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Angiotensin Ⅱ induced upregulation of Gαq/11, phospholipase Cβ3 and extracellular signal-regulated kinase 1/2 via angiotensin Ⅱtype 1 receptor

白桦 吴立玲 邢东琦 刘洁 赵亚莉

中华医学杂志(英文版)2004,Vol.117Issue(1):88-93,6.
中华医学杂志(英文版)2004,Vol.117Issue(1):88-93,6.

Angiotensin Ⅱ induced upregulation of Gαq/11, phospholipase Cβ3 and extracellular signal-regulated kinase 1/2 via angiotensin Ⅱtype 1 receptor

Angiotensin Ⅱ induced upregulation of Gαq/11, phospholipase Cβ3 and extracellular signal-regulated kinase 1/2 via angiotensin Ⅱtype 1 receptor

白桦 1吴立玲 2邢东琦 2刘洁 2赵亚莉2

作者信息

  • 1. Department of Cardiology, Peking Union Medical College Hospital, Beijing 100730, China
  • 2. Department of Physiology and Pathophysiology, Peking University Health Science Cencer, Beijing 100083, China
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摘要

Abstract

Background The role of the Gαq/11-mediated signal transduction pathway in angiotensin Ⅱ (Ang Ⅱ) induced cardiac hypertrophy remains unclear. This study was to investigate the role of the Gαq/11 signal transduction pathway in the development of cardiac hypertrophy in 2K1C hypertensive rats and in cultured neonatal rat ventricular myocytes (NRVMs) and to elucidate the effects of the pathway on Ang Ⅱ induced cardiac hypertrophy.Methods Renal hypertension was induced in 2K1C hypertensive rats by placing a silver clip around the left renal artery. At 8 weeks after operation, the systolic blood pressure, the ratio of left ventricular weight to body weight (LV/BW), and the concentration of AngⅡ in the heart were measured. The protein levels of Gαq/11 and extracellular signal-regulated kinase 1/2 (ERK1/2) were assayed by Western blot analysis, and the activity of phospholipase C (PLC) in the myocardium was detected using [3H]-PIP2 as a substrate. Changes in [3H]-leucine incorporation and in the protein levels of the signal molecules Gαq/11, PLCβ3, and ERK1/2 were measured after NRVMs were stimulated with 10-7mol/L AngⅡ. Results The protein levels of Gαq/11 and ERK1/2 in the hearts of 2K1C rats increased by 35.8% and 31.9%, respectively, compared with the sham group. The PLC activity in the 2K1C group was also significantly increased (P<0.05). The levels of Gαq/11, PLCβ3, and ERK1/2 increased significantly after NRVMs were stimulated by AngⅡ. The upregulation of Gαq/11, PLCβ3 and ERK1/2 in NRVMs occurred prior to [3H]-leucine incorporation increases, and could be inhibited with losartan. Conclusion AngⅡ can initiate cardiac hypertrophy and upregulate signal molecules in the Gαq/11-mediated signal transduction pathway, such as Gαq/11, PLCβ3 and ERK1/2, at both tissue and cellular levels.

关键词

angiotensin Ⅱ/G protein/signal transduction/cardiac hypertrophy

Key words

angiotensin Ⅱ/G protein/signal transduction/cardiac hypertrophy

分类

医药卫生

引用本文复制引用

白桦,吴立玲,邢东琦,刘洁,赵亚莉..Angiotensin Ⅱ induced upregulation of Gαq/11, phospholipase Cβ3 and extracellular signal-regulated kinase 1/2 via angiotensin Ⅱtype 1 receptor[J].中华医学杂志(英文版),2004,117(1):88-93,6.

基金项目

This project was supported by grants of the National Natural Science Foundation of China (No. 30170379 and 39870356) and the Research Fund for Doctoral Programs of Higher Education (No. 20020001084). (No. 30170379 and 39870356)

中华医学杂志(英文版)

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