Overexpression of TNNI3K, a cardiac-specific MAP kinase, promotes P19CL6-derived cardiac myogenesis and prevents myocardial infarction-induced injury
Overexpression of TNNI3K, a cardiac-specific MAP kinase, promotes P19CL6-derived cardiac myogenesis and prevents myocardial infarction-induced injury
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TNNI3K（一种心脏特异性 MAP 激酶）的过度表达可促进 P19CL6 衍生的心肌生成并预防心肌梗塞引起的损伤
DOI：
10.1152/ajpheart.00252.2008
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发表时间：
2008-08-01
影响因子：
4.8
通讯作者：
Kim-Mitsuyama, Shokei
中科院分区：
文献类型：
--
作者：
Lai, Zhong-Fang;Chen, Yu-Zhen;Kim-Mitsuyama, Shokei
TNNI3K是一种新的心脏特异性MAP激酶，其基因定位于1p31.1，属于人类基因组激酶树中的酪氨酸激酶样分支。在本研究中，我们研究了TNNI3K在心肌形成过程和缺血损伤修复中的作用。用转染或未转染pcDNA6-TNNI3K质粒的多能P19CL6细胞诱导分化为搏动心肌细胞。从搏动质量增加和α -肌动素阳性细胞数量增加来看，TNNI3K促进了分化过程。在不增加单细胞大小的情况下，TNNI3K通过增加心跳频率、增加收缩力和自发动作电位的肾上腺素反应来改善心功能。TNNI3K抑制心肌肌钙蛋白I、膜联蛋白v +细胞、Bax蛋白和p38/ jnk介导的细胞凋亡的磷酸化。心肌梗死小鼠心肌内注射过表达tnni3k的P19CL6细胞，与注射野生型P19CL6细胞相比，可改善心脏功能，减轻心室重构。综上所述，我们的研究清楚地表明，TNNI3K通过抑制p38/ jnk介导的细胞凋亡，促进心肌形成，提高心脏机能，保护心肌免受缺血性损伤。因此，调节TNNI3K活性将是缺血性心脏病的有效治疗方法。
TNNI3K is a new cardiac-specific MAP kinase whose gene is localized to 1p31.1 and that belongs to a tyrosine kinase-like branch in the kinase tree of the human genome. In the present study we investigated the role of TNNI3K in the cardiac myogenesis process and in the repair of ischemic injury. Pluripotent P19CL6 cells with or without transfection by pcDNA6-TNNI3K plasmid were used to induce differentiation into beating cardiomyocytes. TNNI3K promoted the differentiation process, judging from the increasing beating mass and increased number of alpha-actinin-positive cells. TNNI3K improved cardiac function by enhancing beating frequency and increasing the contractile force and epinephrine response of spontaneous action potentials without an increase of the single-cell size. TNNI3K suppressed phosphorylation of cardiac troponin I, annexin-V+ cells, Bax protein, and p38/JNK-mediated apoptosis. Intramyocardial administration of TNNI3K-overexpressing P19CL6 cells in mice with myocardial infarction improved cardiac performance and attenuated ventricular remodeling compared with injection of wild-type P19CL6 cells. In conclusion, our study clearly indicates that TNNI3K promotes cardiomyogenesis, enhances cardiac performance, and protects the myocardium from ischemic injury by suppressing p38/JNK-mediated apoptosis. Therefore, modulation of TNNI3K activity would be a useful therapeutic approach for ischemic cardiac disease.