Mechanism of superoxide dismutase/H2O2-mediated nitric oxide release from S-nitrosoglutathione - Role of glutamate

Ravinder Jit Singh, Neil Hogg, Steven P.A. Goss, William E. Antholine, B. Kalyanaraman

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

S-Nitrosoglutathione (GSNO), a physiologically relevant nitric oxide (·NO) donor, exhibits antioxidant, anti-ischemic, and antiplatelet properties. The exact mechanism of ·NO release from GSNO in biological systems has not been determined. Both copper ions and copper-containing enzymes have been shown to catalyze ·NO release from GSNO. In this study we observed that copper-zinc superoxide dismutase (Cu,Zn-SOD) in the presence of H2O2 caused a rapid decomposition of GSNO, forming oxidized glutathione (GSSG) and ·NO. The cupric ions (Cu2+) released from Cu,Zn-SOD were bound to the glutamate moiety of GSNO, yielding a 2:1 (GSNO)2Cu2+ complex. Strong chelators of cupric ions, such as histidine and diethylenetriaminepentaacetic acid, inhibited the formation of (GSNO)2Cu2+ complex, GSSG, and ·NO. GSSG alone inhibited Cu2+-induced decomposition of GSNO. This effect is attributed to complexation of copper by GSSG. We conclude that binding of copper to GSNO is obligatory for ·NO release from GSNO; however, the rate of this reaction was considerably slowed due to binding of Cu2+ by GSSG. The glutamate moiety in GSNO and GSSG controls copper-catalyzed ·NO release from GSNO, Cu,ZnSOD and H2O2 enhanced peroxidation of unsaturated lipid that was inhibited by GSNO. The antioxidant function of GSNO is related to the sequestering of copper by GSNO and its ability to slowly release ·NO. Implications of these findings are discussed in relation to GSNO-induced cardioprotection and to neuropathological processes.

Original languageEnglish (US)
Pages (from-to)8-15
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume372
Issue number1
DOIs
StatePublished - Dec 1 1999

Keywords

  • Copper complex
  • ESR
  • Nitric oxide
  • Nitrosothiols

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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