Role of Calcium Signaling Pathway for Cardiac Cell Injury

钙信号通路在心肌细胞损伤中的作用

• 批准号: 05304033
• 负责人: TADA Michihiko
• 金额: $ 2.56万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Co-operative Research (A)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05304033/
• 关键词: Adhesion molecule; Calcium signaling; Myocardial injury; Reperfusion; Heart failure; Low molecuar weight G-protein; Intercalated disc; Gap junction; 病態生理学; ホスホランバン; カルシウムポンプ; アラキドン酸; カルシウム遊離チャネル

In cardiac muscle, calcium plays a key role in excitation-contraction coupling. In this study, we investigated contribution of the proteins mediating excitation-contraction coupling for myocardial injury.We identified the interaction sites in phospholamban and the Ca ATPase molecule by using molecular biological methods. We investigated gene regulation of phospholamban and the Ca ATPase, indicating thyroid hormone is a key foactor for the regulation of those gene expression. Regulator binding domain was identified in the Ca release channel of the cardiac sarcoplasmic reticulum. Electrophysiological study on gap junction showed that the activity of gap junction is regulated by calmodulin. We purified and determined the primary structure of adherens junction proteins. We showed that a low molecular weight G-protein, rho regulates cell shape and mobility via actomyosin system.Calcium overload is a dominating factor for reperfusion injury of myocardium. This might mediated by Ca-dependent proteinase.

在心肌中，钙在兴奋-收缩偶联中起关键作用。本研究通过分子生物学方法鉴定受磷蛋白与钙ATP酶分子的相互作用位点，探讨了介导兴奋-收缩偶联的蛋白质在心肌损伤中的作用。我们研究了受磷蛋白和钙ATP酶的基因调控，表明甲状腺激素是调节这些基因表达的关键因素。在心肌肌浆网的钙释放通道中鉴定了调节剂结合结构域。缝隙连接的电生理研究表明，缝隙连接的活性受钙调素的调节。我们纯化并确定了粘附连接蛋白的一级结构。rho是一种低分子量的G蛋白，它通过肌动球蛋白系统调节细胞的形态和运动，钙超载是心肌再灌注损伤的主要因素。这可能是由钙依赖性蛋白酶介导的。

项目成果

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Toyama,et al: "Ca^<2+>-calmodulin mediated modulation of the electrical coupling of ventricular myocytes isolated from quinea pig heart." J.Mol.Cell.Cardiol.26. 1007-1015 (1994)

Toyama等人：“Ca ^ 2 -钙调蛋白介导对从奎尼亚猪心脏分离的心室肌细胞的电耦合的调节。”

Sasayama,et al: "Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium:evidence from aequorin-loaded ferret ventricular muscles." J.Clin.Invest.93. 1275-1284 (1994)

Sasayama 等人：“哺乳动物工作心肌缺氧后复氧期间，钠/钙交换调节细胞内钙超载：来自负载水母发光蛋白的雪貂心室肌肉的证据。”

Kuzuya,et al: "Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia." Circ.Res.72. 1293-1299 (1993)

Kuzuya 等人：“亚致死性缺血对获得缺血耐受性的延迟影响。”