p42/p44 mitogen-activated protein kinases inhibit atrial natriuretic peptide mRNA transcription in g

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Objective:To understand the role ofANP mRNA transcription regulation in gp130-mediated cardiomyocyte hypertrophy, and the involved mitogen-activated protein kinase kinase(MEK)-extracellular signal-regulated kinase(ERK, also called p42/p44MAPK) signaling pathway. Methods:Isolated neonatal ventricular myocytes were treated with different concentrations of CT-1(10-9,10-8 and10-7 mol/L).MTT was used to analyze the viability andRT-PCR was used to detectANP mRNA levels in cardiomyocyte.To inhibit p42/p44MAPK activity in hypertrophic cardiomyocytes, the cells were pretreated with a specificMEK1 inhibitor.Results:CT-1 significantly inducedANP mRNA expression and the viability of cardiomyocytes in a dose- and time-dependent manner.Furthermore, blocking p42/p44MAPK activity by the special MEK1 inhibitor upregulated theANP mRNA.Conclusions: p42/p44MAPK have an important role in suppressingANP mRNA transcription and cell activity in gp130-mediated hypertrophic ventricular myocytes.
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