The role of intracellular anionic phospholipids in the production of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2ε

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28685
Title
The role of intracellular anionic phospholipids in the production of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2ε
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Description

Abstract

N-Acyl-phosphatidylethanolamines (NAPEs) represent a class of glycerophospholipids and serve as the precursors of bioactive N-acylethanolamines, including arachidonoylethanolamide (anandamide), palmitoylethanolamide and oleoylethanolamide. NAPEs are produced in mammals by N-acyltransferases, the enzymes which transfer an acyl chain of glycerophospholipids to the amino group of phosphatidylethanolamine. Recently, the ɛ isoform of cytosolic phospholipase A2 (cPLA2ɛ, also called PLA2G4E) was identified as Ca2+-dependent N-acyltransferase. We showed that the activity is remarkably stimulated by phosphatidylserine (PS) in vitro. In the present study, we investigated whether or not endogenous PS regulates the function of cPLA2ɛ in living cells. When PS synthesis was suppressed by the knockdown of PS synthases in cPLA2ɛ-expressing cells, the cPLA2ɛ level and its N-acyltransferase activity were significantly reduced. Mutagenesis studies revealed that all of C2, lipase and polybasic domains of cPLA2ɛ were required for its proper localization as well as the enzyme activity. Liposome-based assays showed that several anionic glycerophospholipids, including PS, phosphatidic acid and phosphatidylinositol 4,5-bisphosphate, enhance the Ca2+-dependent binding of purified cPLA2ɛ to liposome membrane and stimulate its N-acyltransferase activity. Altogether, these results suggested that endogenous PS and other anionic phospholipids affect the localization and enzyme activity of cPLA2ɛ.

KEYWORDS:

N-acyl-phosphatidylethanolamine; N-acylethanolamine; N-acyltransferase; lipid mediator; phosphatidylserine

(医博甲708)

Author
著者 Smriti Sultana Binte Mustafiz
著者(ヨミ) スリーテイ スルタナ ビンテ ムスタフィズ
著者(別表記)
Publication Title
Journal of Biochemistry
Volume
165
Issue
4
Start Page
343
End Page
352
Publisher
Japanese Biochemical Society
日本製科学会
Oxford University Press
Published Date
2018-12-08
ISSN
0021-924X
NCID
AA00694073
PMID
30517655
DOI
10.1093/jb/mvy104
Resource Type
Thesis or Dissertation
Language
eng
Relation
出版社版DOIリンク(URL): https://doi.org/10.1093/jb/mvy104
Resource URL
https://doi.org/10.1093/jb/mvy104
Rights
"This is the Accepted version of the following article: The role of intracellular anionic phospholipids in the production of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2ε.; Journal of Biochemistry;Volume 165 Issue 4 (2018) Pages 343-352; doi:10.1093/jb/mvy104 , which has been published in final form at https://doi.org/10.1093/jb/mvy104 . "
2019年12月8日以降にAccepted versionを公開します。 / Accepted version will be released after December 8, 2019.
Text Version
none
Grant ID
博甲第708号
Grant Date
2019-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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