Reference - Detail
| RRC ID | 51916 |
|---|---|
| Author | Arai S, Ikeda M, Ide T, Matsuo Y, Fujino T, Hirano K, Sunagawa K, Tsutsui H. |
| Title | Functional loss of DHRS7C induces intracellular Ca2+ overload and myotube enlargement in C2C12 cells via calpain activation. |
| Journal | Am J Physiol Cell Physiol |
| Abstract |
Dehydrogenase/reductase member 7C (DHRS7C) is a newly identified NAD/NADH-dependent dehydrogenase that is expressed in cardiac and skeletal muscle and localized in the endoplasmic/sarcoplasmic reticulum (ER/SR). However, its functional role in muscle cells remains to be fully elucidated. Here, we investigated the role of DHRS7C by analyzing mouse C2C12 myoblasts deficient in DHRS7C (DHRS7C-KO cells), overexpressing wild-type DHRS7C (DHRS7C-WT cells), or expressing mutant DHRS7C [DHRS7C-Y191F or DHRS7C-K195Q cells, harboring point mutations in the NAD/NADH-dependent dehydrogenase catalytic core domain (YXXXK)]. DHRS7C expression was induced as C2C12 myoblasts differentiated into mature myotubes, whereas DHRS7C-KO myotubes exhibited enlarged cellular morphology after differentiation. Notably, both DHRS7C-Y191F and DHRS7C-K195Q cells also showed similar enlarged cellular morphology, suggesting that the NAD/NADH-dependent dehydrogenase catalytic core domain is pivotal for DHRS7C function. In DHRS7C-KO, DHRS7C-Y191F, and DHRS7C-K195Q cells, the resting level of cytosolic Ca2+ and total amount of Ca2+ storage in the ER/SR were significantly higher than those in control C2C12 and DHRS7C-WT cells after differentiation. Additionally, Ca2+ release from the ER/SR induced by thapsigargin and 4-chloro-m-cresol was augmented in these cells and calpain, a calcium-dependent protease, was significantly activated in DHRS7C-KO, DHRS7C-Y191F, and DHRS7C-K195Q myotubes, consistent with the higher resting level of cytosolic Ca2+ concentration and enlarged morphology after differentiation. Furthermore, treatment with a calpain inhibitor abolished the enlarged cellular morphology. Taken together, our findings suggested that DHRS7C maintains intracellular Ca2+ homeostasis involving the ER/SR and that functional loss of DHRS7C leads to Ca2+ overload in the cytosol and ER/SR, resulting in enlarged cellular morphology via calpain activation. |
| Volume | 312(1) |
| Pages | C29-C39 |
| Published | 2017-1-1 |
| DOI | 10.1152/ajpcell.00090.2016 |
| PII | ajpcell.00090.2016 |
| PMID | 27806939 |
| MeSH | Animals Calcium / metabolism* Calcium Signaling / physiology Calpain / metabolism* Cell Line Cell Size Mice Muscle Fibers, Skeletal / cytology* Muscle Fibers, Skeletal / metabolism* Oxidoreductases / metabolism* Signal Transduction / physiology* Up-Regulation / physiology* |
| IF | 3.485 |
| Times Cited | 4 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 6 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | C2C12(RCB0987) |