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NR4A1 enhances MKP7 expression to diminish JNK activation induced by ROS or ER-stress in pancreatic β cells for surviving.

التفاصيل البيبلوغرافية
العنوان: NR4A1 enhances MKP7 expression to diminish JNK activation induced by ROS or ER-stress in pancreatic β cells for surviving.
المؤلفون: Pu ZQ; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Yu TF; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Liu D; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Jin CW; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Sadiq E; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Qiao X; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Li X; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Chen Y; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Zhang J; Shandong University School of Medicine, Jinan, China., Tian M; Laboratory of Human Genetics, Shandong Provincial Hospital (Dongying Branch), Affiliated to Shandong University, Dongying, China., Li S; Shandong University School of Medicine, Jinan, China., Zhao RX; Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China. zhaoruxing@qiluhospital.com., Wang XD; Department of Cell Biology, Shandong University School of Medicine, Jinan, China. xdongw@sdu.edu.cn.; Shandong University School of Medicine, Jinan, China. xdongw@sdu.edu.cn.
المصدر: Cell death discovery [Cell Death Discov] 2021 Jun 04; Vol. 7 (1), pp. 133. Date of Electronic Publication: 2021 Jun 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 101665035 Publication Model: Electronic Cited Medium: Print ISSN: 2058-7716 (Print) Linking ISSN: 20587716 NLM ISO Abbreviation: Cell Death Discov Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [New York, NY] : Nature Publishing Group, [2015]-
مستخلص: Under adverse conditions, such as sustained or chronic hyperglycemia or hyperlipidemia, ROS (reactive oxygen species) or/and ER-stress (endoplasmic reticulum stress) will be induced in pancreatic β cells. ROS or ER-stress damages β-cells even leads to apoptosis. Previously we found ROS or ER-stress resulted in JNK activation in β cells and overexpressing NR4A1 in MIN6 cells reduced JNK activation via modulating cbl-b expression and subsequent degrading the upstream JNK kinase (MKK4). To search other possible mechanisms, we found the mRNA level and protein level of MKP7 (a phosphatase for phospho-JNK) were dramatic reduced in pancreatic β cells in the islets from NR4A1 KO mice compared with that from wild type mice. To confirm what we found in animals, we applied pancreatic β cells (MIN6 cells) and found that the expression of MKP7 was increased in NR4A1-overexpression MIN6 cells. We further found that knocking down the expression of MKP7 increased the p-JNK level in pancreatic β cells upon treatment with TG or H 2 O 2 . After that, we figured out that NR4A1 did enhance the transactivation of the MKP7 promoter by physical association with two putative binding sites. In sum, NR4A1 attenuates JNK phosphorylation incurred by ER-stress or ROS partially via enhancing MKP7 expression, potentially decreases pancreatic β cell apoptosis induced by ROS or ER-stress. Our finding provides a clue for diabetes prevention.
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تواريخ الأحداث: Date Created: 20210605 Latest Revision: 20210608
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8178316
DOI: 10.1038/s41420-021-00521-0
PMID: 34088892
قاعدة البيانات: MEDLINE
الوصف
تدمد:2058-7716
DOI:10.1038/s41420-021-00521-0