, Volume 32, Issue 5, pp 333–339 | Cite as

Cyclooxygenase-2 is Upregulated in Copper-Deficient Rats

  • Dale A. SchuschkeEmail author
  • Ayotunde S. O. Adeagbo
  • Phani K. Patibandla
  • Uchechi Egbuhuzo
  • Rafael Fernandez-Botran
  • W. Thomas Johnson


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.


copper 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.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Dale A. Schuschke
    • 1
    Email author
  • Ayotunde S. O. Adeagbo
    • 1
  • Phani K. Patibandla
    • 1
  • Uchechi Egbuhuzo
    • 1
  • Rafael Fernandez-Botran
    • 2
  • W. Thomas Johnson
    • 3
  1. 1.Department of Physiology and Biophysics, Health Sciences Center A1111University of Louisville School of MedicineLouisvilleUSA
  2. 2.Department of Pathology and Laboratory MedicineUniversity of Louisville School of MedicineLouisvilleUSA
  3. 3.Grand Forks Human Nutrition Research CenterGrand ForksUSA

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