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Related Experiment Videos

Prostaglandin E synthases in zebrafish.

Barbara Pini1, Tilo Grosser, John A Lawson

  • 1Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia 19104-6084, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|December 4, 2004
PubMed
Summary
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Zebrafish prostaglandin E synthases (PGESs) and cyclooxygenases (COX) show distinct developmental expression patterns. Microsomal (m)-PGES-1 and COX-2 are co-expressed in vasculature, suggesting a potential high-throughput model for anti-inflammatory drug discovery.

Area of Science:

  • Biochemistry
  • Developmental Biology
  • Pharmacology

Background:

  • Prostaglandin E synthases (PGESs) are investigated as anti-inflammatory drug targets, offering an alternative to cyclooxygenase (COX)-2 inhibitors.
  • PGESs are crucial enzymes in the prostaglandin E2 (PGE2) synthesis pathway, located downstream of COX enzymes.
  • Targeting microsomal (m)-PGES-1, which catalyzes PGE2 formation, is a promising strategy for reducing inflammation.

Purpose of the Study:

  • To investigate the developmental expression patterns of COX and PGES enzymes in zebrafish.
  • To characterize the roles of these enzymes during embryonic development.
  • To evaluate the zebrafish as a model system for discovering novel PGES inhibitors.

Main Methods:

  • Cloning of zebrafish cytosolic (c)-PGES and m-PGES orthologs.

Related Experiment Videos

  • Mapping of these genes to specific chromosomes.
  • Analysis of gene expression during zebrafish development using various techniques.
  • Experiments involving antisense morpholinos and nonsteroidal anti-inflammatory drugs (NSAIDs).

    • Main Results:

    • Zebrafish c-PGES and m-PGES orthologs were successfully cloned and mapped.
    • cPGES exhibited broad developmental expression, coordinated with zCOX-1 in specific organs.
    • COX-2 and mPGES-1 showed restricted expression in the aortic arch vasculature, though anatomically segregated.
    • Initial experiments suggested these genes may not be essential for zebrafish development.

    Conclusions:

    • Microsomal prostaglandin E synthase (mPGES)-1 is developmentally co-regulated with COX-2 in the vasculature.
    • The zebrafish, with its high fecundity and optical transparency, presents a suitable high-throughput screening model for novel PGES inhibitors.
    • mPGES-1, downstream of COX-2, represents a potential target for developing new anti-inflammatory therapies.