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(H_(2)O_(2))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 H_(2)O_(2)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 H_(2)O_(2)-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.

Decrease in myostatin by ladder-climbing training is associated with insulin resistance in diet-induced obese rats

Background Suppression of myostatin （MSTN） has been associated with skeletal muscle atrophy and insulin resistance （IR）.However,few studies link MSTN suppression by ladder-climbing training （LCT） and IR.Therefore,we intended to identify the correlation with IR between LCT and to analyze the signaling pathways through which MSTN suppression by LCT regulates IR.Methods The rats were randomly assigned to two types of diet：normal pellet diet （NPD,n=8） and high-fat diet （HFD,n=16）.After 8 weeks,the HFD rats were randomly re-assigned to two groups （n=8 for each group）：HFD sedentary （HFD-S） and high-fat diet ladder-climbing training （HFD-LCT）.HFD-LCT rats were assigned to LCT for 8 weeks.Western blotting,immunohistochemistry and enzyme assays were used to measure expression levels and activities of MSTN,GLUT4,PI3K,Akt and Akt-activated targets （mTOR,FoxO1 and GSK-3β）.Results The LCT significantly improved IR and whole-body insulin sensitivity in HDF-fed rats.MSTN protein levels decreased in matching serum （42％,P=0.007） and muscle samples （25％,P=0.035） and its receptor mRNA expression also decreased （16％,P=0.041） from obese rats after LCT.But the mRNA expression of insulin receptor had no obvious changes in LCT group compared with NPD and HFD-S groups （P=0.074）.The ladder-climbing training significantly enhanced PI3K activity （1.7-fold,P=0.024） and Akt phosphorylation （83.3％,P=0.022） in HFD-fed rats,significantly increased GLUT4 protein expression （84.5％,P=-0.036）,enhanced phosphorylation of mTOR （4.8-fold,P ＜0.001） and inhibited phosphorylation of FoxO1 （57.7％,P=0.020）,but did not affect the phosphorylation of GSK-3β.Conclusions The LCT significantly reduced IR in diet-induced obese rats.MSTN may play an important role in regulating IR and fat accumulation by LCT via PI3K/Akt/mTOR and PI3K/Akt/FoxO1 signaling pathway in HFD-fed rats.