Physiological role of polyamines and search for a detoxifying medicine against its toxic metabolite acrolein

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06714
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Chiba Institute of Science
• Principal Investigator: Kashiwagi Keiko 千葉科学大学, 薬学部, 教授 (80169424)
• Co-Investigator(Kenkyū-buntansha): 五十嵐 一衛 株式会社アミンファーマ研究所, その他部局等, 代表取締役 (60089597)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ポリアミン / アクロレイン / 翻訳 / ヒストン修飾 / ヒストン脱メチル化酵素 / アクロレイン除去剤

Outline of Final Research Achievements

Polyamines (putrescine, spermidine, and spermine) are cationic aliphatic amines present in almost all living organisms. Polyamines are essential for cell growth and viability, interact with mainly RNA and stimulate protein synthesis which is important for cell growth and viability at the translational level. We have proposed that a set of genes whose expression is enhanced by polyamines at the level of translation can be classified as a “polyamine modulon”. Since histone methylation, one of the epigenetic controls, is reduced by polyamines, we identified three histone demethylases as members of polyamine modulon.
Acrolein is produced by the oxidative decomposition of spermine and is an aggravating factor for tissue-damaging diseases in old age such as cerebral infarction and Alzheimer's disease. It was discovered that lysine and taurine, which are food ingredients inside, reduce the toxicity of acrolein.

Free Research Field

病態生化学

Academic Significance and Societal Importance of the Research Achievements

ヒストン修飾などのエピジェネティックな遺伝子発現制御に異常が起こると、発がんや、免疫制御異常が起こることが知られているが、その制御機構は不明な点が多い。本研究では、細胞増殖必須因子ポリアミンがヒストン脱メチル化酵素の翻訳レベルにおける発現調節因子であることを明らかにし、ヒストン修飾異常解明や新薬開発に繋がる端緒となる成果が得られた。また、ポリアミン代謝により生じる不飽和アルデヒドであるアクロレインは脳梗塞、アルツハイマー病等の老齢時の組織障害性疾患の増悪因子であるが、この毒性を軽減する物質を同定できた。超老齢化社会を迎える日本に大いに役立つと考えられる。