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ORIGINAL ARTICLE
Year : 2022  |  Volume : 65  |  Issue : 5  |  Page : 226-232

Calpain inhibitors inhibit mitochondrial calpain activity to ameliorate apoptosis of cocultured myoblast


1 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
2 Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
3 Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China

Correspondence Address:
Dr. Lingjun Kong
Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350004, Fujian
China
Prof. Sizeng Chen
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350004, Fujian
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0304-4920.359797

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Cancer cachexia is a fatal syndrome associated with muscle regeneration disability. Tumor factors induce the apoptosis of myoblasts to impair the regeneration of skeletal muscle. Cancer cachectic myoblast apoptosis is associated with mitochondria injury. It has been reported that activated mitochondrial calpain caused mitochondria injury in mouse cardiomyocytes and pulmonary smooth muscle. We wondered if mitochondrial calpains exist in skeletal myoblast and their potential role in myoblast apoptosis of cancer cachexia. We used a transwell to build a novel myoblast-carcinoma cell coculture model to simulate the cancer cachexia environment in vitro. Calpain inhibitors, calpastatin (CAST) and calpeptin (CAPT), were used during coculture. We found for the first time that two calpains (calpain-1 and calpain-2) and CAST were present in the mitochondria of myoblast. The activation of mitochondrial calpain decreased mitochondrial complex I activity, promoted mitochondrial permeability transition pore opening, and impaired mitochondrial membrane potential in myoblast during coculture, which induced myoblasts apoptosis. CAST and CAPT protected myoblasts from apoptosis by inhibiting mitochondrial calpain activity, which may attenuate or even reverse cancer cachectic muscle atrophy by improving muscle regeneration ability. Our study provides a new perspective for understanding the mechanism of cancer cachexia, and will further contribute to treat cancer cachexia by focusing on the mitochondrial calpain activity.


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