Biological impact Mechanism maintenance and assessment of biological impact of intracellular reactive oxygen species produced by normal physiological reaction

2015 Fiscal Year Final Research Report

• Project/Area Number: 24510072
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyoto University
• Principal Investigator: Tano Keizo 京都大学, 原子炉実験所, 准教授 (00183468)
• Co-Investigator(Kenkyū-buntansha): MASUNAGA Shin-ichiro 京都大学, 原子炉実験所, 教授 (80238914)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 活性酸素種 / 細胞内至適環境維持 / ラジカルスカベンジャー

Outline of Final Research Achievements

Superoxide dismutases (SODs) are antioxidant proteins converting superoxide to hydrogen peroxide. In vertebrate cells, SOD1 is present in the cytoplasm, with small levels found in the nucleus and mitochondrial intermembrane space. SOD2 is present in the mitochondrial matrix. We conditionally disrupted the SOD1 or SOD2 gene in DT40 cells and found that depletion of SOD1 caused lethality, while depletion of SOD2 led to growth retardation. The lethality in SOD1-depleted cells was rescued by ascorbic acid. We demonstrated that ascorbic acid off set growth defects observed in SOD2-depleted cells and lowered mitochondrial superoxide to physiological levels in both SOD1- or SOD2-depleted cells. Depletion of SOD1 or SOD2 resulted in the accumulation of intracellular oxidative stress. This oxidative stress was reduced by ascorbic acid. Our study suggests that ascorbic acid can be applied as an antioxidant that mimics the functions of cytoplasmic and mitochondrial SODs.

Free Research Field

放射線生物学