Cardioprotection of exercise preconditioning involving heat shock protein 70 and concurrent autophagy: a potential chaperone-assisted selective macroautophagy effect
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It has been confirmed that exercise preconditioning (EP) has a protective effect on acute cardiovascular stress. However, how Hsp70 participates in EP-induced cardioprotection is unknown. EP may involve Hsp70 to repair unfolded proteins or may also stabilize the function of the endoplasmic reticulum via Hsp70-related autophagy to work on a protective formation. Our EP protocol involves four periods of 10 min running with 10 min recovery intervals. We added a period of exhaustive running to test this protective effect, using histology and molecular biotechnology methods to detect related markers. EP provided cardioprotection at its early and late phases against exhaustive exercise-induced ischemic myocardial injury. Results showed that Hsp70 co-chaperone protein BAG3, ubiquitin adaptor p62 and critical autophagy protein LC3 were significantly upregulated at the early phase. Meanwhile, Hsp70, Hsp70/BAG3 co-localization extent, LC31 and LC3II were significantly upregulated at the late phase. Hsp70 mRNA levels and LC3II/I ratios were also consistent with the extent of myocardial injury following exhaustive exercise. Hsp70 increase was delayed relative to BAG3 and p62 after EP, indicating a pre-synthesized phenomenon of BAG3 and p62 for chaperone-assisted selective autophagy (CASA). The decreased Hsp70, BAG3 and p62 levels and increased Hsp70/BAG3 co-localization extent and LC3 levels induced by exhaustive exercise after EP suggest that EP-induced cardioprotection might associate with CASA. Hsp70 has a cardioprotective role and has a closer link with CASA in LEP. Additionally, EP may not cause exhaustion-dependent excessive autophagy regulation. Collectively, during early and late EP, CASA potentially plays different roles in cardioprotection.
KeywordsExercise preconditioning Cardioprotection Molecular chaperone Macroautophagy Hsp70
Early exercise preconditioning
Late exercise preconditioning
Heat shock protein 70
Bcl-2 associated athanogene 3
Microtubule-associated protein 1A/1B light chain 3
Unfolded protein response
Endoplasmic reticulum stress
70 kDa heat shock cognate protein
Chaperone-assisted selective autophagy
Cardiac troponin I
Heat shock factor
This work was supported by the National Natural Science Foundation of China (no. 31471136).
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
- 18.Li B, Tian J, Sun Y, Xu TR, Chi RF, Zhang XL, Hu XL, Zhang YA, Qin FZ, Zhang WF (2015) Activation of NADPH oxidase mediates increased endoplasmic reticulum stress and left ventricular remodeling after myocardial infarction in rabbits. Biochim Biophys Acta 1852(5):805–815. doi: 10.1016/j.bbadis.2015.01.010 PubMedCrossRefGoogle Scholar
- 25.Jarrett CL, D’Lugos AC, Mahmood TN, Gonzales RJ, Hale TM, Carroll CC, Dickinson JM, Angadi SS (2016) Effect of high intensity exercise preconditioning and training on antioxidant enzymes in cardiomyocytes during doxorubicin treatment. FASEB J 30(1 Supplement):lb601–lb601Google Scholar
- 53.Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282(33):24131–24145. doi: 10.1074/jbc.M702824200 PubMedCrossRefGoogle Scholar