Rat parathyroid hormone 1-34 signals through the MEK/ERK pathway to induce cardiac hypertrophy.
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.
Liu
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Department of Nephrology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
Xie
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Liu
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D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology; D007930:Leucine / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D005419:Flavonoids; D010281:Parathyroid Hormone; D009320:Atrial Natriuretic Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D007930:Leucine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one