Participation of manganese-superoxide dismutase in the neuroprotection exerted by copper sulfate against 1-methyl 4-phenylpyridinium neurotoxicity.
Neurodegenerative effects of 1-methyl-4-phenylpyridinium (MPP+), the main metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) include enhancement of lipid peroxidation in the striatum of mice, associated to overproduction of free radicals. Copper acts as a prosthetic group of several copper-dependent antioxidant enzymes, and we previously showed the neuroprotective effect of CuSO4 pretreatment against the MPP+-induced neurotoxicity. In those studies, acute administration of CuSO4 (2.5 mg/kg) blocked MPP+-induced striatal lipid peroxidation, suggesting the activation of Cu-dependent proteins that defend neurons from damage elicited by free radicals. In the present study, we evaluated the activity of superoxide dismutase in mice pretreated with CuSO4 16 h or 24 h prior to MPP+ administration. Copper administration produced a specific and significant increase in manganese superoxide dismutase activity in both the CuSO4/saline (fivefold increase) and the CuSO4/MPP+ groups of animals (sevenfold increase). The Na2SO4/MPP+ group showed a twofold increase in manganese superoxide dismutase activity versus control levels. The results suggest that the load of copper activating manganese-dependent superoxide dismutase could be responsible for neuroprotection against the MPP+ insult.
Alcaraz-Zubeldia
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Department of Neurochemistry, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez", México City, México.
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D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D019327:Copper Sulfate / Q000494:pharmacology*; D004334:Drug Administration Schedule; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D020267:MPTP Poisoning / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D013431:Sulfates / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000187:drug effects* / Q000378:metabolism
D000975:Antioxidants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D013431:Sulfates; C012036:sodium sulfate; D013482:Superoxide Dismutase; D019327:Copper Sulfate; D015655:1-Methyl-4-phenylpyridinium