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*
D015259:Dopamine Agents; D009419:Nerve Tissue Proteins; D009566:Nitrates; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase; D019327:Copper Sulfate; D004298:Dopamine