Department of Neurology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Biochem Biophys Res Commun. 2011 Nov 4;414(4):826-31. doi: 10.1016/j.bbrc.2011.10.036. Epub 2011 Oct 14.
Histone deacetylase inhibitors (HDACIs) are known to promote skeletal muscle formation. However, their mechanisms that include effects on the expression of major muscle components such as the dystrophin-associated proteins complex (DAPC) or myogenic regulatory factors (MRFs) remain unknown. In this study, we investigated the effects of HDACIs on skeletal muscle formation using the C2C12 cell culture system. C2C12 myoblasts were exposed to trichostatin A (TSA), one of the most potent HDACIs, and differentiation was subsequently induced. We found that TSA enhances the expression of myosin heavy chain without affecting DAPC expression. In addition, TSA increases the expression of the early MRFs, Myf5 and MEF2, whereas it suppresses the expression of the late MRF, myogenin. Interestingly, TSA also enhances the expression of Id1, Id2, and Id3 (Ids). Ids are myogenic repressors that inhibit myogenic differentiation. These findings suggest that TSA promotes gene expression in proliferation and suppresses it in the differentiation stage of muscle formation. Taken together, our data demonstrate that TSA enhances myogenesis by coordinating the expression of MRFs and myogenic repressors.
组蛋白去乙酰化酶抑制剂 (HDACIs) 已知可促进骨骼肌形成。然而，其机制包括对主要肌肉成分（如肌营养不良相关蛋白复合物 (DAPC) 或肌生成调节因子 (MRFs)）表达的影响仍不清楚。在这项研究中，我们使用 C2C12 细胞培养系统研究了 HDACIs 对骨骼肌形成的影响。C2C12 成肌细胞暴露于曲古抑菌素 A (TSA)，这是最有效的 HDACIs 之一，随后诱导分化。我们发现 TSA 增强肌球蛋白重链的表达而不影响 DAPC 的表达。此外，TSA 增加早期 MRFs，Myf5 和 MEF2 的表达，而抑制晚期 MRF，myogenin 的表达。有趣的是，TSA 还增强了 Id1、Id2 和 Id3（Ids）的表达。Ids 是抑制肌生成分化的肌生成抑制剂。这些发现表明 TSA 通过协调 MRFs 和肌生成抑制因子的表达来促进基因表达。总之，我们的数据表明 TSA 通过协调 MRFs 和肌生成抑制因子的表达来增强成肌作用。
