Reduction of arginase I activity and manganese levels in the liver during exposure of rats to methylmercury: A possible mechanism

Hironori Kanda, Daigo Sumi, Akiko Endo, Takashi Toyama, Cheng Liang Chen, Makoto Kikushima, Yoshito Kumagai

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

The toxicity of methylmercury (MeHg) is, in part, thought to be due to its interaction with thiol groups in a variety of enzymes, but the molecular targets of MeHg are poorly understood. Arginase I, an abundant manganese (Mn)-binding protein in the liver, requires Mn as an essential element to exhibit maximal enzyme activity. In the present study, we examined the effect of MeHg on hepatic arginase I in vivo and in vitro. Subcutaneous administration of MeHg (10 mg/kg) for 8 days to rats resulted in marked suppression of arginase I activity. With purified arginase I, we found that interaction of MeHg with arginase I caused the aggregation of arginase I as evaluated by centrifugation and subsequent precipitation, and then the reduction of catalytic activity. Experiments with organomercury column confirmed that arginase I has reactive thiols that are covalently bound to organomercury. While MeHg inhibited arginase I activity, Mn ions were released from this enzyme. These results suggest that MeHg-mediated suppression of hepatic arginase I activity in vivo is, at least in part, attributable to covalent modification of MeHg or substantial leakage of Mn ions from the active site.

Original languageEnglish
Pages (from-to)803-808
Number of pages6
JournalArchives of Toxicology
Volume82
Issue number11
DOIs
Publication statusPublished - 2008 Nov 1
Externally publishedYes

Keywords

  • Arginase I
  • Covalent modification
  • Cysteine
  • Manganese
  • Methylmercury

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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