دورية أكاديمية
NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic β-cells for protection.
العنوان: | NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic β-cells for protection. |
---|---|
المؤلفون: | Pu ZQ; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Liu D; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Lobo Mouguegue HPP; 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., Qin DD; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Yu TF; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Zong C; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Chen JC; Blood Transfusion Department, Qilu Hospital of Shandong University, Jinan, China., Zhao RX; Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China., Lin JY; Department of Physiology, Shandong University School of Medicine, Jinan, China., Cheng J; Department of Physiology, Shandong University School of Medicine, Jinan, China., Yu X; Department of Physiology, Shandong University School of Medicine, Jinan, China.; Key Laboratory of Protein Sciences for Chronic Degenerative Diseases in Universities of Shandong (Shandong University), Jinan, China., Li X; Department of Cell Biology, Shandong University School of Medicine, Jinan, China., Zhang YC; Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, China., Liu YT; Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, China., Guan QB; Department of Endocrinology, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan, China., Wang XD; Department of Cell Biology, Shandong University School of Medicine, Jinan, China.; Key Laboratory of Protein Sciences for Chronic Degenerative Diseases in Universities of Shandong (Shandong University), Jinan, China. |
المصدر: | Journal of cellular and molecular medicine [J Cell Mol Med] 2020 Dec; Vol. 24 (24), pp. 14171-14183. Date of Electronic Publication: 2020 Oct 30. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101083777 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1582-4934 (Electronic) Linking ISSN: 15821838 NLM ISO Abbreviation: J Cell Mol Med Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Oxford, England : Wiley-Blackwell Original Publication: Bucharest : "Carol Davila" University Press, 2000- |
مواضيع طبية MeSH: | Endoplasmic Reticulum Stress*, Insulin-Secreting Cells/*metabolism , JNK Mitogen-Activated Protein Kinases/*metabolism , Nuclear Receptor Subfamily 4, Group A, Member 1/*metabolism , Reactive Oxygen Species/*metabolism, Animals ; Cell Line ; Gene Expression Regulation ; Hydrogen Peroxide/metabolism ; MAP Kinase Kinase 4/metabolism ; Mice ; Mice, Knockout ; Models, Biological ; Nuclear Receptor Subfamily 4, Group A, Member 1/genetics ; Phosphorylation ; Promoter Regions, Genetic ; Protein Binding ; Ubiquitination |
مستخلص: | Sustained hyperglycaemia and hyperlipidaemia incur endoplasmic reticulum stress (ER stress) and reactive oxygen species (ROS) overproduction in pancreatic β-cells. ER stress or ROS causes c-Jun N-terminal kinase (JNK) activation, and the activated JNK triggers apoptosis in different cells. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an inducible multi-stress response factor. The aim of this study was to explore the role of NR4A1 in counteracting JNK activation induced by ER stress or ROS and the related mechanism. qPCR, Western blotting, dual-luciferase reporter and ChIP assays were applied to detect gene expression or regulation by NR4A1. Immunofluorescence was used to detect a specific protein expression in β-cells. Our data showed that NR4A1 reduced the phosphorylated JNK (p-JNK) in MIN6 cells encountering ER stress or ROS and reduced MKK4 protein in a proteasome-dependent manner. We found that NR4A1 increased the expression of cbl-b (an E3 ligase); knocking down cbl-b expression increased MKK4 and p-JNK levels under ER stress or ROS conditions. We elucidated that NR4A1 enhanced the transactivation of cbl-b promoter by physical association. We further confirmed that cbl-b expression in β-cells was reduced in NR4A1-knockout mice compared with WT mice. NR4A1 down-regulates JNK activation by ER stress or ROS in β-cells via enhancing cbl-b expression. (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.) |
