Regulation of mast cell quality by an atypical bioactive fatty acid production system
| Project/Area Number |
17H05053
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (A)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Kono Nozomu 東京大学, 大学院薬学系研究科(薬学部), 准教授 (50451852)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2019: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2018: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2017: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
|
|---|
| Keywords | エポキシ化オメガ３脂肪酸 / マスト細胞 / 脂肪酸 / ホスホリパーゼA2 |
|---|
| Outline of Final Research Achievements |
We established a highly sensitive quantitative method for oxidized phospholipids and oxidized fatty acids by using LC-MS/MS. Using this method, we identified enzymes that produce ω3 epoxide-containing phospholipids and demonstrated that PAF-AH2 hydrolyzes oxidized phospholipids to release ω3 epoxides. We identified a candidate nuclear receptor that could be a target for ω3 epoxides. We found that the downregulation of Srcin1 by ω3 epoxides is a molecular mechanism of ω3 epoxide-mediated regulation of mast cell activation.
|
| Academic Significance and Societal Importance of the Research Achievements |
エポキシ化ω3脂肪酸の産生酵素や作用標的の候補がみつかったことで、酸化リン脂質から産生されるオメガ3系生理活性脂肪酸の産生・作用機構の全貌が見えてきた。GPCRを主な作用標的とするアラキドン酸カスケードと産生・作用機構が対照的であり、学術的意義は非常に大きい。エポキシ化ω3脂肪酸の産生酵素や作用標的は、アレルギー疾患治療薬の有効な創薬ターゲットとなる可能性があり、社会的にも重要な成果である。
|
Report
(4 results)
Research Products
(49 results)
-
[Journal Article] LPIAT1/MBOAT7 depletion increases triglyceride synthesis fueled by high phosphatidylinositol turnover.2020
Author(s)
Tanaka Y, Shimanaka Y, Caddeo A, Kubo T, Mao Y, Kubota T, Kubota N, Yamauchi T, Mancina RM, Baselli G, Luukkonen P, Pihlajamaki J, Yki-Jarvinen H, Valenti L, Arai H, Romeo S, Kono N.
-
Journal Title
Gut
Volume: -
Issue: 1
Pages: 180-193
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
[Journal Article] Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P22019
Author(s)
Nishimura, T., Gecht, M., Covino, R., Hummer, G., Surma, M. A., Klose, C., Arai, H., Kono, N., and Stefan, C. J.
-
Journal Title
Mol Cell
Volume: 75
Issue: 5
Pages: 1043-1057.e8
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Vitamin C and vitamin E double-deficiency increased neuroinflammation and impaired conditioned fear memory2019
Author(s)
Takahashi, K., Yanai, S., Takisawa, S., Kono, N., Arai, H., Nishida, Y., Yokota, T., Endo, S., and Ishigami, A
-
Journal Title
Arch Biochem Biophys
Volume: 663
Pages: 120-128
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Reelin deficiency leads to aberrant lipid composition in mouse brain.2018
Author(s)
Mizukami T, Ikeda K, Shimanaka Y, Korogi K, Zhou C, Takase H, Tsuiji H, Kono N, Kohno T, Arai H, Arita M, Hattori M.
-
Journal Title
Biochem Biophys Res Commun
Volume: 505
Issue: 1
Pages: 81-86
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
