Phytoestrogen α-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  μ mol/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.

• Authors: Teng Liu, Dan-Dan Hou, Qian Zhao, Wei Liu, Pan-Pan Zhen, Jian-Ping Xu, Ke Wang, Hai-Xia Huang, Xiao Li, Hui Zhang, Hai-Bo Xu, Wen Wang
• Journal: BioMed research international (Biomed Res Int) Vol. 2013 Pg. 813450 ( 2013) ISSN: 2314-6141 [Electronic] United States
• PMID: 24195080 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAX protein, human
• Estrogens, Non-Steroidal
• bcl-2-Associated X Protein
• Homocysteine
• Zeranol
• CASP9 protein, human
• Caspase 9

Topics

• Animals
• Apoptosis (drug effects)
• Atherosclerosis (drug therapy, metabolism, pathology)
• Caspase 9 (metabolism)
• Down-Regulation (drug effects)
• Estrogens, Non-Steroidal (pharmacology)
• Female
• Homocysteine (metabolism, pharmacology)
• Human Umbilical Vein Endothelial Cells (metabolism, pathology)
• Humans
• Hyperhomocysteinemia (drug therapy, metabolism, pathology)
• Rats
• Zeranol (pharmacology)
• bcl-2-Associated X Protein (biosynthesis)