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2022 Fiscal Year Final Research Report

Regulatory mechanisms for cell death and inflammatory signaling mediated by the diversity of membrane fatty acid species

Research Project

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Project/Area Number 20KK0361
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))

Allocation TypeMulti-year Fund
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionTohoku University

Principal Investigator

Hirata Yusuke  東北大学, 薬学研究科, 助教 (10748221)

Project Period (FY) 2020 – 2022
Keywordsトランス脂肪酸 / 細胞老化 / 炎症 / 細胞死 / フェロトーシス / 機械刺激受容体
Outline of Final Research Achievements

In collaboration with Professor Sergio Grinstein and Assistant Professor Spencer A. Freeman of the Department of Biochemistry, University of Toronto (The Hospital for Sick Children, Canada, we identified IL-1 receptor as a direct target of trans-fatty acids (TFAs), such as elaidic acid, that functions as the most upstream molecule in a pro-inflammatory signaling. We also identified NADPH oxidase, which produces reactive oxygen species (ROS) mainly on the plasma membrane, as the target of trans-arachidonic acids that play an anti-ferroptotic role. Furthermore, we revealed that mechanosensitive channels, including Piezo1 and TRP channels, are targets of membrane phospholipid peroxidation during ferroptosis, which play a critical role in ferroptosis execution.

Free Research Field

生化学、分子細胞生物学、衛生化学

Academic Significance and Societal Importance of the Research Achievements

トランス脂肪酸は、疫学研究などから、循環器系疾患をはじめとした諸疾患のリスクファクターとされてきたが、分子・細胞レベルでの知見に乏しく、疾患発症機序についてはほとんど不明である。本研究成果により、トランス脂肪酸の生体膜上の直接的な作用点が明らかとなり、その全容解明に繋がる重要な成果となった。また、フェロトーシスについても、神経変性疾患などの様々な疾患増悪に寄与することが知られている一方で、脂質過酸化に伴って細胞死が起きるメカニズムは現在も全く不明である。本研究成果により、その実行因子として、Piezo1、TRPチャネルが新たに同定され、関連疾患の発症機序の一端が解明できた。

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Published: 2024-01-30   Modified: 2025-01-30  

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