Rat Parathyroid Hormone 1-34 Signals through the MEK/ERK Pathway to Induce Cardiac Hypertrophy
Rat Parathyroid Hormone 1-34 Signals through the MEK/ERK Pathway to Induce Cardiac Hypertrophy
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DOI：
10.1177/147323000803600510
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发表时间：
2008-09-01
影响因子：
1.6
通讯作者：
Liu, S.
中科院分区：
文献类型：
--
作者：
Liu, X.;Xie, R.;Liu, S.
本研究旨在探讨丝裂原活化蛋白激酶（MAPK）激酶（MEK）/细胞外信号调节激酶（ERK）通路在甲状旁腺激素（PTH）诱导的心肌肥大中的作用。使用不同浓度的大鼠PTH 1 -34诱导新生大鼠心室心肌细胞肥大，并将其效果与对照细胞和用MEK 1选择性抑制剂PD 98059处理的细胞进行比较。根据细胞直径、心房利钠肽（ANP）mRNA表达和蛋白质合成评估肥大;通过测量磷酸化ERK 1/2水平评估MEK/ERK通路。与正常对照细胞相比，100 nM PTH 1 -34处理24 h可有效诱导心肌肥大（细胞直径增加，蛋白质合成和ANP mRNA表达增加），并增加磷酸化ERK 1/2的水平。用PTH 1 -34加PD 98059处理显著减弱了这些变化。这些结果表明，抑制MEK/ERK通路阻断PTH 1 -34诱导的心肌肥大，提示PTH 1 -34可能通过MAPK通路发出信号以诱导心肌细胞肥大。
This study aimed to characterize the role of the mitogen-activated protein kinase (MAPK) kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway in cardiac hypertrophy induced by parathyroid hormone (PTH). Various concentrations of rat PTH1-34 were used to induce hypertrophy in neonatal rat ventricular cardiomyocytes, and the effects were compared with control cells and those treated with PD98059, a selective inhibitor of MEK1. Hypertrophy was assessed in terms of cell diameter, atrial natriuretic peptide (ANP) mRNA expression and protein synthesis; the MEK/ERK pathway was assessed by measuring levels of phosphorylated ERK1/2. Treatment with PTH1-34 at 100 nM for 24 h effectively induced cardiac hypertrophy (increased cell diameter, protein synthesis and ANP mRNA expression) and also increased levels of phosphorylated ERK1/2 compared with normal control cells. Treatment with PTH1-34 plus PD98059 significantly attenuated these changes. These results demonstrate that inhibition of the MEK/ERK pathway blocks PTH1-34-induced cardiac hypertrophy, suggesting that PTH1-34 might signal through the MAPK pathway to induce hypertrophy in cardiomyocytes.