Analysis on molecular mechanisms for tissue-specific toxicity of heavy metals

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03375
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Showa University
• Principal Investigator: Hara Shuntaro 昭和大学, 薬学部, 教授 (50222229)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脂質代謝 / 過酸化脂質 / 毒性発現 / 重金属 / 生理活性脂質

Outline of Final Research Achievements

In order to reveal molecular mechanisms for tissue-specific toxicity of heavy metals, we performed toxicolipidomics, in which we comprehensively investigated chemicals-induced alterations in lipid profiles, and investigated the effects of gene knockout or knockdown of lipid metabolizing enzymes, which are involved in generation or elimination of lipid peroxides and/or production of bioactive lipids, on heavy metals-induced tissue-specific toxicity. As the results, we found that expressions of long-chain acyl-CoA synthetase ACSL4 and calcium-independent phospholipase A2 gamma and the generation of lipid peroxides controlled by these enzymes in target tissues might be critical for tissue-specific toxicity of heavy metals.

Free Research Field

環境毒性学、脂質生化学、衛生薬学

Academic Significance and Societal Importance of the Research Achievements

メチル水銀やカドミウムといった重金属を過剰に摂取すると、脳や腎臓といった特異的な組織に障害がもたらされるが、その組織特異的な毒性発現機構についてはほとんどわかっていない。この機構がわかれば、毒性をいかに軽減するか、解毒するかにつながることも期待される。本研究では、組織における脂質組成や脂質代謝酵素発現に関する解析を通じて、毒性が発現する組織での過酸化脂質の生成が重金属毒性に深く関与することを明らかにすることができた。