論文 - 詳細
| RRC ID | 44623 |
|---|---|
| 著者 | Uyama T, Inoue M, Okamoto Y, Shinohara N, Tai T, Tsuboi K, Inoue T, Tokumura A, Ueda N. |
| タイトル | Involvement of phospholipase A/acyltransferase-1 in N-acylphosphatidylethanolamine generation. |
| ジャーナル | Biochim Biophys Acta |
| Abstract |
Anandamide and other bioactive N-acylethanolamines (NAEs) are a class of lipid mediators and are produced from glycerophospholipids via N-acylphosphatidylethanolamines (NAPEs). Although the generation of NAPE by N-acylation of phosphatidylethanolamine is thought to be the rate-limiting step of NAE biosynthesis, the enzyme responsible, N-acyltransferase, remains poorly characterized. Recently, we found that five members of the HRAS-like suppressor (HRASLS) family, which were originally discovered as tumor suppressors, possess phospholipid-metabolizing activities including NAPE-forming N-acyltransferase activity, and proposed to call HRASLS1-5 phospholipase A/acyltransferase (PLA/AT)-1-5, respectively. Among the five members, PLA/AT-1 attracts attention because of its relatively high N-acyltransferase activity and predominant expression in testis, skeletal muscle, brain and heart of human, mouse and rat. Here, we examined the formation of NAPE by PLA/AT-1 in living cells. As analyzed by metabolic labeling with [(14)C]ethanolamine or [(14)C]palmitic acid, the transient expression of human, mouse and rat PLA/AT-1s in COS-7 cells as well as the stable expression of human PLA/AT-1 in HEK293 cells significantly increased the generation of NAPE and NAE. Liquid chromatography-tandem mass spectrometry also exhibited that the stable expression of PLA/AT-1 enhanced endogenous levels of NAPE, N-acylplasmenylethanolamine, NAE and glycerophospho-NAE. Furthermore, the knockdown of endogenous PLA/AT-1 in mouse ATDC5 cells lowered NAPE levels. Interestingly, the dysfunction of peroxisomes, which was caused by PLA/AT-2 and -3, was not observed in the PLA/AT-1-expressing HEK293 cells. Altogether, these results suggest that PLA/AT-1 is at least partly responsible for the generation of NAPE in mammalian cells. |
| 巻・号 | 1831(12) |
| ページ | 1690-701 |
| 公開日 | 2013-12-1 |
| DOI | 10.1016/j.bbalip.2013.08.017 |
| PII | S1388-1981(13)00188-1 |
| PMID | 23994608 |
| MeSH | Acylation Animals COS Cells Carbon Radioisotopes Chlorocebus aethiops Ethanolamine / metabolism Ethanolamines / metabolism* Gene Expression Regulation HEK293 Cells Humans Isoenzymes / antagonists & inhibitors Isoenzymes / genetics Isoenzymes / metabolism Membrane Transport Proteins / genetics Membrane Transport Proteins / metabolism* Mice Palmitic Acid / metabolism Peroxisomes / metabolism Phosphatidylethanolamines / biosynthesis* Phospholipases A / antagonists & inhibitors Phospholipases A / genetics Phospholipases A / metabolism* RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Rats Signal Transduction |
| IF | 3.411 |
| 引用数 | 17 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |