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Relationship among superoxide-related enzyme, PPARs, and endothelium-dependent relaxation in murine aortas previously organ-cultured in high-glucose conditions
- Source :
- Canadian Journal of Physiology and Pharmacology. 88:760-769
- Publication Year :
- 2010
- Publisher :
- Canadian Science Publishing, 2010.
-
Abstract
- The aim of the present study was to investigate the relationship among superoxide anion, peroxisome proliferator-activated receptors (PPARs), and endothelium-dependent relaxation in murine aortas organ-cultured in a high-glucose condition. Aortas organ-cultured with a high concentration of glucose (40 mmol/L, 20 h; HG group) exhibited the following characteristics (versus aortas cultured in serum-free medium): (i) significantly weaker relaxation to acetylcholine, but unchanged relaxation to SNP and unchanged contractions to norepinephrine and isotonic K+, (ii) significantly greater superoxide generation (indicated by the amount of nitroblue tetrazolium reduced, (iii) significantly higher protein expression levels of gp91phox, NAD(P)H oxidase subunits, and endothelial NO synthase, (iv) significantly lower protein expression level of Mn-superoxide dismutase (SOD), and (v) markedly greater reduction in the protein expression of PPARγ than in that of PPARα. The HG-induced impairment of endothelium-dependent relaxation was prevented by cotreatment with tempol (a SOD mimetic). These results suggest that in the mouse aorta, exposure to high glucose levels may lead to an excessive generation of superoxide via increased gp91phox and decreased Mn-SOD protein expression and that this may in turn trigger an impairment of endothelium-dependent relaxation. Moreover, such protein changes in gp91phox and Mn-SOD may be secondary to a decreased expression of PPARγ protein.
- Subjects :
- Male
medicine.medical_specialty
Nitric Oxide Synthase Type III
Endothelium
Physiology
Peroxisome Proliferator-Activated Receptors
Peroxisome proliferator-activated receptor
Superoxide dismutase
Mice
chemistry.chemical_compound
Organ Culture Techniques
Superoxides
Physiology (medical)
Internal medicine
medicine
Animals
PPAR alpha
Receptor
Aorta
Pharmacology
chemistry.chemical_classification
Mice, Inbred ICR
Oxidase test
Membrane Glycoproteins
biology
Superoxide Dismutase
Superoxide
NADPH Oxidases
General Medicine
Reactive Nitrogen Species
PPAR gamma
Vasodilation
Glucose
Endocrinology
medicine.anatomical_structure
chemistry
NADPH Oxidase 2
cardiovascular system
biology.protein
Dismutase
Endothelium, Vascular
Acetylcholine
medicine.drug
Subjects
Details
- ISSN :
- 12057541 and 00084212
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Canadian Journal of Physiology and Pharmacology
- Accession number :
- edsair.doi.dedup.....b04f47b94ab8aa9fe68384550ed767ea
- Full Text :
- https://doi.org/10.1139/y10-045