Atorvastatin attenuates parathyroid hormone1-34 induced cardiomyocytes hypertrophy through downregulating K-Ras-ERK1/2 pathway
10.3760/cma.j.issn.0253-3758.2012.12.015
- VernacularTitle:小鸟苷酸三磷酸结合蛋白-细胞外信号调节激酶1/2途径参与了阿托伐他汀抗大鼠心肌肥厚的作用
- Author:
Xiao-Gang LIU
1
;
Nan MIAO
;
Man-Shu SUI
;
Su-Hong MU
;
Shi-Lei ZHAO
;
Ru-Juan XIE
Author Information
1. 150036,哈尔滨医科大学附属第一医院肾内科
- Keywords:
Myocytes,cardiac;
Hypertrophy;
Teriparatide;
Extracellular signal-regulated MAP kinases;
Atorvastatin
- From:
Chinese Journal of Cardiology
2012;40(12):1051-1055
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of atorvastatin on parathyroid hormone1-34 (PTH1-34) induced neonatal rat cardiomyocytes hypertrophy and on the expression changes of small GTP-binding protein (K-Ras) and extracellular signal regulated protein kinases 1/2 (ERK1/2).Methods Neonatal rat cardiomyocytes hypertrophy was established with 10-7 mol/L rPTH1-34 in the presence or absence of 10-5 mol/L atorvastatin or 10-4 mol/L mevalonic acid (MVA).Cardiomyocyte diameter was measured by Motic Images Advanced 3.0 software,the synthetic rate of protein in cardiomyocytes was determined by 3 H-leucine incorporation and single-cell protein content was measured by BCA.The concentration of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined by ELISA.Protein expression of ERK1/2、p-ERK1/2 and K-Ras was detected by Western blot.Results Compared to PTH1-34 group,cellular diameter was decreased 12.07 μm,3 H-leucine incorporation decreased 1622 cpm/well and singlecell protein content decreased 84.34 pg,ANP or BNP concentration reduced 7.13 μg/L or 20.04 μg/L,protein expression of K-Ras,ERK1/2 or p-ERK1/2 downregulated 0.81,0.19 and 1.44 fold,respectively,in PTH1-34 plus atrovastatin co-treated cardiomyocytes (all P ＜ 0.05).Compared to PTH1-34 plus atrovastatin co-treated group,cardiomyocyte diameter increased 4.95 μm,3H-leucine incorporation increased 750 cpm/well and single-cell protein content increased 49.08 pg,ANP or BNP increased 3.12μg/L or 9.35 μg/L aud protein expression of K-Ras,ERK1/2 or p-ERK1/2 upregulated 0.52,0.06 and 1.19 fold (all P ＜ 0.05) in MVA,PTH1-34 and atrovastatin co-treated cardiomyocytes.Conclusions Atrovastatin attenuates PTH1-34 induced neonatal rat cardiomyocytes hypertrophy through downregulating K-Ras and ERK1/2 pathway.
