Elucidation of cell cycle dependence of ferrotosis and active oxygen production pathway caused by cell proliferation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06850
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Yamagata University
• Principal Investigator: Fujii Junichi 山形大学, 大学院医学系研究科, 教授 (00222258)
• Co-Investigator(Kenkyū-buntansha): 本間 拓二郎 大阪公立大学, 大学院医学研究科, 講師 (70743566)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 細胞周期 / グルタチオン代謝 / システイン欠乏 / アセトアミノフェン肝障害

Outline of Final Research Achievements

Removal of cysteine from the cultured medium induced ferroptosis, but simultaneous removal of methionine, the precursor of cysteine, actually suppressed cell death, indicating that cell cycle arrest is the cause. Administration of S-adenosylmethionine, a metabolic intermediate of methionine, restored cell proliferation, and, at this time, reactive oxygen species also increased and induced ferroptosis. It is conceivable that reactive oxygen species generated during the progression of the cell cycle are involved in the induction of ferroptosis.
Until now, there was no method to specifically detect cells undergoing ferroptosis in the body, but the rat monoclonal antibody produced in this study was highly specific for cells undergoing ferroptosis.

Free Research Field

病態医化学

Academic Significance and Societal Importance of the Research Achievements

・フェロトーシスは神経変性疾患・虚血性疾患・炎症・がんなどの原因と考えられており、その解明はこうした疾患の予防や治療法の改善に繋がる可能性がある。
・増殖中の細胞の産生する活性酸素が細胞死に関係することが明らかになったことから、活性酸素の原因となるラジカルの生成を抑える治療の有効性が示唆された。作出した特異抗体は、フェロトーシスの関係する疾患の診断に有用な可能性を示唆している。