Inoue Manami, Tsuboi Kazuhito, Okamoto Yoko, Hidaka Mayumi, Uyama Toru, Tsutsumi Toshihiko, Tanaka Tamotsu, Ueda Natsuo, Tokumura Akira
Department of Pharmaceutical Health Chemistry, Institute of Biomedical Sciences, Tokushima University, 1-78 Shomachi, Tokushima 770-8505, Japan.
Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
J Biochem. 2017 Dec 1;162(6):449-458. doi: 10.1093/jb/mvx054.
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.
N-酰基乙醇胺（NAEs）是一类脂质介质，可通过多种途径由N-酰基磷脂酰乙醇胺（NAPE）产生，包括NAPE特异性磷脂酶D（NAPE-PLD）的直接释放或经由sn-甘油-3-磷酸-N-酰基乙醇胺（Gp-NAE）的多步途径。我们使用液相色谱-串联质谱法比较了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。研究表明，NAPE-PLD在心脏、肾脏和肝脏的NAPE降解中起主要作用，但在空肠中不起主要作用，因为除空肠外，NAPE-PLD-/-小鼠的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分析证实了这些外周组织中存在不依赖NAPE-PLD的途径。在这些外周组织中，具有22个碳和6个双键的酰基部分的Gp-NAE种类富集。至于NAPE的sn-2酰基种类，在心脏、肝脏和空肠中，含18:2-酰基的NAPE种类比含18:1的种类占优势。我们的结果表明，外周组织中NAPE、NAE和Gp-NAE的分子种类组成及其对Napepld的依赖性各不相同，这表明每个组织都有独特的代谢途径，这些含NAE的脂质发挥着组织特异性作用。
