Tae Hyun-Jin, Petrashevskaya Natalia, Kim In Hye, Park Joon Ha, Lee Jae-Chul, Won Moo-Ho, Kim Yang Hee, Ahn Ji Hyeon, Park Jinseu, Choi Soo Young, Jeon Yong Hwan
Bio‑Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeollabuk 54596, Republic of Korea.
Cardiopulmonary Genomics Program, Departments of Medicine and Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Mol Med Rep. 2017 Jun;15(6):4049-4054. doi: 10.3892/mmr.2017.6526. Epub 2017 Apr 28.
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.
β1和β2肾上腺素能受体（ARs）调节心脏收缩力、钙处理和蛋白质磷酸化。本研究旨在通过蛋白质印迹分析，检测6月龄过表达β1AR或β2AR的转基因（TG）小鼠离体心脏中血管内皮生长因子A（VEGF‑A）和几种G蛋白的表达水平，以及转录因子GATA结合蛋白4（GATA4）的磷酸化情况。与野生型相比，β1AR TG和β2AR TG小鼠心脏的心脏收缩力/舒张和心率均增加；然而，β1AR和β2AR TG小鼠心脏之间未观察到显著差异。两种TG小鼠中抑制性鸟嘌呤核苷酸结合蛋白（Gi）2、Gi3和G蛋白偶联受体激酶2的蛋白质表达水平均上调，尽管Gi2的上调在β2AR TG小鼠中更为明显。两种TG小鼠中VEGF‑A的表达水平也增加，且在β1AR TG小鼠中最高。此外，β1AR和β2AR TG小鼠中磷酸化GATA4的表达水平增加。总之，本研究表明β1AR TG和β2AR TG小鼠的心脏收缩力/舒张和心率增加，提示这种增加可能与G蛋白和G蛋白相关蛋白的过表达有关。
