The Subcellular Localization of cyclin A Regulates Apoptosis in Cardiomyocytes
细胞周期蛋白 A 的亚细胞定位调节心肌细胞凋亡
基本信息
- 批准号:15590727
- 负责人:
- 金额:$ 1.79万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2003
- 资助国家:日本
- 起止时间:2003 至 2004
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Doxorubicin (Dox) is an anticancer agent which has the side effect of cardiac toxicity. However, the precise molecular mechanism of doxorubicin-induced myocardial apoptosis is still unknown. We have previously reported that cyclin A/cdk2 kinase activity, which is one of the cell cycle regulators, is mediated hypoxia-induced apoptosis in cardiomyocytes. Because apoptosis typically begins in the cytoplasm in the proliferating cells, we tested the hypothesis that the subcellular localization of cyclin A determines the apoptotic fate. Primary rat cardiomyocytes were exposed to doxorubicin and increased apoptosis dose-dependently (10-5 to 10-7M) evaluated by TUNEL method and the number of viable cells. The cyclin A protein level assessed by immunoblot analysis accumulated with a maximum response after 6 hours treatment in cardiomyocytes. Also, doxorubicin increased in the activity of cyclin A-and cdk2-associated kinase by histone-H1 kinase assay. By immnohistochemistry, cyclin A was cytoplasm in cardiomyocytes, however, cyclin A was nuclear in proliferating condition of fibroblasts. To test whether the cyclin A-associated kinase was the effector for apoptosis, cardiomyocytes were infected by dominant-negative cdk2 adenovirus (dncdk2). The apoptosis by doxorubicin(10-6M) was significantly reduced (cont. 4.8± 1.8%, Dox. 46.2±4.0%, Dox+dncdk2 25.8±6.0%), suggesting that cyclin A/cdk2 kinase activity play significant roles in the doxorubicin induced apoptosis. In conclusion, these findings confirm that the activation of cyclin A in cytoplasm mediates doxorubicin-induced apoptosis in cardiomyocytes.
阿霉素(DOX)是一种抗癌剂,具有心脏毒性的副作用。然而,阿霉素诱导的心肌凋亡的精确分子机制仍然未知。我们以前已经报道了细胞周期调节剂之一的细胞周期蛋白A/CDK2激酶活性是介导的缺氧诱导的心肌细胞凋亡。由于凋亡通常在增殖细胞的细胞质中开始,因此我们测试了细胞周期蛋白A的亚细胞定位确定凋亡命运的假设。将原发性大鼠心肌细胞暴露于阿霉素中,并通过TUNEL方法和可行细胞的数量评估凋亡剂量依赖性剂量依赖性剂量(10-5至10-7M)。通过免疫印迹分析评估的细胞周期蛋白A蛋白水平在心肌细胞中6小时治疗后积累了最大反应。同样,阿霉素通过组蛋白-H1激酶测定法中细胞周期蛋白A和CDK2相关激酶的活性增加。通过IMMNO组织化学,Cyclin a在心肌细胞中是细胞质,但是,在成纤维细胞增殖状态下,细胞周期蛋白A是核的。为了测试细胞周期蛋白A相关激酶是否是凋亡的效应子,心肌细胞被显性阴性CDK2腺病毒感染(DNCDK2)。阿霉素(10-6M)的凋亡显着降低(续4.8±1.8%,dox。46.2±4.0%,dox+dncdk2 25.8±6.0%),表明环氧蛋白A/CDK2激酶活性在doxorubiubicin staus opopopopopopopopopopsiss中起着显着的疾病。总之,这些发现证实了细胞质中细胞周期蛋白A的激活介导阿霉素诱导的心肌细胞中的凋亡。
项目成果
期刊论文数量(16)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nitric oxide inhibits myocardial apoptosis by preventing caspase-3 activity via S-nitrosylation
- DOI:10.1016/j.yjmcc.2004.10.012
- 发表时间:2005-01-01
- 期刊:
- 影响因子:5
- 作者:Maejima, Y;Adachi, S;Isobe, M
- 通讯作者:Isobe, M
Critical role of cyclin Dl nuclear import in cardiomyocyte proliferation
细胞周期蛋白 D1 入核在心肌细胞增殖中的关键作用
- DOI:
- 发表时间:2003
- 期刊:
- 影响因子:0
- 作者:Maejima Y;Tamamori-Adachi M;Maejima Y;Adachi S;Tamamori-Adachi M
- 通讯作者:Tamamori-Adachi M
Nitric oxide inhibits ischemia/reperfusion-induced myocardial apoptosis by modulating cyclin A-associated kinase activity
- DOI:10.1016/s0008-6363(03)00425-5
- 发表时间:2003-08-01
- 期刊:
- 影响因子:10.8
- 作者:Maejima, Y;Adachi, S;Isobe, M
- 通讯作者:Isobe, M
Critical role of cyclin D1 nuclear import in cardiomyocyte proliferation
- DOI:10.1161/01.res.0000049105.15329.1c
- 发表时间:2003-01-10
- 期刊:
- 影响因子:20.1
- 作者:Tamamori-Adachi, M;Ito, H;Ikeda, MA
- 通讯作者:Ikeda, MA
Tamamori-Adaclli M: "Critical role of cyclin D1 nuclear import in cardiomyocyte proliferation"Circulation Research. 92. e12-e19 (2003)
Tamamori-Adaclli M:“细胞周期蛋白 D1 核输入在心肌细胞增殖中的关键作用”循环研究。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
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{{ truncateString('ADACHI Susumu', 18)}}的其他基金
The mechanism of senescence in cardiomyocytes and application of a therapeutic approach for heart failure
心肌细胞衰老机制及其在心力衰竭治疗中的应用
- 批准号:
17590711 - 财政年份:2005
- 资助金额:
$ 1.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Studies on the structure of capsular polysaccharide produced fron dairy Lactic acid bacteria.
乳品乳酸菌荚膜多糖结构的研究。
- 批准号:
61470141 - 财政年份:1986
- 资助金额:
$ 1.79万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Development of a new biotechnological manufacturing process of bifidogenic substances in milk
牛奶中双歧物质的新生物技术制造工艺的开发
- 批准号:
61860030 - 财政年份:1986
- 资助金额:
$ 1.79万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research
On formation and chemical structure of functional oligasaccharide from lactose
乳糖功能性低聚糖的形成及其化学结构
- 批准号:
59430022 - 财政年份:1984
- 资助金额:
$ 1.79万 - 项目类别:
Grant-in-Aid for General Scientific Research (A)
Preparative method of functional oligasaccharides from bovine colostrum
牛初乳功能性低聚糖的制备方法
- 批准号:
59860031 - 财政年份:1984
- 资助金额:
$ 1.79万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research
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