on December 2, 2004
Published online before print December 2, 2004, doi: 10.1161/01.ATV.0000152355.97808.10
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Submitted on October 11, 2004
Accepted on November 22, 2004
Prostaglandin E Synthases in Zebrafish
Barbara Pini ;
From the Institute for Translational Medicine and Therapeutics (B.P., T.G., J.A.L., T.S.P., G.A.F.) and the Department of Medicine, Gastroenterology Division (M.A.P.), University of Pennsylvania School of Medicine, Philadelphia.
* To whom correspondence should be addressed. E-mail: garret{at}spirit.gcrc.upenn.edu.
Objective--Prostaglandin E synthases (PGESs) are being explored as antiinflammtory drug targets as alternatives to cyclooxygenase (COX)-2. Located downstream of the cyclooxygenases, PGESs catalyze PGE2 formation, and deletion of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize the developmental expression of COX and PGES in zebrafish.
Methods and 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.
Key words: prostaglandin E synthase • cyclooxygenase • zebrafish • Danio rerio • vascular biology
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