E2F6在物理性低氧及化学性低氧诱导的凋亡中的表达特征

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)和氯化钻(cobalt chloride,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.

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

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.HoweveL 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.