Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and-2
Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and-2
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DOI：
10.1074/jbc.m305108200
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发表时间：
2003-09-26
影响因子：
4.8
通讯作者：
Kudo, I
中科院分区：
文献类型：
--
作者：
Murakami, M;Nakashima, K;Kudo, I
目前的证据表明，在前列腺素（PG） E合成酶（PGES）生物合成途径中，两种形式的前列腺素（PG） E合成酶（PGES），细胞质PGES和膜结合PGES (mPGES) -1，分别优先位于环氧化酶(COX) -1和-2的下游。在这项研究中，我们检测了第三种PGES酶mPGES-2在哺乳动物细胞和组织中的表达和功能方面。mPGES-2是作为高尔基膜相关蛋白合成的，其n端疏水结构域的自发裂解形成了一个截断的成熟蛋白，该蛋白分布在细胞质中，并有在核周区域富集的趋势。在一些细胞系中，mPGES-2通过COX-1和COX-2在即时和延迟反应中促进PGE2的产生，并具有适度的COX-2偏好。与mPGES-1的显著诱导性相反，mPGES-2在各种细胞和组织中组成性表达，并且在组织炎症或损伤期间不明显增加。有趣的是，在人类结直肠癌中观察到mPGES-2表达的显著升高。总的来说，mPGES-2是一种独特的PGES，可以与两种cox偶联，并可能在参与组织稳态和疾病的PGE的产生中发挥作用(2)。
Current evidence suggests that two forms of prostaglandin (PG) E synthase (PGES), cytosolic PGES and membrane-bound PGES (mPGES) -1, preferentially lie downstream of cyclooxygenase (COX) -1 and -2, respectively, in the PGE(2) biosynthetic pathway. In this study, we examined the expression and functional aspects of the third PGES enzyme, mPGES-2, in mammalian cells and tissues. mPGES-2 was synthesized as a Golgi membrane-associated protein, and spontaneous cleavage of the N-terminal hydrophobic domain led to the formation of a truncated mature protein that was distributed in the cytosol with a trend to be enriched in the perinuclear region. In several cell lines, mPGES-2 promoted PGE2 production via both COX-1 and COX-2 in the immediate and delayed responses with modest COX-2 preference. In contrast to the marked inducibility of mPGES-1, mPGES-2 was constitutively expressed in various cells and tissues and was not increased appreciably during tissue inflammation or damage. Interestingly, a considerable elevation of mPGES-2 expression was observed in human colorectal cancer. Collectively, mPGES-2 is a unique PGES that can be coupled with both COXs and may play a role in the production of the PGE(2) involved in both tissue homeostasis and disease.