Prostaglandin endoperoxide synthase: why two isoforms?
Prostaglandin endoperoxide synthase-1 [prostaglandin G/H synthase-1 (PGHS-1)] and PGHS-2 are key enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. We refer to these isoforms as cyclooxygenase-1 (COX-1) and COX-2 in this review. This brief review focuses on recent developments in the study of these enzymes. Alterations in the expression levels of COX-2 result in distinct phenotypic changes in intestinal epithelial cells. Overexpression of COX-2 in intestinal epithelial cells results in increased adhesion to extracellular matrix proteins and inhibition of apoptosis. Disruption of the COX-2 gene in mice results in renal dysplasia, cardiac fibrosis, and defects in the ovary. Interestingly, disruption of the COX-1 gene results in distinct phenotypic changes different from those observed for COX-2. COX-1 null mice survive well, have no gastric pathology, and show less indomethacin-induced gastric ulceration than wild-type mice. These two closely related enzymes must have distinct functions in the organisms, since lack of their expression causes distinct phenotypic changes for each respective isoform.
Williams
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Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2279, USA.
DuBois
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D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic; D017124:Conserved Sequence; D006801:Humans; D007414:Intestinal Neoplasms / Q000201:enzymology / Q000235:genetics; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D011451:Prostaglandin-Endoperoxide Synthases