Peripheral tissue levels and molecular species compositions of N-acyl-phosphatidylethanolamine and its metabolites in mice lacking N-acyl-phosphatidylethanolamine-specific phospholipase D
Peripheral tissue levels and molecular species compositions of N-acyl-phosphatidylethanolamine and its metabolites in mice lacking N-acyl-phosphatidylethanolamine-specific phospholipase D
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DOI：
10.1093/jb/mvx054
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发表时间：
2017-12-01
影响因子：
2.7
通讯作者：
Tokumura, Akira
中科院分区：
文献类型：
--
作者：
Inoue, Manami;Tsuboi, Kazuhito;Tokumura, Akira
N-酰基乙醇胺（N-acylethanolamines，NAE）是由N-酰基磷脂酰乙醇胺（N-acylphosphatidyleethanolamine，NAPE）通过多种途径合成的一类脂质介质，包括NAPE特异性磷脂酶D（NAPE-PLD）的直接释放途径和甘油磷酸化N-酰基乙醇胺（Gp-NAE）的多步释放途径。使用液相色谱-串联质谱法，我们比较了NAPE-PLD缺陷型（NAPE-PLD-/-）和野生型（WT）小鼠外周组织中NAPE、Gp-NAE和NAE的水平。NAPE-PLD在心脏、肾脏和肝脏中的NAPE降解中起主要作用，但在空肠中不起作用，因为NAPE-PLD-/-小鼠中除空肠外的NAPE水平显著高于WT小鼠。NAPE-PLD的缺失未能改变这些组织的NAE水平，表明其在NAE产生中的作用有限。用组织匀浆进行的酶测定证实了这些外周组织中存在NAPE-PLD非依赖性途径。具有22个碳和6个双键的酰基部分的Gp-NAE物质在这些外周组织中富集。至于sn-2酰基的NAPE物种，18：2-酰基的NAPE物种在心脏，肝脏和空肠中占主导地位，而不是18：1的物种。我们的研究结果表明，无论是分子种类组成的NAPE，NAE和Gp-NAE和它们的依赖性Napepld之间的外周组织是不同的，这表明每个组织有不同的代谢途径，这些NAE含有脂质发挥组织特异性的作用。
N-acylethanolamines (NAEs), a class of lipid mediators, are produced from N-acyl-phosphatidylethanolamine (NAPE) by several pathways, including the direct release by NAPE-specific phospholipase D (NAPE-PLD) or the multistep pathway via sn-glycero-3-phospho-N-acylethanolamine (Gp-NAE). Using liquid chromatography-tandem mass spectrometry, we compared peripheral tissue levels of NAPE, Gp-NAE and NAE in NAPE-PLD-deficient (NAPE-PLD-/-) and wild type (WT) mice. NAPE-PLD was suggested to play a major role in the NAPE degradation in heart, kidney, and liver, but not in jejunum, because the NAPE levels except jejunum were significantly higher in NAPE-PLD-/- mice than in WT mice. The deletion of NAPE-PLD failed to alter the NAE levels of these tissues, suggesting its limited role in the NAE production. The enzyme assays with tissue homogenates confirmed the presence of NAPE-PLD-independent pathways in these peripheral tissues. Gp-NAE species having an acyl moiety with 22 carbons and 6 double bonds was enriched in these peripheral tissues. As for sn-2 acyl species of NAPE, 18:2-acyl-containing NAPE species were predominant over 18:1-containing species in heart, liver, and jejunum. Our results show that both molecular species composition of NAPE, NAE and Gp-NAE and their dependencies on Napepld are different among the peripheral tissues, suggesting that each tissue has distinct metabolic pathways and these NAE-containing lipids play tissue-specific roles.