|SCHUSCHKE, DALE - University Of Louisville|
|ADEAGBO, AYOTUNDE - University Of Louisville|
|PATIBANDLA, PHANI - University Of Louisville|
|FERNANDEZ-BOTRAN, RAFAEK - University Of Louisville|
Submitted to: Journal of Inflammation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/9/2009
Publication Date: 10/15/2009
Citation: Schuschke, D.A., Adeagbo, A.S., Patibandla, P.K., Fernandez-Botran, R., Johnson, W.T. 2009. Cyclooxygenase-2 is Upregulated in Copper-Deficient Rats. Inflammation. 32(5):333-339.
Interpretive Summary: Experiments with laboratory animals have shown that low dietary copper intake promotes inflammation. A potential mechanism underlying the promotion of inflammation by low copper intake is the reduction of nitric oxide (NO) levels caused by the accumulation of reactive oxygen species (ROS) that react with NO to form peroxynitrite. Reduction in NO levels can increase the amount of an enzyme called cyclooxygenase (COX) that synthesizes chemicals involved in producing inflammation in blood vessels. The present study showed that low copper intake increases COX in the aorta of rats. It was also shown that the increase in COX was accompanied by increased production of chemicals that produce inflammation. However, inhibition of ROS production in the aortas of the copper-deficient rats did not lower COX or the production of inflammatory chemicals. This indicates that inflammation in the aorta caused by low copper intake is independent of ROS production and NO levels. Thus, a way that low copper intake can increase the risk for cardiovascular disease is by increasing the production of pro-inflammatory chemicals in blood vessels by a mechanism that does not involve increased production of ROS.
Technical 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 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-deficient (Cu-D), or the Cu-D diet combined with the SOD mimetic Tempol (1mM) (Cu-D/T) 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. Tempol protected against an attenuation of NO-mediated vaodilation 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.