Williams C S, DuBois R N
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2279, USA.
Am J Physiol. 1996 Mar;270(3 Pt 1):G393-400. doi: 10.1152/ajpgi.1996.270.3.G393.
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.
前列腺素内过氧化物合酶-1[前列腺素G/H合酶-1（PGHS-1）]和PGHS-2是将花生四烯酸转化为前列腺素和其他类二十烷酸的关键酶。在本综述中，我们将这些同工型称为环氧化酶-1（COX-1）和COX-2。这篇简短的综述聚焦于这些酶研究的最新进展。COX-2表达水平的改变会导致肠上皮细胞出现明显的表型变化。肠上皮细胞中COX-2的过表达会导致其与细胞外基质蛋白的黏附增加以及细胞凋亡受到抑制。小鼠中COX-2基因的缺失会导致肾发育异常、心脏纤维化以及卵巢缺陷。有趣的是，COX-1基因的缺失会导致与COX-2不同的明显表型变化。COX-1基因敲除小鼠存活良好，没有胃部病变，并且与野生型小鼠相比，吲哚美辛诱导的胃溃疡更少。这两种密切相关的酶在生物体中必定具有不同的功能，因为它们各自同工型的表达缺失会导致不同的表型变化。
