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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Altered calcium regulation in isolated cardiomyocytes from Egr-1 knock-out mice
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Altered calcium regulation in isolated cardiomyocytes from Egr-1 knock-out mice

机译:Egr-1基因敲除小鼠离体心肌细胞中钙调节的改变

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摘要

Early growth response-1 one gene (Egr-1), one of the immediate early response genes, plays an important role in the adaptive response of the myocardium to hypertrophic stimuli. We aimed to investigate the effects of Egr-1 deletion on cardiac function. Egr-1 knock-out (Egr-1~(-/-)) homozygous mice were employed to evaluate the electrophysiological and molecular properties of left ventricular cardiomyocytes (VCM) by using patch-clamp technique, intracellular calcium measurements, real-time PCR, and Western blot. Action potential was prolonged and diastolic potential was positive-shifted in VCMs isolated from Egr-1~(-/-) mice, in comparison with those from their wild-type (WT) littermates. The calcium content of the sarcoplasmic reticulum was reduced and the decay time for steady-state calcium transient slowed down. Serca2, Ryr, L-type Ca~(-1)-channel, and PUB mRNA expression were reduced in Egr-1~(-/-) mice compared with the controls. Moreover, Serca2 protein was reduced, while the amount of Ncxl protein was increased in Egr-1~(-/-) hearts compared with those of the WT littermates. Furthermore, genes involved in heart development (GATA-4, TGF-beta) and in Egr-1 regulation (Nab1, Nab2) were down regulated in Egr-1~(-/-) mice. These results suggest that Egr-1 plays a pivotal role in regulating excitation-contraction coupling in cardiac myocytes.
机译:早期生长应答-1一个基因(Egr-1)是立即早期应答基因之一,在心肌对肥大刺激的适应性应答中起重要作用。我们旨在研究Egr-1缺失对心脏功能的影响。利用膜片钳技术,细胞内钙测量,实时PCR,使用Egr-1敲除(Egr-1〜(-/-))纯合小鼠评估左心室心肌细胞(VCM)的电生理和分子特性。和Western blot。与野生型(WT)同窝幼仔相比,从Egr-1〜(-/-)小鼠中分离出的VCM的动作电位延长,舒张电位正移。肌浆网中的钙含量降低,稳态钙瞬变的衰减时间减慢。与对照组相比,Egr-1〜(-/-)小鼠的Serca2,Ryr,L型Ca〜(-1)-通道和PUB mRNA表达降低。此外,与WT同窝仔相比,Egr-1〜(-/-)心脏的Serca2蛋白减少,而Ncxl蛋白的量增加。此外,在Egr-1〜(-/-)小鼠中,参与心脏发育的基因(GATA-4,TGF-beta)和Egr-1调控的基因(Nab1,Nab2)被下调。这些结果表明,Egr-1在调节心肌细胞的兴奋-收缩偶联中起关键作用。

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