Wu K K, Sanduja R, Tsai A L, Ferhanoglu B, Loose-Mitchell D S
Department of Medicine, University of Texas Medical School, Houston 77030.
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2384-7. doi: 10.1073/pnas.88.6.2384.
Prostaglandin H (PGH) synthase (EC 1.14.99.1) is a key enzyme in the biosynthesis of prostaglandins, thromboxane, and prostacyclin. In cultured human umbilical vein endothelial cells, interleukin 1 (IL-1) is known to induce the synthesis of this enzyme, thereby raising the level of PGH synthase protein severalfold over the basal level. Pretreatment with aspirin at low concentrations (0.1-1 micrograms/ml) inhibited more than 60% of the enzyme mass and also the cyclooxygenase activity in IL-1-induced cells with only minimal effects on the basal level of the synthase enzyme in cells without IL-1. Sodium salicylate exhibited a similar inhibitory action whereas indomethacin had no apparent effect. Similarly low levels of aspirin inhibited the increased L-[35S]methionine incorporation into PGH synthase that was induced by IL-1 and also suppressed expression of the 2.7-kilobase PGH synthase mRNA. These results suggest that in cultured endothelial cells a potent inhibition of eicosanoid biosynthetic capacity can be effected by aspirin or salicylate at the level of PGH synthase gene expression. The aspirin effect may well be due to degradation of salicylate.
前列腺素H（PGH）合酶（EC 1.14.99.1）是前列腺素、血栓素和前列环素生物合成中的关键酶。在培养的人脐静脉内皮细胞中，已知白细胞介素1（IL-1）可诱导该酶的合成，从而使PGH合酶蛋白水平比基础水平提高几倍。用低浓度（0.1 - 1微克/毫升）的阿司匹林预处理可抑制IL-1诱导细胞中60%以上的酶量以及环氧化酶活性，而对无IL-1细胞中合酶酶的基础水平影响极小。水杨酸钠表现出类似的抑制作用，而吲哚美辛则无明显作用。同样低水平的阿司匹林抑制了IL-1诱导的L-[35S]甲硫氨酸掺入PGH合酶的增加，并且也抑制了2.7千碱基PGH合酶mRNA的表达。这些结果表明，在培养的内皮细胞中，阿司匹林或水杨酸盐可在PGH合酶基因表达水平上有效抑制类花生酸生物合成能力。阿司匹林的作用很可能是由于水杨酸盐的降解。
