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Biological Functions of Group X Secretory PLA2

  • Kohji Hanasaki
  • Hitoshi Arita
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 525)

Abstract

Secretory phospholipase A2s (sPLA2s) are a diverse family of low molecular mass enzymes that hydrolyze the sn-2 fatty acid ester bond of glycerophospholipids to produce free fatty acids and lysophospholipids. In addition to the classical types of group IB and IIA (sPLA2-IB and IIA), recent advances in molecular biology have led to the identification of novel types of sPLA2s, including group IID and IIE that we have cloned [1]. Among the nine types of human sPLA2s, group X sPLA2 (sPLA2-X) has a structural similarity with the classical type of sPLA2-IB and IIA [2]. We have shown that sPLA2-X has a potent hydrolyzing activity toward phosphatidylcholine (PC) and elicits more potent production of unsaturated fatty acids and lysophosphatidylcholine (lysoPC) in various inflammatory cells and colon cancer cells compared with sPLA2-IB and IIA [3,4]. The released arachidonic acid by sPLA2-X was efficiently converted to prostaglandins (PGs) by the action of endogenous cyclooxygenase (COX). The expression of sPLA2-X was detected in human lung epithelial cells and mouse splenic macrophages, and greatly augmented in human colon adenocarcinoma tissues in concert with enhanced expression of COX-2 [4]. These findings suggest that sPLA2-X plays a critical role in the lipid mediator productions under various inflammatory states and in the COX-2- dependent PGE2 biosynthesis during colon tumorigenesis. Recently, we have shown that sPLA2-X is a high-affinity ligand for mouse PLA2 receptor (PLA2R) and identified a soluble PLA2R in mouse plasma [5]. Using PLA2 receptor-deficient mice, we have shown that the membrane and soluble form of the receptor are involved in the endogenous inhibitory mechanisms against the strong PC-hydrolizing activity of sPLA2-X in mice [5].

Keywords

Lipid Droplet Secretory Phospholipase Human Lung Epithelial Cell Macrophage Foam Cell Arterial Intima 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Kohji Hanasaki
    • 1
  • Hitoshi Arita
    • 1
  1. 1.Shionogi Research LaboratoriesShionogi & Co., Ltd.Fukushima-kuOsakaJapan

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