Role of transient receptor potential protein 7(TRP7), receptor-activated Ca^<2+> channels, in myocardial apoptosis

我们进行了1)体外培养细胞研究和2)心力衰竭大鼠模型体内研究。1)利用HEK293细胞和大鼠新生培养心肌细胞转染TRP7的研究。(1)与未转染细胞相比，TRP7转染的HEK细胞中carbachol激活的Ca^<2+>-瞬时增强，表明TRP7作为G蛋白偶联的Ca^<2+>通道。(2) trp7转染心肌细胞可诱导细胞凋亡，TUNEL染色检测血管紧张素II（angii）激活后，细胞凋亡发生率进一步升高。Ang II受体阻滞剂、Ca^<2+>通道阻滞剂和钙调磷酸酶抑制剂均能抑制Ang II诱导的细胞凋亡。(3)凋亡细胞中心房利钠因子（ANF）表达减少，肌动蛋白纤维破坏。(4) TRP7 mRNA的表达被Ang II受体阻滞剂、Ca^<2+>通道阻滞剂和钙调磷酸酶抑制剂抑制。2) TRP7在达尔盐敏感大鼠心力衰竭中的作用。(1)心力衰竭大鼠心肌中TRP7 mRNA表达升高，且长期应用血管紧张素转换酶抑制剂可抑制其表达。(2)心力衰竭大鼠心肌细胞凋亡增加，血管紧张素转换酶抑制剂长期治疗可抑制细胞凋亡增加。综上所述，TRP7可能作为受体激活的Ca^<2+>通道，通过钙调磷酸酶依赖途径介导angii诱导的心肌凋亡，并参与凋亡导致心力衰竭的过程。

We performed 1)In vitro study using cultured cells and 2)In vivo study using a rat model with heart failure.1)TRP7 transfection study using HEK293 cells and rat neonatal cultured cardiomyocytes.(1)Ca^<2+>-transient activated by carbachol was augmented in TRP7-transfected HEK cells more than in non-transfected cells, suggesting that TRP7 acts as G protein-coupled Ca^<2+> channels.(2)Apoptosis was induced in TRP7-transfected myocardial cells, and the incidence of apoptosis was further increased when activated by angiotensin II(Ang II), as detected by TUNEL stain. The Ang II-induced apoptosis was inhibited by Ang II receptor blocker, Ca^<2+> channel blocker, and calcineurin inhibitor.(3)In apoptotic cells, the expression of atrial natriuretic factor(ANF) was decreased, and the destruction of actin fibers was noted.(4)The expression of TRP7 mRNA was increased by Ang II, and this increase was inhibited by Ang II receptor blocker, Ca^<2+> channel blocker, and calcineurin inhibitor.2)Role of TRP7 in Dahl salt-sensitive rats with heart, failure.(1)The expression of TRP7 mRNA was increased in the myocardium of heart failure rats, and this increase was inhibited by long-term treatment with an angiotensin-converting enzyme inhibitor.(2)Apoptosis was increased in the myocardium of heart failure rats, and this increase was inhibited by long-term treatment with an angiotensin-converting enzyme inhibitor.Based on these results, TRP7 may act as receptor-activated Ca^<2+> channels mediating Ang II-induced myocardial apoptosis via calcineurin-dependent pathway, and this signaling may contribute to the process of apoptosis leading to heart failure.