Overexpression of Glyoxalase-I Reduces Hyperglycemia-induced Levels of Advanced Glycation End Products and Oxidative Stress in Diabetic Rats
| Autor: | Olaf Brouwers, Tom Teerlink, Toshio Miyata, Petra Niessen, Peter G. Scheffer, Casper G. Schalkwijk, Michael Brownlee, Coen D.A. Stehouwer, Isabel Ferreira, Patrick Schrauwen |
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| Přispěvatelé: | Laboratory Medicine, ICaR - Ischemia and repair, RS: CAPHRI School for Public Health and Primary Care, RS: NUTRIM - R1 - Metabolic Syndrome, Interne Geneeskunde, Epidemiologie, Humane Biologie, MUMC+: KIO Kemta (9), RS: CARIM School for Cardiovascular Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Glycation End Products
Advanced medicine.medical_specialty medicine.disease_cause Biochemistry Gene Expression Regulation Enzymologic Oxidative Phosphorylation Diabetes Mellitus Experimental Lipid peroxidation chemistry.chemical_compound Pregnancy Glycation Internal medicine medicine Animals Humans Rats Wistar Molecular Biology Chemistry Nitrotyrosine Methylglyoxal Lactoylglutathione Lyase Glyoxal Cell Biology Pyruvaldehyde Malondialdehyde Streptozotocin Mitochondria Rats Disease Models Animal Oxidative Stress Metabolism Endocrinology Hyperglycemia Advanced glycation end-product Female Rats Transgenic Biomarkers Oxidative stress medicine.drug |
| Zdroj: | Journal of Biological Chemistry, 286(2), 1374-1380. American Society for Biochemistry and Molecular Biology Inc. Journal of Biological Chemistry, 286(2), 1374-1380. American Society for Biochemistry and Molecular Biology, Inc. Brouwers, O, Niessen, P M, Ferreira, I, Miyata, T, Scheffer, P G, Teerlink, T, Schrauwen, P, Brownlee, M, Stehouwer, C D A & Schalkwijk, C G 2011, ' Overexpression of Glyoxalase-I Reduces Hyperglycemia-induced Levels of Advanced Glycation End Products and Oxidative Stress in Diabetic Rats ', Journal of Biological Chemistry, vol. 286, no. 2, pp. 1374-1380 . https://doi.org/10.1074/jbc.M110.144097 |
| ISSN: | 1083-351X 0021-9258 |
| DOI: | 10.1074/jbc.M110.144097 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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