Increased oxidative stress in the streptozotocin-induced diabetic apoE-deficient mouse: Changes in expression of NADPH oxidase subunits and eNOS

Ding, H, Hashem, M and Triggle, C 2007, 'Increased oxidative stress in the streptozotocin-induced diabetic apoE-deficient mouse: Changes in expression of NADPH oxidase subunits and eNOS', European Journal of Pharmacology, vol. 561, pp. 121-128.


Document type: Journal Article
Collection: Journal Articles

Title Increased oxidative stress in the streptozotocin-induced diabetic apoE-deficient mouse: Changes in expression of NADPH oxidase subunits and eNOS
Author(s) Ding, H
Hashem, M
Triggle, C
Year 2007
Journal name European Journal of Pharmacology
Volume number 561
Start page 121
End page 128
Total pages 8
Publisher Elsevier Science
Abstract Elevated oxidative stress plays a key role in the development of atherosclerosis and endothelial dysfunction in diabetes-associated vascular disease. Glucose-induced changes in the activity of NADPH oxidase and endothelial nitric oxide synthase (eNOS) may result in vascular endothelial cell dysfunction via dysregulation of eNOS and/or changes in the expression of the subunits of NADPH oxidase. In this study, we have investigated whether changes in the expression of the subunits of NADPH oxidase, or eNOS mRNA, can be associated with oxidative stress in the streptozotocin-induced type 1 diabetic apolipoprotein E-deficient (apoE(-/-)) diabetic mouse. Oxidative stress was assessed in aorta and mesenteric arteries by immunofluorescence labelling with dihydroethidium and levels of NADPH oxidase subunits and eNOS were determined by a real-time polymerase chain reaction protocol. Blood glucose levels and oxidative stress were significantly increased following 4, 8 and 16 weeks after treatment with streptozotocin in both streptozotocin-apoE(-/-) aorta and mesenteric arteries compared to the time- and age-matched vehicle (citrate buffer)-treated non-diabetic apoE(-/-). In the mesenteric arteries the expression of nox4 (4 weeks) and gp91phox (nox2) (8 weeks) subunits of NADPH oxidase from streptozotocin-apoE(-/-) were enhanced as were eNOS mRNA and protein (P < 0.05). However, only eNOS mRNA and protein remained increased at 16 weeks. These data indicate that increased oxidative stress in the vasculature of streptozotocin-apoE(-/-) mice is linked to changes in eNOS, superoxide dismutase (SOD) and NADPH oxidase expression.
Subject Basic Pharmacology
Keyword(s) Small Mesenteric-Arteries
Endothelium-Dependent Relaxation
Superoxide-Dismutase Isoforms
Nitric-Oxide
Cardiovascular-Disease
Vascular-Disease
Nad(P)H Oxidase
Smooth-Muscle
Dysfunction
Mice
DOI - identifier 10.1016/j.ejphar.2006.12.034
Copyright notice Copyright © 2007 Elsevier B.V. All rights reserved.
ISSN 0014-2999
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