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Article

Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells

  • Authors:
    • Xianliang Zeng
    • Li Zhao
    • Sizeng Chen
    • Xiantao Li
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350004, P.R. China, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350004, P.R. China, Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350004, P.R. China
  • Article Number: 124
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    Published online on: December 17, 2020
       https://doi.org/10.3892/ol.2020.12385
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Abstract

Cancer cachexia is a life‑threatening syndrome characterized by muscle atrophy. Cancer cachectic muscle atrophy (CCMA) is associated with mitochondrial injury. Mitochondrial calpains have been reported to induce mitochondrial injury in mouse cardiomyocytes and pulmonary smooth muscle. In the present study, the presence of calpain in the mitochondria of skeletal muscle and its potential role in CCMA were investigated. Transwell plates were used to develop a myotube‑carcinoma cell co‑culture model to simulate the cancer cachexia environment in vitro. The calpain inhibitors, calpastatin (CAST) and calpeptin (CAPT), were used to inhibit calpain activity in myotubes during co‑culture. Calpain‑1, calpain‑2 and CAST were found to be present in mouse myotube mitochondria. Co‑culture activated calpain in both cytoplasm and mitochondria, which caused myotube atrophy. CAST and CAPT treatment prevented calpain activation in both cytoplasm and mitochondria, which inhibited myotube atrophy during co‑culture. Additionally, CAST and CAPT treatment increased mitochondrial complex I activity, decreased mitochondrial permeability transition pore opening and improved mitochondrial membrane potential in myotubes during co‑culture. In addition, CAST and CAPT treatment increased AKT/mTOR activity, inhibited FoxO3a activity and decreased atrogin‑1 content in myotubes during co‑culture. The present findings provide new insights to understand the mechanism of CCMA and further help the development of focused approaches to treat CCMA by manipulating the mitochondrial and cytosolic calpain activity.
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Copy and paste a formatted citation
Spandidos Publications style
Zeng X, Zhao L, Chen S and Li X: Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells. Oncol Lett 21: 124, 2021.
APA
Zeng, X., Zhao, L., Chen, S., & Li, X. (2021). Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells. Oncology Letters, 21, 124. https://doi.org/10.3892/ol.2020.12385
MLA
Zeng, X., Zhao, L., Chen, S., Li, X."Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells". Oncology Letters 21.2 (2021): 124.
Chicago
Zeng, X., Zhao, L., Chen, S., Li, X."Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells". Oncology Letters 21, no. 2 (2021): 124. https://doi.org/10.3892/ol.2020.12385
Copy and paste a formatted citation
x
Spandidos Publications style
Zeng X, Zhao L, Chen S and Li X: Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells. Oncol Lett 21: 124, 2021.
APA
Zeng, X., Zhao, L., Chen, S., & Li, X. (2021). Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells. Oncology Letters, 21, 124. https://doi.org/10.3892/ol.2020.12385
MLA
Zeng, X., Zhao, L., Chen, S., Li, X."Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells". Oncology Letters 21.2 (2021): 124.
Chicago
Zeng, X., Zhao, L., Chen, S., Li, X."Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells". Oncology Letters 21, no. 2 (2021): 124. https://doi.org/10.3892/ol.2020.12385
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