التفاصيل البيبلوغرافية
| العنوان: |
Cathepsin S activity controls chronic stress-induced muscle atrophy and dysfunction in mice. |
| المؤلفون: |
Wan, Ying, Piao, Limei, Xu, Shengnan, Meng, Xiangkun, Huang, Zhe, Inoue, Aiko, Wang, Hailong, Yue, Xueling, Jin, Xueying, Nan, Yongshan, Shi, Guo-Ping, Murohara, Toyoaki, Umegaki, Hiroyuki, Kuzuya, Masafumi, Cheng, Xian Wu |
| المصدر: |
Cellular & Molecular Life Sciences; Sep2023, Vol. 80 Issue 9, p1-20, 20p |
| مستخلص: |
Exposure to chronic psychological stress (CPS) is an intractable risk factor for inflammatory and metabolic diseases. Lysosomal cysteinyl cathepsins play an important role in human pathobiology. Given that cathepsin S (CTSS) is upregulated in the stressed vascular and adipose tissues, we investigated whether CTSS participates in chronic stress-induced skeletal muscle mass loss and dysfunction, with a special focus on muscle protein metabolic imbalance and apoptosis. Eight-week-old male wildtype (CTSS+/+) and CTSS-knockout (CTSS−/−) mice were randomly assigned to non-stress and variable-stress groups. CTSS+/+ stressed mice showed significant losses of muscle mass, dysfunction, and fiber area, plus significant mitochondrial damage. In this setting, stressed muscle in CTSS+/+ mice presented harmful alterations in the levels of insulin receptor substrate 2 protein content (IRS-2), phospho-phosphatidylinositol 3-kinase, phospho-protein kinase B, and phospho-mammalian target of rapamycin, forkhead box-1, muscle RING-finger protein-1 protein, mitochondrial biogenesis-related peroxisome proliferator-activated receptor-γ coactivator-α, and apoptosis-related B-cell lymphoma 2 and cleaved caspase-3; these alterations were prevented by CTSS deletion. Pharmacological CTSS inhibition mimics its genetic deficiency-mediated muscle benefits. In C2C12 cells, CTSS silencing prevented stressed serum- and oxidative stress-induced IRS-2 protein reduction, loss of the myotube myosin heavy chain content, and apoptosis accompanied by a rectification of investigated molecular harmful changes; these changes were accelerated by CTSS overexpression. These findings demonstrated that CTSS plays a role in IRS-2-related protein anabolism and catabolism and cell apoptosis in stress-induced muscle wasting, suggesting a novel therapeutic strategy for the control of chronic stress-related muscle disease in mice under our experimental conditions by regulating CTSS activity. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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