Department of Cardiology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
Department of Pathogen Biology, Medical College, Nantong University, Nantong 226001, Jiangsu, China.
Int J Biol Macromol. 2018 Jun;112:608-615. doi: 10.1016/j.ijbiomac.2018.02.009. Epub 2018 Feb 2.
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.
氧化应激诱导的细胞凋亡会阻碍心肌缺血再灌注损伤（MIRI）中心脏功能的恢复。过氧化物酶 1（Prdx1）可抑制氧化应激。然而，Prdx1 在 MIRI 中的表达和功能尚不清楚。在本研究中，在大鼠 MIRI 模型中观察到 Prdx1 蛋白水平增加，与心肌细胞凋亡有关。用缺氧/复氧（H/R）处理培养的大鼠胚胎心室心肌 H9c2 细胞来模拟体外 MIRI，结果表明 H/R 处理增加了 p-p38/p38、p-JNK/JNK 的比值和细胞凋亡指数。但 Prdx1 改善了 p-p38/p38 比值和 p-JNK/JNK 比值的上调，并降低了 H9c2 细胞的凋亡。SB203580（p38 抑制剂）和 SP600125（JNK 抑制剂）抑制 H9c2 细胞凋亡，同时 Prdx1 在 H/R 处理过程中下调了 p38 MAPK 和 JNK 的激活。此外，ROS 清除剂 N-乙酰半胱氨酸（NAC）下调了 p-p38、p-JNK 和 Prdx1 的蛋白水平，并降低了 H9c2 细胞的凋亡。综上所述，这些发现表明 Prdx1 抑制了 MAPK 通路诱导的细胞凋亡，而 ROS 是 H/R 诱导凋亡的上游调节因子。
