Up-regulation of Thioredoxin 1 by aerobic exercise training attenuates endoplasmic reticulum stress and cardiomyocyte apoptosis following myocardial infarction.

Exercise training (ET) has been reported to reduce oxidative stress and endoplasmic reticulum (ER) stress in the heart following myocardial infarction (MI). Thioredoxin 1 (Trx1) plays a protective role in the infarcted heart. However, whether Trx1 regulates ER stress of the infarcted heart and participates in ET-induced cardiac protective effects are still not well known. In this work, H9c2 cells were treated with hydrogen peroxide (HO) and recombinant human Trx1 protein (TXN), meanwhile, adult male C57B6L mice were used to establish the MI model, and subjected to a six-week aerobic exercise training (AET) with or without the injection of Trx1 inhibitor, PX-12. Results showed that HO significantly increased reactive oxygen species (ROS) level and the expression of TXNIP, CHOP and cleaved caspase12, induced cell apoptosis; TXN intervention reduced ROS level and the expression of CHOP and cleaved caspase12, and inhibited cell apoptosis in HO-treated H9c2 cells. Furthermore, AET up-regulated endogenous Trx1 protein expression and down-regulated TXNIP expression, restored ROS level and the expression of ER stress-related proteins, inhibited cell apoptosis as well as improved cardiac fibrosis and heart function in mice after MI. PX-12 partly inhibited the AET-induced beneficial effects in the infarcted heart. This study demonstrates that Trx1 attenuates ER stress-induced cell apoptosis, and AET reduces MI-induced ROS overproduction, ER stress and cell apoptosis partly through up-regulating of Trx1 expression in mice with MI.