title: 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.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, You An Men Wai, Fengtai District, Beijing 100069, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Liu
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Hou
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Zhen
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Xu
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Huang
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Xu
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053453:Caspase 9 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D006710:Homocysteine / Q000378:metabolism* / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015029:Zeranol / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C494826:BAX protein, human; D004968:Estrogens, Non-Steroidal; D051028:bcl-2-Associated X Protein; D006710:Homocysteine; D015029:Zeranol; C506433:CASP9 protein, human; D053453:Caspase 9