The inhibitory effect of sodium nitroprusside on HIF-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway

Satoshi Takabuchi, Kiichi Hirota, Kenichiro Nishi, Seiko Oda, Tomoyuki Oda, Koh Shingu, Arimichi Takabayashi, Takehiko Adachi, Gregg L. Semenza, Kazuhiko Fukuda

Research output: Contribution to journalArticle

Abstract

Adaptation to hypoxia and maintenance of O 2 homeostasis involve a wide range of responses that occur at different organizational levels in the body. One of the most important transcription factors that activate the expression of O 2-regulated genes is hypoxia-inducible factor 1 (HIF-1). Nitric oxide (NO) mediates a variety of biological effects including relaxation of blood vessels and cytotoxicity of activated macrophages. We investigated the effect of the clinically used nitrates nitroglycerin (NTG), isosorbide dinitrate (ISDN), and sodium nitroprusside (SNP) on HIF-1-mediated transcriptional responses to hypoxia. We demonstrate that among the three nitrates, only SNP inhibits HIF-1 activation in response to hypoxia. In contrast, NTG or ISDN does not affect HIF-1 activity. SNP inhibits the accumulation of HIF-1α, the regulatory subunit of HIF-1, and the transcriptional activation of HIF-1α via a mechanism that is not dependent on either NO or soluble guanylate cyclase.

Original languageEnglish (US)
Pages (from-to)417-423
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume324
Issue number1
DOIs
StatePublished - Nov 5 2004

Keywords

  • Hydroxylase
  • Hypoxia
  • Hypoxia-inducible factor 1
  • Isosorbide dinitrate
  • Nitric oxide
  • Nitroglycerin
  • Sodium nitroprusside
  • Von Hippel-Lindau

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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