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Regulation of hypoxia inducible factor‐1 by nitric oxide in contrast to hypoxia in microvascular endothelium
Author(s) -
Natarajan Ramesh,
Fisher Bernard J,
Fowler Alpha A
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00798-1
Subject(s) - hypoxia (environmental) , protein kinase b , transactivation , nitric oxide , microbiology and biotechnology , signal transduction , phosphorylation , phosphatidylinositol , chemistry , hypoxia inducible factors , nitric oxide synthase , transcription factor , kinase , biology , biochemistry , endocrinology , oxygen , organic chemistry , gene
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‐1α 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‐1α induction by hypoxia. The lipid and protein phosphatase activities of PTEN also appear to be involved in regulation of HIF‐1α by NO.