Natarajan Ramesh, Fisher Bernard J, Fowler Alpha A
Department of Internal Medicine, Virginia Commonwealth University, PO Box 980050, Richmond, VA 23298, USA.
FEBS Lett. 2003 Aug 14;549(1-3):99-104. doi: 10.1016/s0014-5793(03)00798-1.
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.
缺氧可激活转录因子——缺氧诱导因子-1（HIF-1）。除缺氧外，HIF-1在常氧条件下可被一氧化氮激活。微血管内皮细胞中，一氧化氮和缺氧介导的HIF-1α稳定、HIF-1与DNA结合及反式激活所涉及的信号转导通路尚不清楚。我们报告，蛋白质磷酸化参与缺氧和一氧化氮作用下的HIF-1激活过程。磷脂酰肌醇3激酶（PI-3K）/Akt通路对缺氧和一氧化氮激活HIF-1具有不同作用。我们的数据表明，PI-3K/Akt通路不足以介导缺氧诱导HIF-1α。PTEN的脂质和蛋白质磷酸酶活性似乎也参与一氧化氮对HIF-1α的调控。
