权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

受体激活的Ca^2通道瞬时受体电位蛋白7(TRP7)在心肌细胞凋亡中的作用

基本信息

批准号：
15590756
负责人：
SATOH Shinji
金额：
$ 2.11万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590756/
关键词：
Transient receptor potential channel G protein Ca^<2+> channel Angiotensin II Apoptosis Calcineurin Heart failure Transient Receptor Potential Protein GTP-binding Protein 心筋細胞肥大 Ca^<2+>アデノウィルス・ベクター

项目摘要

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.

我们利用体外培养的细胞进行了体外实验和体内实验。1)用HEK293细胞和培养的大鼠心肌细胞进行了TRP7的转染性研究。(1)经氨甲胆碱激活的HEK细胞中瞬时钙离子浓度比未转染组显著增加，提示TRP7是G蛋白偶联的钙离子通道。(2)经血管紧张素Ⅱ(Ang II)激活后，TRP7基因可诱导心肌细胞发生凋亡，并进一步增加细胞凋亡率。Ang II受体阻滞剂、钙通道阻滞剂和钙调神经磷酸酶抑制剂可抑制Ang II诱导的细胞凋亡.(3)在凋亡细胞中，心房利钠因子(ANF)表达减少，肌动蛋白纤维破坏.(4)Ang II上调TRP7mRNA的表达，这种增加可被Ang II受体阻滞剂Ca^&lt；通道阻滞剂和钙调神经磷酸酶抑制剂2)TRP7在Dahl盐敏感型心力衰竭大鼠心肌中的作用。(1)心衰大鼠心肌中TRP7的表达增加，长期应用血管紧张素转换酶抑制剂可抑制这种增加。(2)心衰大鼠心肌细胞凋亡增加，长期应用血管紧张素转换酶抑制剂抑制这种增加。Ang II通过钙调神经磷酸酶依赖性途径介导心肌细胞凋亡，该信号转导通路可能参与细胞凋亡导致心力衰竭的过程。