論文 - 詳細
| RRC ID | 63019 |
|---|---|
| 著者 | Takehara M, Kobayashi K, Nagahama M. |
| タイトル | Clostridium perfringens α-toxin inhibits myogenic differentiation of C2C12 myoblasts. |
| ジャーナル | Anaerobe |
| Abstract |
Clostridium perfringens type A is the causative agent of clostridial myonecrosis, and α-toxin has been reported to be responsible for the pathogenesis. Recently, it was reported that regeneration of skeletal muscle after C. perfringens-induced muscle disorders is delayed, but the detailed mechanisms have not been elucidated. Here, we tested whether α-toxin impairs the differentiation of C2C12 myoblasts, a useful cell line to study muscle growth, maturation, and regeneration in vitro. α-Toxin dose-dependently inhibited myotube formation in C2C12 cultures after induction of their differentiation by horse serum. Also, immunoblot analysis revealed that α-toxin dose-dependently decreases the expressions of two skeletal muscle differentiation markers, myogenic differentiation 1 (MyoD) and myogenin. These results demonstrate that α-toxin impairs the myogenic differentiation of C2C12 myoblasts. To reveal the mechanism behind α-toxin-mediated impairment of myogenic differentiation, we focused on ceramide production since α-toxin is known to promote the formation of ceramide by its sphingomyelinase activity. Immunofluorescent analysis revealed that ceramide production is accelerated by treatment with α-toxin. Furthermore, a synthetic cell-permeable ceramide analog, C2-ceramide, inhibited myotube formation in C2C12 cells and decreased the expressions of MyoD and myogenin, suggesting that accelerated ceramide production is involved in the α-toxin-mediated blockage of myogenic differentiation. Together, our results illustrate that the impairment of myogenic differentiation by α-toxin might be crucial for the pathogenesis of C. perfringens to delay regeneration of severely damaged skeletal muscles. |
| 巻・号 | 65 |
| ページ | 102265 |
| 公開日 | 2020-10-1 |
| DOI | 10.1016/j.anaerobe.2020.102265 |
| PII | S1075-9964(20)30121-9 |
| PMID | 32860931 |
| MeSH | Animals Bacterial Toxins / pharmacology* Biomarkers Calcium-Binding Proteins / pharmacology* Cell Differentiation / drug effects* Cell Line Cell Proliferation / drug effects Cells, Cultured Dose-Response Relationship, Drug Mice Muscle Development MyoD Protein / metabolism Myoblasts / cytology* Myoblasts / drug effects* Myoblasts / metabolism Myogenin / metabolism Type C Phospholipases / pharmacology* |
| IF | 2.709 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) |