Urade Yoshihiro, Eguchi Naomi, Aritake Kosuke, Hayaishi Osamu
Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Osaka, Japan.
Nihon Yakurigaku Zasshi. 2004 Jan;123(1):5-13. doi: 10.1254/fpj.123.5.
Prostaglandin (PG) D synthase (PGDS) catalyzes the isomerization of PGH(2) to PGD(2), which acts as an endogenous somnogen and an allergic mediator. There are two distinct types of PGDS: one is lipocalin-type PGDS (L-PGDS) localized in the central nervous system, male genitals, and heart; and the other is hematopoietic PGDS (H-PGDS) in mast cells and Th2 lymphocytes. L-PGDS is the same as beta-trace, a major protein in human cerebrospinal fluid, and is also secreted into the seminal plasma and plasma. The L-PGDS concentration in various body fluids is useful as a marker for various diseases such as renal failure and coronary atherosclerosis. H-PGDS is a cytosolic enzyme and is a member of the Sigma class of glutathione S-transferase. We determined the X-ray crystallographic structures of H-PGDS and L-PGDS. We also generated the gene-knockout (KO) mice and the human enzyme-overexpressing transgenic mice for each PGDS. L-PGDS-KO mice lacked PGE(2)-induced tactile allodynia and rebound of non-rapid eye movement sleep after sleep deprivation. Human L-PGDS-overexpressing transgenic mice showed an increase in non-rapid eye movement sleep due to accumulation of PGD(2) in the brain after tail clipping. H-PGDS-KO mice showed an allergic reaction weaker than that of the wild-type mice.
前列腺素（PG）D合成酶（PGDS）催化PGH₂异构化为PGD₂，PGD₂是一种内源性促眠剂和过敏介质。PGDS有两种不同类型：一种是定位于中枢神经系统、男性生殖器和心脏的脂质运载蛋白型PGDS（L-PGDS）；另一种是肥大细胞和Th2淋巴细胞中的造血PGDS（H-PGDS）。L-PGDS与人类脑脊液中的主要蛋白质β-微量蛋白相同，也分泌到精浆和血浆中。各种体液中的L-PGDS浓度可作为肾衰竭和冠状动脉粥样硬化等各种疾病的标志物。H-PGDS是一种胞质酶，是谷胱甘肽S-转移酶西格玛类的成员。我们测定了H-PGDS和L-PGDS的X射线晶体结构。我们还分别为每种PGDS生成了基因敲除（KO）小鼠和人类酶过表达转基因小鼠。L-PGDS-KO小鼠缺乏PGE₂诱导的触觉异常性疼痛以及睡眠剥夺后非快速眼动睡眠的反弹。人类L-PGDS过表达转基因小鼠在剪尾后由于脑中PGD₂的积累而出现非快速眼动睡眠增加。H-PGDS-KO小鼠表现出比野生型小鼠更弱的过敏反应。
