Abstract
This study aimed to explore the occurrence of necroptosis in skeletal muscle after eccentric exercise and investigate the role and possible mechanisms of ZBP1 and its related pathway proteins in the process, providing a theoretical basis for the study of exercise-induced skeletal muscle injury and recovery. Forty-eight male adult Sprague–Dawley rats were randomly divided into a control group (C, n = 8) and an exercise group (E, n = 40). The exercise group was further divided into 0 h (E0), 12 h (E12), 24 h (E24), 48 h (E48), and 72 h (E72) after exercise, with 8 rats in each subgroup. At each time point, gastrocnemius muscle was collected under general anesthesia. The expression levels of ZBP1 and its related pathway proteins were assessed using Western blot analysis. The colocalization of pathway proteins was examined using immunofluorescence staining. After 48 h of eccentric exercise, the expression of necroptosis marker protein MLKL reached its peak (P < 0.01), and the protein levels of ZBP1, RIPK3, and HMGB1 also peaked (P < 0.01). At 48 h post high-load eccentric exercise, there was a significant increase in colocalization of ZBP1/RIPK3 pathway proteins, reaching a peak (P < 0.01). (1) Eccentric exercise induced necroptosis in skeletal muscle, with MLKL, p-MLKLS358, and HMGB1 significantly elevated, especially at 48 h after exercise. (2) After eccentric exercise, the ZBP1/RIPK3-related pathway proteins ZBP1, RIPK3, and p-RIPK3S232 were significantly elevated, particularly at 48 h after exercise. (3) Following high-load eccentric exercise, there was a significant increase in the colocalization of ZBP1/RIPK3 pathway proteins, with a particularly pronounced elevation observed at 48 h post-exercise.
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The data used in this study are available upon request. Researchers interested in accessing the data can contact shikexin0611@126.com for further information.
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This work was supported by the Special Funded Project of the Basic Scientific Research Operation Fee of the Central University [Grant Nos. 2019PT013].
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KS, XW, ZK, and JL collectively conceived and designed the entire study; KS and XW conducted the experiments and analyzed the data; KS drafted the manuscript; JL, ZK, and XW reviewed and edited the manuscript. We thank all the participants for their contributions to the project.
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Shi, K., Wang, X., Ke, Z. et al. The role of ZBP1 in eccentric exercise-induced skeletal muscle necroptosis. J Muscle Res Cell Motil 44, 311–323 (2023). https://doi.org/10.1007/s10974-023-09660-6
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DOI: https://doi.org/10.1007/s10974-023-09660-6