Molecular Mechanism for Calcium Signaling in Cardiomyocyte

心肌细胞钙信号传导的分子机制

• 批准号: 09307013
• 负责人: TADA Michihiko
• 金额: $ 23.94万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09307013/
• 关键词: Ca signaling; sarcoplasmic reticulum; Ca release channel; phospholamban; heart failure; gene expression; Caジクナリング; カルシウムシグナリング; 興奮収縮連関; 筋小胞体カルシウム遊離チャネル; 心筋症; 遺伝子診断

Muscle contractility is regulated by Intracellualr calcium. Upon depolarization of plasma membrane, Ca is released into cytoplasm from the sarcoplasmic reticulum through Ca release channel, leading to muscle contraction. On the other hand, Ca uptake by Ca ATPase in sarcoplasmic reticulum lowers Ca concentration to induce muscle relaxation. Ca, which binds to calsequestrin, is stored in the sarcoplasmic reticulum. The activity of Ca ATPase is regulated by phospholamban. The sarcoplasmic reticulum plays an important role in exitation-contraction coupling. The changes in expression levels of the Ca signaling proteins in cardiac hypertrophy and heart failure may influence on a cardiac performance. In this study, we analyzed the mechanism for gene expression of Ca release channel and phospholamban. We identified the promotor regions in the genes and possible transcriptional factors for expression. Our structure- function analysis of Ca ATPase and phopholamban revealed that a functional unit of phopholamban is a monomer and an oligomer serves as a pool of the molecule. We showed that extracellular disuffide bonds of connexin 43 are crucial for formation of gap junction, through which cardiomyocytes communicate each other.

肌肉收缩性受细胞内钙调节。当质膜去极化时，Ca通过Ca释放通道从肌浆网释放到细胞质中，导致肌肉收缩。另一方面，肌浆网中Ca ATP酶对Ca的摄取降低了Ca浓度，从而引起肌肉松弛。结合钙螯合蛋白的钙储存在肌浆网中。受磷蛋白调节Ca ATP酶的活性。肌浆网在兴奋-收缩偶联中起重要作用。心肌肥厚和心力衰竭时钙信号蛋白表达水平的变化可能影响心脏功能。本研究分析了钙释放通道和受磷蛋白基因表达的机制。我们确定了基因中的启动子区域和可能的表达转录因子。我们对Ca ATP酶和phopholamban的结构-功能分析表明，phopholamban的功能单元是单体，而低聚物作为分子库。我们发现，细胞外连接蛋白43的二硫键是形成缝隙连接的关键，通过缝隙连接，心肌细胞相互沟通。

项目成果

Yamashita N, Hoshida S, Tada M, et al.: "Time course of tolerance to ischemia-reperfusion injury and induction of heat shock protein 72 by heat stress in the rat heart." J.Mol.Cell.Cardiol.29. 1815-1821 (1997)

Yamashita N、Hoshida S、Tada M 等人：“大鼠心脏对缺血再灌注损伤的耐受性和热应激诱导热休克蛋白 72 的时间过程。”

Kimura Y, et al.: "Phospholamban inhibitory function is activated by depolymerization." J.Biol.Chem.272. 15061-15064 (1997)

Kimura Y 等人：“Phospholamban 抑制功能是通过解聚作用激活的。”

Toyofuku T, Yabuki Y, Tada M, et al.: "Intercellular calcium signaling via gap junction in connexin-43-transfected cells." J.Biol.Chem. 273. 1519-1528 (1998)

Toyofuku T、Yabuki Y、Tada M 等人：“连接蛋白 43 转染细胞中通过间隙连接的细胞间钙信号传导。”

Yamashita N, Hoshida S, Tada M, et al.: "Heat shock-induced manganese superoxide dismutase enhances the tolerance ofcardiac myocytes to hypoxia-reoxygenation injury." J.Mol.Cell.Cardiol.29. 1807-1813 (1997)

Yamashita N、Hoshida S、Tada M 等人：“热休克诱导的锰超氧化物歧化酶增强心肌细胞对缺氧-复氧损伤的耐受性。”

Yamashita N, et al.: "Time course of tolerance to ischemia-reperfusion injury and induction of heat shock protein 72 by heat stress in the rat heart." J.Mol.Cell.Cardiol.29. 1815-1821 (1997)

Yamashita N 等人：“大鼠心脏对缺血再灌注损伤的耐受性和热应激诱导热休克蛋白 72 的时间过程。”