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E2F6在物理性低氧及化学性低氧诱导的凋亡中的表达特征

束波, 杨巍维, 杨黄恬

上海交通大学医学院/中科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；中科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

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。{sl E2F6}是{sl E2F}转录因子家族成员之一,作者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。在该研究中,作者初步探讨了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, CoCl_(2))均能有效诱导H9c2细胞发生凋亡。在物理性低氧及CoCl_(2)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CoCl_(2)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CoCl_(2)模拟低氧诱导的细胞凋亡机制不同。

关键词： E2F6; 凋亡; 物理性低氧; 氯化钴; 去铁胺; H9c2细胞

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

Shu Bo, Yang Weiwei, Yang Huangtian

Laboratory of Molecular Cardiology of Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine （SJTUSM） and Shanghai Institutes for Biological Sciences （SIBS）, Chinese Academy of Sciences （CAS）.Shanghai 200025；China

Abstract

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 （CoCl_(2)） induced apoptosis in H9c2 cells. Physical hypoxia- and CoCl_(2)-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 CoCl_(2)-induced apoptosis in H9c2 cells. In addition, the apoptosis induced by DFO may share different pathways from that induced by physical hypoxia and CoCl_(2).

Key words: E2F6;Apoptosis;physical hypoxia;cobalt chloride;desferrioxamine;H9c2 cells

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引用本文：

束波, 杨巍维, 杨黄恬. E2F6在物理性低氧及化学性低氧诱导的凋亡中的表达特征[J]. 生理学报 2008; 60 (1): 1-10.

Shu Bo, Yang Weiwei, Yang Huangtian. Expression pattern of E2F6 in physical and chemical hypoxia--induced apoptosis. Acta Physiol Sin 2008; 60 (1): 1-10 (in Chinese with English abstract).