Elucidation of a biosynthetic mechanism of cyclic phosphatidic acid

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K19732
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kawasaki Medical School
• Principal Investigator: Kitakaze Keisuke 川崎医科大学, 医学部, 助教 (80840545)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 脂質メディエーター / 環状ホスファチジン酸 / リゾホスファチジン酸 / グリセロホスホジエステラーゼ / リゾホスホリパーゼ / リゾリン脂質 / 生活習慣病

Outline of Final Research Achievements

Cyclic phosphatidic acid (cPA) is a lipid mediator that exhibits a variety of physiological activities including prevention of atherosclerosis and suppression of osteoarthritis pathology, and is regulating lifestyle- and age-related diseases. However, its biosynthetic mechanism are not fully understood. In this study, we performed functional analysis of glycerophosphodiesterase 7 (GDE7), a lysophospholipase D-type enzyme, and found that GDE7 produces cPA in endoplasmic reticulum. Furthermore, we developed of a selective fluorescence-based enzyme assay for glycerophosphodiesterase family members GDE4 and GDE7.
These findings allow high-throughput assays of GDE4 and GDE7 activities, which could lead to the development of selective inhibitors and stimulators as well as a new treatment of lifestyle- and age-related diseases.

Free Research Field

生物系薬学

Academic Significance and Societal Importance of the Research Achievements

cPA生合成酵素としては、血中に存在するオートタキシンが知られている。それに対し、GDE7は小胞体内で働く膜結合性酵素である。細胞内脂質メディエーターの標的は報告が少なく、本研究成果は他の脂質メディエーター研究への応用も期待できる。また、本研究で開発した活性測定系はハイスループットスクリーニングに適用可能であり、GDE7の活性調節を介した生活習慣病や加齢性疾患に対する新規治療法の開発に繋がることが期待される。