PMID- 37895057
OWN - NLM
STAT- MEDLINE
DCOM- 20231030
LR  - 20231030
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 20
DP  - 2023 Oct 19
TI  - Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy.
LID - 10.3390/ijms242015376 [doi]
LID - 15376
AB  - 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 
      beta-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.
FAU - Nahum-Ankonina, Ortal
AU  - Nahum-Ankonina O
AD  - The Division of Cardiovascular and Thoracic Surgery, Rabin Medical Center, 
      Petach-Tikva 4941492, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
FAU - Kurtzwald-Josefson, Efrat
AU  - Kurtzwald-Josefson E
AD  - The Division of Cardiovascular and Thoracic Surgery, Rabin Medical Center, 
      Petach-Tikva 4941492, Israel.
FAU - Ciechanover, Aaron
AU  - Ciechanover A
AD  - The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of 
      Technology, Haifa 3109601, Israel.
FAU - Waldman, Maayan
AU  - Waldman M
AD  - The Division of Cardiovascular and Thoracic Surgery, Rabin Medical Center, 
      Petach-Tikva 4941492, Israel.
FAU - Shwartz-Rohaker, Orna
AU  - Shwartz-Rohaker O
AD  - The Division of Cardiovascular and Thoracic Surgery, Rabin Medical Center, 
      Petach-Tikva 4941492, Israel.
FAU - Hochhauser, Edith
AU  - Hochhauser E
AD  - The Division of Cardiovascular and Thoracic Surgery, Rabin Medical Center, 
      Petach-Tikva 4941492, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
FAU - Meyer, Sam J
AU  - Meyer SJ
AUID- ORCID: 0000-0001-6887-815X
AD  - The Division of Cardiovascular and Thoracic Surgery, Rabin Medical Center, 
      Petach-Tikva 4941492, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
FAU - Aravot, Dan
AU  - Aravot D
AD  - The Division of Cardiovascular and Thoracic Surgery, Rabin Medical Center, 
      Petach-Tikva 4941492, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
FAU - Phillip, Moshe
AU  - Phillip M
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
AD  - The Division of Endocrinology, Schneider Medical Center, Petach-Tikva 4920235, 
      Israel.
FAU - Barac, Yaron D
AU  - Barac YD
AUID- ORCID: 0000-0002-4688-2358
AD  - The Division of Cardiovascular and Thoracic Surgery, Rabin Medical Center, 
      Petach-Tikva 4941492, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
LA  - eng
PT  - Journal Article
DEP - 20231019
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - 0 (Ubiquitin)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Ubiquitin/metabolism
MH  - *Diabetes Mellitus, Type 2/complications/genetics/metabolism
MH  - *Diabetes Mellitus, Experimental/complications/genetics/metabolism
MH  - *Diabetic Cardiomyopathies/genetics/metabolism
MH  - *Diabetes Complications/complications
MH  - RNA, Messenger/genetics
PMC - PMC10607702
OTO - NOTNLM
OT  - T2DM
OT  - UPS
OT  - heart
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/28 11:48
MHDA- 2023/10/30 06:46
PMCR- 2023/10/19
CRDT- 2023/10/28 01:19
PHST- 2023/08/09 00:00 [received]
PHST- 2023/09/28 00:00 [revised]
PHST- 2023/10/02 00:00 [accepted]
PHST- 2023/10/30 06:46 [medline]
PHST- 2023/10/28 11:48 [pubmed]
PHST- 2023/10/28 01:19 [entrez]
PHST- 2023/10/19 00:00 [pmc-release]
AID - ijms242015376 [pii]
AID - ijms-24-15376 [pii]
AID - 10.3390/ijms242015376 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Oct 19;24(20):15376. doi: 10.3390/ijms242015376.