| High glucose increases expression of cyclooxygenase-2, increases oxidative stress and decreases the generation of nitric oxide in mouse microvessel endothelial cells. | |
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MedLine Citation:
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PMID: 19950211 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Mohamad Aljofan; Hong Ding |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 222 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-01-04 Completed Date: 2010-01-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 669-75 Citation Subset: IM |
Affiliation:
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School of Medical Sciences, RMIT University, Victoria, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetophenones
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pharmacology Animals Benzophenanthridines / pharmacology Blotting, Western Cells, Cultured Cyclooxygenase 1 / metabolism Cyclooxygenase 2 / metabolism* Cyclooxygenase 2 Inhibitors / pharmacology Down-Regulation Endothelial Cells / drug effects, enzymology* Glucose / metabolism* Hyperglycemia / enzymology* Indomethacin / pharmacology Isoxazoles / pharmacology Membrane Proteins / metabolism Mice Microvessels / enzymology NADPH Oxidase / antagonists & inhibitors, metabolism NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide / metabolism* Nitric Oxide Synthase Type III / antagonists & inhibitors, metabolism* Oxidative Stress* / drug effects Protein Kinase C / antagonists & inhibitors, metabolism Protein Kinase Inhibitors / pharmacology Protein Multimerization Sulfones / pharmacology Superoxides / metabolism Time Factors Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/3-(4-methylsulfonylphenyl)-4-phenyl-5-trifluoromethylisoxazole; 0/Acetophenones; 0/Benzophenanthridines; 0/Cyclooxygenase 2 Inhibitors; 0/Isoxazoles; 0/Membrane Proteins; 0/Protein Kinase Inhibitors; 0/Sulfones; 10102-43-9/Nitric Oxide; 11062-77-4/Superoxides; 34316-15-9/chelerythrine; 498-02-2/acetovanillone; 50-99-7/Glucose; 50903-99-6/NG-Nitroarginine Methyl Ester; 53-86-1/Indomethacin; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse; EC 1.14.99.-/Ptgs2 protein, mouse; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Ptgs1 protein, mouse; EC 1.6.3.1/NADPH Oxidase; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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