T‐type calcium channel blockade induces apoptosis in C2C12 myotubes and skeletal muscle via endoplasmic reticulum stress activation
Loss of T‐type calcium channel (TCC) function has been reported to result in decreased cell viability and impaired muscle regeneration, but the underlying mechanisms remain largely unknown. We previously found that expression of TCC is reduced in aged pelvic floor muscle of multiple vaginal delivery...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.12965 |
| _version_ | 1818264600343216128 |
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| author | Mao Chen Suting Li Menglei Hao Jue Chen Zhihan Zhao Shasha Hong Jie Min Jianming Tang Ming Hu Li Hong |
| author_facet | Mao Chen Suting Li Menglei Hao Jue Chen Zhihan Zhao Shasha Hong Jie Min Jianming Tang Ming Hu Li Hong |
| author_sort | Mao Chen |
| collection | DOAJ |
| description | Loss of T‐type calcium channel (TCC) function has been reported to result in decreased cell viability and impaired muscle regeneration, but the underlying mechanisms remain largely unknown. We previously found that expression of TCC is reduced in aged pelvic floor muscle of multiple vaginal delivery mice, and this is related to endoplasmic reticulum stress (ERS) activation and autophagy flux blockade. In the present work, we further investigated the effects of TCC function loss on C2C12 myotubes and skeletal muscle, which is mediated by promotion of ERS and ultimately contributes to mitochondrial‐related apoptotic cell death. We found that application of a TCC inhibitor induced mitochondria‐related apoptosis in a dose‐dependent manner and also reduced mitochondrial transmembrane potential (MMP), induced mito‐ROS generation, and enhanced expression of mitochondrial apoptosis proteins. Functional inhibition of TCC induced ERS, resulting in disorder of Ca2+ homeostasis in endoplasmic reticulum, and ultimately leading to cell apoptosis in C2C12 myotubes. Tibialis anterior muscles of T‐type α1H channel knockout mice displayed a smaller skeletal muscle fiber size and elevated ERS‐mediated apoptosis signaling. Our data point to a novel mechanism whereby TCC blockade leads to ERS activation and terminal mitochondrial‐related apoptotic events in C2C12 myotubes and skeletal muscles. |
| first_indexed | 2024-12-12T19:37:29Z |
| format | Article |
| id | doaj.art-74b45ca0da6b45b2838ba09b42327578 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-12-12T19:37:29Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-74b45ca0da6b45b2838ba09b423275782022-12-22T00:14:17ZengWileyFEBS Open Bio2211-54632020-10-0110102122213610.1002/2211-5463.12965T‐type calcium channel blockade induces apoptosis in C2C12 myotubes and skeletal muscle via endoplasmic reticulum stress activationMao Chen0Suting Li1Menglei Hao2Jue Chen3Zhihan Zhao4Shasha Hong5Jie Min6Jianming Tang7Ming Hu8Li Hong9Department of Gynecology and Obstetrics Renmin Hospital of Wuhan University ChinaDepartment of Gynecology and Obstetrics Renmin Hospital of Wuhan University ChinaDepartment of Gynecology and Obstetrics Renmin Hospital of Wuhan University ChinaDepartment of Gynecology and Obstetrics Renmin Hospital of Wuhan University ChinaDepartment of Gynecology and Obstetrics Renmin Hospital of Wuhan University ChinaDepartment of Gynecology and Obstetrics Renmin Hospital of Wuhan University ChinaDepartment of Gynecology and Obstetrics Renmin Hospital of Wuhan University ChinaDepartment of Gynecology and Obstetrics Renmin Hospital of Wuhan University ChinaDepartment of Gynecology and Obstetrics Renmin Hospital of Wuhan University ChinaDepartment of Gynecology and Obstetrics Renmin Hospital of Wuhan University ChinaLoss of T‐type calcium channel (TCC) function has been reported to result in decreased cell viability and impaired muscle regeneration, but the underlying mechanisms remain largely unknown. We previously found that expression of TCC is reduced in aged pelvic floor muscle of multiple vaginal delivery mice, and this is related to endoplasmic reticulum stress (ERS) activation and autophagy flux blockade. In the present work, we further investigated the effects of TCC function loss on C2C12 myotubes and skeletal muscle, which is mediated by promotion of ERS and ultimately contributes to mitochondrial‐related apoptotic cell death. We found that application of a TCC inhibitor induced mitochondria‐related apoptosis in a dose‐dependent manner and also reduced mitochondrial transmembrane potential (MMP), induced mito‐ROS generation, and enhanced expression of mitochondrial apoptosis proteins. Functional inhibition of TCC induced ERS, resulting in disorder of Ca2+ homeostasis in endoplasmic reticulum, and ultimately leading to cell apoptosis in C2C12 myotubes. Tibialis anterior muscles of T‐type α1H channel knockout mice displayed a smaller skeletal muscle fiber size and elevated ERS‐mediated apoptosis signaling. Our data point to a novel mechanism whereby TCC blockade leads to ERS activation and terminal mitochondrial‐related apoptotic events in C2C12 myotubes and skeletal muscles.https://doi.org/10.1002/2211-5463.12965apoptosisendoplasmic reticulum stressskeletal muscle wastingT‐type calcium channel |
| spellingShingle | Mao Chen Suting Li Menglei Hao Jue Chen Zhihan Zhao Shasha Hong Jie Min Jianming Tang Ming Hu Li Hong T‐type calcium channel blockade induces apoptosis in C2C12 myotubes and skeletal muscle via endoplasmic reticulum stress activation FEBS Open Bio apoptosis endoplasmic reticulum stress skeletal muscle wasting T‐type calcium channel |
| title | T‐type calcium channel blockade induces apoptosis in C2C12 myotubes and skeletal muscle via endoplasmic reticulum stress activation |
| title_full | T‐type calcium channel blockade induces apoptosis in C2C12 myotubes and skeletal muscle via endoplasmic reticulum stress activation |
| title_fullStr | T‐type calcium channel blockade induces apoptosis in C2C12 myotubes and skeletal muscle via endoplasmic reticulum stress activation |
| title_full_unstemmed | T‐type calcium channel blockade induces apoptosis in C2C12 myotubes and skeletal muscle via endoplasmic reticulum stress activation |
| title_short | T‐type calcium channel blockade induces apoptosis in C2C12 myotubes and skeletal muscle via endoplasmic reticulum stress activation |
| title_sort | t type calcium channel blockade induces apoptosis in c2c12 myotubes and skeletal muscle via endoplasmic reticulum stress activation |
| topic | apoptosis endoplasmic reticulum stress skeletal muscle wasting T‐type calcium channel |
| url | https://doi.org/10.1002/2211-5463.12965 |
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