RRC ID 39558
著者 Tanioka T, Nakatani Y, Semmyo N, Murakami M, Kudo I.
タイトル Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis.
ジャーナル J Biol Chem
Abstract Here we report the molecular identification of cytosolic glutathione (GSH)-dependent prostaglandin (PG) E(2) synthase (cPGES), a terminal enzyme of the cyclooxygenase (COX)-1-mediated PGE(2) biosynthetic pathway. GSH-dependent PGES activity in the cytosol of rat brains, but not of other tissues, increased 3-fold after lipopolysaccharide (LPS) challenge. Peptide microsequencing of purified enzyme revealed that it was identical to p23, which is reportedly the weakly bound component of the steroid hormone receptor/hsp90 complex. Recombinant p23 expressed in Escherichia coli and 293 cells exhibited all the features of PGES activity detected in rat brain cytosol. A tyrosine residue near the N terminus (Tyr(9)), which is known to be critical for the activity of cytosolic GSH S-transferases, was essential for PGES activity. The expression of cPGES/p23 was constitutive and was unaltered by proinflammatory stimuli in various cells and tissues, except that it was increased significantly in rat brain after LPS treatment. cPGES/p23 was functionally linked with COX-1 in marked preference to COX-2 to produce PGE(2) from exogenous and endogenous arachidonic acid, the latter being supplied by cytosolic phospholipase A(2) in the immediate response. Thus, functional coupling between COX-1 and cPGES/p23 may contribute to production of the PGE(2) that plays a role in maintenance of tissue homeostasis.
巻・号 275(42)
ページ 32775-82
公開日 2000-10-20
DOI 10.1074/jbc.M003504200
PII S0021-9258(20)89163-7
PMID 10922363
MeSH 3T3 Cells Amino Acid Sequence Amino Acid Substitution Animals Brain / enzymology* CHO Cells Cell Line Cricetinae Cyclooxygenase 1 Cytosol / enzymology Dinoprostone / biosynthesis* Escherichia coli HeLa Cells Humans Intramolecular Oxidoreductases / chemistry Intramolecular Oxidoreductases / metabolism* Isoenzymes / chemistry Isoenzymes / metabolism* L Cells Lipopolysaccharides / pharmacology Male Membrane Proteins Mice Mutagenesis, Site-Directed Osteoblasts Prostaglandin-E Synthases Prostaglandin-Endoperoxide Synthases / chemistry Prostaglandin-Endoperoxide Synthases / metabolism* Rats Rats, Wistar Recombinant Proteins / chemistry Recombinant Proteins / metabolism Sequence Alignment Sequence Homology, Amino Acid
IF 4.238
引用数 569
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126) L929 MKN45(RCB1001) WI-38(RCB0702) HeLa(RCB0007)