Late Exercise Preconditioning Promotes Autophagy against Exhaustive Exercise-Induced Myocardial Injury through the Activation of the AMPK-mTOR-ULK1 Pathway.

Hong-Tao Liu,Shan-Shan Pan

doi:10.1155/2019/5697380

Abstract

Accumulating evidence shows that the AMPK-mTOR pathway modulates autophagy via coordinated phosphorylation of ULK1. The aim of the present study was to investigate the relationship between AMPK, mTOR, and ULK1 during late exercise preconditioning (LEP), and to explore whether LEP-induced myocardial protection is related to the autophagy. The exercise preconditioning (EP) protocol was as follows: rats were instructed to for run four repeated in duration of 10 minutes (including 10 minutes rest between each period) on a treadmill. Exhaustive exercise (EE) after LEP pretreatment and administration of wortmannin (an autophagy inhibitor that suppresses Class III PI3K-kinase (PI3KC3) activity) were added to test the protective effect. Cardiac troponin I (cTnI), and transmission electron microscopy (TEM), along with hematoxylin-basic fuchsin-picric acid (HBFP) staining, were used to evaluate the myocardial ischemic-hypoxic injury and protection. Western blot was used to analyze the relationship of autophagy-associated proteins. Exhaustive exercise caused severe myocardial ischemic-hypoxic injury, which led to an increase in cTnI levels, changes of ischemia–hypoxia, and cells ultrastructure. Compared with the EE group, LEP significantly suppressed exhaustive exercise-induced myocardial injury. However, wortmannin attenuated LEP-induced myocardial protection by inhibiting autophagy. Compared with the C group, AMPK was increased in the LEP, EE, and LEP+EE groups, but phosphorylation of AMPK at Thr172 was not significantly changed. Exercise did not have any effect on mTOR expression. Compared with the C group, ULK1 was increased and the ULK1ser757/ULK1 ratio was decreased in the LEP and LEP+EE groups. ULK1 was not significantly affected in the EE group, however, phosphorylation of ULK1 at Ser757 was remarkably decreased. To sum up, our results suggested that LEP promoted autophagy through the activation of AMPK-mTOR-ULK1 pathway, and that activated autophagy was partially involved in myocardial protection against EE-induced myocardial ischemic-hypoxic injury.

Highlights

Acute exercise-induced cardiac preconditioning has confer immediate cardioprotection against ischemic events [1]
The results showed that inhibited autophagy led to higher Cardiac troponin I (cTnI) levels in the W+late exercise preconditioning (LEP)+EE group compared to the LEP plus EE (LEP+EE) group
Combined with the previously mentioned injuries in the wortmannin plus LEP (W+LEP)+EE group, these results suggested that LEP-induced autophagy was partially involved in myocardial protection, while the beneficial effects were suppressed by the application of autophagy inhibitor

Summary

Introduction

Acute exercise-induced cardiac preconditioning has confer immediate cardioprotection against ischemic events [1]. Is form of exercise-induced intrinsic myocardial protection is termed exercise preconditioning (EP), which exerts myocardial protective effects on subsequent permanent myocardial ischemichypoxic injury. E intrinsic myocardial protection initiated by EP is similar to ischemic preconditioning (IPC), and may cause reduction of myocardial stunning [5], and the reduction in infarct size [6, 7]. Similar to IPC, EP has two protection phases: early exercise preconditioning (EEP) and late exercise preconditioning (LEP). A er EP, EEP occurs immediately and sustains 2 ~ 3 hours, and LEP emerges 24 hours later and can last several days [1]. The underlying mechanisms of EP-induced myocardial protection are still not fully understood

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Discussion

Conclusion