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CUEDC2 modulates cardiomyocyte oxidative capacity by regulating GPX1 stability.

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  • معلومة اضافية
    • المصدر:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101487380 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1757-4684 (Electronic) Linking ISSN: 17574676 NLM ISO Abbreviation: EMBO Mol Med Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Chichester, West Sussex : Wiley-Blackwell
    • الموضوع:
      Glutathione Peroxidase/*metabolism ; Myocytes, Cardiac/*physiology ; Repressor Proteins/*metabolism; Animals ; Mice ; Mice, Knockout ; Myocardial Infarction/pathology ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Glutathione Peroxidase GPX1
    • نبذة مختصرة :
      The irreversible loss of cardiomyocytes due to oxidative stress is the main cause of heart dysfunction following ischemia/reperfusion (I/R) injury and ageing-induced cardiomyopathy. Here, we report that CUEDC2, a CUE domain-containing protein, plays a critical role in oxidative stress-induced cardiac injury. Cuedc2(-/-) cardiomyocytes exhibited a greater resistance to oxidative stress-induced cell death. Loss of CUEDC2 enhanced the antioxidant capacity of cardiomyocytes, promoted reactive oxygen species (ROS) scavenging, and subsequently inhibited the redox-dependent activation of signaling pathways. Notably, CUEDC2 promoted E3 ubiquitin ligases tripartite motif-containing 33 (TRIM33)-mediated the antioxidant enzyme, glutathione peroxidase 1 (GPX1) ubiquitination, and proteasome-dependent degradation. Ablation of CUEDC2 upregulated the protein level of GPX1 in the heart significantly. Strikingly, in vivo, the infarct size of Cuedc2(-/-) heart was significantly decreased after I/R injury, and aged Cuedc2(-/-) mice preserved better heart function as the overall ROS levels in their hearts were significantly lower. Our results demonstrated a novel role of CUEDC2 in cardiomyocyte death regulation. Manipulating CUEDC2 level might be an attractive therapeutic strategy for promoting cardiomyocyte survival following oxidative stress-induced cardiac injury.
      (© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)
    • References:
      N Engl J Med. 2012 Jan 5;366(1):54-63. (PMID: 22216842)
      EMBO J. 2007 Apr 4;26(7):1831-42. (PMID: 17347654)
      Biochem J. 2002 Nov 1;367(Pt 3):889-94. (PMID: 12153397)
      Nat Immunol. 2008 May;9(5):533-41. (PMID: 18362886)
      Antioxid Redox Signal. 2011 Oct 1;15(7):1957-97. (PMID: 21087145)
      Circulation. 2001 Aug 28;104(9):979-81. (PMID: 11524388)
      Lancet. 2007 Aug 18;370(9587):575-9. (PMID: 17707752)
      Free Radic Biol Med. 2010 Dec 15;49(12):1925-36. (PMID: 20937380)
      Nat Med. 2011 Nov 07;17(11):1391-401. (PMID: 22064429)
      Cell Rep. 2014 Jun 26;7(6):1982-93. (PMID: 24882011)
      Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8852-7. (PMID: 15184668)
      Nat Cell Biol. 2011 Jul 10;13(8):924-33. (PMID: 21743465)
      Pediatr Res. 2012 Dec;72(6):568-75. (PMID: 23007029)
      J Clin Invest. 2012 Apr;122(4):1222-32. (PMID: 22426211)
      Antioxid Redox Signal. 2010 Jun 1;12(11):1235-46. (PMID: 20070187)
      Circ Res. 2014 Jul 18;115(3):354-63. (PMID: 24833660)
      EMBO Mol Med. 2016 Jul 01;8(7):813-29. (PMID: 27286733)
      Biochem J. 1997 Aug 15;326 ( Pt 1):117-23. (PMID: 9337858)
      Circ Res. 2012 Sep 28;111(8):1091-106. (PMID: 23023511)
      Circ Res. 2005 Apr 29;96(8):831-7. (PMID: 15802613)
      Circulation. 2002 Aug 27;106(9):1154-8. (PMID: 12196344)
      J Mol Cell Cardiol. 1996 Aug;28(8):1759-67. (PMID: 8877785)
      Nat Med. 2011 Jun;17(6):708-14. (PMID: 21572428)
      Nat Med. 2016 Feb;22(2):175-82. (PMID: 26726877)
      J Biol Chem. 2011 Apr 22;286(16):13995-4006. (PMID: 21324895)
      Cell Death Differ. 2006 May;13(5):730-7. (PMID: 16341124)
      Cell. 2014 Apr 24;157(3):565-79. (PMID: 24766806)
      Circ Res. 2009 Nov 20;105(11):1110-7. (PMID: 19815822)
      J Clin Invest. 2005 Mar;115(3):500-8. (PMID: 15765131)
      J Exp Med. 2005 Apr 4;201(7):1135-43. (PMID: 15795240)
      J Exp Med. 2011 Mar 14;208(3):549-60. (PMID: 21383058)
      Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):11017-22. (PMID: 23776205)
    • Contributed Indexing:
      Keywords: CUEDC2; GPX1; ageing‐induced cardiomyopathy; antioxidant capacity; ischemia/reperfusion injury
    • الرقم المعرف:
      0 (CUEDC2 protein, mouse)
      0 (Reactive Oxygen Species)
      0 (Repressor Proteins)
      EC 1.11.1.9 (Glutathione Peroxidase)
      EC 1.11.1.9 (Glutathione Peroxidase GPX1)
      EC 1.11.1.9 (Gpx1 protein, mouse)
    • الموضوع:
      Date Created: 20160612 Date Completed: 20170913 Latest Revision: 20221207
    • الموضوع:
      20221213
    • الرقم المعرف:
      PMC4931293
    • الرقم المعرف:
      10.15252/emmm.201506010
    • الرقم المعرف:
      27286733