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前列腺素E2生物合成途径的分子生物学与生理学的最新进展

Recent advances in molecular biology and physiology of the prostaglandin E2-biosynthetic pathway.

作者信息

Murakami Makoto, Kudo Ichiro

机构信息

Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

出版信息

Prog Lipid Res. 2004 Jan;43(1):3-35. doi: 10.1016/s0163-7827(03)00037-7.

DOI:10.1016/s0163-7827(03)00037-7
PMID:14636669
Abstract

Prostanoids represent a group of lipid mediators that are produced from arachidonic acid via the cyclooxygenase pathway. Once formed, the prostanoids are released from the cells and act on their cognate receptors on cell surfaces to exert their biological actions. Of these, prostaglandin E(2) (PGE(2)) is the most common prostanoid, being produced by a wide variety of cells and tissues and has a broad range of bioactivity. Recent advance in this field has led to identification and characterization of a number of enzymes that play roles in the biosynthesis of PGE(2), namely phospholipase A(2), cyclooxygenase and terminal PGE synthase. Each of these three reactions can be rate-limiting and involves multiple enzymes/isozymes that can act in different phases of cell activation and exhibit distinct functional coupling. In this review, we will overview a recent understanding of the molecular biology, regulatory mechanisms, and physiological functions of these enzymes.

摘要

前列腺素是一类脂质介质,它们通过环氧化酶途径由花生四烯酸产生。一旦形成,前列腺素就会从细胞中释放出来,并作用于细胞表面的同源受体以发挥其生物学作用。其中,前列腺素E(2)(PGE(2))是最常见的前列腺素,由多种细胞和组织产生,具有广泛的生物活性。该领域的最新进展已导致鉴定和表征了许多在PGE(2)生物合成中起作用的酶,即磷脂酶A(2)、环氧化酶和末端PGE合酶。这三个反应中的每一个都可能是限速反应,并且涉及多种酶/同工酶,它们可以在细胞活化的不同阶段起作用,并表现出不同的功能偶联。在这篇综述中,我们将概述对这些酶的分子生物学、调节机制和生理功能的最新认识。

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Recent advances in molecular biology and physiology of the prostaglandin E2-biosynthetic pathway.前列腺素E2生物合成途径的分子生物学与生理学的最新进展
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Cyclooxygenase-2-issued prostaglandin e(2) enhances the production of endogenous IL-10, which down-regulates dendritic cell functions.环氧化酶-2产生的前列腺素E2增强内源性白细胞介素-10的产生,从而下调树突状细胞功能。
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Paracetamol effectively reduces prostaglandin E2 synthesis in brain macrophages by inhibiting enzymatic activity of cyclooxygenase but not phospholipase and prostaglandin E synthase.对乙酰氨基酚通过抑制环氧化酶的酶活性,而非磷脂酶和前列腺素E合酶的活性,有效降低脑巨噬细胞中前列腺素E2的合成。
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Lipopolysaccharide-induced increase of prostaglandin E(2) is mediated by inducible nitric oxide synthase activation of the constitutive cyclooxygenase and induction of membrane-associated prostaglandin E synthase.脂多糖诱导的前列腺素E2增加是由组成型环氧化酶的诱导型一氧化氮合酶激活以及膜相关前列腺素E合酶的诱导介导的。
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