Aerobic exercise upregulates the thioredoxin system and inhibits cardiomyocyte apoptosis in aging rats

doi:10.12307/2024.841

Abstract

Abstract: BACKGROUND: Studies have shown that cardiomyocyte apoptosis is closely related to cardiac decompensation and the cardiac aging process. Appropriate exercise can alter heart pump function in patients with heart failure as well as attenuate aging-induced cardiomyocyte apoptosis, hypertrophy, and fibrotic damage.
OBJECTIVE: To investigate the effects of long-term aerobic exercise on cardiomyocyte apoptosis and the thioredoxin system in aging rats.
METHODS: Thirty-six male Sprague-Dawley rats were selected and divided into three age groups: 3-month-old young group, 9-month-old middle-aged group, and 18-month-old elderly group, with 12 rats in each group. Within each age group, rats were randomly assigned to sedentary and exercise subgroups (n=6 per group). The sedentary groups did not undergo any exercise intervention. The exercise groups were acclimated to a treadmill environment and subsequently subjected to treadmill exercise for 45 minutes per day, at a speed of 15 m/min, 5 days per week for 10 weeks in total. At 24 hours after the final intervention, ELISA was employed to measure serum levels of cardiac troponin I and creatine kinase-MB in rats. TUNEL assay was utilized to detect cardiomyocyte apoptosis, while western blot assay was employed to assess the protein expression of Bax, Bcl-2, Caspase 3, thioredoxin-1, thioredoxin-2, thioredoxin reductase-1, thioredoxin reductase-2, thioredoxin-interacting protein, apoptosis signal-regulating kinase 1, and P38 mitogen-activated protein kinase in rat myocardial tissue.
RESULTS AND CONCLUSION: Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged sedentary groups and elderly exercise group (P < 0.01). Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged exercise groups and elderly exercise group (P < 0.01). Positive apoptotic cells in rat myocardial tissue, along with increased protein expression of Bax and Caspase 3, exhibited an age-related upward trend, while Bcl-2 protein expression showed a declining trend. In comparison with the sedentary groups within each age category, the number of apoptotic cardiomyocytes and the expression of Bax and Caspase 3 proteins were reduced to different degrees, and the expression of Bcl-2 protein was increased to different degrees in the corresponding exercise groups. Compared with the young sedentary group, middle-aged sedentary group and elderly exercise group, elderly sedentary rats showed a significant decrease in the expression of myocardial thioredoxin 1, thioredoxin 2, thioredoxin reductase 1, and thioredoxin reductase 2 proteins (P < 0.05, P < 0.01). The expression of myocardial thioredoxin 1, thioredoxin 2, and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the young exercise group (P < 0.05, P < 0.01), while the expression of thioredoxin reductase 1 and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the middle-aged exercise group (P < 0.01). The protein expression of thioredoxin-interacting protein, apoptosis signal-regulating kinase 1, and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly sedentary group than the young sedentary group, middle-aged sedentary group and elderly exercise group (P < 0.01). The protein expression of thioredoxin-interacting protein, apoptosis signal-regulating kinase 1, and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly exercise group than the young exercise group and middle-aged exercise group (P < 0.01). To conclude, aerobic exercise may enhance the anti-apoptotic effects of thioredoxin by down-regulating the expression of thioredoxin-interacting protein in aging rat hearts, leading to the downregulation of apoptosis signal-regulated kinase 1 and P38 mitogen-activated kinase protein, thereby alleviating myocardial cell apoptosis in aging rat hearts.

Key words: aerobic exercise, aging rat, cardiomyocyte, apoptosis, thioredoxin

CLC Number:

Xu Zheng, Zhao Xiaoqin, Chen Xiaodan, Wang Jiapu, Bao Fenmiao, Yu Liang, Li Junping, Wei Yan. Aerobic exercise upregulates the thioredoxin system and inhibits cardiomyocyte apoptosis in aging rats[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(34): 5508-5515.

Figures/Tables 6

安静组间对比：与青年安静组相比，中年安静组大鼠心肌硫氧还蛋白1和硫氧还蛋白2蛋白表达降低(P < 0.01，P < 0.05)，硫氧还蛋白还原酶1和硫氧还蛋白还原酶2蛋白表达无明显变化(P > 0.05)；老年安静组大鼠心肌组织硫氧还蛋白1、硫氧还蛋白2、硫氧还蛋白还原酶1、硫氧还蛋白还原酶2蛋白表达均降低(P < 0.01，P < 0.05)。与中年安静组相比，老年安静组大鼠心肌硫氧还蛋白1、硫氧还蛋白2、硫氧还蛋白还原酶和硫氧还蛋白还原酶2蛋白表达均降低(P < 0.01，P < 0.05)。运动前后对比：与青年安静组相比，青年运动组大鼠心肌硫氧还蛋白1和硫氧还蛋白2蛋白表达升高(P < 0.05)，硫氧还蛋白还原酶1和硫氧还蛋白还原酶2蛋白表达无明显变化(P > 0.05)；与中年安静组相比，中年运动组大鼠心肌组织硫氧还蛋白1、硫氧还蛋白2、硫氧还蛋白还原酶1、硫氧还蛋白还原酶2蛋白表达均升高(P < 0.01，P < 0.05)。与老年安静组相比，老年运动组大鼠心肌组织硫氧还蛋白1、硫氧还蛋白2、硫氧还蛋白还原酶1、硫氧还蛋白还原酶2蛋白表达均升高(P < 0.01，P < 0.05)。运动组间对比：与青年运动组大鼠比，中年运动组大鼠心肌硫氧还蛋白1和硫氧还蛋白2蛋白表达均降低(P < 0.01，P < 0.05)，硫氧还蛋白还原酶1蛋白表达无明显变化(P > 0.05)，硫氧还蛋白还原酶2蛋白表达升高(P < 0.05)；老年运动组大鼠心肌组织硫氧还蛋白1、硫氧还蛋白2和硫氧还蛋白还原酶2蛋白表达降低(P < 0.01，P < 0.05)，硫氧还蛋白还原酶1蛋白表达无明显变化(P > 0.05)。与中年运动组大鼠比，老年运动组大鼠心肌组织硫氧还蛋白1和硫氧还蛋白2蛋白表达均无明显变化(P > 0.05)，硫氧还蛋白还原酶1和硫氧还蛋白还原酶2蛋白表达均显著降低(P < 0.01)。 2.6 各组大鼠心肌组织硫氧还蛋白系统下游蛋白表达见图4。"

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