Glycosylation of human cyclooxygenase-2 (COX-2) decreases the efficacy of certain COX-2 inhibitors

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 74kDa, the latter result...

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Bibliographic Details
Published in:Pharmacological research 2012-04, Vol.65 (4), p.445-450
Main Authors: Sevigny, Mary B., Graham, Kamara, Ponce, Esmeralda, Louie, Maggie C., Mitchell, Kylie
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Cercopithecus aethiops
COS Cells
Cyclooxygenase 2 - genetics
Cyclooxygenase 2 - metabolism
Cyclooxygenase 2 Inhibitors - pharmacology
Cyclooxygenase-2 glycoforms
Enzyme inhibition
Glycosylation
Humans
NSAIDs
Selective COX-2 inhibitors
Transfection
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Summary: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 74kDa, the latter resulting from an additional glycosylation at Asn580. In this study, Asn580 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 Asn580 decreases the efficacy of some inhibitors.
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2012.01.001