[Prostaglandin E2 synthases].
Prostaglandin E2 (PGE2) is widely distributed in various tissues, and exhibits various biologically important activities. PGE2 synthase (PGES) catalyzes conversion of COX-derived PGH2 to PGE2. It now appears that there are at least three distinct types of PGES in mammals. We identified two distinct glutathione-dependent PGESs. Cytosolic PGES (cPGES), known as p23, is constitutively and ubiquitously expressed and predominantly converts COX-1-derived PGH2 to PGE2. We find that the regulation of cPGES/p23 activity in cells depends on its association with hsp90. Microsomal PGES-1 (mPGES-1), identical to MGST1-L1, is an inducible perinuclear enzyme that is functionally linked with COX-2 in marked preference to COX-1. COX-2 and mPGES-1 are essential components for delayed PGE2 synthesis, which may be linked to inflammation, fever, osteogenesis, and even cancer. Most recently, glutathione-nonspecific mPGES-2, homologous to glutaredoxin and thioredoxin, was identified. These PGESs seem to be a potential novel target for drug development.
Nakatani
Yoshihito
Y
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. nakatani@pharm.showa-u.ac.jp
Kudo
Ichiro
I
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis; D015195:Drug Design; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D044262:Prostaglandin H2; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011463:Prostaglandins H / Q000378:metabolism
D018832:Molecular Chaperones; D010750:Phosphoproteins; D011463:Prostaglandins H; D044262:Prostaglandin H2; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; C000605863:PTGES2 protein, human; C490849:PTGES3 protein, human; D000071876:Prostaglandin-E Synthases; D005978:Glutathione; D015232:Dinoprostone