Up-regulation of microsomal prostaglandin E synthase-1 in COX-1 and COX-2 knock-out mouse fibroblast cell lines.
In this paper we investigated the possible involvement of prostaglandin E synthases (PGESs) in compensatory mechanism. Our findings showed that microsomal (m)PGES-1 expression was significantly up-regulated in COX knock-out (K/O) cells whereas the expression of cytosolic PGES was not changed indicating that the induction of mPGES-1 may, at least in part, contribute to the substantial increase of PGE(2) production in COX K/O cell lines. The selective up-regulation of mPGES-1 in COX-2 K/O cells suggests that mPGES-1 may be metabolically coupled with COX-1 for PGE(2) formation. Addition of arachidonic acid caused significant induction of mPGES-1 and COX-2 in WT cells, whereas COX-1 and cPGES were not affected. Our earlier and the current studies demonstrate the coregulation of cPLA(2), COX, and mPGES-1, in PGE(2) synthesis pathway, and that these enzymes contribute to the elevation of PGE(2) level when one COX isoform is absent.
Sandee
Duanpen
D
The National Center for Genetic Engineering and Biotechnology, Klong Luang, Pathumthani 12120, Thailand. duanpensandee@hotmail.com
Sivanuntakorn
Sasitorn
S
Vichai
Vanicha
V
Kramyu
Jarin
J
Kirtikara
Kanyawim
K
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D051545:Cyclooxygenase 1 / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000071876:Prostaglandin-E Synthases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D016718:Arachidonic Acid; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse