Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2.
Current evidence suggests that two forms of prostaglandin (PG) E synthase (PGES), cytosolic PGES and membrane-bound PGES (mPGES) -1, preferentially lie downstream of cyclooxygenase (COX) -1 and -2, respectively, in the PGE2 biosynthetic pathway. In this study, we examined the expression and functional aspects of the third PGES enzyme, mPGES-2, in mammalian cells and tissues. mPGES-2 was synthesized as a Golgi membrane-associated protein, and spontaneous cleavage of the N-terminal hydrophobic domain led to the formation of a truncated mature protein that was distributed in the cytosol with a trend to be enriched in the perinuclear region. In several cell lines, mPGES-2 promoted PGE2 production via both COX-1 and COX-2 in the immediate and delayed responses with modest COX-2 preference. In contrast to the marked inducibility of mPGES-1, mPGES-2 was constitutively expressed in various cells and tissues and was not increased appreciably during tissue inflammation or damage. Interestingly, a considerable elevation of mPGES-2 expression was observed in human colorectal cancer. Collectively, mPGES-2 is a unique PGES that can be coupled with both COXs and may play a role in the production of the PGE2 involved in both tissue homeostasis and disease.
Murakami
Makoto
M
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Nakashima
Karin
K
Kamei
Daisuke
D
Masuda
Seiko
S
Ishikawa
Yukio
Y
Ishii
Toshiharu
T
Ohmiya
Yoshihiro
Y
Watanabe
Kikuko
K
Kudo
Ichiro
I
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000201:enzymology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000032:analysis / Q000502:physiology*; D007527:Isoenzymes / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000502:physiology*; D009203:Myocardial Infarction / Q000201:enzymology; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats
D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; C000605863:PTGES2 protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone