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

• Published in: Biochemical and biophysical research communications Vol. 324; no. 1; pp. 417 - 423
• Main Authors: Takabuchi, Satoshi, Hirota, Kiichi, Nishi, Kenichiro, Oda, Seiko, Oda, Tomoyuki, Shingu, Koh, Takabayashi, Arimichi, Adachi, Takehiko, Semenza, Gregg L., Fukuda, Kazuhiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.11.2004
• Subjects: Animals; Cell Line; Cyclic N-Oxides - chemistry; Cyclic N-Oxides - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Free Radical Scavengers - chemistry; Free Radical Scavengers - metabolism; Gene Expression Regulation; Guanylate Cyclase; Humans; Hydroxylase; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Imidazoles - chemistry; Imidazoles - metabolism; Isosorbide dinitrate; Isosorbide Dinitrate - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Donors - metabolism; Nitric Oxide Donors - pharmacology; Nitroglycerin; Nitroglycerin - metabolism; Nitroprusside - metabolism; Nitroprusside - pharmacology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oxygen - metabolism; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; Receptors, Cytoplasmic and Nuclear - metabolism; Signal Transduction; Sodium nitroprusside; Soluble Guanylyl Cyclase; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Vasodilator Agents - metabolism; Von Hippel–Lindau; Sodium nitroprusside; Isosorbide dinitrate; Hypoxia-inducible factor 1; Nitroglycerin; Nitric oxide; Hydroxylase; Von Hippel–Lindau; Hypoxia
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.09.064

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.