2019 Fiscal Year Research-status Report
Investigation of the neuroprotective effect of the rare phospholipid NAPE using gene-deficient mice
| Project/Area Number |
19K23828
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Keywords | N-Acylethanolamine / N-Acyl-PE / Anandamide / Calcium ionophore / PLA2G4E / Phospholipid |
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| Outline of Annual Research Achievements |
N-Acyl-phosphatidylethanolamines (NAPEs) are known to be precursors of bioactive N-acylethanolamines (NAEs). In mammals, NAPEs are produced by N-acyltransferases, which transfer an acyl chain from a glycerophospholipid (like phosphatidylcholine (PC)) to the amino group of phosphatidylethanolamine (PE). Recently, the e isoform of cytosolic phospholipase A2 (cPLA2e) was found to be Ca2+-dependent N-acyltransferase. However, it was less understood which types of phospholipids serve as substrates in living cells. In this study, we established a human embryonic kidney 293 cell line, in which doxycycline potently induces human cPLA2e-expression, and used these cells to investigate endogenous substrates and products of cPLA2e with liquid chromatography-tandem mass spectrometry. When treated with doxycycline and Ca2+ ionophore, the cells produced massive amounts of various species of diacyl- and alkenylacyl-types of NAPEs as well as NAEs. Moreover, the levels of various PEs and PCs decreased, while those of lysoPE and lysoPC increased. These results suggested that cPLAe Ca2+-dependently produces NAPEs by utilizing endogenous PEs as acyl acceptors and PCs as well as PEs as acyl donors.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Most of experiments are in progress as described in the research proposal.
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| Strategy for Future Research Activity |
We will do the experiments as described in the research proposal.
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| Causes of Carryover |
We will use the grant appropriately.
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[Journal Article] Intracellular Ca2+-Dependent Formation of N-Acyl-phosphatidylethanolamines by Human Cytosolic Phospholipase A2ε2019
Author(s)
Smriti Sultana Binte Mustafiz, Toru Uyama, Katsuya Morito, Naoko Takahashi, Katsuhisa Kawai, Zahir Hussain, Kazuhito Tsuboi, Nobukazu Araki, Kei Yamamoto, Tamotsu Tanaka, and Natsuo Ueda
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Journal Title
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume: 1864
Pages: 158515
DOI
Peer Reviewed
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