Murakami Makoto, Kudo Ichiro
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Shinagawa-ku, Tokyo, Japan.
Curr Pharm Des. 2006;12(8):943-54. doi: 10.2174/138161206776055912.
Prostaglandin E synthase (PGES), which converts cyclooxygenase (COX)-derived prostaglandin (PG) H(2) to PGE(2), occurs in multiple forms with distinct enzymatic properties, modes of expression, cellular and subcellular localizations and intracellular functions. Two of them are membrane-bound enzymes and have been designated as mPGES-1 and mPGES-2. mPGES-1 is a perinuclear protein belonging to the MAPEG (for membrane-associated proteins involved in eicosanoid and GSH metabolism) family. This enzyme is markedly induced by proinflammatory stimuli, is down-regulated by anti-inflammatory glucocorticoids, and is functionally coupled with cyclooxygenase (COX)-2 in marked preference to COX-1. mPGES-2 is synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme. This enzyme is rather constitutively expressed in various cells and tissues and is functionally coupled with both COX-1 and COX-2. Cytosolic PGES (cPGES) is constitutively expressed in a wide variety of cells and is functionally linked to COX-1 to promote immediate PGE(2) production. This review highlights the latest understanding of the expression, regulation and functions of these three PGES enzymes. In particular, recent gene targeting studies of mPGES-1 have revealed that this enzyme represents a novel target for anti-inflammatory and anti-cancer drugs.
前列腺素E合酶（PGES）可将环氧化酶（COX）衍生的前列腺素（PG）H2转化为PGE2，它以多种形式存在，具有不同的酶学特性、表达模式、细胞和亚细胞定位以及细胞内功能。其中两种是膜结合酶，分别被命名为mPGES-1和mPGES-2。mPGES-1是一种属于MAPEG（参与类花生酸和谷胱甘肽代谢的膜相关蛋白）家族的核周蛋白。该酶在促炎刺激下显著诱导表达，受抗炎糖皮质激素下调，并且在功能上与环氧化酶（COX）-2优先偶联，而不是COX-1。mPGES-2最初作为一种与高尔基体膜相关的蛋白合成，N端疏水结构域的蛋白水解去除导致成熟胞质酶的形成。该酶在各种细胞和组织中相当组成性地表达，并且在功能上与COX-1和COX-2都偶联。胞质PGES（cPGES）在多种细胞中组成性表达，并且在功能上与COX-1相连以促进PGE2的即时产生。本综述重点介绍了对这三种PGES酶的表达、调节和功能的最新认识。特别是，最近对mPGES-1的基因靶向研究表明，该酶是抗炎和抗癌药物的新靶点。
