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

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Takabuchi S, Hirota K, Nishi K, Oda S, Oda T, Shingu K, Takabayashi A, Adachi T, Semenza GL, Fukuda K

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

Biochem Biophys Res Commun. 2004 Nov 5;324(1):417-23.

PubMed ID

15465035 [ View in PubMed

]

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-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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Isosorbide dinitrate	Atrial natriuretic peptide receptor 1	Protein	Humans	Yes	Agonist	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Nitroprusside	Approved Investigational	HIF1A	3091	downregulated	Nitroprusside results in decreased expression of HIF1A mRNA	14q23.2

Pharmaco-proteomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Nitroprusside	Approved Investigational	HIF1A	3091	decreased	Nitroprusside results in decreased expression of HIF1A protein	14q23.2