Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy
Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy
复制标题
DOI：
10.1126/science.280.5363.574
复制
发表时间：
1998-04-24
期刊：
影响因子：
56.9
通讯作者：
Koch, WJ
中科院分区：
文献类型：
--
作者：
Akhter, SA;Luttrell, LM;Koch, WJ
激素和神经递质可以通过与同种异源三聚体鸟嘌呤核苷酸结合（G）蛋白偶联的受体介导共同的反应。例如，与G（q）类蛋白偶联的几种受体可以诱导心肌细胞肥大。通过靶向表达α亚基G α（q）的羧基末端肽，在转基因小鼠的心脏中产生G（q）介导的信号传导的类别特异性抑制。当通过手术诱导压力超负荷时，转基因小鼠的心室肥大明显低于对照组。这些数据证明了心肌G（q）在心肌肥大启动中的作用，并表明了通过同时阻断与G（q）偶联的多种受体来预防病理生理信号传导的可能策略。
Hormones and neurotransmitters may mediate common responses through receptors that couple to the same class of heterotrimeric guanine nucleotide-binding (G) protein. For example, several receptors that couple to G(q) class proteins can induce cardiomyocyte hypertrophy. Class-specific inhibition of G(q)-mediated signaling was produced in the hearts of transgenic mice by targeted expression of a carboxyl-terminal peptide of the alpha subunit G alpha(q). When pressure overload was surgically induced, the transgenic mice developed significantly less ventricular hypertrophy than control animals. The data demonstrate the role of myocardial G(q) in the initiation of myocardial hypertrophy and indicate a possible strategy for preventing pathophysiological signaling by simultaneously blocking multiple receptors coupled to G(q).