Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression

International Journal of Molecular Sciences

Olaf Brouwers⁴  Joyce M. J. de Vos-Houben²  Petra M. G. Niessen⁴  Toshio Miyata¹  Frans van Nieuwenhoven³  Ben J. A. Janssen⁵  Geja Hageman²  Coen D. A. Stehouwer⁴ 

[1] Centre of Translational and Advanced Research, Tohoku University, Sendai 980-8575, Japan; E-Mail:;Department of Toxicology, Maastricht University Medical Center, 6200MD Maastricht, The Netherlands; E-Mails:;Department of Physiology, Maastricht University Medical Center, 6200MD Maastricht, The Netherlands; E-Mail:;Laboratory for Metabolism and Vascular Medicine, Division of General Internal Medicine, Department of Internal Medicine, Maastricht University Medical Center, Universiteitssingel 50, PO Box 616 (#14), 6200MD Maastricht, The Netherlands; E-Mails:;Department of Pharmacology, Maastricht University Medical Center, 6200MD Maastricht, The Netherlands; E-Mail:

关键词: glycation;    oxo-aldehydes;    glyoxalase-I;    oxidative stress;    cardiac function;   

DOI  :  10.3390/ijms140815724

来源: mdpi

【 摘 要 】

Diabetes significantly increases the risk of heart failure. The increase in advanced glycation endproducts (AGEs) and oxidative stress have been associated with diabetic cardiomyopathy. We recently demonstrated that there is a direct link between AGEs and oxidative stress. Therefore, the aim of the current study was to investigate if a reduction of AGEs by overexpression of the glycation precursor detoxifying enzyme glyoxalase-I (GLO-I) can prevent diabetes-induced oxidative damage, inflammation and fibrosis in the heart. Diabetes was induced in wild-type and GLO-I transgenic rats by streptozotocin. After 24-weeks of diabetes, cardiac function was monitored with ultrasound under isoflurane anesthesia. Blood was drawn and heart tissue was collected for further analysis. Analysis with UPLC-MSMS showed that the AGE N^ɛ-(1-carboxymethyl)lysine and its precursor 3-deoxyglucosone were significantly elevated in the diabetic hearts. Markers of oxidative damage, inflammation, and fibrosis were mildly up-regulated in the heart of the diabetic rats and were attenuated by GLO-I overexpression. In this model of diabetes, these processes were not accompanied by significant changes in systolic heart function, i.e., stroke volume, fractional shortening and ejection fraction. This study shows that 24-weeks of diabetes in rats induce early signs of mild cardiac alterations as indicated by an increase of oxidative stress, inflammation and fibrosis which are mediated, at least partially, by glycation.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland