New regulation mechanism of Nrf2 (SKN-1) and Effects of these factors on lifespan elongation.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08581
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Kwansei Gakuin University
• Principal Investigator: Imaoka Susumu 関西学院大学, 理工学部, 教授 (60145795)
• Co-Investigator(Kenkyū-buntansha): 大黒 亜美 広島大学, 統合生命科学研究科, 助教 (20634497)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ビスフェノールA / クロロゲン酸 / 酸化ストレス / Nrf2 (SKN-1) / 線虫 / 寿命

Outline of Final Research Achievements

Nrf2 is a main regulator of cellular redox homeostasis and is regulated by Keap1. In this study, we proved that WDR23 as well as Keap1 regulated Nrf2 in mammalian cell. BPA and CGA induced Nrf２ in mammalian cell and SKN-1 in C.elegans. CGA but not BPA increased the lifespan of C. elegans. BPA induced Nrf2 by Keap1 inactivation and CGA induced Nrf2 by decrease of DDB-1, a factor of WDR23 system. Although both BPA and CGA induced SKN-1 which contributes to elongation of lifespan, differences in elongation of lifespan by both compounds may be due to difference in the mechanism behind the induction of SKN-1.

Free Research Field

環境生理学

Academic Significance and Societal Importance of the Research Achievements

酸化ストレスはがん、糖尿病、脳神経変性疾患（Alzheimer病など）の病態や成因と深く関わっていると考えられている。当該研究では、酸化ストレス応答の鍵因子であるNrf2の発現を調節している新規因子を明らかにした。線虫を用いて酸化ストレスと寿命の関係を検討し、酸化ストレス（あるいは応答因子SKN-1）が寿命と深く関わっていることを解明し、このメカニズムについて検討し、その一部を明らかにした。