Regulation of mast cell quality by an atypical bioactive fatty acid production system

2019 Fiscal Year Final Research Report

• 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
• Keywords: エポキシ化オメガ３脂肪酸 / マスト細胞

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.

Free Research Field

脂質生物学

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。