Atorvastatin attenuates parathyroid hormone 1-34 induced cardiomyocytes hypertrophy through downregulating K-Ras-ERK1/2 pathway.
- Author:
Xiao-gang LIU
1
;
Nan MIAO
;
Man-shu SUI
;
Su-hong MU
;
Shi-lei ZHAO
;
Ru-juan XIE
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Animals, Newborn; Atorvastatin Calcium; Cardiomegaly; drug therapy; metabolism; Cells, Cultured; Heptanoic Acids; pharmacology; therapeutic use; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 3; metabolism; Myocytes, Cardiac; drug effects; metabolism; Parathyroid Hormone; metabolism; Pyrroles; pharmacology; therapeutic use; Rats; Rats, Wistar
- From: Chinese Journal of Cardiology 2012;40(12):1051-1055
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of atorvastatin on parathyroid hormone 1-34 (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).
METHODSNeonatal 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.
RESULTSCompared to PTH1-34 group, cellular diameter was decreased 12.07 µm, (3)H-leucine incorporation decreased 1622 cpm/well and single-cell 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, (3)H-leucine incorporation increased 750 cpm/well and single-cell protein content increased 49.08 pg, ANP or BNP increased 3.12 µg/L or 9.35 µg/L and 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.
CONCLUSIONSAtrovastatin attenuates PTH1-34 induced neonatal rat cardiomyocytes hypertrophy through downregulating K-Ras and ERK1/2 pathway.