生理学报
生理學報
생이학보
ACTA PHYSIOLOGICA SINICA
2008年
1期
1-10
,共10页
E2F6%凋亡%物理性低氧%氯化钴%去铁胺%H9C2细胞
E2F6%凋亡%物理性低氧%氯化鈷%去鐵胺%H9C2細胞
E2F6%조망%물이성저양%록화고%거철알%H9C2세포
E2F6%apoptosis%physical hypoxia%cobalt chloride%desferrioxamine%H9c2 cells
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.
心肌細胞凋亡性死亡是低氧髮生時的重要病理學特徵,但低氧誘導的心肌細胞凋亡的調控機製尚未完全闡明.E2F6是E2F轉錄因子傢族成員之一,我們新近的研究證實其具有抑製DNA損傷誘導的細胞凋亡作用.但是,E2F6是否參與瞭低氧誘導的心肌細胞凋亡的調控尚不清楚.在本研究中,我們初步探討瞭E2F6在物理性低氧及化學性低氧模擬物誘導大鼠心肌細胞繫H9c2細胞凋亡中的錶達特徵.結果錶明:物理性低氧、化學性低氧模擬物去鐵胺(desferrioxamine,DFO)和氯化鑽(cobalt chloride,CoCl2)均能有效誘導H9c2細胞髮生凋亡.在物理性低氧及CoCl2,誘導的H9c2細胞凋亡中,內源性E2F6 mRNA錶達明顯下調,但蛋白錶達沒有明顯變化.而在DFO誘導的凋亡中,內源性E2F6 mRNA及蛋白錶達均髮生明顯下調.這些結果提示,E2F6可能參與調控DFO模擬低氧誘導的H9c2細胞凋亡,而對物理性低氧及CoCl2,模擬低氧誘導的細胞凋亡敏感性較低.此外,DFO模擬低氧誘導的細胞凋亡機製可能與物理性低氧及CoCl2.模擬低氧誘導的細胞凋亡機製不同.
심기세포조망성사망시저양발생시적중요병이학특정,단저양유도적심기세포조망적조공궤제상미완전천명.E2F6시E2F전록인자가족성원지일,아문신근적연구증실기구유억제DNA손상유도적세포조망작용.단시,E2F6시부삼여료저양유도적심기세포조망적조공상불청초.재본연구중,아문초보탐토료E2F6재물이성저양급화학성저양모의물유도대서심기세포계H9c2세포조망중적표체특정.결과표명:물이성저양、화학성저양모의물거철알(desferrioxamine,DFO)화록화찬(cobalt chloride,CoCl2)균능유효유도H9c2세포발생조망.재물이성저양급CoCl2,유도적H9c2세포조망중,내원성E2F6 mRNA표체명현하조,단단백표체몰유명현변화.이재DFO유도적조망중,내원성E2F6 mRNA급단백표체균발생명현하조.저사결과제시,E2F6가능삼여조공DFO모의저양유도적H9c2세포조망,이대물이성저양급CoCl2,모의저양유도적세포조망민감성교저.차외,DFO모의저양유도적세포조망궤제가능여물이성저양급CoCl2.모의저양유도적세포조망궤제불동.
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.
