PRMT1 promotes H2O2 induced cardiomyocytes cell via mediating arginine methylation of P53

Background: Abnormal methylation of protein arginine can cause dysfunction of cardiomyocytes, it is important to further elucidate the molecular mechanism.

Method: Candidate protein arginine methyltransferases (PRMTs) were selected using blood samples of myocardial infarction (MI) and control group. The isolated primary cardiomyocyte (PC) and H9C2 cells were treated with H₂O₂ to mimic MI in vitro and rats with myocardial ischemia-reperfusion (I/R) were established to mimic MI in vivo. The protein content of PRMT1 methylation product P53 was detected to reflect the PRMT1 activity.

Result: PRMT1 was aberrant upregulated in MI models. PRMT1 ablation suppressed cell Apoptosis and inflammatory cytokine secretion to reverse the H₂O₂ function. The upregulation of PRMT1 accelerated the degradation of P53 protein through the arginine methylation. Inhibition of PRMT1 alleviated cardiac damage after I/R in rats.

Conclusion: PRMT1 promoted MI by mediating arginine methylation of P53. PRMT1 may be a promising therapeutic target for MI.

Arginine methylation; Myocardial infarction; P53; Protein arginine methyltransferase 1 (PRMT1).