Activating transcription factor 6 protects insulin receptor from ER stress-stimulated desensitization via p42/44 ERK pathway
文献类型：期刊论文
| 作者 | Tang, Xuan1; Shen, Hong1; Chen, Jing1 ; Wang, Xu2; Zhang, Yu1; Chen, Li-li1; Rukachaisirikul, Vatcharin3,4; Jiang, Hua-liang1; Shen, Xu1
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2011-09 |
| 卷号 | 32期号:9页码:1138-1147 |
| 关键词 | activating transcription factor 6 ER stress insulin receptor MEK/ERK pathway type 2 diabetes |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2011.75 |
| 文献子类 | Article |
| 英文摘要 | Aim: Activating transcription factor 6 (ATF6) is a key signal transducer of endoplasmic reticulum stress (ER stress). This study was conducted to clarify the potential role of ATF6 in the insulin signaling pathway under chronic ER stress. Methods: ER stress of HEK293 cells was induced with tunicamycin (2 mu g/mL). The cells were transfected with ATF6 alpha or ATF6 beta. The phosphorylation level of insulin receptor (IR) was analyzed using Western blot. The changes in ER stress and ERK signaling pathways were explored using Western blot and quantitative real-time PCR. Results: Tunicamycin-induced chronic ER stress attenuated IR tyrosine phosphorylation in a time-dependent manner, whereas overexpression of ATF6 protected IR from desensitization. ATF6 modulation of IR suppression was associated with insulin-stimulated extracellular signal-regulated kinase (ERK) phosphorylation. The treatment of the cells with a specific ERK inhibitor U0126 (10 mu mol/L) mimicked the effect of ATF6 over-expression and restored the insulin-stimulated IR phosphorylation. The treatment of the cells with the ERK activator epidermal growth factor (EGF, 200 ng/mL) decreased the protection effect of ATF6 on IR. Conclusion: Our results demonstrate that ATF6 may serve as a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes. |
| WOS关键词 | ENDOPLASMIC-RETICULUM STRESS ; NECROSIS-FACTOR-ALPHA ; INDUCED CELL-DEATH ; 3T3-L1 ADIPOCYTES ; TRANSMEMBRANE PROTEIN ; GENE-EXPRESSION ; GLUCOSE-UPTAKE ; MUSCLE-CELLS ; ATF6 ; RESISTANCE |
| 资助项目 | State Key Program of Basic Research of China[2010CB912501] ; State Key Program of Basic Research of China[2007CB914304] ; National Natural Science Foundation of China[90713046] ; National Natural Science Foundation of China[30890044] ; Shanghai Science and Technology Commission[11ZR1444500] ; Key Laboratory of Biotherapy, West China Hospital, West China Medicine School, Sichuan University[SKLB200901] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000294495700008 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278422]  |
| 专题 | 药物安全性评价中心 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 | Chen, Jing |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Oral & Maxillofacial Surg,Shanghai Key Lab S, Shanghai 200011, Peoples R China; 3.Prince Songkla Univ, Dept Chem, Hat yai, Thailand; 4.Prince Songkla Univ, Ctr Innovat Chem, Fac Sci, Hat yai, Thailand |
| 推荐引用方式 GB/T 7714 | Tang, Xuan,Shen, Hong,Chen, Jing,et al. Activating transcription factor 6 protects insulin receptor from ER stress-stimulated desensitization via p42/44 ERK pathway[J]. ACTA PHARMACOLOGICA SINICA,2011,32(9):1138-1147. |
| APA | Tang, Xuan.,Shen, Hong.,Chen, Jing.,Wang, Xu.,Zhang, Yu.,...&Shen, Xu.(2011).Activating transcription factor 6 protects insulin receptor from ER stress-stimulated desensitization via p42/44 ERK pathway.ACTA PHARMACOLOGICA SINICA,32(9),1138-1147. |
| MLA | Tang, Xuan,et al."Activating transcription factor 6 protects insulin receptor from ER stress-stimulated desensitization via p42/44 ERK pathway".ACTA PHARMACOLOGICA SINICA 32.9(2011):1138-1147. |
入库方式： OAI收割
来源：上海药物研究所
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