Calcium-dependent generation of N-acylethanolamines and lysophosphatidic acids by glycerophosphodiesterase GDE7

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28497
タイトル
Calcium-dependent generation of N-acylethanolamines and lysophosphatidic acids by glycerophosphodiesterase GDE7
ファイル
内容記述

Abstract

N-Acylethanolamines form a class of lipid mediators and include an endocannabinoid arachidonoylethanolamide (anandamide), analgesic and anti-inflammatory palmitoylethanolamide, and appetite-suppressing oleoylethanolamide. In animal tissues, N-acylethanolamines are synthesized from N-acylated ethanolamine phospholipids directly by N-acylphosphatidylethanolamine-hydrolyzing phospholipase D or through multi-step pathways via N-acylethanolamine lysophospholipids. We previously reported that glycerophosphodiesterase (GDE) 4, a member of the GDE family, has lysophospholipase D (lysoPLD) activity hydrolyzing N-acylethanolamine lysophospholipids to N-acylethanolamines. Recently, GDE7 was shown to have lysoPLD activity toward lysophosphatidylcholine to produce lysophosphatidic acid (LPA). Here, we examined the reactivity of GDE7 with N-acylethanolamine lysophospholipids as well as the requirement of divalent cations for its catalytic activity. When overexpressed in HEK293 cells, recombinant GDE7 proteins of human and mouse showed lysoPLD activity toward N-palmitoyl, N-oleoyl, and N-arachidonoyl-lysophosphatidylethanolamines and N-palmitoyl-lysoplasmenylethanolamine to generate their corresponding N-acylethanolamines and LPAs. However, GDE7 hardly hydrolyzed glycerophospho-N-palmitoylethanolamine. Overexpression of GDE7 in HEK293 cells increased endogenous levels of N-acylethanolamines and LPAs. Interestingly, GDE7 was stimulated by micromolar concentrations of Ca2+ but not by millimolar concentrations of Mg2+, while GDE4 was stimulated by Mg2+ but was insensitive to Ca2+. GDE7 was widely distributed in various tissues of humans and mice with the highest levels in their kidney tissues. These results suggested that GDE7 is a novel Ca2+-dependent lysoPLD, which is involved in the generation of both N-acylethanolamines and LPAs.

KEYWORDS:

Glycerophosphodiesterase; Lysophosphatidic acid; Lysophospholipase D; N-acylethanolamine; Phospholipid

(医博甲652)

著者
著者 Iffat Ara Sonia Rahman
著者(ヨミ) イファット アラ ソニア ラハマン
著者(別表記) Rahman Iffat Ara Sonia
掲載誌
Biochimica et Biophysica Acta
掲載誌(別表記)
Biochim Biophys Acta.
1861
12
開始ページ
1881
終了ページ
1892
出版者
Elsevier
出版年月日
2016-09-13
ISSN
0006-3002
NCID
AA00564635
PMID
27637550
DOI
10.1016/j.bbalip.2016.09.008
資料タイプ
学位論文
言語
英語
関連情報
出版社版DOIリンク(URL) : https://doi.org/10.1016/j.bbalip.2016.09.008
関連情報URL
https://doi.org/10.1016/j.bbalip.2016.09.008
関連情報(isVersionOf)
Publisher's Version
関連情報URL(isReplacedBy)
https://doi.org/10.1016/j.bbalip.2016.09.008
関連情報(hasVersion)
Publisher's Version
権利関係
Copyright © 2016 Elsevier B.V.
この博士論文の本文については、次のエルゼビアの著作権ポリシーの規定により公開しています。「博士論文の場合は、エンバーゴ期間に関係なく機関リポジトリに出版社版を公開することができます。」 The text of this doctoral dissertation is published according to the following Elsevier copyright policy. "In the case of doctoral dissertations, publishers can be published in institutional repositories regardless of the Embargo period."
Publisher's Version DOI: https://doi.org/10.1016/j.bbalip.2016.09.008
博士論文(全文を含む)
学位授与番号
博甲第652号
学位授与年月日
2017-03-24
学位名
博士(医学)
学位授与機関
香川大学
区分
香川大学
Copyright (C) 2009 Kagawa University All rights reserved.