Bilim Olga, Shishido Tetsuro, Toyama Shuji, Suzuki Satoshi, Sasaki Toshiki, Kitahara Tatsuro, Sadahiro Mitsuaki, Takeishi Yasuchika, Kubota Isao
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
J Cardiothorac Surg. 2011 May 8;6:65. doi: 10.1186/1749-8090-6-65.
Evidence from several studies indicates the importance of Gαq protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG), and protein kinase C, in the development of heart failure. DAG kinase (DGK) acts as an endogenous regulator of GPCR signaling pathway by catalyzing and regulating DAG. Expressions of DGK isoforms α, ε, and ζ in rodent hearts have been detected; however, the expression and alteration of DGK isoforms in a failing human heart has not yet been examined. In this study, we detected mRNA expressions of DGK isoforms γ, η, ε, and ζ in failing human heart samples obtained from patients undergoing cardiovascular surgery with cardiopulmonary bypass. Furthermore, we investigated modulation of DGK isoform expression in these hearts. We found that expressions of DGKη and DGKζ were increased and decreased, respectively, whereas those of DGKγ and DGKε remained unchanged. This is the first report that describes the differential regulation of DGK isoforms in normal and failing human hearts.
多项研究的证据表明,Gαq蛋白偶联受体(GPCR)信号通路在心力衰竭发展过程中具有重要作用,该信号通路包括二酰基甘油(DAG)和蛋白激酶C。二酰基甘油激酶(DGK)通过催化和调节二酰基甘油,作为GPCR信号通路的内源性调节剂。已检测到啮齿动物心脏中DGK亚型α、ε和ζ的表达;然而,尚未研究衰竭人类心脏中DGK亚型的表达及变化情况。在本研究中,我们检测了接受体外循环心血管手术患者的衰竭人类心脏样本中DGK亚型γ、η、ε和ζ的mRNA表达。此外,我们研究了这些心脏中DGK亚型表达的调节情况。我们发现,DGKη和DGKζ的表达分别增加和减少,而DGKγ和DGKε的表达保持不变。这是首篇描述正常和衰竭人类心脏中DGK亚型差异调节的报告。