Neural cells undergo glutamate-induced apoptosis in ischaemic brain tissue,in which prostate apoptosis response-4 gene (Par-4)is involved.Human-bone mesenehymal stem cells can be utilized as an effective therapy for i...Neural cells undergo glutamate-induced apoptosis in ischaemic brain tissue,in which prostate apoptosis response-4 gene (Par-4)is involved.Human-bone mesenehymal stem cells can be utilized as an effective therapy for ischemic brain injury.In this study,we found that glutamate could induce apoptosis in human-bone mesenehymal stem cells,accompanied by increased expression of Par-4 gene and Smac release from mitochondria.Repressing Par-4 expression attenuated the glutamate-induced apoptosis.Both Par-4 protein and E2F1 protein could bind to E2F1-binding BS3 site on Smac promoter and participated in the formation of a pro- teins-DNA complex.Moreover,in the eomplex,E2F1,not Par-4,was found to be directly bound to the Smac promoter,suggesting that Par-4 exerted indireetly its transcriptional control on the Smac gene though interacting with E2F1.Expression of full-length Par-4 in human-bone mesenchymal cells resulted in increased activity of the Smac promoter.In addition,the indirect transcripional regula- tion of Par-4 on Smac depended on its COOH terminus-mediated interaction between Par-4 and E2F1.We conclude that the forma- tion of proteins-DNA complex,containing Par-4 protein,E2F1 protein and the Smac promoter,contributes to the pro-apoptotic effect on glutamate-treated human-bone mesenchymal stem cells.展开更多
文摘Neural cells undergo glutamate-induced apoptosis in ischaemic brain tissue,in which prostate apoptosis response-4 gene (Par-4)is involved.Human-bone mesenehymal stem cells can be utilized as an effective therapy for ischemic brain injury.In this study,we found that glutamate could induce apoptosis in human-bone mesenehymal stem cells,accompanied by increased expression of Par-4 gene and Smac release from mitochondria.Repressing Par-4 expression attenuated the glutamate-induced apoptosis.Both Par-4 protein and E2F1 protein could bind to E2F1-binding BS3 site on Smac promoter and participated in the formation of a pro- teins-DNA complex.Moreover,in the eomplex,E2F1,not Par-4,was found to be directly bound to the Smac promoter,suggesting that Par-4 exerted indireetly its transcriptional control on the Smac gene though interacting with E2F1.Expression of full-length Par-4 in human-bone mesenchymal cells resulted in increased activity of the Smac promoter.In addition,the indirect transcripional regula- tion of Par-4 on Smac depended on its COOH terminus-mediated interaction between Par-4 and E2F1.We conclude that the forma- tion of proteins-DNA complex,containing Par-4 protein,E2F1 protein and the Smac promoter,contributes to the pro-apoptotic effect on glutamate-treated human-bone mesenchymal stem cells.
