PMID- 37759966
OWN - NLM
STAT- Publisher
LR  - 20231003
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 12
IP  - 9
DP  - 2023 Aug 23
TI  - Molecular Link between Glo-1 Expression and Markers of Hyperglycemia and 
      Oxidative Stress in Vascular Complications of Type 2 Diabetes Mellitus.
LID - 10.3390/antiox12091663 [doi]
LID - 1663
AB  - Chronic hyperglycemia and oxidative stress in Type 2 Diabetes Mellitus trigger 
      cellular dysfunction via the formation of Advanced Glycation End Products (AGEs), 
      resulting in dicarbonyl stress. Glyoxalase-1 (Glo-1) is the main defense against 
      dicarbonyl stress. The aim of this study was to explore any cross-talk between 
      Glo-1 and markers of hyperglycemia and oxidative stress. The siRNA-mediated 
      downregulation of Glo-1 was performed in human microvascular endothelial cell 
      line (HMEC-1). A Glo-1 transgenic rat model was developed. Glo-1 activity, as 
      determined spectrophotometrically, and methylglyoxal were quantified using 
      UPLC-MS/MS and the expression of representative markers of hyperglycemia and 
      oxidative stress was performed using quantitative real-time PCR. A significant 
      increase in the expression of Vascular Cell Adhesion Molecule-1 (VCAM-1) was 
      observed in the case of the siRNA-mediated downregulation of Glo-1 in the 
      microvasculature model under hyperglycemic conditions (p-value < 0.001), as well 
      the as overexpression of Glo-1 in the macrovasculature (p-value = 0.0125). The 
      expression of thioredoxin interacting protein (TXNIP) was found to be 
      significantly upregulated in wildtype diabetic conditions vs. Glo-1 transgenic 
      control conditions (p-value = 0.008), whereas the downregulation of Glo-1 had no 
      impact on TXNIP expression. These findings substantiate the role of VCAM as an 
      important marker of dicarbonyl stress (represented by Glo-1 downregulation), as 
      well as of hyperglycemia, in diabetic vascular complications. Our findings also 
      suggest a potential feedback loop that may exist between Glo-1 and TXNIP, as the 
      highest expression of TXNIP is observed in cases of wildtype diabetic conditions, 
      and the lowest expression of TXNIP is observed when Glo-1 transgene is being 
      expressed in absence of dicarbonyl stress.
FAU - Syed, Nida Ali
AU  - Syed NA
AUID- ORCID: 0000-0003-3664-6754
AD  - Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied 
      Biosciences, National University of Sciences and Technology, Islamabad 44000, 
      Pakistan.
AD  - Department of Internal Medicine, Faculty of Health, Medicine and Life Science, 
      Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
FAU - Bhatti, Attya
AU  - Bhatti A
AD  - Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied 
      Biosciences, National University of Sciences and Technology, Islamabad 44000, 
      Pakistan.
FAU - John, Peter
AU  - John P
AD  - Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied 
      Biosciences, National University of Sciences and Technology, Islamabad 44000, 
      Pakistan.
LA  - eng
GR  - 1-8/HEC/HRD/2019/9993/Higher Education Commission/
PT  - Journal Article
DEP - 20230823
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC10525326
OTO - NOTNLM
OT  - Glyoxalase-1
OT  - TXNIP
OT  - Type 2 Diabetes Mellitus
OT  - VCAM
OT  - hyperglycemia
OT  - inflammation
OT  - oxidative stress
OT  - vascular complications
COIS- The authors declare no conflicts of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript; or in the decision to publish the results.
EDAT- 2023/09/28 06:43
MHDA- 2023/09/28 06:43
PMCR- 2023/08/23
CRDT- 2023/09/28 01:03
PHST- 2023/06/30 00:00 [received]
PHST- 2023/08/09 00:00 [revised]
PHST- 2023/08/21 00:00 [accepted]
PHST- 2023/09/28 06:43 [medline]
PHST- 2023/09/28 06:43 [pubmed]
PHST- 2023/09/28 01:03 [entrez]
PHST- 2023/08/23 00:00 [pmc-release]
AID - antiox12091663 [pii]
AID - antioxidants-12-01663 [pii]
AID - 10.3390/antiox12091663 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2023 Aug 23;12(9):1663. doi: 10.3390/antiox12091663.