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Selected Works of Mary Sevigny
Presentation
Glycosylation of cyclooxygenase-2 (COX-2) interferes with the efficacy of COX-2 inhibitors
National Conference on Undergraduate Research, University of Montana (2010)
  • Katherine Goricki, Department of Natural Sciences and Mathematics, Dominican University of California
  • Mary-Neama Latu, Department of Natural Sciences and Mathematics, Dominican University of California
  • Mandy Omoregie, Department of Natural Sciences and Mathematics, Dominican University of California
  • Kamara Graham, Department of Natural Sciences and Mathematics, Dominican University of California
  • Mary B. Sevigny, Department of Natural Sciences and Mathematics, Dominican University of California
Abstract
Cyclooxygenase-2 (COX-2) is the rate-limiting enzyme in the prostanoid biosynthesis pathway which produces hormone-like chemicals called prostaglandins. Prostaglandins play a key role in many physiological processes such as pregnancy, bone metabolism, and inflammation. However, high levels of prostaglandins resulting from overexpression of COX-2 are believed to play a role in the development of diseases such as rheumatoid arthritis, cancer, and Alzheimer’s. COX-2 exists as 72 and 74kDa glycoforms due to a variable glycosylation site at Asn580. The purpose of this study is to determine if the effectiveness of the nonselective COX-2 inhibitors, aspirin and flurbiprofen, is influenced by glycosolation of COX-2 at Asn580. COS-1 cells were transfected with either an Asn580-mutant human COX-2 gene or the wild-type human COX-2 gene, and then subsets of cells were treated with different concentrations of either aspirin or flurbiprofen. After incubation in the presence of the COX-2 substrate arachidonic acid, the media were removed and analyzed via ELISA for prostaglandin E2, a downstream product of the COX-2 pathway and thus a reliable indicator of COX-2 activity. Results show that low-dose aspirin (2- 10 µM) and flurbiprofen (0.02- 0.1 µM) have a greater inhibitory effect on the COX-2 enzyme expressed by the Asn580-mutant cells. These results indicate that glycosylation of COX-2 at Asn580 interferes with the inhibitory abilities of aspirin and flurbiprofen. Future studies will test the nonselective inhibitor ibuprofen and the selective COX-2 inhibitor celecoxib.
Keywords
  • COX-2 INHIBITORS,
  • CYCLOOXYGENASE-2 (COX-2)
Disciplines
Publication Date
April, 2010
Location
Missoula, MT
Citation Information
Katherine Goricki, Mary-Neama Latu, Mandy Omoregie, Kamara Graham, et al.. "Glycosylation of cyclooxygenase-2 (COX-2) interferes with the efficacy of COX-2 inhibitors" National Conference on Undergraduate Research, University of Montana (2010)
Available at: http://works.bepress.com/mary-sevigny/19/