Effects of heavy-load exercise on skeletal muscle cells apoptosis and mechanisms of mitochondrial apoptosis in rats

doi:10.12047/j.cjap.6319.2022.106

Abstract

Abstract: Objective: To analyze the molecular mechanisms of skeletal muscle cells apoptosis induced by heavy-load exercise with Omi as the entry point. Methods: One hundred and twenty-six adult SD rats were randomly divided into five groups: control group(C), eccentric exercise group (E), simple blocking group (U), DMSO group (D) and exercise block group (EU). In addition to the C group, the other four groups were randomly divided into 0 h after experiment, 12 h after experiment, 24 h after experiment, 48 h after experiment and 72 h after experiment with 6 rats in each group. E and EU group were submitted to a heavy-load exercise on a treadmill down a 16° decline, 16 m/min for 90 minutes. U, D and EU group were one-time intervened with drugs. U and EU groups were intraperitoneally injected with 1.5 μmol/kg ucf-101, D group were intraperitoneally injected with 1.5 μmoL/kg 0.5% DMSO. The rats were sacrificed in batches at different time points after experiment, then the soleus were saved to detect the Caspase-3,-8,-9,-12 activities and protein expressions of Omi and XIAP. Results: Compared with group C, the mitochondrial distribution and morphology appeared the typical ultrastructure pathological changes, the opening degree of MPTP was increased significantly (P＜0.01) or (P＜0.05), protein expressions of Omi and XIAP were increased significantly (P＜0.01 or P＜0.05), the activities of Caspase-9 and Caspase-3 were increased significantly (P＜0.01 or P＜0.05) in group E. Compared with group C, there was no significant difference in XIAP protein and caspase-9, - 3 activities in group U and Group D. The change trend of XIAP protein and Caspase-9, - 3 activities was the same as those between EU group and E group, but the change range of XIAP protein in EU group was significantly higher than that in E group (P＜0.01), and the change ranges of caspase-9, - 3 activities in EU group were significantly lower than those in E group (P＜0.01). Conclusion: A single heavy-load exercise can induce changes in the mitochondria morphology and structure in rats, open the high permeability of MPTP, and improve the expression of Omi protein, then through its downstream XIAP-Caspase pathway, start the mitochondrial apoptosis pathway mediated by caspase-9, and finally lead to myocyte apoptosis. The inhibition of Omi can reduce the cell apoptosis level of motor induced skeletal muscle cells.

Key words: exercise, skeletal muscle, cell apoptosis, Omi, XIAP, Ucf-101, rat

CLC Number:

G804.2

ZHAO Xiao-qin, YOU Jia-qi, LIU Xiao-ran, SUN Jun-zhi, LI Jun-ping, WANG Rui-yuan. Effects of heavy-load exercise on skeletal muscle cells apoptosis and mechanisms of mitochondrial apoptosis in rats[J]. CJAP, 2022, 38(5): 569-576.

References

[1] 宋卫红, 汤长发, 刘文锋. 离心运动对大鼠骨骼肌细胞凋亡和增殖的影响[J]. 中国应用生理学杂志, 2013, 29(1): 86-90.
[2] Du Y, Yang D, Dong X, et al. Omi inhibition ameliorates neuron apoptosis and neurological deficit after subarachnoid hemorrhage in rats[J]. Genes Genom, 2021, 43(12): 1423-1432.
[3] Su XJ, Huang L, Qu Y, et al. Progress in research on the role of Omi/HtrA2 in neurologicaldiseases[J]. Rev Neurosci, 2019, 30(3): 279-287.
[4] 赵晓琴, 孙君志, 白胜超, 等. 针刺对离心运动大鼠骨骼肌Omi/XIAP信号通路的影响[J]. 西安体育学院学报, 2018, 35(4): 468-477.
[5] 张欣, 王瑞元. 大负荷运动诱导大鼠骨骼肌损伤对其自噬超微结构及Beclin1和LC-3Ⅱ/Ⅰ的影响[J]. 中国应用生理学杂志, 2020, 36(4): 296-300.
[6] Wang P, Hu Y, Yao D, et al. Omi/HtrA2 regulates a mitochondria-dependent apoptotic pathwayn a murine model of septic encephalopathy[J]. Cell Physiol Biochem, 2018, 49(6): 2163-2173.
[7] 连婷, 张瑞君, 熊晓兰, 等. 线粒体通透性转换孔在锌缺乏模型大鼠心肌缺血 /再灌注损伤中的作用[J]. 基础医学与临床, 2022, 42(3): 389-394.
[8] 张海平, 宋吉锐. 一次力竭性离心运动对大鼠肱三头肌超微结构的影响[J]. 上海体育学院学报, 2008, 32(5): 44-47.
[9] Halestrap AP. What is the mitochondrial permeability transition pore[J]. J Mol Cell Cardiol, 2009, 46(6): 821-831.
[10] 王振涛, 任雪萍, 吴鸿, 等. 抗纤益心方干预线粒体通透性转换孔抑制心肌细胞凋亡的机制[J]. 中国实验方剂学杂志, 2021, 27(18): 42-48.
[11] Chung HJ, Jamal MAHM, Hong ST. The function of bacterial HtrA is evolutionally conserved in mammalian HtrA2/Omi[J]. Sci Rep, 2020, 10(1): 5284.
[12] Liu D, Wu L, Wu Y, et al. Heat shock factor 1-mediated transcription activation of Omi/HtrA2 induces myocardial mitochondrial apoptosis in the aging heart[J]. Aging (Albany NY), 2019, 11(20): 8982-8997.
[13] Liu X, Lei J, Wang K, et al. Mitochondrial Omi/HtrA2 promotes caspase activation through cleavage of HAX-1 in aging heart[J]. Rejuv Res, 2017, 20(3): 183-192.
[14] Jost PJ, Vucic D. Regulation of cell death and immunity by XIAP[J]. Cold Spring Harb Perspect Biol, 2020, 12(8): a036426.
[15] Tu H, Costa M. XIAP's profile in human cancer[J]. Biomolecules, 2020, 10(11): 1493-1493.
[16] Winkler J, Rand ML, Schmugge M, et al. Omi/HtrA2 and XIAP are components of platelet apoptosis signalling[J]. Thromb Haemost, 2013, 109(3): 532-539.
[17] Wang P, Hu Y, Yao D, et al. Omi/HtrA2 regulates a mitochondria-dependent apoptotic pathwayn a murine model of septic encephalopathy[J]. Cell Physiol Biochem, 2018, 49(6): 2163-2173.