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

Department of Anesthesia, The Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan.

Biochemical and biophysical research communications 2004 Nov 5

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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-1alpha, the regulatory subunit of HIF-1, and the transcriptional activation of HIF-1alpha via a mechanism that is not dependent on either NO or soluble guanylate cyclase.

Citation

Satoshi Takabuchi, Kiichi Hirota, Kenichiro Nishi, Seiko Oda, Tomoyuki Oda, Koh Shingu, Arimichi Takabayashi, Takehiko Adachi, Gregg L Semenza, Kazuhiko Fukuda. The inhibitory effect of sodium nitroprusside on HIF-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway. Biochemical and biophysical research communications. 2004 Nov 5;324(1):417-23