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HO Signaling-Triggered PI3K Mediates Mitochondrial Protection to Participate in Early Cardioprotection by Exercise Preconditioning

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Publisher Wiley
Date 2018 Aug 28
PMID 30147831
Citations 14
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Abstract

Previous studies have shown that early exercise preconditioning (EEP) imparts a protective effect on acute cardiovascular stress. However, how mitophagy participates in exercise preconditioning- (EP-) induced cardioprotection remains unclear. EEP may involve mitochondrial protection, which presumably crosstalks with predominant HO oxidative stress. Our EEP protocol involves four periods of 10 min running with 10 min recovery intervals. We added a period of exhaustive running and a pretreatment using phosphoinositide 3-kinase (PI3K)/autophagy inhibitor wortmannin to test this protective effect. By using transmission electron microscopy (TEM), laser scanning confocal microscopy, and other molecular biotechnology methods, we detected related markers and specifically analyzed the relationship between mitophagic proteins and mitochondrial translocation. We determined that exhaustive exercise associated with various elevated injuries targeted the myocardium, oxidative stress, hypoxia-ischemia, and mitochondrial ultrastructure. However, exhaustion induced limited mitochondrial protection through a HO-independent manner to inhibit voltage-dependent anion channel isoform 1 (VDAC1) instead of mitophagy. EEP was apparently safe to the heart. In EEP-induced cardioprotection, EEP provided suppression to exhaustive exercise (EE) injuries by translocating Bnip3 to the mitochondria by recruiting the autophagosome protein LC3 to induce mitophagy, which is potentially triggered by HO and influenced by Beclin1-dependent autophagy. Pretreatment with the wortmannin further attenuated these effects induced by EEP and resulted in the expression of proapoptotic phenotypes such as oxidative injury, elevated Beclin1/Bcl-2 ratio, cytochrome c leakage, mitochondrial dynamin-1-like protein (Drp-1) expression, and VDAC1 dephosphorylation. These observations suggest that HO generation regulates mitochondrial protection in EEP-induced cardioprotection.

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References
1.
Dorn 2nd G . Mitochondrial pruning by Nix and BNip3: an essential function for cardiac-expressed death factors. J Cardiovasc Transl Res. 2010; 3(4):374-83. PMC: 2900478. DOI: 10.1007/s12265-010-9174-x. View

2.
Ostojic S . Exercise-induced mitochondrial dysfunction: a myth or reality?. Clin Sci (Lond). 2016; 130(16):1407-16. DOI: 10.1042/CS20160200. View

3.
Martindale J, Metzger J . Uncoupling of increased cellular oxidative stress and myocardial ischemia reperfusion injury by directed sarcolemma stabilization. J Mol Cell Cardiol. 2013; 67:26-37. PMC: 3920738. DOI: 10.1016/j.yjmcc.2013.12.008. View

4.
Xu Q, Li X, Lu Y, Shen L, Zhang J, Cao S . Pharmacological modulation of autophagy to protect cardiomyocytes according to the time windows of ischaemia/reperfusion. Br J Pharmacol. 2015; 172(12):3072-85. PMC: 4459024. DOI: 10.1111/bph.13111. View

5.
Shen Y, Pan S, Zhuang T, Wang F . Exercise preconditioning initiates late cardioprotection against isoproterenol-induced myocardial injury in rats independent of protein kinase C. J Physiol Sci. 2010; 61(1):13-21. PMC: 10716974. DOI: 10.1007/s12576-010-0116-9. View