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：抗肌营养不良蛋白是一种膜蛋白，可保护肌膜免受物理应激引起的肿瘤坏死，因为缺血预处理 (IPC) 可保护线粒体并防止再灌注过程中的肿瘤肿瘤，我们发现抗肌营养不良蛋白是线粒体保护远端 IPC 的靶标。将离体的大鼠心脏缺血30分钟，然后通过5分钟缺血和5分钟的3个周期进行IPC再灌注。再灌注期间，对照组和 IPC 心脏中肌膜肌营养不良蛋白和心肌 ATP 的损失相似，当用 2,4-二硝基苯酚 (DNP)（一种解偶联剂）处理心脏时，观察到类似的肌膜肌营养不良蛋白和心肌 ATP 损失。线粒体呼吸，或寡霉素，一种线粒体F_1F_0-ATP酶抑制剂，但IPC心脏增加。再灌注期间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 (Δψm) 和心肌 ATP 增加以及心肌细胞癌变的抑制相关。IPC 介导的肌膜肌营养不良蛋白和心肌 ATP 重新定位的增加受到抑制。再灌注期间用 DNP 或寡霉素治疗此外，缺血的 IPC 心脏线粒体。肌营养不良蛋白从不溶性部分到可溶性部分的重新定位增加，与体外以 DNP 和寡霉素敏感方式增加 ATP 生成相关。 结论：这些结果表明，再灌注期间肌营养不良蛋白向肌膜的重新定位增强可能是 IPC-介导线粒体功能的改善及其对再灌注时肿瘤坏死的保护。

项目成果

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

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.