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

By T. Tanioka, Yoshihito Nakatani, Natsuki Semmyo, M. Murakami, I. Kudo. Journal of Biological Chemistry, 2000

731 citations recorded by the source corpus.

Here we report the molecular identification of cytosolic glutathione (GSH)-dependent prostaglandin (PG) E2 synthase (cPGES), a terminal enzyme of the cyclooxygenase (COX)-1-mediated PGE2 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 (Tyr9), which is known to be critical for the activity of cytosolic GSHS-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 PGE2 from exogenous and endogenous arachidonic acid, the latter being supplied by cytosolic phospholipase A2 in the immediate response. Thus, functional coupling between COX-1 and cPGES/p23 may contribute to production of the PGE2 that plays a role in maintenance of tissue homeostasis.

Subfields: Cancer Research, Genetics, Pharmacology

View Paper: https://www.semanticscholar.org/paper/611993a2026f1d6cff0872f83f97883c63b86160

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Citations in the corpus

Why there are two cyclooxygenase isozymes. (2001, background): “There also appears to be an mPGE synthase that is coordinately induced with PGHS-2 and seems to function preferentially with PGHS-2, rather than PGHS-1 (24, 36).”
Cytokines, prostaglandins and parturition--a review. (2003, background): “two separate genes, a cytosolic (cPGES) (Tanioka et al., 2000) and membrane bound (mPGES) form (Jakobsson et al.”
Pharmacokinetics and Pharmacodynamics of Systemically Administered Glucocorticoids (2005, background): “[83] Panophyllins, HSP70, p23, and src.[136-138] The glucotients with cystic fibrosis had a higher volume of corticoid receptor isoform GRβ, a splice variant, distribution and normal half-life of oral prednisodoes not bind glucocorticoids and its relevance in lone,[126] whereas prednisolone pharmaco”