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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 879516, 12 pages
http://dx.doi.org/10.1155/2013/879516
Research Article

Therapeutic Effect of MG132 on the Aortic Oxidative Damage and Inflammatory Response in OVE26 Type 1 Diabetic Mice

1The Second Hospital of Jilin University, Changchun 130041, China
2KCHRI, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA
3Department of Ophthalmology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China
4The First Hospital of Jilin University, Changchun 130021, China
5Normal Bethune Medical College of Jilin University, Changchun 130021, China
6Department of Pathology, Inner Mongolia Forestry General Hospital, Yakeshi, Inner Mongolia 022150, China
7Chinese American Research Institute for Diabetic Complications, Wenzhou Medical College, Wenzhou 325000, China
8Departments of Radiation Oncology and Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA
9Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China

Received 15 January 2013; Accepted 28 February 2013

Academic Editor: Narasimham L. Parinandi

Copyright © 2013 Xiao Miao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The present study tested whether MG132 increases vascular nuclear factor E2-related factor-2 (Nrf2) expression and transcription to provide a therapeutic effect on diabetes-induced pathogenic changes in the aorta. To this end, three-month-old OVE26 diabetic and age-matched control mice were intraperitoneally injected with MG-132, 10 μg/kg daily for 3 months. OVE26 transgenic type 1 diabetic mice develop hyperglycemia at 2-3 weeks of age and exhibit albuminuria at 3 months of age with mild increases in TNF-α expression and 3-NT accumulation in the aorta. Diabetes-induced significant increases in the wall thickness and structural derangement of aorta were found in OVE26 mice with significant increases in aortic oxidative and nitrosative damage, inflammation, and remodeling at 6 months of diabetes, but not at 3 months of diabetes. However, these pathological changes seen at the 6 months of diabetes were abolished in OVE26 mice treated with MG-132 for 3 months that were also associated with a significant increase in Nrf2 expression in the aorta as well as transcription of downstream genes. These results suggest that chronic treatment with low-dose MG132 can afford an effective therapy for diabetes-induced pathogenic changes in the aorta, which is associated with the increased Nrf2 expression and transcription.