Zhang S, Watson N, Zahner J, Rottman J N, Blumer K J, Muslin A J
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
J Mol Cell Cardiol. 1998 Feb;30(2):269-76. doi: 10.1006/jmcc.1997.0591.
RGS family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes when tested in vitro and in vivo. Although the function of RGS proteins in cardiac physiology is unknown, their ability to deactivate Galpha subunits suggests that they may inhibit the action of muscarinic, alpha-adrenergic, endothelin, and other agonists. To evaluate the role of RGS family members in the regulation of cardiac physiology, we investigated the expression pattern of two RGS genes in normal and diseased rat heart tissue. RGS3 and RGS4 mRNAs and proteins were detected in adult myocardium. RGS3 and RGS4 gene expression was markedly enhanced in two model systems of cardiac hypertrophy: growth factor-stimulated cultured neonatal rat cardiomyocytes and pulmonary artery-banded (PAB) mice. RGS3 and RGS4 mRNA levels were reduced in failing myocardium obtained from SHHF/Mcc-fa(cp) (SHHF) rats. These findings support the hypothesis that RGS gene expression is highly regulated in myocardium and imply that RGS family members play an important role in the regulation of cardiac function.
RGS家族成员是作为异源三聚体G蛋白的Gα亚基的GTP酶激活蛋白（GAPs）起作用的调节分子。在体外和体内进行测试时，RGS蛋白能够使Giα、Goα和Gqα亚型的G蛋白亚基失活。尽管RGS蛋白在心脏生理学中的功能尚不清楚，但它们使Gα亚基失活的能力表明它们可能抑制毒蕈碱、α-肾上腺素能、内皮素和其他激动剂的作用。为了评估RGS家族成员在心脏生理学调节中的作用，我们研究了两种RGS基因在正常和患病大鼠心脏组织中的表达模式。在成年心肌中检测到RGS3和RGS4的mRNA和蛋白质。在两种心脏肥大模型系统中，RGS3和RGS4基因表达明显增强：生长因子刺激的培养新生大鼠心肌细胞和肺动脉环扎（PAB）小鼠。从SHHF/Mcc-fa(cp)（SHHF）大鼠获得的衰竭心肌中，RGS3和RGS4的mRNA水平降低。这些发现支持了RGS基因表达在心肌中受到高度调节的假说，并暗示RGS家族成员在心脏功能调节中起重要作用。
