Prostaglandin E synthases in zebrafish.
OBJECTIVE
Prostaglandin E synthases (PGESs) are being explored as antiinflammatory drug targets as alternatives to cyclooxygenase (COX)-2. Located downstream of the cyclooxygenases, PGESs catalyze PGE(2) formation, and deletion of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize the developmental expression of COX and PGES in zebrafish.


RESULTS
We cloned zebrafish cytosolic (c) and m-PGES orthologs and mapped them to syntenic regions of chromosomes 23 and 5. cPGES was widely expressed during development and was coordinately regulated with zCOX-1 in the inner ear, the pronephros, and intestine. COX-2 and mPGES-1 exhibited restricted expression, dominantly in the vasculature of the aortic arch. However, the enzymes were anatomically segregated within the vessel wall. Experiments with antisense morpholinos and with nonsteroidal antiinflammatory drugs suggest that these genes may not be critical for development.


CONCLUSIONS
mPGES-1 is developmentally coregulated with COX-2 in vasculature. Given the high fecundidity and translucency of the zebrafish, this model may afford a high throughput system for characterization of novel PGES inhibitors. Microsomal prostaglandin E synthase (mPGES)-1, located downstream of COX-2, may represent a novel antiinflammatory drug target. Zebrafish cytosolic (c) PGES-1 and COX-1 were coordinately expressed; mPGES-1 and COX-2 were expressed particularly in the vasculature. Zebrafish may afford a high throughput system for detection of novel PGES inhibitors.
Pini
Barbara
B
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia 19104-6084, USA.
Grosser
Tilo
T
Lawson
John A
JA
Price
Tom S
TS
Pack
Michael A
MA
FitzGerald
Garret A
GA
D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D002874:Chromosome Mapping; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D007814:Larva; D008861:Microsomes / Q000201:enzymology; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D011458:Prostaglandins E / Q000096:biosynthesis*; D012665:Semicircular Canals / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics*
D007527:Isoenzymes; D011458:Prostaglandins E; D029961:Zebrafish Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605872:ptges protein, zebrafish