Interactions of manganese with human brain glutathione-S-transferase

A. Vescovi, M. Gebbia, G. Cappelletti, E. A. Parati, A. Santagostino

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalToxicology
Volume57
Issue number2
DOIs
Publication statusPublished - Jul 17 1989

Keywords

  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Glutathione-S-transferases
  • Manganese chloride
  • Parkinson's disease

ASJC Scopus subject areas

  • Toxicology

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