Elevation of NR4A3 Expression and Its Possible Role in Modulating Insulin Expression in the Pancreatic Beta Cell
文献类型：期刊论文
| 作者 | Gao, Weina; Fu, Yuchang; Yu, Cong; Wang, Shunke; Zhang, Yuchao; Zong, Chen; Xu, Tongfu; Liu, Yong（刘勇） ; Li, Xia; Wang, Xiangdong
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| 刊名 | PLOS ONE
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| 出版日期 | 2014 |
| 卷号 | 9期号:3页码:e91462 |
| 通讯作者 | Li, X (reprint author), Shandong Univ, Dept Cell Biol, Sch Med, Jinan 250100, Peoples R China. |
| 英文摘要 | Background: NR4A3/NOR-1 is a member of the NR4A orphan nuclear receptor subfamily, which contains early response genes that sense and respond to a variety of stimuli in the cellular environment. The role of NR4A3 in insulin expression in pancreatic beta cells remains unknown. Methods: Dynamic changes in NR4A3 were examined in a pancreatic beta-cell line, MIN6, treated with thapsigargin (TG), palmitate (PA), tunicamycin (TM), and dithiothreitol (DTT), chemicals that produce cell stress and even apoptosis. We exploited virus infection techniques to induce expression of NR4A3 or three deletion mutants, and determined expression of insulin and insulin regulatory genes in MIN6 cells. Results: TG and PA, two endoplasmic reticulum (ER) stress inducers, were able to induce unfolded protein response (UPR) activation and elevation of NR4A3 expression in MIN6 cells, whereas TM and DTT, two other ER stress inducers, were able to induce UPR activation but not NR4A3 elevation. MIN6 cells over-expressing NR4A3 protein after adenoviral infection exhibited reduced transcription of the insulin genes Ins1 and Ins2, and reduced insulin protein secretion, which were negatively correlated with NR4A3 expression levels. Functional analysis of different deletion mutants of NR4A3 showed that deleting the activation domain AF1 or the DNA-binding domain abolished the down-regulation of insulin transcription by NR4A3 in MIN6 cells, indicating that this down-regulative role was closely related to the NR4A3 trans-activation activity. Over-expression of NR4A3 in MIN6 cells resulted in reduced mRNA transcription of the insulin positive-regulation genes, Pdx1 and NeuroD1. Conclusion: Some ER stress inducers, such as TG or PA, are able to elevate NR4A3 expression in MIN6 cells, while others, such as TM or DTT, are not. Over-expression of NR4A3 in MIN6 cells results in down-regulation of insulin gene transcription and insulin secretion. NR4A3 reduces insulin gene expression by modulating the expression of Pdx1 and NeuroD1. |
| 类目[WOS] | Multidisciplinary Sciences |
| 研究领域[WOS] | Science & Technology - Other Topics |
| 关键词[WOS] | UNFOLDED PROTEIN RESPONSE ; NUCLEAR RECEPTOR NOR-1 ; ORPHAN RECEPTOR ; ENDOPLASMIC-RETICULUM ; TRANSCRIPTIONAL ACTIVITY ; METABOLIC DISEASE ; INDUCED APOPTOSIS ; GENE-EXPRESSION ; ER STRESS ; NGFI-B |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000333254100036 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/274]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 |
| 推荐引用方式 GB/T 7714 | Gao, Weina,Fu, Yuchang,Yu, Cong,et al. Elevation of NR4A3 Expression and Its Possible Role in Modulating Insulin Expression in the Pancreatic Beta Cell[J]. PLOS ONE,2014,9(3):e91462. |
| APA | Gao, Weina.,Fu, Yuchang.,Yu, Cong.,Wang, Shunke.,Zhang, Yuchao.,...&Wang, Xiangdong.(2014).Elevation of NR4A3 Expression and Its Possible Role in Modulating Insulin Expression in the Pancreatic Beta Cell.PLOS ONE,9(3),e91462. |
| MLA | Gao, Weina,et al."Elevation of NR4A3 Expression and Its Possible Role in Modulating Insulin Expression in the Pancreatic Beta Cell".PLOS ONE 9.3(2014):e91462. |
入库方式： OAI收割
来源：上海营养与健康研究所
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