Elucidation of physiological functions of glutathione-related metabolites and its metabolic enzymes in ferroptosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16141
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Yamagata University
• Principal Investigator: Kobayashi Sho 山形大学, 農学部, 准教授 (10779490)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: グルタチオン代謝 / フェロトーシス / システイン供給経路 / システイン再利用経路 / フェロトーシス細胞認識抗体 / フェロトーシスを制御する食品由来成分

Outline of Final Research Achievements

The research conducted during this period and its results are as follow. 1)To investigate the physiological function of CNDP2, a novel ferroptosis-suppressing gene found in previous study, CNDP2-deficient mice were established by genome editing. The CNDP2-deficient mice are more vulnerable to acetaminophen-induced liver injury than wild-type mice. Biochemical and histological analysis showed liver damage and renal damage are more severe in CNDP2-deficient mice. 2) We have developed a method for directly determining ferroptotic cells and succeeded in producing a rat monoclonal antibody that recognizes ferroptotic cells with higher specificity than the existing antibody that recognize lipid peroxidation marker 4-HNE. 3) We searched for food-derived ingredients that control ferroptosis and found that garlic and Phellodendron amurense extract had the effect of suppressing ferroptosis.

Free Research Field

生化学、食品栄養科学

Academic Significance and Societal Importance of the Research Achievements

本研究により樹立したCNDP2欠損マウスを用いて解析を行うことで、グルタチオンの分解を介したシステイン再利用経路の生理機能を解明することは、抗がん剤耐性を持つ癌を標的とした新たな治療薬の開発にもつながると考えている。また、本研究により作出したフェロトーシス認識ラットモノクローナル抗体は、フェロトーシスの分子機構や各種の病態におけるフェロトーシスの関与を解明するツールとして有用であると考えられる。