Depletion of [Ca2+]i inhibits hypoxia-induced vascular permeability factor (vascular endothelial growth factor) gene expression.
We have investigated the role of ion channels and intracellular Ca2+ in the regulation of hypoxia-mediated VPF/VEGF activation. Known channel activator and blockers like lemakalim, glibenclamide, tetraethylammonium, 4-aminopyridine and nifedipine do not inhibit VPF/VEGF induction due to hypoxia. Whereas, 5 mM caffeine pretreatment of the 293 cells exhibits a complete inhibition of hypoxia inducted VPF/VEGF expression. Moreover, the cells treated with BAPTA-AM prior to hypoxia also show a dramatic decrease in the VPF/VEGF message level, which suggests an important role of intracellular Ca2+ in this signaling pathway. Caffeine pretreatment also inhibits hypoxia-mediated c-Src kinase activity. These findings demonstrate the importance of intracellular Ca2+ in the event of hypoxia-induced VPF/VEGF expression.
Mukhopadhyay
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Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA. dmukhopa@bih.harvard.edu
Akbarali
H I
HI
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D015687:Cell Hypoxia; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D006801:Humans; D017136:Ion Transport; D008222:Lymphokines / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015220:Calcium Channels; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D002118:Calcium