PLAAT5 as an N-acyltransferase responsible for the generation of anti-inflammatory N-acylethanolamines in testis

IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mohammad Mamun Sikder , Sumire Sasaki , Yoshimi Miki , Yuki Nagasaki , Ken-ichi Ohta , Zahir Hussain , Hiroyuki Saiga , Mari Ohmura-Hoshino , Katsuaki Hoshino , Masaki Ueno , Miki Okada-Iwabu , Makoto Murakami , Natsuo Ueda , Toru Uyama
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引用次数: 0

Abstract

N-Acylethanolamines (NAEs) are a class of lipid mediators that exhibit anti-inflammatory and appetite-suppressive activities. Among them, palmitoylethanolamide (PEA) and arachidonoylethanolamide (AEA) bind to peroxisomal proliferator-activated receptor (PPAR) α and cannabinoid receptor CB1, respectively. N-Acyl-phosphatidylethanolamine (NAPE) as a precursor of NAEs is biosynthesized from membrane phospholipids by N-acyltransferases, which consist of group IVE cytosolic phospholipase A2ε (cPLA2ε) and PLAAT (phospholipase A and acyltransferase) family enzymes. While cPLA2ε is responsible for the production of NAEs not only in specific tissues, including muscle, skin, and the stomach, but also under pathological conditions, such as psoriasis and brain ischemia, the involvement of the PLAAT family in vivo remains unclear. Considering the specific expression of PLAAT5 in testes, we investigated the potential role of PLAAT5 in the formation of NAEs in testes using PLAAT5-deficient (Plaat5−/−) mice. High-performance liquid chromatography coupled with tandem mass spectrometry showed that PLAAT5 deficiency decreased the total level of NAEs by 61 %, with PEA and AEA being reduced by 64 % and 87 %, respectively. Following a treatment with cadmium chloride, an environmental toxin that induces testicular inflammation, the expression of inflammatory genes (Il6, Tnf, and Nos2) in testes was markedly higher in Plaat5−/− mice than in Plaat5+/+ mice, and their expression was attenuated by the administration of PEA and AEA. Furthermore, these anti-inflammatory effects were canceled by a co-treatment with the antagonists of PPARα or CB1. These results suggest that PLAAT5 is responsible for the biosynthesis of anti-inflammatory NAEs in testes.

Abstract Image

PLAAT5 是一种 N-酰基转移酶,负责在睾丸中生成抗炎的 N-酰乙醇胺。
N-酰乙醇胺(NAEs)是一类具有抗炎和抑制食欲活性的脂质介质。其中,棕榈酰乙醇酰胺(PEA)和花生四烯醇酰胺(AEA)分别与过氧化物酶体增殖激活受体(PPAR)α 和大麻素受体 CB1 结合。N-酰基磷脂酰乙醇胺(NAPE)是由膜磷脂通过 N-酰基转移酶生物合成的,N-酰基转移酶由 IVE 组细胞质磷脂酶 A2ε (cPLA2ε)和 PLAAT(磷脂酶 A 和酰基转移酶)家族酶组成。cPLA2ε不仅在肌肉、皮肤和胃等特定组织中,而且在银屑病和脑缺血等病理情况下都负责产生非乙酰胆碱酯酶,但 PLAAT 家族在体内的参与情况仍不清楚。考虑到 PLAAT5 在睾丸中的特异性表达,我们利用 PLAAT5 缺失(Plaat5-/-)小鼠研究了 PLAAT5 在睾丸中形成 NAE 的潜在作用。高效液相色谱-串联质谱法显示,缺乏 PLAAT5 会使 NAEs 的总含量减少 61%,其中 PEA 和 AEA 的含量分别减少了 64% 和 87%。氯化镉是一种能诱发睾丸炎的环境毒素,在用氯化镉处理小鼠后,Plaat5-/-小鼠睾丸中炎症基因(Il6、Tnf和Nos2)的表达明显高于Plaat5+/+小鼠,而PEA和AEA的施用可减轻这些基因的表达。此外,这些抗炎作用被 PPARα 或 CB1 拮抗剂的联合处理所抵消。这些结果表明,PLAAT5负责睾丸中抗炎性NAEs的生物合成。
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来源期刊
CiteScore
11.00
自引率
2.10%
发文量
109
审稿时长
53 days
期刊介绍: BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.
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