Reference - Detail
| RRC ID | 39558 |
|---|---|
| Author | Tanioka T, Nakatani Y, Semmyo N, Murakami M, Kudo I. |
| Title | Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. |
| Journal | 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. |
| Volume | 275(42) |
| Pages | 32775-82 |
| Published | 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 |
| Times Cited | 569 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 11 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| Human and Animal Cells | MC3T3-E1(RCB1126) L929 MKN45(RCB1001) WI-38(RCB0702) HeLa(RCB0007) |