Prdx1 alleviates cardiomyocyte apoptosis through ROS-activated MAPK pathway during myocardial ischemia/reperfusion injury

Abstract

Apoptosis induced by oxidative stress blocks the recovery of heart function in myocardial ischemia reperfusion injury (MIRI). Peroxiredoxin 1 (Prdx1) inhibits oxidative stress. However, the expression and function of Prdx1 in MIRI are unclear. In present study, Prdx1 protein level increased in rat MIRI model, associated with cardiomyocyte apoptosis. Cultured rat embryonic ventricular myocardial H9c2 cells with hypoxia/reoxygenation (H/R) treatment was utilized to mimic MIRI in vitro, showing that H/R treatment increased the ratio of p-p38/p38, p-JNK/JNK and apoptosis index. But Prdx1 ameliorate the up-regulation of p-p38/p38 ratio and p-JNK/JNK ratio, as well as decreased H9c2 cell apoptosis. SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor) inhibited H9c2 cell apoptosis, and at the same time Prdx1 down-regulated the activation of p38 MAPK and JNK during H/R treatment. In addition, a ROS scavenger N-acetyl-l-cysteine (NAC) down-regulated the protein level of p-p38, p-JNK and Prdx1, and H9c2 cell apoptosis. In summary, these findings indicated that Prdx1 inhibited MAPK pathway induced cells apoptosis, and ROS is the upstream regulator of H/R induced apoptosis.

Keywords: Cardiomyocyte apoptosis; JNK; Myocardial ischemia/reperfusion injury; Peroxiredoxin 1; Reactive oxygen species; p38.