Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/genetics ; Diabetes Mellitus, Type 2*/metabolism ; Diabetes Mellitus, Experimental*/complications ; Diabetes Mellitus, Experimental*/genetics ; Diabetes Mellitus, Experimental*/metabolism ; Diabetic Cardiomyopathies*/genetics ; Diabetic Cardiomyopathies*/metabolism ; Diabetes Complications*/complications; Mice ; Animals ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism ; RNA, Messenger/genetics

This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of db/db mice with decreased levels of nppb mRNA and increased levels of Myh7 , indicating potential cardiac dysfunction. The mRNA levels of USP18 (deubiquitinating enzyme), PSMB8 , and PSMB9 (proteasome β-subunits) were down-regulated in db/db mice, while the mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were down-regulated in db/db mice, and RNF167 was elevated in Adult diabetic mice. The reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to the future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.

Nat Rev Mol Cell Biol. 2005 Jan;6(1):79-87. (PMID: 15688069)
Front Mol Neurosci. 2017 Oct 26;10:347. (PMID: 29123470)
Int J Cardiol. 2018 Dec 1;272:194-201. (PMID: 30173922)
Circulation. 2019 Nov 5;140(19):1569-1577. (PMID: 31474116)
Mol Cell Endocrinol. 2015 Sep 15;413:36-48. (PMID: 26116825)
Am J Physiol Endocrinol Metab. 2014 Mar;306(6):E592-605. (PMID: 24425761)
Prog Mol Biol Transl Sci. 2012;109:295-346. (PMID: 22727426)
Clin Sci (Lond). 2015 Jun;128(11):751-60. (PMID: 25599194)
Biochim Biophys Acta. 2016 Dec;1862(12):2259-2269. (PMID: 27421947)
J Heart Lung Transplant. 2017 Jul;36(7):708-714. (PMID: 28341100)
Biochem J. 2014 Apr 1;459(1):27-36. (PMID: 24387786)
World J Diabetes. 2013 Oct 15;4(5):177-89. (PMID: 24147202)
J Muscle Res Cell Motil. 2017 Aug;38(3-4):291-302. (PMID: 29101517)
Curr Hypertens Rep. 2009 Dec;11(6):396-405. (PMID: 19895750)
Exp Physiol. 2016 Jan;101(1):113-23. (PMID: 26446173)
Nat Rev Mol Cell Biol. 2002 Feb;3(2):112-21. (PMID: 11836513)
J Bioenerg Biomembr. 2014 Jun;46(3):173-87. (PMID: 24733503)
J Mol Cell Cardiol. 2012 Mar;52(3):526-37. (PMID: 22085703)
Am J Physiol Renal Physiol. 2021 Apr 1;320(4):F548-F558. (PMID: 33586497)
Nature. 1997 Feb 20;385(6618):737-40. (PMID: 9034192)
Bioessays. 2000 May;22(5):442-51. (PMID: 10797484)
Biochimie. 2001 Mar-Apr;83(3-4):311-8. (PMID: 11295491)
Front Physiol. 2018 Nov 21;9:1575. (PMID: 30519189)
Oncogene. 2005 Jan 13;24(3):314-25. (PMID: 15678131)
Mol Ther. 2020 Jan 8;28(1):279-292. (PMID: 31636038)
Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H146-53. (PMID: 16113078)
Cold Spring Harb Perspect Biol. 2020 Jun 1;12(6):. (PMID: 31653642)
Biomolecules. 2020 Jul 16;10(7):. (PMID: 32708792)
Int J Mol Sci. 2020 Sep 11;21(18):. (PMID: 32933049)
Physiol Rev. 2002 Apr;82(2):373-428. (PMID: 11917093)
Hypertension. 2016 Nov;68(5):1160-1170. (PMID: 27572150)
Cardiovasc Diabetol. 2015 Aug 05;14:98. (PMID: 26242308)
PLoS One. 2020 Mar 2;15(3):e0229462. (PMID: 32119722)
Transl Res. 2019 Mar;205:64-76. (PMID: 30342797)
Phys Ther. 2008 Nov;88(11):1254-64. (PMID: 18801858)
Hum Mol Genet. 2015 May 1;24(9):2528-38. (PMID: 25612572)
Diabetes Metab Res Rev. 2020 Jan;36(1):e3213. (PMID: 31465625)
Rev Endocr Metab Disord. 2010 Mar;11(1):31-9. (PMID: 20180026)
Biochem J. 2011 Jan 1;433(1):31-42. (PMID: 21158740)
Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19426-31. (PMID: 23129617)
J Mol Cell Cardiol. 2008 Mar;44(3):618-21. (PMID: 18308332)
J Cell Sci. 2020 Jun 11;133(11):. (PMID: 32409562)
Circ Res. 2019 Jan 4;124(1):121-141. (PMID: 30605420)
Circulation. 2010 Mar 2;121(8):997-1004. (PMID: 20159828)
Mol Immunol. 2017 Mar;83:147-153. (PMID: 28157553)
Cardiovasc Res. 2010 Jan 15;85(2):367-75. (PMID: 19564153)

Keywords: T2DM; UPS; heart

EC 3.4.25.1 (Proteasome Endopeptidase Complex)
0 (Ubiquitin)
0 (RNA, Messenger)

Date Created: 20231028 Date Completed: 20231030 Latest Revision: 20231030

20231030

PMC10607702

10.3390/ijms242015376

37895057