Takagi C, Urasawa K, Yoshida I, Takagi Y, Kaneta S, Nakano N, Onozuka H, Kitabatake A
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, 060, Japan.
Biochem Biophys Res Commun. 1999 Aug 19;262(1):206-10. doi: 10.1006/bbrc.1999.1179.
GTP binding protein-coupled receptor kinase 5 (GRK5) cDNA was cloned from the hearts of Syrian hamsters. The hamster GRK5 cDNA contained 1770 nucleotides encoding 590 amino acids, and the nucleotide sequence had 89.6% homology to the human homologue. An inbred cardiomyopathic hamster strain, J2N-k, was used to investigate the alteration of GRK5 mRNA expression in the setting of congestive heart failure. M-mode echocardiography revealed significant dilatation of the left ventricle and a decrease of left ventricular contractility in 20-week-old J2N-k hamsters compared with age-matched control hamsters, J2N-n. Semi-quantitative RT-PCR showed that GRK5 mRNA expression in the hearts of J2N-k was significantly higher than in those of J2N-n (J2N-k 60.3 +/- 13.3, J2N-n 25.8 +/- 17.2 arbitrary units, p < 0.005, n = 6 in each group). These results suggest that an enhanced GRK5 expression might play a role in the reduced responsiveness to catecholamines in failing hearts via beta-adrenergic receptor phosphorylation.
从叙利亚仓鼠心脏中克隆出GTP结合蛋白偶联受体激酶5（GRK5）的互补DNA（cDNA）。仓鼠GRK5 cDNA含有1770个核苷酸，编码590个氨基酸，其核苷酸序列与人类同源物有89.6%的同源性。利用近交系心肌病仓鼠品系J2N-k研究充血性心力衰竭情况下GRK5信使核糖核酸（mRNA）表达的变化。M型超声心动图显示，与年龄匹配的对照仓鼠J2N-n相比，20周龄的J2N-k仓鼠左心室明显扩张，左心室收缩力下降。半定量逆转录聚合酶链反应（RT-PCR）表明，J2N-k心脏中GRK5 mRNA表达显著高于J2N-n（J2N-k为60.3±13.3，J2N-n为25.8±17.2任意单位，p<0.005，每组n = 6）。这些结果表明，GRK5表达增强可能通过β-肾上腺素能受体磷酸化在衰竭心脏对儿茶酚胺反应性降低中起作用。
