Identification of a novel prostaglandin reductase reveals the involvement of prostaglandin E2 catabolism in regulation of peroxisome proliferator-activated receptor γ activation

Wen Ling Chou, Lee Ming Chuang, Chi Chi Chou, Andrew H.J. Wang, John A. Lawson, Garret A. FitzGerald, Zee Fen Chang

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)

Abstract

This report identifies a novel gene encoding 15-oxoprostaglandin- Δ13-reductase (PGR-2), which catalyzes the reaction converting 15-keto-PGE2 to 13,14-dihydro-15-keto-PGE2. The expression of PGR-2 is up-regulated in the late phase of 3T3-L1 adipocyte differentiation and predominantly distributed in adipose tissue. Overexpression of PGR-2 in cells decreases peroxisome proliferator-activated receptor γ (PPARγ)-dependent transcription and prohibits 3T3-L1 adipocyte differentiation without affecting expression of PPARγ. Interestingly, we found that 15-keto-PGE2 can act as a ligand of PPARγ to increase coactivator recruitment, thus activating PPARγ-mediated transcription and enhancing adipogenesis of 3T3-L1 cells. Overexpression of 15-hydroxyprostaglandin dehydrogenase, which catalyzes the oxidation reaction of PGE2 to form 15-keto-PGE2, significantly increased PPARγ-mediated transcription in a PGE2-dependent manner. Reciprocally, overexpression of wild-type PGR-2, but not the catalytically defective mutant, abolished the effect of 15-keto-PGE2 on PPARγ activation. These results demonstrate a novel link between catabolism of PGE2 and regulation of ligand-induced PPARγ activation.

Original languageEnglish
Pages (from-to)18162-18172
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number25
DOIs
Publication statusPublished - Jun 22 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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