Cyclooxygenase-2 is Upregulated in Copper-Deficient Rats
- 76 Downloads
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, PGE2 (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 PGE2 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.
KEY WORDScopper cyclooxygenase-2 prostaglandin E2 isoprostane Tempol
We thank Sharon Gordon for her expert technical assistance. This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-55030. The US Department of Agriculture, Agricultural Research Service, Northern Plains Area, is an equal opportunity/affirmative action employer, and all agency services are available without discrimination.
- 1.Gordon, S. A., D. Lominadze, J. T. Saari, A. B. Lentsch, and D. A. Schuschke. 2005. Impaired deformability of copper-deficient neutrophils. Exp. Biol. Med. 230:543–548.Google Scholar
- 3.Lentsch, A. B., A. Kato, J. T. Saari, and D. A. Schuschke. 2001. Augmented metalloproteinase activity and acute lung injury in copper deficient rats. Am. J. Physiol. 281:L387–L393.Google Scholar
- 6.Dalle Lucca, J. J., J. T. Saari, and D. A. Schuschke. 2002. Neointima formation in the rat carotid artery is exacerbated by dietary copper deficiency. Exp. Biol Med. 227:487–491.Google Scholar
- 9.Morita-Fujimura, Y., M. Fujimura, Y. Gasche, J. C. Copin, and P. H. Chan. 2000. Overexpression of copper and zinc superoxide dismutase in transgenic mice prevents the induction and activation of matrix metalloproteinases after cold injury-induced brain trauma. J. Cereb. Blood Flow Metab. 20:130–138.PubMedCrossRefGoogle Scholar
- 17.Kalea, A. Z., D. A. Schuschke, P. D. Harris, and D. J. Klimis-Zacas. 2006. Cyclo-oxygenase inhibition restores the attenuated vasodilation in manganese-deficient rat aorta. J. Nutr. 136:1–6.Google Scholar
- 30.Henrion, D., E. Dechaux, F. J. Dowell, J. Maclour, J.-L. Samuel, B. I. Lévy, and J.-B. Michel. 1997. Alteration of flow-induced dilatation in mesenteric resistance arteries of L-NAME treated rats and its partial association with induction of cyclo-oxygenase-2. Br. J. Pharmacol. 121:83–90.PubMedCrossRefGoogle Scholar
- 31.Lynch, S. M., B. Frei, J. D. Morrow, L. J. Roberts, A. Xu, T. Jackson, R. Reyna, L. M. Klevay, J. A. Vita, and J. F. Keaney. 1997. Vascular superoxide dismutase deficiency impairs endothelial vasodilator function through direct inactivation of nitric oxide and increased lipid peroxidation. Arterioscler. Thromb. Vasc. Biol. 17:2975–2981.PubMedGoogle Scholar