Overexpression of diacylglycerol kinase zeta inhibits endothelin-1-induced decreases in Ca2+ transients and cell shortening in mouse ventricular myocytes.
Overexpression of diacylglycerol kinase zeta inhibits endothelin-1-induced decreases in Ca2+ transients and cell shortening in mouse ventricular myocytes.
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二酰甘油激酶 zeta 的过度表达可抑制内皮素 1 诱导的小鼠心室肌细胞中 Ca2 瞬变的减少和细胞缩短。
DOI：
10.1016/j.yjmcc.2007.12.007
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发表时间：
2008
影响因子：
5
通讯作者：
M. Endoh
中科院分区：
文献类型：
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作者：
K. Nishimaru;T. Arimoto;Y. Takeishi;I. Kubota;K. Ishii;M. Endoh
内皮素-1(ET-1)在包括充血性心力衰竭在内的多种心血管疾病中被释放，并可能通过对血管和心肌细胞功能和基因调控的强大作用而显著调节疾病的进程。在INDO-1负载的成年小鼠心肌细胞上，ET-1诱导持续的负性变力效应(NIE)，并伴随着钙瞬变的减少。在高表达ζ的小鼠心室肌细胞中，ET-1对钙瞬变和细胞缩短的影响被取消。非选择性蛋白激酶C(PKC)抑制剂GF109203X以浓度依赖的方式抑制ET-1诱导的钙瞬变和细胞缩短，而选择性的钙依赖PKC抑制剂Gö6976不影响ET-1的作用。磷脂酶Cβ抑制剂U73122和磷脂酶D抑制剂C2-神经酰胺部分但显著地减弱ET-1的作用。无特异性作用的抑制剂U73343和二氢C2神经酰胺的衍生物不影响ET-1的作用。综上所述，这些结果表明，1，2-DAG激活磷脂酶Cβ和磷脂酶D激活并通过DAG激酶磷酸化而失活的1，2-DAG激活非钙依赖的PKC同工酶是ET-1引起的小鼠心肌细胞钙瞬变减少和细胞缩短的原因。
Endothelin-1 (ET-1) is released in various cardiovascular disorders including congestive heart failure, and may modulate significantly the disease process by its potent action on vascular and cardiac muscle cell function and gene regulation. In adult mouse ventricular cardiomyocytes loaded with indo-1, ET-1 induced a sustained negative inotropic effect (NIE) in association with decreases in Ca2+transients. The ET-1-induced effects on Ca2+transients and cell shortening were abolished in diacylglycerol (DAG) kinase ζ-overexpressing mouse ventricular myocytes. A nonselective protein kinase C (PKC) inhibitor, GF109203X, inhibited the ET-1-induced decreases in Ca2+transients and cell shortening in concentration-dependent manners, whereas a selective Ca2+-dependent PKC inhibitor, Gö6976, did not affect the ET-1-induced effects. A phospholipase Cβ inhibitor, U73122, and an inhibitor of phospholipase D, C2-ceramide, partially, but significantly, attenuated the ET-1-induced effects. Derivatives of the respective inhibitors with no specific effects, U73343 and dihydro-C2-ceramide, did not affect the ET-1-induced effects. Taken together, these results indicate that activation of a Ca2+-independent PKC isozyme by 1,2-DAG, which is generated by phospholipase Cβ and phospholipase D activation and inactivated by phosphorylation via DAG kinase, is responsible for the ET-1-induced decreases in Ca2+transients and cell shortening in mouse ventricular cardiomyocytes.
DOI：
--
发表时间：
1994-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Michel Pucéat;R. Hilal-Dandan;B. Strulovici;L. Brunton;Joan Heller Brown
通讯作者：
Michel Pucéat;R. Hilal-Dandan;B. Strulovici;L. Brunton;Joan Heller Brown
大鼠心室肌细胞中二酰甘油介导的正性肌力。
影响因子：
20.1
作者：
Pi,Y;Sreekumar,R;Huang,X;Walker,JW
通讯作者：
Walker,JW