Effects of P38 MAPK signaling pathway on anacardic acid attenuating mouse cardiomyocyte hypertrophy induced by phenylephrine

AIM: To investigate the roles of P38 mitogen-activated protein kinase (P38 MAPK) in the process of anacardic acid (AA) attenuating mouse cardiomyocyte hypertrophy induced by phenylephrine (PE). METHODS: Cardiomyocyte hypertrophy was induced by PE in primary neonatal mouse myocardial cells. According to random number table method, the experiments were designed in 6 groups as following: control group, PE+ DMSO group, PE group, PE+ AA group, PE+ AA+ P38 inhibitor group and PE+ P38 inhibitor group. Mouse myocardial cells were collected after intervention for 48 h. The protein levels of p-P38, acetylated histone H3 at lysine 9 (H3K9ac) and atrial natriuretic peptide (ANP) were determined by Western blot. The interaction between p-P38 and H3K9ac was verified by co-immunoprecipitation (Co-IP). The mRNA expression of myocyte enhancer factor 2C (MEF2C) were tested by RT-qPCR. Mouse myocardial cell surface area was observed by immunofluorescence staining. RESULTS: The results of Western blot showed that the protein levels of p-P38 and H3K9ac in PE group were significantly increased compared with control group (P<0.05), and the levels of MEF2C mRNA and ANP protein in PE group were apparently increased compared with control group (P<0.05). However, P38 inhibitor and histone acetylase inhibitor AA attenuated P38 phosphorylation and H3K9 acetylation induced by PE, and down-regulated the over-expression of MEF2C and ANP in the mouse myocardial cells (P<0.05). The results of immunofluorescence staining showed that PE apparently increased mouse myocardial cell surface area (P<0.05), while P38 inhibitor and AA attenuated cardiomyocyte hypertrophy induced by PE (P<0.05). CONCLUSION: The mechanism of AA attenuating cardiomyocyte hypertrophy induced by PE may be related to the regulation of histone acetylation modification imbalance mediated by P38 MAPK signaling pathway.