title: Prostaglandin E synthase.
abstract: Prostaglandin E synthase (PGES), which converts cyclooxygenase (COX)-derived prostaglandin (PG)H2 to PGE2, occurs in multiple forms with distinct enzymatic properties, modes of expression, cellular and subcellular localizations and intracellular functions. Cytosolic PGES (cPGES) is a cytosolic protein that is constitutively expressed in a wide variety of cells and tissues and is associated with heat shock protein 90 (Hsp90). Membrane-associated PGES (mPGES), the expression of which is stimulus-inducible and is downregulated by anti-inflammatory glucocorticoids, is a perinuclear protein belonging to the microsomal glutathione S-transferase (GST) family. These two PGESs display distinct functional coupling with upstream COXs in cells; cPGES is predominantly coupled with the constitutive COX-1, whereas mPGES is preferentially linked with the inducible COX-2. Several cytosolic GSTs also have the capacity to convert PGH2 to PGE2 in vitro. Accumulating evidence has suggested that mPGES participates in various pathophysiological states in which COX-2 is involved, implying that mPGES represents a potential novel target for drug development.
authors.affiliation: Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Japan. mako@pharm.showa-u.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanioka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kudo
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D051546:Cyclooxygenase 2; D005334:Fever / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism; D010146:Pain / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012098:Reproduction / Q000502:physiology; D016415:Sequence Alignment
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D005982:Glutathione Transferase; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases