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首页> 外文期刊>Cellular Signalling >RGS2 is upregulated by and attenuates the hypertrophic effect of alpha(1)-adrenergic activation in cultured ventricular myocytes
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RGS2 is upregulated by and attenuates the hypertrophic effect of alpha(1)-adrenergic activation in cultured ventricular myocytes

机译：RGS2由培养的心室肌细胞中的α（1）-肾上腺素激活的肥大作用上调并减弱

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摘要

Regulator of G protein signaling (RGS) proteins counter the effects of G protein-coupled receptors (GPCRs) by limiting the abilities of G proteins to propagate signals, although little is known concerning their role in cardiac pathophysiology. We investigated the potential role of RGS proteins on alpha(1)-adrenergic receptor signals associated with hypertrophy in primary cultures of neonatal rat cardiomyocytes. Levels of mRNA encoding RGS proteins 1-5 were examined, and the a alpha(1)-adrenergic agonist phenylephrine (PE) significantly increased RGS2 gene expression but had little or no effect on the others. The greatest changes in RGS2 mRNA occurred within the first hour of agonist addition. We next investigated the effects of RGS2 overexpression produced by infecting cells with an adenovirus encoding RGS2-cDNA on cardiomyocyte responses to PE. As expected, PE increased cardiomyocyte size and also significantly upregulated alpha-skeletal actin and ANP expression, the markers of hypertrophy, as well as the Na-H exchanger 1 isoform. These effects were blocked in cells infected with the adenovirus expressing RGS2. We also examined hypertrophy-associated MAP kinase pathways, and RGS2 overexpression completely prevented the activation of ERK by PE. In contrast, the activation of both JNK and p38 unexpectedly were increased by RGS2, although the ability of PE to further activate the p38 pathway was reduced. These results indicate that RGS2 is an important negative-regulatory factor in cardiac hypertrophy produced by alpha(1)-adrenergic receptor stimulation through complex mechanisms involving the modulation of mitogen-activated protein kinase signaling pathways. (c) 2006 Elsevier Inc. All rights reserved.
机译：G蛋白信号转导（RGS）蛋白的调节剂通过限制G蛋白传播信号的能力来抵消G蛋白偶联受体（GPCR）的作用，尽管对其在心脏病理生理学中的作用知之甚少。我们调查了新生大鼠心肌细胞原代培养中RGS蛋白对与肥大相关的α（1）-肾上腺素能受体信号的潜在作用。检查了编码RGS蛋白1-5的mRNA的水平，并且α（1）-肾上腺素能激动剂去氧肾上腺素（PE）显着增加了RGS2基因的表达，但对其他受体几乎没有影响。 RGS2 mRNA的最大变化发生在添加激动剂的第一个小时内。接下来，我们研究了用编码RGS2-cDNA的腺病毒感染细胞对心肌对PE的反应所产生的RGS2过表达的影响。正如预期的那样，PE增加了心肌细胞的大小，并且还显着上调了α-骨骼肌肌动蛋白和ANP表达，肥大的标志物以及Na-H交换子1亚型。在感染了表达RGS2的腺病毒的细胞中，这些作用被阻断。我们还检查了肥大相关的MAP激酶途径，RGS2的过表达完全阻止了PE激活ERK。相反，RGS2意外地增加了JNK和p38的激活，尽管PE进一步激活p38途径的能力降低了。这些结果表明，RGS2是心脏肥大中重要的负调节因子，它是由α（1）-肾上腺素能受体刺激通过复杂的机制参与的，涉及到促分裂原激活的蛋白激酶信号通路的调节。 （c）2006 Elsevier Inc.保留所有权利。

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