Genistein inhibited hypoxia-inducible factor-1alpha expression induced by hypoxia and cobalt chloride in human retinal pigment epithelium cells.
The time-dependent changes of hypoxia-inducible factor-1alpha (HIF-1alpha) expression induced by hypoxia and CoCl2 treatment and the effects of genistein on the level of HIF-1alpha expression in human retinal pigment epithelium cells were examined. Judging by relative fluorescence using a confocal scanning laser microscope coupled to a computer, HIF-1alpha expression was determined. It was found that hypoxia could markedly increase the expression of HIF-1alpha. The highest expression of HIF-1alpha was detected at 1 h, which was 313.9% +/- 38.2% of the control level. After pretreatment with genistein (50, 100, and 200 micromol/l), the hypoxia-evoked HIF-1alpha expression was concentration-dependently inhibited. CoCl2 treatment could significantly elevate the level of HIF-1alpha expression. At 0.5 h after CoCl2 treatment, the highest level was observed, which was 141.4% +/- 14.1% of the control level. Genistein 50, 100, 200 micromol/L could also suppress HIF-1alpha expression in a concentration-dependent manner. These results suggested that the inhibition of HIF-1alpha protein expression by genistein may partly account for its effect on retinal neovascularization in vivo.
Wang
B
B
Department of Pharmacology, Nanjing Medical University, Nanjing, China. binwang@njmu.edu.cn
Li
H
H
Yan
H
H
Xiao
J-G
JG
D015687:Cell Hypoxia; D002460:Cell Line; D003035:Cobalt / Q000633:toxicity*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018613:Microscopy, Confocal; D010857:Pigment Epithelium of Eye / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D003470:Culture Media; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D003035:Cobalt; D019833:Genistein; C018021:cobaltous chloride