Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF-1α protein
作者:, Yoshihiko Funae
摘要:Abstract Apigenin, a plant-derived flavone, is a potent inhibitor of cell proliferation and angiogenesis, but the mechanisms leading to the pathological anti-angiogenic effects of apigenin are still unclear. In this study, we found that apigenin inhibited the hypoxia-induced expression of vascular endothelial growth factor (VEGF) mRNA in human umbilical artery endothelial cells. Apigenin also suppressed the expression of erythropoietin mRNA, which is a typical hypoxia-inducible gene, via the degradation of hypoxia-inducible factor 1 (HIF-1) α. We investigated the effect of apigenin on the interaction of HIF-1α with heat shock protein 90 (Hsp90), which is reported to be important for the stabilization of HIF-1α, and found that VEGF expression was inhibited via degradation of HIF-1α through interference with the function of Hsp90.
关键词:Apigenin; Angiogenesis; Vascular endothelial growth factor; Hypoxia; Hypoxia-inducible factor; Heat shock protein 90; VEGF, vascular endothelial growth factor; HIF-1, hypoxia-inducible factor 1; EPO, erythropoietin; pVHL, von Hippel–Lindau protein; Hsp90, heat shock protein 90; HRE, hypoxia response element; ARNT, aryl hydrocarbon receptor nuclear translocator; ODD, oxygen-dependent degradation; NPR, NADPH-P450 reductase; HUA-EC, human umbilical artery endothelial cells; RT-PCR, reverse-transcription PCR; SDS–PAGE, SDS–polyacrylamide gel electrophoresis; PAS, Per-ARNT-Sim; bHLH, basic helix loop helix
论文方向:[{"id":13,"name":"细胞生物学"},{"id":879,"name":"生物化学"}]
发表期刊:FEBS Letters Volume 575, Issues 1–3
发表时间:Fri Sep 24 00:00:00 CST 2004
数字识别码:10.1016/j.febslet.2004.08.036
是否作者本人: 否
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