Significances of modifying TNNI3 function by overexpression of MAP kinase TNNI3K

TNNI 3 K是一种特异性持续表达于心肌的MAP激酶，与心肌肌钙蛋白I（cardiac troponin I，TNNI 3或：cTnI）相互作用。本研究的目的是探讨TNNI 3 K与cTnI相互作用对心肌细胞生理功能的影响，抑制某些病理损伤，阐明TNNI 3 K突变体在缺血性冠心病发病中的新的分子机制，并希望为临床治疗提供新的思路。在体外实验中，1）研究PKC抑制剂（GF 109203 X）和PKA激活剂（Br-8-cAMP）对P19 CL 6来源的培养搏动心肌细胞搏动频率的影响。结果表明，TNNI 3 K过表达通过激活PKA通路而不是通过阻断PKC通路来增加收缩力和搏动频率，同时抑制cTnI的磷酸化。2)使用抗TNNI 3 K多聚抗体在诊断为AMI（n=40）、慢性心力衰竭（CHF，n=18）和急性肾衰竭（ARF，n=6）的患者中以及在健康志愿者（n=12）中研究血浆TNNI 3 K水平的可用性。数据显示，AMI患者循环中TNNI 3 K水平显著升高（p

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