Phytoestrogenα-Zearalanol Attenuates Homocysteine-Induced Apoptosis in Human Umbilical Vein Endothelial Cells

Abstract

Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. The enhanced nitrative stress plays an important role in homocysteine-induced endothelial dysfunction. Previous studies have showed that phytoestrogen α-zearalanol alleviated endothelial injury in ovariectomized hyperhomocysteinemic rats; however, the underlying mechanism remains to be clarified. This study was to investigate the effects of α-zearalanol on homocysteine-induced endothelial apoptosis in vitro and explore the possible role of nitrative stress in these effects. Results showed that homocysteine (500 μmol/L, 24 h) induced the apoptosis of human umbilical vein endothelial cells (HUVECs) obviously, and this effect was significantly attenuated by pretreatment with α-zearalanol (10−8~10−6 mol/L). Moreover, α-zearalanol downregulated proapoptotic protein Bax, upregulated antiapoptotic proteins Bcl-2 and Bcl-XL, and decreased the expression and activity of caspase-9. These findings demonstrated that α-zearalanol could effectively alleviate homocysteine-induced endothelial apoptosis, and this antiapoptosis effect might be related to the inhibition of the intrinsic pathway. Western blot indicated an enhanced 3-nitrotyrosine expression in HUVECs when challenged with homocysteine, which was attenuated by pretreatment with α-zearalanol. This result implied that inhibition of nitrative stress might play a role in the protective effect of α-zearalanol on endothelial cells. Such discovery may shed a novel light on the antiatherogenic activities of α-zearalanol in hyperhomocysteinemia.

Sitagliptin Attenuates Endothelial Dysfunction of Zucker Diabetic Fatty Rats: Implication of the Antiperoxynitrite and Autophagy

“…The formation of 3-NT was usually used for monitoring the generation of ONOO − in vivo. 19 Both immunohistochemistry and Western blot results indicated that the enhanced 3-NT expression in ZDF rats could be attenuated by sitagliptin treatment (Figure 3E, F). All these results implied that inhibition of nitro-oxidative stress might play a role in the protective effect of sitagliptin.…”

MiR-30b Is Involved in the Homocysteine-Induced Apoptosis in Human Coronary Artery Endothelial Cells by Regulating the Expression of Caspase 3

“…So, the expression of caspase-3 was used to evaluate Hcy-induced apoptosis in HCAECs in this study. Previous studies have found that 500 µmol/L–1 mmol/L Hcy can significantly increase the apoptosis in HUVECs [ 7 , 8 ]. In our study, the expression of caspase-3 mRNA was significantly upregulated by 1 mmol/L Hcy, and the results were consistent with the previous date.…”

“…There is a close relationship between dysfunction of endothelial cells and cardiovascular diseases [ 5 ]. Hcy can induce apoptosis in endothelial cells [ 6 , 7 , 8 ], and the apoptosis induced by Hcy in endothelial cells is regarded as the one of the mechanisms leading to these cardiovascular diseases. Previous studies have found that Hcy induces endothelial cells apoptosis mainly through the death receptor pathway, the mitochondrial apoptotic pathway and the endoplasmic reticulum stress pathway, but the exact mechanism for how Hcy induces apoptosis in endothelial cells is not fully understood.…”

Turkish propolis supresses MCF-7 cell death induced by homocysteine

“…There are limited researches explaining the effects of Hcy on cancer cells [11] though numerous in vivo and in vitro studies have been performed to suggest its deleterious effects on normal cells [8,12,13]. It has been shown that Hcy accumulates in tumour sites because of dysfunction of methionine metabolism in cancer cells [14].…”