Reference - Detail
| RRC ID | 56116 |
|---|---|
| Author | Hussain Z, Uyama T, Kawai K, Binte Mustafiz SS, Tsuboi K, Araki N, Ueda N. |
| Title | Phosphatidylserine-stimulated production of N-acyl-phosphatidylethanolamines by Ca2+-dependent N-acyltransferase. |
| Journal | Biochim Biophys Acta Mol Cell Biol Lipids |
| Abstract |
N-acyl-phosphatidylethanolamine (NAPE) is known to be a precursor for various bioactive N-acylethanolamines including the endocannabinoid anandamide. NAPE is produced in mammals through the transfer of an acyl chain from certain glycerophospholipids to phosphatidylethanolamine (PE) by Ca2+-dependent or -independent N-acyltransferases. The ε isoform of mouse cytosolic phospholipase A2 (cPLA2ε) was recently identified as a Ca2+-dependent N-acyltransferase (Ca-NAT). In the present study, we first showed that two isoforms of human cPLA2ε function as Ca-NAT. We next purified both mouse recombinant cPLA2ε and its two human orthologues to examine their catalytic properties. The enzyme absolutely required Ca2+ for its activity and the activity was enhanced by phosphatidylserine (PS). PS enhanced the activity 25-fold in the presence of 1 mM CaCl2 and lowered the EC50 value of Ca2+ >8-fold. Using a PS probe, we showed that cPLA2ε largely co-localizes with PS in plasma membrane and organelles involved in the endocytic pathway, further supporting the interaction of cPLA2ε with PS in living cells. Finally, we found that the Ca2+-ionophore ionomycin increased [14C]NAPE levels >10-fold in [14C]ethanolamine-labeled cPLA2ε-expressing cells while phospholipase A/acyltransferase-1, acting as a Ca2+-independent N-acyltransferase, was insensitive to ionomycin for full activity. In conclusion, PS potently stimulated the Ca2+-dependent activity and human cPLA2ε isoforms also functioned as Ca-NAT. |
| Volume | 1863(5) |
| Pages | 493-502 |
| Published | 2018-5-1 |
| DOI | 10.1016/j.bbalip.2018.02.002 |
| PII | S1388-1981(18)30022-2 |
| PMID | 29447909 |
| MeSH | Acyltransferases / chemistry Acyltransferases / metabolism* Amino Acid Sequence Animals Biosynthetic Pathways / drug effects COS Cells Calcium / pharmacology* Cations, Divalent / pharmacology Cell Survival / drug effects Chlorocebus aethiops Ethanolamines / metabolism Humans Ionomycin / pharmacology Mice Phosphatidylethanolamines / metabolism* Phosphatidylserines / metabolism* Phospholipases A2, Cytosolic / chemistry Phospholipases A2, Cytosolic / metabolism Plasmalogens / metabolism RAW 264.7 Cells Sequence Homology, Amino Acid |
| IF | 4.402 |
| Times Cited | 5 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 6 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) |