Significances of modifying TNNI3 function by overexpression of MAP kinase TNNI3K

过表达 MAP 激酶 TNNI3K 改变 TNNI3 功能的意义

• 批准号: 22590244
• 负责人: YORINAKA Hoichi
• 金额: $ 2.91万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590244/
• 关键词: TNNI3K; 心筋トロポニン I; 遺伝子機能; ELISA; 心筋細胞分化; 心筋トロポニンI; 不整脈; 遺伝子導入; 抗TNNI3Kポリクローナル抗体; MAPキナーゼ; 心筋トロポニンI(cTnI); 心筋細胞の拍動頻度; 抗TNNI3K抗体; 急性心筋梗塞; 血中TNNI3K濃度

TNNI3K is a MAP kinase specifically and continuouslyexpressed in cardiac muscle and interacted with cardiac troponin I (TNNI3, or: cTnI). The aim of this study is to investigate role of TNNI3K interacting with cTnI on modification the physiological function of cardiomyocytes, suppressing some pathological injuries and to explain the new molecular mechanism for TNNI3K-mutant in the ischemic coronary heart diseases, and hope to develop some new therapeutic strategies. In the in vitro experiments, 1) Effects of PKC inhibitor (GF109203X) or PKA activator (Br-8-cAMP) on the beating frequency were investigated in P19CL6-derived culture beating cardiomyocytes. Results showed that TNNI3K-overexpression increased the contractility and beating frequency together with restrained phosphorylation of cTnI through activation of the PKA pathway but not by blocking of the PKC pathway. 2) Availability of plasma TNNI3K level was investigated using with anti-TNNI3K poly-antibodies in patients diagnosed as AMI (n=40), chronic heart failure (CHF, n=18) and acute renal failure (ARF, n=6); and in healthy volunteers (n=12). Data shown that circulating TNNI3K levels were significantly higher in AMI (p

TNNI3K是一种MAP激酶，在心肌中特异性和持续表达，并与心肌肌钙蛋白I （TNNI3，或：cTnI）相互作用。本研究旨在探讨TNNI3K与cTnI相互作用在改变心肌细胞生理功能、抑制某些病理性损伤中的作用，并解释TNNI3K突变体在缺血性冠心病中的新的分子机制，以期找到新的治疗策略。在体外实验中，1)研究PKC抑制剂（GF109203X）或PKA激活剂（Br-8-cAMP）对p19cl6来源的培养搏动心肌细胞搏动频率的影响。结果表明，tnni3k -过表达通过激活PKA通路而不是阻断PKC通路，增加了收缩性和跳动频率，并抑制了cTnI的磷酸化。2)应用抗TNNI3K多抗体检测AMI （n=40）、慢性心力衰竭（CHF, n=18）和急性肾功能衰竭（ARF, n=6）患者血浆TNNI3K水平；健康志愿者（n=12）。数据显示AMI患者的循环TNNI3K水平明显升高(p

项目成果

How TNNI3K interacts with TNNI3? the hypothesis, evidences and significances

TNNI3K 如何与 TNNI3 相互作用？

• 发表时间: 2011
• 作者: 江頭伸昭;他;Yorinaka H
• 通讯作者: Yorinaka H

Urine of AKI patients promotes metanephric cell growth and recovery of renal function after ischemia-reperfusion injury in mouse.

AKI患者尿液促进小鼠缺血再灌注损伤后肾细胞生长和肾功能恢复。

• 发表时间: 2012
• 作者: Kitamoto Y;Kitamura H;Sugai H;Taguma Y;Imamura T;Yorinaka H:
• 通讯作者: Yorinaka H:

心原性突然死リスク抑圧向けたTNNI3K遺伝子の機能解析と新薬開発

TNNI3K基因功能分析及抑制心源性猝死风险的新药开发

• 发表时间: 2011
• 作者: 頼仲方一;頼仲玉珍
• 通讯作者: 頼仲玉珍

血中TNNI3Kレベルの変化に基づく急性虚血性心疾患の新しい診断法

基于血液TNNI3K水平变化的急性缺血性心脏病诊断新方法

• 发表时间: 2011
• 期刊: 平成22年度 熊本大学総合技術研究会報告集 (CD-ROM)
• 作者: 頼仲方一;頼仲玉珍
• 通讯作者: 頼仲玉珍

Mechanisms of chloride in cardiomyocyte anoxia-reoxygenation injury: the involvement of oxidative stress and NF-kappaB activation

• DOI: 10.1007/s11010-011-0855-9
• 发表时间: 2011-05
• 期刊: Molecular and Cellular Biochemistry
• 影响因子: 4.3
• 作者: D. Liu;H. He;G. L. Li;J. Chen;D. Yin;Z. Liao;L. Tang;Q. Huang;Z. Lai;M. He