Isoflavone genistein protected high glucose-induced human aortic endothelial cell apoptosis through estrogen receptor-mediated pathway

Objective The aim of this study was to determine if isoflavone genistien had protective effects against high glucose-induced cell apoptosis in human aortic endlthelial cells, and investigate the possible mechanism for this protection. Methods Human aortic endothelial cells subjected to normal (5mM) or high glucose (25mM) were treated with genistein at 0, 50, 100nM. Parallel experiments were performed with 100nM 17b-estradiol, and also in the presence and absence of the pure anti-estrogen ICI-182,780 (100nM). The effects on cell apoptotic DNA fragmentation were determined using cell death ELISA, and the effects on cellular proliferation were determined using tritiated thymidine incorporation assay. Estrogen receptor expression was detected by Taqman quantitative PCR. Results 100nM Genistein significantly reduced high glucose-induced DNA fragmentation, and reversed cell DNA synthesis inhibition (P <0.001) after 24 hours’ incubation. The effect of genistein was completely blocked by ICI-182,780 administration. Estrogen receptor beta, but not alpha was found to be expressed in these cells. Conclusion Isoflavone genistein gave protection against high glucoseinduced cell damage through estrogen receptor beta, reducing apoptotic DNA damage and protecting from the inhibition of cell proliferation.(J Geriatr Cardiol 2008; 5: )