Cited by 716Inflammatory mediators and NSAID effectsEicosanoids and Hypertension PharmacologyGlutathione Transferases and Polymorphisms

Molecular Identification of Cytosolic Prostaglandin E2 Synthase That Is Functionally Coupled with Cyclooxygenase-1 in Immediate Prostaglandin E2Biosynthesis

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Tanioka, Toshihiro, Nakatani, Yoshihito, Semmyo, Natsuki, Murakami, Makoto, Kudo, Ichiro·2000·Journal of Biological Chemistry

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.

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Crossref · 10.1074/jbc.m003504200

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Authors
Tanioka, T., Nakatani, Y., Semmyo, N., Murakami, M., & Kudo, I.
Affiliations
SHOWA Medical University (JP)
Corresponding author
Kudo, Ichiro
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-10
Volume
275
Issue
42
Pages
32775-32782
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2077641423
Cited by
708
References
41
Citations by year
2026: 7 · 2025: 6 · 2024: 6 · 2023: 15 · 2022: 9 · 2021: 12 · 2020: 14 · 2019: 19 · 2018: 13 · 2017: 19 · 2016: 15 · 2015: 17 · 2014: 31 · 2013: 30 · 2012: 32
FWCI
25.67
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Keywords
p23, cyclooxygenase-1, prostaglandin E2 synthesis, glutathione-dependent enzymes, arachidonic acid, cytosolic phospholipase A2, lipopolysaccharide, brain, cyclooxygenase-2, tissue homeostasis
MeSH terms
Prostaglandin-E Synthases, Amino Acid Sequence, Animals, Brain, Cell Line, Cytosol, Escherichia coli, Cricetinae, HeLa Cells, Humans, Isoenzymes, L Cells, Lipopolysaccharides, Male, Membrane Proteins, Osteoblasts, Prostaglandin-Endoperoxide Synthases, Recombinant Proteins, Dinoprostone, Mutagenesis, Site-Directed, Sequence Alignment, CHO Cells, 3T3 Cells, Rats, Wistar, Sequence Homology, Amino Acid, Intramolecular Oxidoreductases, Amino Acid Substitution, Mice, Rats, Cyclooxygenase 1

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