H2O2 Signaling-Triggered PI3K Mediates Mitochondrial Protection to Participate in Early Cardioprotection by Exercise Preconditioning

作者：Yuan, Yang; Pan, Shan-Shan^*; Wan, Dong-Feng; Lu, Jiao; Huang, Yue

来源：Oxidative Medicine and Cellular Longevity, 2018, 2018: 1916841.

DOI：10.1155/2018/1916841

• PERMEABILITY TRANSITION PORE
• ISCHEMIA-REPERFUSION INJURY
• OXIDATIVE STRESS
• POSTCONDITIONING PROTECTS
• EXHAUSTIVE EXERCISE
• MYOCARDIAL INJURY
• HYDROGEN-PEROXIDE
• PKC-EPSILON
• AUTOPHAGY
• HEART

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 H2O2 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 mitochondria' 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 H2O2-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 H2O2 and influenced by Bedinl-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 Bedinl/Bcl-2 ratio, cytochrome c leakage, mitochondrial dynamin-1-like protein (Drp-1) expression, and VDAC1 dephosphorylation. These observations suggest that H2O2 generation regulates mitochondria' protection in EEP-induced cardioprotection.

• 出版日期2018
• 单位上海体育学院