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Regulation of prostaglandin synthase-1 and prostaglandin synthase-2

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Abstract

It has been assumed that the rate-limiting step in the ligand-induced synthesis of prostaglandins is the release of arachidonic acid from membrane phospholipid stores as a result of the activation of phospholipase. The assumption has been that the arachidonic acid is converted to PGH2 by the constitutive prostaglandin synthase/cyclooxygenase EC1.14.99.1 (PGS-1) enzyme present in cells. In this model, PGS-1 is proposed to be present in excess, and the production of arachidonic acid is thought to be rate limiting. However, a second prostaglandin synthase gene, PGS-2 has recently been described. The PGS-2 gene is induced by a variety of ligands, in cells as diverse as fibroblasts, monocytes, macrophages, smooth muscle cells, ovarian granulosa cells, epithelial cells, endothelial cells, and neurons. Moreover, PGS-2 induction is inhibited in nearly all contexts by glucocorticoids. It seems likely, therefore, that the regulation of PGS-2 expression plays a critical role in the production of prostanoids, both in normal physiological processes and in pathophysiological processes involving these paracrine mediators. In this review, we consider the regulation of the two genes, PGS-1 and PGS-2, that encode the isoforms of prostaglandin synthase.

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  1. Department of Biological Chemistry and Laboratory of Structural Biology and Molecular Medicine, Center for the Health Sciences, University of California, 90024, Los Angeles, CA, USA

    Harvey R. Herschman

  2. UCLA, 900 Veteran Avenue, 90024, Los Angeles, CA, USA

    Warren Hall

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Herschman, H.R., Hall, W. Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. Cancer Metast Rev 13, 241–256 (1994). https://doi.org/10.1007/BF00666095

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