Interactions of manganese with human brain glutathione-S-transferase.
Chronic exposure to manganese-laden dusts induces, in humans and lower primates, neurological disorders with clinicopathological features that resemble idiopathic Parkinson's disease. As many authors have suggested, manganese neurotoxicity could be related to the capability of this metal to increase catechol autoxidation in catecholaminergic neurons, therefore increasing the formation of toxic compounds such as peroxides, superoxides, free radicals, and semi-orthoquinones. Oxidative stresses and consequent neuronal damage could then occur if physiological scavenger mechanisms fail in their detoxifying action. We here report that manganese chloride weakly inhibits, in a dose-dependent way by a reversible competitive mechanism, human brain glutathione-S-transferases possibly suggesting that manganese intoxication could cause intraneuronal accumulation of cytotoxic compounds. We also report that both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin known to induce in man Parkinson-like syndromes, and one of its metabolites 1-methyl-4-phenylpyridinium failed to decrease glutathione-S-transferase activity.
Vescovi
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A
Lab. of Neuropharmacology, Neurological Institute C. Besta, Milan, Italy.
Gebbia
M
M
Cappelletti
G
G
Parati
E A
EA
Santagostino
A
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D001921:Brain / Q000201:enzymology*; D002712:Chlorides; D003600:Cytosol / Q000201:enzymology; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology*; D017895:Manganese Compounds; D011725:Pyridines / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology
D002712:Chlorides; D017895:Manganese Compounds; D011725:Pyridines; D011726:Pyridinium Compounds; D008345:Manganese; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005982:Glutathione Transferase; C025340:manganese chloride; D015655:1-Methyl-4-phenylpyridinium