Identification of a Novel Prostaglandin Reductase Reveals the Involvement of Prostaglandin E2 Catabolism in Regulation of Peroxisome Proliferator-activated Receptor γ Activation

Abstract

This report identifies a novel gene encoding 15-oxoprostaglandin-⌬ 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 ␥ (PPAR␥)-dependent transcription and prohibits 3T3-L1 adipocyte differentiation without affecting expression of PPAR␥. Interestingly, we found that 15-keto-PGE 2 can act as a ligand of PPAR␥ to increase coactivator recruitment, thus activating PPAR␥-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␥-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␥ activation. These results demonstrate a novel link between catabolism of PGE 2 and regulation of ligand-induced PPAR␥ activation.

Gene expression profiling in developing pig adipose tissue: non-secreted regulatory proteins

“…A unique aspect of PTGR2 action was revealed in studies that indicated a unique link between PGE2 catabolism and regulation of ligand-induced PPAR gamma activation of adipogenesis (Chou et al, 2007). For instance, overexpression of PTGR2 represses transcriptional activity of PPARG and inhibits 3T3-L1 adipocyte differentiation (Chou et al, 2007). These observations on PTGR2 coupled with the age-associated increase in adipose tissue PTGR1 in this study may indicate that PTGR1 may have a role in adipogenesis in porcine adipose tissue.…”

“…Enzyme assays detected PTGR1 activity in a number of swine tissues, but adipose tissue contained the highest PTGR1 specific activity (Anggard et al, 1971). It is important to consider information on another Pig adipose tissue genes prostaglandin reductase, that is, PTGR2, which is also a 15-oxoprostaglandin 13-reductase (Chou et al, 2007) as both PTGR1 and PTGR2 are predominantly distributed in adipose tissue and both catalyze the NADH/NADPH dependent reduction of the D 13 double bond of 15-ketoprostaglandins to yield 15-keto-13,14-dihydroprostaglandins which results in a further reduction of the biological activities of prostaglandins. Furthermore, mouse PTGR2 protein has 40% amino acid sequence identity with mouse PTGR1 and human PTGR1 (Chou et al, 2007).…”

“…It is important to consider information on another Pig adipose tissue genes prostaglandin reductase, that is, PTGR2, which is also a 15-oxoprostaglandin 13-reductase (Chou et al, 2007) as both PTGR1 and PTGR2 are predominantly distributed in adipose tissue and both catalyze the NADH/NADPH dependent reduction of the D 13 double bond of 15-ketoprostaglandins to yield 15-keto-13,14-dihydroprostaglandins which results in a further reduction of the biological activities of prostaglandins. Furthermore, mouse PTGR2 protein has 40% amino acid sequence identity with mouse PTGR1 and human PTGR1 (Chou et al, 2007). In addition, pig PTGR1 (NM_214385) has 97% query coverage and 82% max identity to human PTGR1 (NM_012212.2), when BLASTed against the human Genome and has 83% query coverage and 81% max identity to mouse PTGR1 (NM_025968.3), when BLASTed against the mouse genome.…”

“…In addition, pig PTGR1 (NM_214385) has 97% query coverage and 82% max identity to human PTGR1 (NM_012212.2), when BLASTed against the human Genome and has 83% query coverage and 81% max identity to mouse PTGR1 (NM_025968.3), when BLASTed against the mouse genome. PTGR2 catalyzes the reaction converting 15-keto-PGE 2 to 13,14-dihydro-15-keto-PGE 2 (Chou et al, 2007). A unique aspect of PTGR2 action was revealed in studies that indicated a unique link between PGE2 catabolism and regulation of ligand-induced PPAR gamma activation of adipogenesis (Chou et al, 2007).…”

“…PTGR2 catalyzes the reaction converting 15-keto-PGE 2 to 13,14-dihydro-15-keto-PGE 2 (Chou et al, 2007). A unique aspect of PTGR2 action was revealed in studies that indicated a unique link between PGE2 catabolism and regulation of ligand-induced PPAR gamma activation of adipogenesis (Chou et al, 2007). For instance, overexpression of PTGR2 represses transcriptional activity of PPARG and inhibits 3T3-L1 adipocyte differentiation (Chou et al, 2007).…”