Prostaglandin endoperoxide synthase: why two isoforms.
Williams, Christopher S., and Raymond N. Dubois.
The Departments of Medicine and Cell Biology, Vanderbilt University
Medical Center, and The Veterans Administration Medical Center
Nashville, TN 37232 USA
APStracts 2:0245G, 1995.
Prostaglandin endoperoxide synthase (PGHS)-1 and -2 are key enzymes in
the conversion of arachidonic acid to prostaglandins and other
eicosanoids. We refer to these isoforms as cyclooxygenase (COX)-1 and
-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 results 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 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 wildtype mice. These two
closely related enzymes must have distinct functions in the organism
since lack of their expression causes distinct phenotypic changes for
each respective isoform.
Received 18 September 1995; accepted in final form 11 November
1995.
APS Manuscript Number G412-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95