MAPK pathway mediates the induction of visfatin in neonatal SD rat cardiomyocytes pretreated with glucose

Abstract

The protein visfatin is an insulin mimetic that has been shown to reduce plasma glucose levels, increase cytokine production and induce angiogenesis. However, few studies have focused on visfatin expression in cardiomyocytes at the cellular level. Therefore, the aim of the present study was to investigate visfatin expression and its potential mechanisms in cultured neonatal rat cardiomyocytes exposed to high-glucose concentrations. Primary cultures of 2-to 3-day-old Sprague Dawley (SD) rat cardiomyocytes were pretreated with increasing concentrations of glucose. P38 mitogen-activated protein kinase (MAPK) pathway inhibitor SB203580, extra cellular signal-regulated kinase (ERK1/2) pathway inhibitor PD098059 and c-Jun NH 2-terminal kinase (JNK) pathway inhibitor SP600125 were used to block the effect of glucose on visfatin expression. Cell viability following each glucose treatment was determined using the MTT assay. Expression of visfatin was detected using RT-PCR and western blot analysis. Increased glucose concentration directly correlated with an increased expression of visfatin mRNA and protein in neonatal rat cardiomyocytes. Following high doses of glucose, visfatin mRNA and protein expression peaked after 24 h with no significant change thereafter. Increased visfatin expression was blocked by the P38 MAPK inhibitor SB203580, suggesting a potential mechanism not yet identified. Expression of visfatin in cardiomyocytes was increased through the P38 MAPK pathway in the presence of high-glucose concentrations.