Myocardial preservation specific for cardiomyocytes

心肌细胞特异性心肌保存

• 批准号: 16591420
• 负责人: OTANI Hajime
• 金额: $ 2.24万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591420/
• 关键词: Dystrophin; Heart; Ischemia; Reperfusion; Ischemic preconditioning; Mitochondria

Objective : Dystrophin is a membrane protein that protects the sarcolemma from oncosis induced by physical stress. Because ischemic preconditioning (IPC) protects mitochondria and prevents oncosis during reperfusion, we hypothesized that dystrophin is a target of IPC distal to mitochondrial protection. Methods and Results : The isolated rat hearts were subjected to 30 minutes ischemia followed by reperfusion. IPC was introduced by 3 cycles of 5 minutes ischemia and 5 minutes reperfusion. The loss of sarcolemmal dystrophin and myocardial ATP during ischemia was similar in the control and the IPC heart. Similar loss of sarcolemmal dystrophin and myocardial ATP was observed when the heart was treated with 2,4-dinitrophenol (DNP), an uncoupler of mitochondrial respiration, or oligomycin, an inhibitor of mitochondrial F_1F_0-ATPase. However, the IPC heart increased sarcolemmal dystrophin during reperfusion associated with an increase in tetramethylrhodamine ethylester (TMRE) uptake, an indicator of mitochondrial membrane potential (Δψm), and myocardial ATP and inhibition of myocyte oncosis. The increase in relocalization of sarcolemmal dystrophin and myocardial ATP mediated by IPC was inhibited by treatment with DNP or oligomycin during reperfusion. Moreover, the ischemic IPC heart mitochondria increased relocalization of dystrophin from the insoluble to the soluble fractions associated with increased ATP generation in vitro in a DNP and oligomycin-sensitive manner. Conclusions : These results suggest that enhanced relocalization of dystrophin to the sarcolemma during reperfusion may be a mechanistic link between IPC-mediated improvement of mitochondrial function and its protection against oncosis upon reperfusion.

目的：肌营养不良蛋白（Dystrophin，Dystrophin）是一种保护肌膜免受物理应激引起的细胞胀亡的膜蛋白。由于缺血预处理（IPC）在再灌注期间保护线粒体并防止胀亡，我们假设肌营养不良蛋白是IPC的线粒体保护远端的靶点。方法和结果：采用离体大鼠心脏缺血30分钟再灌注模型。通过3个循环的5 min缺血和5 min再灌注引入IPC。心肌肌膜抗肌萎缩蛋白和心肌ATP在缺血期间的损失在对照组和IPC心脏中是相似的。用线粒体呼吸解偶联剂2，4-二硝基苯酚（DNP）或线粒体F_1F_0-ATP酶抑制剂寡霉素处理心肌，也观察到类似的肌膜抗肌萎缩蛋白和心肌ATP的丢失。然而，IPC心脏在再灌注期间增加了肌膜肌营养不良蛋白，与四甲基罗丹明乙酯（TMRE）摄取增加（线粒体膜电位（Δ Km）的指标）和心肌ATP和抑制肌细胞胀亡有关。DNP或寡霉素可抑制IPC介导的肌膜抗肌萎缩蛋白和心肌ATP的再定位。此外，缺血性IPC心脏线粒体增加肌营养不良蛋白从不溶性到可溶性部分的再定位，与体外增加的ATP生成相关，以DNP和寡霉素敏感的方式。结论：这些结果表明，增强再灌注过程中肌营养不良蛋白的肌膜重新定位可能是IPC介导的线粒体功能的改善和再灌注后对胀亡的保护之间的机制联系。

项目成果

Temporary blockade of contractility during reperfusion elicits a cardioprotective effect of the p38 MAP kinase inhibitor SB-203580

• DOI: 10.1152/ajpheart.01183.2004
• 发表时间: 2005-06-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
• 影响因子: 4.8
• 作者: Sumida, T;Otani, H;Imamura, H
• 通讯作者: Imamura, H

Integrated pharmacological preconditioning and Memory of cardioprotection : the role of protein kinase C and phosphatidylinositol 3-kinase.

综合药理学预处理和心脏保护记忆：蛋白激酶 C 和磷脂酰肌醇 3-激酶的作用。

• 发表时间: 2005
• 期刊: American Journal of Physiology 289
• 作者: Okada T;Otani H;Wu Y;Uchiyama T;Kyoi S;Hattori R;Sumide T;Fujiwara H;Imamura H.
• 通讯作者: Imamura H.

Ischemic preconditioning-mediated restoration of membrane dystrophin during reperfusion correlates with protection against contraction-induced myocardial injury

• DOI: 10.1152/ajpheart.01140.2003
• 发表时间: 2004-07-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
• 影响因子: 4.8
• 作者: Kido, M;Otani, H;Imamura, H
• 通讯作者: Imamura, H