Effect of altered redox states on expression and DNA-binding activity of hypoxia-inducible factor 1

Guang L. Wang, Bing Hua Jiang, Gregg L. Semenza

Research output: Contribution to journalArticle

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix (bHLH)-PAS DNA-binding protein tightly regulated by cellular oxygen tension. Cellular redox states are related to hypoxia by changes in the expression of redox regulated genes and the generation of reactive oxygen intermediates. Here, we provide evidence that alteration of cellular redox states by treating cells with H2O2 or dithiothreitol impairs hypoxia signaling mechanisms and the expression of HIF-1α protein in hypoxic cells. In addition, HIF-1 DNA-binding activity in vitro is sensitive to oxidizing reagents diamide and H2O2 and the alkylating agent N-ethylmaleimide. The activity of N-ethylmaleimide-inactivated HIF-1 can be partially restored by addition of nuclear extract from nonhypoxic cells.

Original languageEnglish (US)
Pages (from-to)550-556
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume212
Issue number2
DOIs
StatePublished - Jul 17 1995

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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