Identification of a Novel Prostaglandin Reductase Reveals the Involvement of Prostaglandin E-2 Catabolism in Regulation of Peroxisome Proliferator- Activated Receptor Gamma Activation
Resource
JOURNAL OF BIOLOGICAL CHEMISTRY v.282 n.25 pp.18162-18172
Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Journal Volume
v.282
Journal Issue
n.25
Pages
18162-18172
Date Issued
2007
Date
2007
Author(s)
CHOU, WEN-LING
CHUANG, LEE-MING
WANG, ANDREW H-J
CHANG, ZEE-FEN
Abstract
This report identifies a novel gene encoding 15- oxoprostaglandin-Delta( 13)-reductase (PGR-2), which catalyzes the reaction converting 15-keto-PGE (2) to 13,14- dihydro-15-keto-PGE(2). 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 gamma ( PPAR gamma)-dependent transcription and prohibits 3T3-L1 adipocyte differentiation without affecting expression of PPAR gamma. Interestingly, we found that 15-keto-PGE(2) can act as a ligand of PPAR gamma to increase coactivator recruitment, thus activating PPAR gamma-mediated transcription and enhancing adipogenesis of 3T3-L1 cells. Overexpression of 15-hydroxyprostaglandin dehydrogenase, which catalyzes the oxidation reaction of PGE(2) to form 15- keto-PGE(2), significantly increased PPAR gamma-mediated transcription in a PGE(2)-dependent manner. Reciprocally, overexpression of wild-type PGR-2, but not the catalytically defective mutant, abolished the effect of 15-keto-PGE(2) on PPAR gamma activation. These results demonstrate a novel link between catabolism of PGE(2) and regulation of ligand- induced PPAR gamma activation.
Subjects
PPAR-GAMMA
GENE-EXPRESSION
ADIPOSE-TISSUE
DIFFERENTIATION
CDNA CLONING
LIGAND