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.
| Original language | American English |
|---|---|
| Pages (from-to) | 445-450 |
| Number of pages | 6 |
| Journal | Pharmacological Research |
| Volume | 65 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2012 |
Funding
The authors wish to thank Dr. Timothy Hla (Weill Cornell Medical College) for the generous gift of the human COX-2 cDNA. Special thanks also go out to Chad Schwietert, Chris Endicott, Debashree Banerjee, and Steven Wood for technical support. These studies were supported by the Department of Natural Sciences and Mathematics at Dominican University of California and NSF-MRI 1039728.
| Funders | Funder number |
|---|---|
| Department of Natural Sciences and Mathematics | |
| NSF-MRI | |
| National Science Foundation | 1039728 |
ASJC Scopus Subject Areas
- Pharmacology
Keywords
- cancer
- cyclooxygenase-2
- cox-2
- COX-2 inhibitors
- Animals
- Anti-Inflammatory Agents
- Non-Steroidal
- COS Cells
- Chlorocebus aethiops
- Cyclooxygenase 2
- Cyclooxygenase 2 Inhibitors
- Glycosylation
- Humans
- Transfection
- Selective COX-2 inhibitors
- Cyclooxygenase-2 glycoforms
- NSAIDs
- Enzyme inhibition
Disciplines
- Biochemistry