Elucidation of molecular mechanisms for PKC-dependent ferroptosis induced by unsaturated carbonyl compounds

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K12253
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63030:Chemical substance influence on environment-related
• Research Institution: Hokkaido University
• Principal Investigator: Higashi Tsunehito 北海道大学, 医学研究院, 助教 (90453018)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 不飽和カルボニル化合物 / フェロトーシス / プロテインキナーゼC

Outline of Final Research Achievements

There are a lot of types of chemical compounds in our environments. Among these, cytotoxic compounds exist. Unsaturated carbonyl compounds are one of the cytotoxic chemical compounds, and are produced by combustion of organic compounds such as lipids. Although the unsaturated carbonyl compounds are highly toxic, the molecular mechanism for cytotoxicity has been unclear. In this study, we have revealed that the unsaturated carbonyl compounds induce ferroptosis in immune cells and lung cells. We have also found that protein kinase C plays an important role in ferroptosis induction in these cells.

Free Research Field

化学物質の毒性学

Academic Significance and Societal Importance of the Research Achievements

免疫系細胞や呼吸器系細胞の細胞死は、感染症や慢性閉塞性肺疾患など様々な疾病の原因であると考えられる。本研究の遂行によって有機化合物の燃焼で生じる不飽和カルボニル化合物が免疫系・呼吸器系細胞に対して引き起こす細胞死のメカニズムの一端が明らかになった。本研究成果は、これらの疾病の予防法や治療法の開発の一助となるものと期待される。またフェロトーシスの誘導に関与する因子の特定に成功したことで、フェロトーシス誘導の分子メカニズムの解明につながるものと考えられる。