Overexpression of glyoxalase-I reduces hyperglycemiainduced levels of advanced glycation end products and oxidative stress in diabetic rats

Brouwers, Olaf, Niessen, Petra M., Ferreira, Isabel, Miyata, Toshio, Scheffer, Peter G., Teerlink, Tom, Schrauwen, Patrick, Brownlee, Michael, Stehouwer, Coen D. and Schalkwijk, Casper G. (2011) Overexpression of glyoxalase-I reduces hyperglycemiainduced levels of advanced glycation end products and oxidative stress in diabetic rats. Journal of Biological Chemistry, 286 2: 1374-1380. doi:10.1074/jbc.M110.144097

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Author Brouwers, Olaf
Niessen, Petra M.
Ferreira, Isabel
Miyata, Toshio
Scheffer, Peter G.
Teerlink, Tom
Schrauwen, Patrick
Brownlee, Michael
Stehouwer, Coen D.
Schalkwijk, Casper G.
Title Overexpression of glyoxalase-I reduces hyperglycemiainduced levels of advanced glycation end products and oxidative stress in diabetic rats
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2011-01-14
Sub-type Article (original research)
DOI 10.1074/jbc.M110.144097
Open Access Status File (Publisher version)
Volume 286
Issue 2
Start page 1374
End page 1380
Total pages 7
Place of publication Bethesda, MD United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Abstract The reactive advanced glycation end product (AGE) precursor methylglyoxal (MGO) and MGO-derived AGEs are associated with diabetic vascular complications and also with an increase in oxidative stress. Glyoxalase-I (GLO-I) transgenic rats were used to explore whether overexpression of this MGO detoxifying enzyme reduces levels of AGEs and oxidative stress in a rat model of diabetes. Rats were made diabetic with streptozotocin, and after 12 weeks, plasma and multiple tissues were isolated for analysis of AGEs, carbonyl stress, and oxidative stress. GLO-I activity was significantly elevated in multiple tissues of all transgenic rats compared with wild-type (WT) littermates. Streptozotocin treatment resulted in a 5-fold increase in blood glucose concentrations irrespective of GLO-I overexpression. Levels of MGO, glyoxal, 3-deoxyglucosone, AGEs, and oxidative stress markers nitrotyrosine, malondialdehyde, and F2-isoprostane were elevated in the diabetic WT rats. In diabetic GLO-I rats, glyoxal and MGO composite scores were significantly decreased by 81%, and plasma AGEs and oxidative stress markers scores were significantly decreased by ∼50%. Hyperglycemia induced a decrease in protein levels of the mitochondrial oxidative phosphorylation complex in the gastrocnemius muscle, which was accompanied by an increase in the lipid peroxidation product 4-hydroxy-2-nonenal, and this was counteracted by GLO-I overexpression. This study shows for the first time in an in vivo model of diabetes that GLO-I overexpression reduces hyperglycemia-induced levels of carbonyl stress, AGEs, and oxidative stress. The reduction of oxidative stress by GLO-I overexpression directly demonstrates the link between glycation and oxidative stress.
Keyword Diabetes
Endothelium
Metabolism
Oxidative stress
Rat
Glycation
Glyoxalase-1
Methylglyoxal
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Public Health Publications
 
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