論文 - 詳細
| RRC ID | 42546 |
|---|---|
| 著者 | Ono Y, Sensui H, Sakamoto Y, Nagatomi R. |
| タイトル | Knockdown of hypoxia-inducible factor-1alpha by siRNA inhibits C2C12 myoblast differentiation. |
| ジャーナル | J Cell Biochem |
| Abstract |
We analyzed the role of Hypoxia-inducible factor (HIF)-1alpha in myoblast differentiation by examining the expression and regulation of HIF-1alpha in proliferating and differentiating C2C12 myoblast, and by knocking down HIF-1alpha of C2C12 myoblasts with small interfering RNA (siRNA), given that HIF-1alpha has been shown to be involved in differentiative process in non-muscle tissues. Although HIF-1alpha mRNA was constantly expressed in C2C12 myoblasts both under growth and differentiating phase, HIF-1alpha protein was hardly detectable in the growth phase but became detectable only during myogenic differentiation even under normoxia. During early stage of C2C12 myogenesis, HIF-1alpha accumulated in the nuclei of myogenin-positive myoblasts. The inhibition of proteasome in the growth phase led to HIF-1alpha protein accumulation, whereas in the differentiation phase the inhibition of Hsp90, which stabilizes HIF-1alpha, suppressed HIF-1alpha accumulation. Therefore, we suggest that the level of HIF-1alpha protein expression is regulated by a proteasome-and chaperon-dependent pathway in C2C12 myoblast. Knockdown of HIF-1alpha effectively blocked myotube formation and myosin heavy chain (MHC) expression. Finally, HIF-1alpha expression in vivo was confirmed in the regenerative muscle tissue of mice after eccentric exercise. We conclude that HIF-1alpha is required for C2C12 myogenesis in vitro, and suggest that HIF-1alpha may have an essential role in regenerative muscle tissue in vivo. |
| 巻・号 | 98(3) |
| ページ | 642-9 |
| 公開日 | 2006-6-1 |
| DOI | 10.1002/jcb.20804 |
| PMID | 16440321 |
| MeSH | Animals Cell Differentiation* Gene Expression Regulation HSP90 Heat-Shock Proteins / metabolism Hypoxia-Inducible Factor 1, alpha Subunit / deficiency* Hypoxia-Inducible Factor 1, alpha Subunit / genetics* Mice Muscle Development / genetics Muscles / cytology Muscles / physiology Myoblasts / cytology* Myoblasts / metabolism* Proteasome Inhibitors RNA Interference RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Small Interfering / genetics RNA, Small Interfering / metabolism* Regeneration |
| IF | 4.237 |
| 引用数 | 30 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | |