Neuropeptide Y1 receptor subtype induces cardiomyocyte hypertrophy via CaMKII-MEF2 pathway

Abstract

Objective To investigate the effect of neuropeptide Y (NPY) Y1 receptor subtype on cardiac hypertrophy, and to determine the role of Ca2+/CaM-CaMKⅡ-MEF2 signaling pathway in this process. Methods The primary cultured SD rat cardiomyocytes were stimulated with different concentrations of NPY or Y1 receptor agonists, Leu31 and Pro34 NPY. The 3Tritium-leucine (3H-Leu) incorporation assay was used to assess the rate of protein synthesis in cardiomyocytes. The mRNA expressions of the hypertrophy-related genes ANF and β-MHC were measured by fluorescence quantitative PCR. The immunofluorescence staining was used to determine the surface area of cardiomyocytes and expression of cardiomyocyte MEF2. Results The effects of Leu31, Pro34 NPY and NPY were similar. Both of them significantly increased the incorporation of cardiomyocytes 3H-Leu (P<0.05) . The mRNA expressions of cardiomyocytes ANF and β-MHC were significantly up-regulated (P<0.05) . The surface area of cardiomyocytes significantly increased[ (2 270.93±80.09) μm2 vs (3 340.64±101.06) μm2; (2 256.57±57.0) μm2 vs (2 915.48±43.39) μm2; all P<0.05]. The CaMKⅡ inhibitor KN-93 could effectively block the stimulatory effects of Leu31 and Pro34 NPY on protein synthesis rate and hypertrophy gene expression in cardiomyocytes. The expression of MEF2 in cardiomyocytes remarkably increased after stimulation of Leu31 and Pro34 NPY for 24 h (P<0.05) . Conclusion The neuropeptide Y1 receptor subtype induces cardiac hypertrophy via Ca2+/CaM-CaMKⅡ- MEF2 signalingpathway. Key words: Neuropeptide Y; Y1 receptor; Hypertrophy