Dose-Dependent Increase of Nrf2 Target Gene Expression in Mice Exposed to Ionizing Radiation
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- Shuta Miura
- Department of Radiology, Akita Kousei Medical Center, Akita 011-0948, Japan
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- Masaru Yamaguchi
- Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Aomori 036-8564, Japan
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- Hironori Yoshino
- Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Aomori 036-8564, Japan
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- Yuji Nakai
- Institute for Food Sciences, Hirosaki University, Aomori 038-0012, Japan
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- Ikuo Kashiwakura
- Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Aomori 036-8564, Japan
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説明
Nuclear factor-erythroid-2-related factor 2 transcription factor (Nrf2) is activated by reactive oxygen species (ROS) and binds to antioxidant response elements in the promoter regions of its target genes involved in redox regulation and antioxidative functions. In this study, we elucidated the relationship between radiation dose and the expression response of Nrf2 target genes involved in oxidative stress, such as heme oxygenase 1, ferritin heavy polypeptide 1 ( Fth1), NADPH dehydrogenase quinone 1, glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, glutathione reductase ( Gsr) and thioredoxin reductase 1 genes, in peripheral blood from X-ray irradiated mice. Whole-body radiation doses ranged from 0.5 to 3 Gy, and gene expressions were analyzed using reverse transcription quantitative polymerase chain reaction. A significant relationship was observed only for one gene: a statistically significant positive correlation between radiation dose and Fth1 mRNA expression was detected. However, Fth1 did not show any correlations with the biological damages induced by radiation tested in this study. Furthermore, while Gsr expression was significantly associated with spleen weight loss, splenic cell number reduction and bone marrow cell death apoptosis, no significant correlation was observed between Gsr expression and radiation dose. Together these results indicate that Nrf2 target gene expression is closely related to radiation dose and its level may reflect biological damages induced by ionizing radiation. These findings suggest the possibility for application of these target genes as a bio-dosimeter and/or damage marker in individuals exposed to ionizing radiation.
収録刊行物
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- Radiation Research
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Radiation Research 191 (2), 176-, 2019-12-19
Radiation Research Society