title: Cyclooxygenase-2 is upregulated in copper-deficient rats.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Health Sciences Center A1111, University of Louisville School of Medicine, Louisville, KY 40292, USA. daschu01@louisville.edu
authors.forename: Dale A
authors.initials: DA
authors.lastname: Schuschke
authors.forename: Ayotunde S O
authors.initials: AS
authors.lastname: Adeagbo
authors.forename: Phani K
authors.initials: PK
authors.lastname: Patibandla
authors.forename: Uchechi
authors.initials: U
authors.lastname: Egbuhuzo
authors.forename: Rafael
authors.initials: R
authors.lastname: Fernandez-Botran
authors.forename: W Thomas
authors.initials: WT
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003300:Copper / Q000172:deficiency*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D009569:Nitric Oxide; D003300:Copper; D051546:Cyclooxygenase 2; C001803:tempol