References: | Cell Res. 2008 Aug;18(8):879-88. (PMID: 18663379) Mol Cell. 2017 Apr 6;66(1):141-153.e6. (PMID: 28388439) J Clin Invest. 2016 Oct 3;126(10):3905-3916. (PMID: 27617863) Gastroenterology. 2012 Nov;143(5):1341-1351. (PMID: 22841785) Mol Endocrinol. 2014 Oct;28(10):1729-39. (PMID: 25099012) Trends Endocrinol Metab. 2010 Dec;21(12):707-13. (PMID: 20888782) Diabetes. 2009 Dec;58(12):2788-96. (PMID: 19741162) Nature. 2019 Mar;567(7749):525-529. (PMID: 30814730) J Proteome Res. 2013 Jan 4;12(1):347-62. (PMID: 23170928) Cell Signal. 2017 Jul;35:129-139. (PMID: 28342843) Life Sci. 2018 Jun 15;203:225-232. (PMID: 29678743) Cancer Res. 2010 Sep 1;70(17):6824-36. (PMID: 20660371) Nature. 2019 Mar;567(7749):530-534. (PMID: 30814732) Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12410-12415. (PMID: 31152140) Mol Cancer Res. 2014 Apr;12(4):527-538. (PMID: 24515801) Gastroenterology. 2012 Aug;143(2):307-20. (PMID: 22705006) Nat Immunol. 2011 Jul 03;12(8):778-85. (PMID: 21725321) Hepatology. 2016 Jun;63(6):1987-2003. (PMID: 26845758) J Hepatol. 2015 Jun;62(6):1367-74. (PMID: 25666017) Nat Commun. 2016 Aug 10;7:12365. (PMID: 27507542) Cell Metab. 2006 Nov;4(5):339-40. (PMID: 17084708) J Clin Invest. 2009 Oct;119(10):2925-41. (PMID: 19741297) Blood. 2018 Mar 8;131(10):1081-1093. (PMID: 29343483) Oncogene. 2014 Mar 27;33(13):1629-39. (PMID: 23584473) Sci Signal. 2015 Apr 28;8(374):ra40. (PMID: 25921289) Nat Med. 2006 Sep;12(9):1048-55. (PMID: 16906154) Nat Med. 2007 Jun;13(6):730-5. (PMID: 17515897) Cell Res. 2005 Jan;15(1):36-42. (PMID: 15686625) J Cell Mol Med. 2020 Dec;24(24):14171-14183. (PMID: 33124187) J Hepatol. 2012 Jan;56(1):17-9. (PMID: 21703172) Clin Cancer Res. 2012 Jun 15;18(12):3223-8. (PMID: 22566377) Cell Death Differ. 2016 Nov 1;23(11):1804-1814. (PMID: 27391798) Free Radic Biol Med. 2006 Mar 15;40(6):928-39. (PMID: 16540388) Int J Mol Sci. 2014 Jul 15;15(7):12507-22. (PMID: 25029541) J Biol Chem. 2015 Aug 21;290(34):20687-20699. (PMID: 26157144) PLoS One. 2014 Jan 24;9(1):e87067. (PMID: 24475223) Nat Chem Biol. 2012 Nov;8(11):897-904. (PMID: 22983157) Blood. 2014 Apr 10;123(15):2367-77. (PMID: 24553175) FASEB J. 2010 Oct;24(10):3720-32. (PMID: 20501795) Mol Cancer. 2013 May 02;12:35. (PMID: 23638878) Elife. 2015 Jul 14;4:e07217. (PMID: 26173181) J Cell Physiol. 2018 Apr;233(4):3055-3065. (PMID: 28617956) Mol Cell. 2018 Feb 1;69(3):480-492.e7. (PMID: 29395065) Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8276-80. (PMID: 12815108) Diabetes. 2002 Jan;51(1):66-72. (PMID: 11756324) PLoS One. 2014 Mar 17;9(3):e91462. (PMID: 24638142) Cancers (Basel). 2020 Jun 26;12(6):. (PMID: 32604833) Cell. 2011 Sep 30;147(1):173-84. (PMID: 21962514) Eur Heart J. 2011 Sep;32(17):2179-88. (PMID: 21228009) Hepatology. 2011 Mar;53(3):865-74. (PMID: 21319187) Blood. 2009 Apr 23;113(17):4038-48. (PMID: 19074726) J Exp Med. 2016 Jul 25;213(8):1555-70. (PMID: 27432944) Oncogene. 1995 Jun 15;10(12):2367-77. (PMID: 7784085) Diabetes. 2013 Jun;62(6):1957-69. (PMID: 23349502) Cancer Res. 2004 Nov 15;64(22):8208-12. (PMID: 15548686) Nature. 2003 May 29;423(6939):555-60. (PMID: 12774125) Diabetes. 2003 Jan;52(1):102-10. (PMID: 12502499) J Pineal Res. 2017 Apr;62(3):. (PMID: 28178378) |
فهرسة مساهمة: | Keywords: ER stress; NR4A1 (Nur77); ROS; cbl-b; p-JNK; pancreatic β-cells |
المشرفين على المادة: | 0 (Nr4a1 protein, mouse) 0 (Nuclear Receptor Subfamily 4, Group A, Member 1) 0 (Reactive Oxygen Species) BBX060AN9V (Hydrogen Peroxide) EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) EC 2.7.12.2 (MAP Kinase Kinase 4) |
تواريخ الأحداث: | Date Created: 20201030 Date Completed: 20210519 Latest Revision: 20221005 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC7754045 |
DOI: | 10.1111/jcmm.16028 |
PMID: | 33124187 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1582-4934 |
---|---|
DOI: | 10.1111/jcmm.16028 |