TY - JOUR
T1 - Interactions of manganese with human brain glutathione-S-transferase
AU - Vescovi, A.
AU - Gebbia, M.
AU - Cappelletti, G.
AU - Parati, E. A.
AU - Santagostino, A.
N1 - Funding Information:
This study was supported by grants from the Regione Lombardia --'Pro-getto finalizzato No. 536'. We thank Dr. Danilo Croci for his generous support.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1989/7/17
Y1 - 1989/7/17
N2 - 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.
AB - 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.
KW - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
KW - Glutathione-S-transferases
KW - Manganese chloride
KW - Parkinson's disease
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U2 - 10.1016/0300-483X(89)90164-9
DO - 10.1016/0300-483X(89)90164-9
M3 - Article
C2 - 2787543
AN - SCOPUS:0024318165
SN - 0300-483X
VL - 57
SP - 183
EP - 191
JO - Toxicology
JF - Toxicology
IS - 2
ER -