p42/p44 mitogen-activated protein kinases inhibit atrial natriuretic peptide mRNA transcription in gp130-mediated hypertrophic ventricular myocytes

ObjectiveTo understand the role of ANP 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/p44 MAPK) signaling pathway.MethodsIsolated neonatal ventricular myocytes were treated with different concentrations of CT-1 (10−9, 10−8and 10−7mol/L). MTT was used to analyze the viability and RT-PCR was used to detect ANP mRNA levels in cardiomyocyte. To inhibit p42/p44 MAPK activity in hypertrophic cardiomyocytes, the cells were pretreated with a specific MEK1 inhibitor.ResultsCT-1 significantly induced ANP mRNA expression and the viability of cardiomyocytes in a dose- and time-dependent manner. Furthermore, blocking p42/p44 MAPK activity by the special MEK1 inhibitor upregulated the ANP mRNA.Conclusionsp42/p44 MAPK have an important role in suppressing ANP mRNA transcription and cell activity in gp130-mediated hypertrophic ventricular myocytes.