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Ionizing radiation resistance mediated by the novel selenium‐containing antioxidant selenoneine
Author(s) -
Imamura Shintaro,
Yabu Takeshi,
Ishihara Kenji,
Yamashita Yumiko,
Yamashita Michiaki
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.757.3
Subject(s) - dna damage , apoptosis , tunel assay , chemistry , ionizing radiation , oxidative stress , microbiology and biotechnology , programmed cell death , gene knockdown , morpholino , biology , dna , biochemistry , irradiation , physics , nuclear physics
The novel selenium (Se)‐containing imidazole compound, 2‐selenyl‐trimethyl‐histidine, selenoneine, has been identified from the blood and tissues of the tuna (Yamashita et al, JBC, 285, 18134–18138, 2010). This compound had a strong radical scavenging activity, and had a protective function under oxidative stress conditions. In order to elucidate the molecular mechanism of DNA repair by Se, DNA damage response to γ‐irradiation was characterized in zebrafish embryos (8 hpf) in the presence of selenoneine at 10–100 nM in culture medium at 0.1–8 Gy. Although apoptosis was induced and ionizing radiation had no discernable effects on overall growth and morphology, TUNEL‐positive apoptotic cells were detected in brain, eye and spinal cord. Such apoptosis in CNS was reduced by the treatment of selenoneine at 25 nM after γ‐irradiation. CDC48/VCP/p97, which promotes both ubiquitin‐proteasome system and autophagy, was phosphorylated at Ser‐784 in response to DNA damage, and the treatment of selenoneine blocked CDC48 phosphorylation, suggesting that DNA double strand break by ionizing radiation might be reduced by selenoneine radical scavenging function. Knockdown of CDC48 by antisense morpholino oligos enhanced abnormal morphogenesis and apoptosis in CNS by γ‐irradiation. Therefore, Se redox mechanism by selenoneine and CDC48‐mediated autophagy had a protective function against ionizing radiation.