期刊
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
卷 385, 期 8, 页码 823-831出版社
SPRINGER
DOI: 10.1007/s00210-012-0740-4
关键词
Choline; Cardiomyocyte; Cardiac hypertrophy; Calcineurin; p38 MAPK
资金
- National Basic Research Program of China (973 Program) [2007CB512000 (2007CB512006)]
- National Natural Science Foundation of China [81072639, 30973531]
Choline, an agonist of M-3 muscarinic acetylcholine receptors, is a precursor and metabolite of acetylcholine and is also a functional modulator of cellular membrane. However, the effect of choline on cardiac hypertrophy is not fully understood. The present study was therefore designed to explore whether choline could prevent cardiac hypertrophy induced by angiotensin II (Ang II) and clarify its potential mechanisms. Cardiac hypertrophy was induced by 0.6 mg kg(-1) day(-1) Ang II for 2 weeks in the presence or absence of choline pretreatment, while cardiomyocyte hypertrophy was induced by Ang II 0.1 mu M for 48 h. We found that choline pretreatment attenuated the increment cell size of cardiomyocytes induced by Ang II both in vivo and in vitro. The high ANP and beta-MHC levels induced by Ang II were also reversed by choline in cardiomyocytes. Meanwhile, choline pretreatment prevented the augment of reactive oxygen species (ROS) and intracellular calcium concentration in Ang II-treated cardiomyocytes. Furthermore, the upregulated phospho-p38 mitogen-activated protein kinase (MAPK) and calcineurin levels by Ang II in ventricular myocytes were attenuated by choline. In conclusion, choline prevents Ang II-induced cardiac hypertrophy through inhibition of ROS-mediated p38 MAPK activation as well as regulation of Ca2+-mediated calcineurin signal transduction pathway. Our results provide new insights into the pharmacological role of choline in cardiovascular diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据