Journal
FEBS LETTERS
Volume 549, Issue 1-3, Pages 99-104Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(03)00798-1
Keywords
hypoxia inducible factor-1; nitric oxide; signal transduction; PI-3K/Akt; PTEN
Funding
- NHLBI NIH HHS [R01-HL61359, HL-10355] Funding Source: Medline
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Hypoxia activates the transcription factor, hypoxia inducible factor-1 (HIF-1). Besides hypoxia, HIF-1 can be activated under normoxic conditions by nitric oxide. The signal transduction pathways involved in HIF-1alpha stabilization, HIF-1 DNA binding and transactivation by NO and hypoxia in microvascular endothelium remains unknown. We report that protein phosphorylation is involved in HIF-1 activation during hypoxia and NO. The phosphatidylinositol 3-kinase (PI-3K)/Akt pathway has differential effects on HIF-1 activation by hypoxia and NO. Our data indicate that the PI-3K/Akt pathway is insufficient for HIF-1alpha induction by hypoxia. The lipid and protein phosphatase activities of PTEN also appear to be involved in regulation of HIF-1alpha by NO. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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