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Glycosylation of cyclooxygenase‐2 (COX‐2) influences effectiveness of COX‐2 inhibitors
Author(s) -
Graham Kamara Whitney,
Sevigny Mary B.,
Gabriel Bianca S
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.676.1
Subject(s) - cyclooxygenase , chemistry , celecoxib , flurbiprofen , glycosylation , aspirin , arachidonic acid , enzyme , biochemistry , pharmacology , prostaglandin , biology
Cyclooxygenase‐2 (COX‐2) is an enzyme that catalyzes the rate‐limiting step in the prostanoid synthesis pathway, which plays an important role in a variety of physiological and pathophysiological processes including inflammation and cancer. COX‐2 exists as two major glycoforms of 72 and 74kDa, the latter resulting from an additional oligosaccharide chain at amino acid residue Asn 580 . The purpose of this study is to determine if this additional glycosylation affects the inhibitory ability of various COX‐2 inhibitors. COS‐1 cells were transiently transfected with either the wild‐type or Asn 580 ‐mutant COX‐2 gene. Subsets of both cell groups were treated with various concentrations of either aspirin, flurbiprofen, ibuprofen, or celecoxib. After addition of the COX‐2 substrate arachidonic acid to inhibitor‐treated and untreated (control) cells, media was collected and subjected to an ELISA which measured levels of the downstream product prostaglandin E 2 . Results indicate that, at low concentrations, both aspirin and flurbiprofen are more effective at inhibiting the activity of the 72 than the 74 kDa glycoform, whereas ibuprofen and celecoxib are more effective at inhibiting the 74 kDa glycoform. This indicates that glycosylation of COX‐2 at Asn 580 influences the efficacy of COX‐2 inhibitors. Research supported by the Dept. of Natural Sciences and Mathematics at Dominican University of California.