Analysis of the fucntion of singlet oxygen in vivo during the development of NASH

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07057
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Murotomi Kazutoshi 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (40635281)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 一重項酸素 / 活性酸素種 / 炎症 / NASH

Outline of Final Research Achievements

The purpose of this study was to explore the function and generation mechanism of singlet oxygen, a type of reactive oxygen species (ROS), and to test the hypothesis that singlet oxygen is involved in the pathogenesis of NASH. To analyze the mechanism of singlet oxygen generation, we initiated the development of an intracellular singlet oxygen assay. As a result, we succeeded in quantifying intracellular singlet oxygen by fluorescence time lapse using commercially available singlet oxygen detection probes such as Si-DMA, which led to the publication of this paper. On the other hand, ROS production in the spleen in the early stage of NASH onset was comparable to that in normal mice, but cytokine production was markedly increased compared to that in normal mice. These results suggest that spleen-derived inflammatory cytokines may be involved in the development of NASH.

Free Research Field

生物系薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では、細胞内の一重項酸素を定量的に測定方法を開発することに成功し、成果を論文として社会還元することができた。当該測定方法を用いることで、体に悪影響を与えると考えられている一重項酸素を細胞の中で増加または消去可能か検証することができ、化粧品素材や食品機能性成分の開発に貢献できる。
さらに、NASH発症過程における脾臓の特性、具体的にはNASH初期段階の脾臓におけるROS産生量は正常な脾臓よりもわずかに増加する一方、刺激応答性のサイトカイン産生量は顕著に増加することを明らかにし、論文発表に至った。本成果は、NASH発症時の生体応答の一旦を示すものであり、NASH診断などへの応用が期待される。