title: Glycosylation of human cyclooxygenase-2 (COX-2) decreases the efficacy of certain COX-2 inhibitors.
abstract: Prostanoids play an important role in a variety of physiological and pathophysiological processes including inflammation and cancer. The rate-limiting step in the prostanoid biosynthesis pathway is catalyzed by cyclooxygenase-2 (COX-2). COX-2 exists as two glycoforms, 72 and 74 kDa, the latter resulting from an additional glycosylation at Asn(580). In this study, Asn(580) was mutated, and the mutant and wild-type COX-2 genes were expressed in COS-1 cells to determine how glycosylation affects the inhibition of COX-2 activity by aspirin, flurbiprofen, ibuprofen, celecoxib, and etoricoxib. Results indicate that certain inhibitors were 2-5 times more effective at inhibiting COX-2 activity when the glycosylation site was eliminated, indicating that glycosylation of COX-2 at Asn(580) decreases the efficacy of some inhibitors.
authors.affiliation: Department of Natural Sciences and Mathematics, Dominican University of California, San Rafael, CA 94901, USA. mary.sevigny@dominican.edu
authors.forename: Mary B
authors.initials: MB
authors.lastname: Sevigny
authors.forename: Kamara
authors.initials: K
authors.lastname: Graham
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Ponce
authors.forename: Maggie C
authors.initials: MC
authors.lastname: Louie
authors.forename: Kylie
authors.initials: K
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D014162:Transfection
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human