Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to prostacyclin and prostaglandin E2
Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to prostacyclin and prostaglandin E2
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DOI：
10.1074/jbc.274.17.11660
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发表时间：
1999-04-23
影响因子：
4.8
通讯作者：
Peters-Golden, M
中科院分区：
文献类型：
--
作者：
Brock, TG;McNish, RW;Peters-Golden, M
两种环氧合酶同工型，环氧合酶-1和环氧合酶-2，都将花生四烯酸代谢为前列腺素H-2，随后由下游酶加工为各种前列腺素。在本研究中，我们询问这两种异构体是否在前列腺素类的特征上不同，这些特征最终是由它们对花生四烯酸的作用引起的。驻留的腹腔巨噬细胞仅含有环氧合酶-1，并合成（从内源性或外源性花生四烯酸）四种主要前列腺素的平衡：前列环素，血栓烷A（2），前列腺素D-2和12-羟基十七碳三烯酸。前列腺素E-2是次要的第五产物，尽管这些细胞有效地将外源性前列腺素H-2转化为前列腺素E-2。相比之下，用脂多糖诱导环氧合酶-a导致前列环素和前列腺素E-2的优先生产。如果在环氧合酶-2诱导前用阿司匹林永久灭活环氧合酶-1，则产物谱的这种转变会加重。外源性前列腺素H-2向前列腺素E-2的转化仅通过脂多糖处理适度增加。因此，环氧合酶-a诱导导致花生四烯酸代谢的转变，从由环氧合酶-1介导的具有不同作用的几种前列腺素类的产生转变为两种前列腺素类，前列环素和前列腺素E-2的优先合成，这在细胞水平上引起共同作用。
The two cyclooxygenase isoforms, cyclooxygenase-1 and cyclooxygenase-2, both metabolize arachidonic acid to prostaglandin H-2, which is subsequently processed by downstream enzymes to the various prostanoids. In the present study, we asked if the two isoforms differ in the profile of prostanoids that ultimately arise from their action on arachidonic acid. Resident peritoneal macrophages contained only cyclooxygenase-1 and synthesized (from either endogenous or exogenous arachidonic acid) a balance of four major prostanoids: prostacyclin, thromboxane A(2), prostaglandin D-2, and 12-hydroxyheptadecatrienoic acid. Prostaglandin E-2 was a minor fifth product, although these cells efficiently converted exogenous prostaglandin H-2 to prostaglandin E-2. By contrast, induction of cyclooxygenase-a with lipopolysaccharide resulted in the preferential production of prostacyclin and prostaglandin E-2. This shift in product profile was accentuated if cyclooxygenase-1 was permanently inactivated with aspirin before cyclooxygenase-2 induction. The conversion of exogenous prostaglandin H-2 to prostaglandin E-2 was only modestly increased by lipopolysaccharide treatment. Thus, cyclooxygenase-a induction leads to a shift in arachidonic acid metabolism from the production of several prostanoids with diverse effects as mediated by cyclooxygenase-1 to the preferential synthesis of two prostanoids, prostacyclin and prostaglandin E-2, which evoke common effects at the cellular level.