E2F6在物理性低氧及化学性低氧诱导的凋亡中的表达特征(英文)  

Expression pattern of E2F6 in physical and chemical hypoxia-induced apoptosis

作　　者：束波[1] 杨巍维[2] 杨黄恬[2] 

机构地区：[1]上海交通大学医学院/中国科学院上海生命科学研究院 健康科学研究所分子心脏学课题组,上海200025 [2]中国科学院上海生命科学研究院/上海交通大学医学院 健康科学研究所分子心脏学课题组,上海200025

出　　处：《生理学报》2008年第1期1-10,共10页Acta Physiologica Sinica

基　　金：supported by the National Basic Research Program of China (No. 2006CB504100);Major and General Programs of theNational Natural Science Foundation of China (No. 30393133, 30370536);Knowledge Innovation Program of the Chinese Academy ofSciences (No. KSCX2-YW-R-75)

摘　　要：心肌细胞凋亡性死亡是低氧发生时的重要病理学特征,但低氧诱导的心肌细胞凋亡的调控机制尚未完全阐明。E2F6是E2F转录因子家族成员之一, 我们新近的研究证实其具有抑制DNA损伤诱导的细胞凋亡作用。但是,E2F6 是否参与了低氧诱导的心肌细胞凋亡的调控尚不清楚。在本研究中,我们初步探讨了E2F6 在物理性低氧及化学性低氧模拟物诱导大鼠心肌细胞系H9c2 细胞凋亡中的表达特征。结果表明:物理性低氧、化学性低氧模拟物去铁胺(desferrioxamine, DFO)和氯化钴(cobaltchloride, CoCl2)均能有效诱导 H9c2 细胞发生凋亡。在物理性低氧及 CoCl2 诱导的 H9c2 细胞凋亡中,内源性 E2F6 mRNA 表达明显下调,但蛋白表达没有明显变化。而在DFO 诱导的凋亡中,内源性E2F6 mRNA及蛋白表达均发生明显下调。这些结果提示,E2F6 可能参与调控DFO 模拟低氧诱导的H9c2 细胞凋亡,而对物理性低氧及CoCl2 模拟低氧诱导的细胞凋亡敏感性较低。此外,DFO 模拟低氧诱导的细胞凋亡机制可能与物理性低氧及 CoCl2 模拟低氧诱导的细胞凋亡机制不同。Apoptosis can be caused by hypoxia, a major factor during ischemic injury, in cardiomyocytes. However, the regulatory mechanisms underlying hypoxia-induced cardiomyocyte apoptosis have not yet been fully understood. E2F6, an identified E2F family member, has been demonstrated to repress DNA damage-induced apoptosis in our recent study. However, it is unclear whether E2F6 is involved in hypoxia-induced apoptosis. In this study, we determined the expression property of E2F6 during hypoxia-induced apoptosis in H9c2 cells, a rat ventricular myoblast cell line. The results showed that physical hypoxia and chemical hypoxia-mimetic agents desferrioxamine （DFO） and cobalt chloride （CoCl2） induced apoptosis in H9c2 cells. Physical hypoxia- and CoCl2-induced apoptosis was accompanied with a downregulation of endogenous E2F6 mRNA expression, but not protein expression. DFO treatment resulted in a significant downregulation of both mRNA and protein expressions of endogenous E2F6. These results suggest that E2F6 may be involved in DFO-induced apoptosis, while it is less sensitive in physical hypoxia- and CoCl2-induced apoptosis in H9c2 cells. In addition, the apoptosis induced by DFO may share different pathways from that induced by physical hypoxia and CoCl2.

关 键 词：E2F6 凋亡 物理性低氧 氯化钴 去铁胺 H9C2细胞 

分 类 号：Q255[生物学—细胞生物学]