High glucose increases expression of Cyclooxygenase-2 increases oxidative stress and decreases the generation of nitric oxide in mouse microvessel endothelial cells

Aljofan, M and Ding, H 2009, 'High glucose increases expression of Cyclooxygenase-2 increases oxidative stress and decreases the generation of nitric oxide in mouse microvessel endothelial cells', Journal of Cellular Physiology, pp. 1-7.


Document type: Journal Article
Collection: Journal Articles

Title High glucose increases expression of Cyclooxygenase-2 increases oxidative stress and decreases the generation of nitric oxide in mouse microvessel endothelial cells
Author(s) Aljofan, M
Ding, H
Year 2009
Journal name Journal of Cellular Physiology
Start page 1
End page 7
Total pages 7
Publisher Wiley Interscience
Abstract Hyperglycaemia is a key factor that contributes to the development of diabetes-related microvascular disease. Both cyclooxygenase I and cyclooxygenase II are expressed in endothelial cells and play key roles in the regulation of cardiovascular function. In the current study we tested the hypothesis that hyperglycaemia induced increased expression of cyclooxygenase II is a contributing factor both to the increased oxidative stress and to the reduction in the generation of nitric oxide in microvessel endothelial cells following their exposure to high glucose. We demonstrated that the exposure of mouse microvascular endothelial cells to high glucose for 3 days decreased the generation of nitric oxide and enhanced production of superoxide. Western blots illustrated that exposure to high glucose also increased endothelial nitric oxide synthase and cyclooxygenase II protein expression levels and decreased the dimer/monomer ratio of endothelial nitric oxide synthase protein. All the changes induced by the high glucose culture media could be reversed by either the cyclooxygenase II inhibitor CAY10404, the non-selective cyclooxygenase inhibitor indomethacin or the protein kinase C inhibitor chelerythrine, but not solely by preincubation with the antioxidant and putative NADPH oxidase inhibitor, apocynin. Our data indicate that high glucose induced oxidative stress is linked to an increase in the expression of cyclooxygenase II and a reduced generation of nitric oxide that is associated with an uncoupled endothelial nitric oxide synthase, possibly due to decreased dimer/monomer ratio.
Keyword(s) hypergylycaemia
diabetes-related microvascular disease
cyclooxygenase I
cyclooxygenase II
endothelial cells
cardiovascular function
oxidative stress
nitric oxide
superoxide
microvessel endothelial cells
glucose
Western blots
endothelial nitric oxide synthase protein
CAY10404
indomethacin
chelerythrine
apocynin
DOI - identifier 10.1002/jcp.21986
Copyright notice Wiley-Liss 2009
ISSN 1097-4652
Versions
Version Filter Type
Altmetric details:
Access Statistics: 105 Abstract Views  -  Detailed Statistics
Created: Wed, 17 Nov 2010, 16:09:00 EST by Catalyst Administrator
© 2014 RMIT Research Repository • Powered by Fez SoftwareContact us