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Relationship among superoxide-related enzyme, PPARs, and endothelium-dependent relaxation in murine aortas previously organ-cultured in high-glucose conditions

Authors :
Katsuo Kamata
Yasuhiro Takenouchi
Kumiko Taguchi
Tsuneo Kobayashi
Takayuki Matsumoto
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.

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