Genistein suppressed upregulation of vascular endothelial growth factor expression by cobalt chloride and hypoxia in rabbit retinal pigment epithelium cells.
The time course changes of vascular endothelial growth factor (VEGF) protein expression induced by cobalt chloride (CoCl(2)) and hypoxia and the effects of genistein on CoCl(2)- and hypoxia-induced VEGF expression in rabbit retinal pigment epithelium (RPE) cells were studied. Judged by relative fluorescence using a confocal scanning laser microscope coupled to a computer, VEGF protein expression exposed for different periods to CoCl(2) or hypoxia was investigated. CoCl(2) was found to significantly elevate VEGF protein expression. At 4 h after CoCl(2) treatment, the expression of VEGF protein was about three times as much as that at the start of treatment. Genistein (50, 100 and 200 microM) inhibited VEGF protein expression elicited by CoCl(2) in a concentration-dependent manner. Hypoxia (5% CO(2)/95% N(2)) could markedly increase VEGF protein expression. The elevation of VEGF protein expression was gradual and time-dependently. At 6 h, the highest expression of VEGF protein was observed, it was about three times as much as that at the start of treatment. After preincubation with 50, 100, and 200 microM genistein respectively, the hypoxia-evoked VEGF expression was concentration-dependently suppressed. These results indicated that genistein could be an effective agent in the prevention and treatment of intraretinal and subretinal neovascularization.
Department of Pharmacology, Nanjing Medical University, Nanjing, People's Republic of China.
Bin
B
Wang
Ying
Y
Zou
Zhi-Lan
ZL
Yuan
Ji-Gao
JG
Xiao
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D019833:Genistein; C018021:cobaltous chloride