G protein, phosphorylated-GATA4 and VEGF expression in the hearts of transgenic mice overexpressing β1- and β2-adrenergic receptors

过表达 β1 和 β2 肾上腺素受体的转基因小鼠心脏中的 G 蛋白、磷酸化 GATA4 和 VEGF 表达

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作者:Hyun-Jin Tae, Natalia Petrashevskaya, In Hye Kim, Joon Ha Park, Jae-Chul Lee, Moo-Ho Won, Yang Hee Kim, Ji Hyeon Ahn, Jinseu Park, Soo Young Choi, Yong Hwan Jeon

Abstract

β1- and β2-adrenergic receptors (ARs) regulate cardiac contractility, calcium handling and protein phosphorylation. The present study aimed to examine the expression levels of vascular endothelial growth factor A (VEGF‑A) and several G proteins, and the phosphorylation of transcription factor GATA binding protein 4 (GATA4), by western blot analysis, using isolated hearts from 6 month‑old transgenic (TG) mice that overexpress β1AR or β2AR. Cardiac contractility/relaxation and heart rate was increased in both β1AR TG and β2AR TG mouse hearts compared with wild type; however, no significant differences were observed between the β1‑ and β2AR TG mouse hearts. Protein expression levels of inhibitory guanine nucleotide‑binding protein (Gi) 2, Gi3 and G‑protein‑coupled receptor kinase 2 were upregulated in both TG mice, although the upregulation of Gi2 was more prominent in the β2AR TG mice. VEGF‑A expression levels were also increased in both TG mice, and were highest in the β1AR TG mice. In addition, the levels of phosphorylated‑GATA4 expression were increased in β1‑ and β2AR TG mice. In conclusion, the present study demonstrated that cardiac contractility/relaxation and heart rate is increased in β1AR TG and β2AR TG mice, and indicated that this increase may be related to the overexpression of G proteins and G‑protein‑associated proteins.

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