HC toxin (a HDAC inhibitor) enhances IRS1-Akt signalling and metabolism in mouse myotubes
文献类型：期刊论文
| 作者 | Tan, Hayden Weng Siong1; Sim, Arthur Yi Loong1; Huang, Su Ling2; Leng, Ying2 ; Long, Yun Chau1
|
| 刊名 | JOURNAL OF MOLECULAR ENDOCRINOLOGY
 |
| 出版日期 | 2015-12 |
| 卷号 | 55期号:3页码:197-207 |
| 关键词 | histone deacetylase (HDAC) Akt insulin receptor substrate 1 (IRS1) metabolism exercise myotubes |
| ISSN号 | 0952-5041 |
| DOI | 10.1530/JME-15-0140 |
| 文献子类 | Article |
| 英文摘要 | Exercise enhances numerous signalling pathways and activates substrate metabolism in skeletal muscle. Small molecule compounds that activate these cellular responses have been shown to recapitulate the metabolic benefits of exercise. In this study, a histone deacetylase (HDAC) inhibitor, HC toxin, was investigated as a small molecule compound that activates exercise-induced adaptations. In C2C12 myotubes, HC toxin treatment activated two exercise-stimulated pathways: AMP-activated protein kinase (AMPK) and Akt pathways. HC toxin increased the protein content and phosphorylation of insulin receptor substrate 1 as well as the activation of downstream Akt signalling. The effects of HC toxin on IRS1-Akt signalling were PI3K-dependent as wortmannin abolishes its effects on IRS1 protein accumulation and Akt phosphorylation. HC toxin-induced Akt activation was sufficient to enhance downstream mTOR complex 1 (mTORC1) signalling including p70S6K and S6, which were consistently abolished by PI3K inhibition. Insulin-stimulated glucose uptake, glycolysis, mitochondrial respiration and fatty acid oxidation were also enhanced in HC toxin-treated myotubes. When myotubes were challenged with serum starvation for the induction of atrophy, HC toxin treatment prevented the induction of genes that are involved in autophagy and proteasomal proteolysis. Conversely, IRS1-Akt signalling was not induced by HC toxin in several hepatoma cell lines, providing evidence for a favourable safety profile of this small molecule. These data highlight the potential of HDAC inhibitors as a novel class of small molecules for the induction of exercise-like signalling pathways and metabolism. |
| WOS关键词 | INSULIN-RECEPTOR SUBSTRATE-1 ; STIMULATED GLUCOSE-UPTAKE ; ACTIVATED PROTEIN-KINASE ; SKELETAL-MUSCLE ATROPHY ; HISTONE DEACETYLASES ; RESISTANCE EXERCISE ; MESSENGER-RNA ; MICE ; CELLS ; PHOSPHORYLATION |
| 资助项目 | National Medical Research Council (NMRC), Singapore (NMRC/BNIG)[00000000] ; Singapore Ministry of Education Academic Research Fund[00000000] |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| WOS记录号 | WOS:000365033800008 |
| 出版者 | BIOSCIENTIFICA LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276312]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Long, Yun Chau |
| 作者单位 | 1.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tan, Hayden Weng Siong,Sim, Arthur Yi Loong,Huang, Su Ling,et al. HC toxin (a HDAC inhibitor) enhances IRS1-Akt signalling and metabolism in mouse myotubes[J]. JOURNAL OF MOLECULAR ENDOCRINOLOGY,2015,55(3):197-207. |
| APA | Tan, Hayden Weng Siong,Sim, Arthur Yi Loong,Huang, Su Ling,Leng, Ying,&Long, Yun Chau.(2015).HC toxin (a HDAC inhibitor) enhances IRS1-Akt signalling and metabolism in mouse myotubes.JOURNAL OF MOLECULAR ENDOCRINOLOGY,55(3),197-207. |
| MLA | Tan, Hayden Weng Siong,et al."HC toxin (a HDAC inhibitor) enhances IRS1-Akt signalling and metabolism in mouse myotubes".JOURNAL OF MOLECULAR ENDOCRINOLOGY 55.3(2015):197-207. |
入库方式： OAI收割
来源：上海药物研究所
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