Cyclooxygenase-2 is Upregulated in Copper-Deficient Rats

• Published in: Inflammation Vol. 32; no. 5; pp. 333 - 339
• Main Authors: Schuschke, Dale A., Adeagbo, Ayotunde S. O., Patibandla, Phani K., Egbuhuzo, Uchechi, Fernandez-Botran, Rafael, Johnson, W. Thomas
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-10-2009; Springer Nature B.V
• Subjects: Animals; Antioxidants - pharmacology; Biomedical and Life Sciences; Biomedicine; Copper - deficiency; Cyclic N-Oxides - pharmacology; Cyclooxygenase 2 - metabolism; Immunology; Internal Medicine; Male; Nitric Oxide - metabolism; Pathology; Pharmacology/Toxicology; Rats; Rats, Sprague-Dawley; Rheumatology; Spin Labels; Up-Regulation - physiology; Tempol; copper; isoprostane; prostaglandin E; cyclooxygenase-2
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-009-9140-4

Copper deficiency inactivates Cu/Zn-SOD and promotes accumulation of reactive oxygen species. This process likely impairs nitric oxide (NO)-mediated relaxation as well as triggers vascular inflammation. The current study was designed to determine whether COX-2, a proinflammatory protein, expression and activity are upregulated in the oxidative environment associated with inadequate Cu. Weanling male Sprague Dawley rats were fed purified diets which were either Cu-adequate (Cu-A); Cu-marginal (Cu-M), Cu-deficient (Cu-D), or the Cu-D diet combined with the SOD mimetic Tempol (Cu-D/T; 1 mM in drinking water) for 4 weeks. COX-2 protein, PGE
2
(COX-2 metabolite) and isoprostanes (index of oxidative stress) were all higher in the Cu-D group
vs
Cu-A group, but no significant differences occurred between the Cu-M and Cu-A groups. Tempol protected against an attenuation of NO-mediated vasodilation in the Cu-D rats but did not prevent the elevation of PGE
2
or isoprostanes. Our data suggest a role for copper as a modulator of oxidative stress and inflammation independent of SOD activity or NO-derived oxidants.