Functional analyses of lipocalin-type and hematopoietic prostaglandin D synthases.

  • URADE Yoshihiro
    Department of Molecular Behavioral Biology, Osaka Bioscience Institute
  • EGUCHI Naomi
    Department of Molecular Behavioral Biology, Osaka Bioscience Institute
  • ARITAKE Kosuke
    Department of Molecular Behavioral Biology, Osaka Bioscience Institute
  • HAYAISHI Osamu
    Department of Molecular Behavioral Biology, Osaka Bioscience Institute

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Other Title
  • リポカリン型および造血器型プロスタグランジンD合成酵素の機能解析
  • リポカリンガタ オヨビ ゾウケツキガタ プロスタグランジン D ゴウセイ コウソ ノ キノウ カイセキ

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Abstract

Prostaglandin (PG) D synthase (PGDS) catalyzes the isomerization of PGH2 to PGD2, which acts as an endogeous 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 PGE2-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 PGD2 in the brain after tail clipping. H-PGDS-KO mice showed an allergic reaction weaker than that of the wild-type mice.<br>

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