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Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation
https://repo.qst.go.jp/records/46557
https://repo.qst.go.jp/records/465574cbd3c9b-3b8d-4632-a917-965e698dee69
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2013-06-05 | |||||
| タイトル | ||||||
| タイトル | Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Shirai, Hidenori
× Shirai, Hidenori× Fujimori, Hiroaki× Hirai, Takahisa× Sasai, Keisuke× Okayasu, Ryuichi× Masutani, Mitsuko× et.al× 白井 秀徳× 平井 崇久× 笹井 啓資× 岡安 隆一× 益谷 美都子 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme involved in poly(ADP-ribose) degradation. Here, the effects of Parg deficiency on sensitivity to low and high linear-energy-transfer (LET) radiation were investigated in mouse embryonic stem (ES) cells. Mouse Parg-/- and poly(ADP-ribose) polymerase-1 deficient (Parp-1-/-) ES cells were used and responses to low and high LET radiation were assessed by clonogenic survival and biochemical and biological analysis methods. Parg-/-cells were more sensitive to gamma-irradiation than Parp-1-/- cells. Transient accumulation of poly(ADP-ribose) was enhanced in Parg-/-cells. Augmented levels of phosphorylated H2AX (gamma-H2AX)from early phase were observed in Parg-/- ES cells. The induction level of p53 phophorylation at ser18 was similar in wild-type and Parp-1-/- cells and apoptotic cell death process was mainly observed in the both genotypes. These results suggested that the enhanced sensitivity of Parg-/- ES cells to gamma-irradiation involved defective repair of DNA double strand breaks. The effects of Parg and Parp-1 deficiency on the ES cell response to carbon-ion irradiation (LET13 and 70 keV/um) and Fe-ion irradiation (200 keV/um) were also examined. Parg-/- cells were more sensitive to LET 70 keV/um carbon-ion irradiation than Parp-1-/- cells. Enhanced apoptotic cell death also accompanied augmented levels of gamma-H2AX in a biphasic manner peaked at 1 and 24 h. The induction level of p53 phophorylation at ser18 was not different between wild-type and Parg-/- cells. The augmented level of poly(ADP-ribose) accumulation was noted after carbon-ion irradiation compared to gamma-irradiation even in the wild-type cells. An enhanced poly(ADP-ribose) accumulation was further observed in Parg-/- cells. Both Parg-/- cells and Parp-1-/- cells did not show sensitization to Fe-ion irradiation. Parg deficiency sensitizes mouse ES cells to a wide therapeutic range of LET radiation through the effects on DNA double strand break repair responses and enhanced cell death. |
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| 書誌情報 |
Biochemical and Biophysical Research Communications 巻 435, 号 1, p. 100-106, 発行日 2013-05 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0006-291X | |||||
