Yuan Yang, Pan Shan-Shan, Shen Yu-Jun
School of Kinesiology, Shanghai University of Sport, 399 Changhai Road, Shanghai, 200438, China.
J Physiol Sci. 2018 Jan;68(1):55-67. doi: 10.1007/s12576-016-0507-7. Epub 2016 Dec 7.
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.
已证实运动预处理（EP）对急性心血管应激具有保护作用。然而，热休克蛋白70（Hsp70）如何参与EP诱导的心脏保护尚不清楚。EP可能通过Hsp70修复未折叠蛋白，也可能通过与Hsp70相关的自噬稳定内质网功能来发挥保护作用。我们的EP方案包括四个10分钟的跑步阶段，中间间隔10分钟的恢复时间。我们增加了一个力竭性跑步阶段来测试这种保护作用，采用组织学和分子生物技术方法检测相关标志物。EP在早期和晚期均对力竭性运动诱导的缺血性心肌损伤提供心脏保护。结果显示，早期共伴侣蛋白BAG3、泛素衔接蛋白p62和关键自噬蛋白LC3显著上调。同时，晚期Hsp70、Hsp70/BAG3共定位程度、LC3I和LC3II显著上调。Hsp70 mRNA水平和LC3II/I比率也与力竭性运动后的心肌损伤程度一致。EP后Hsp70的增加相对于BAG3和p62有所延迟，表明BAG3和p62存在伴侣蛋白辅助的选择性自噬（CASA）的预合成现象。EP后力竭性运动导致的Hsp70、BAG3和p62水平降低以及Hsp70/BAG3共定位程度和LC3水平升高表明，EP诱导的心脏保护可能与CASA有关。Hsp70具有心脏保护作用，且在运动预处理中与CASA有更密切的联系。此外，EP可能不会导致依赖于力竭的过度自噬调节。总体而言，在运动预处理的早期和晚期，CASA在心脏保护中可能发挥不同作用。
