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Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts
http://hdl.handle.net/10069/30710
http://hdl.handle.net/10069/30710c553668a-21e0-4355-922b-67e1ff05293f
名前 / ファイル | ライセンス | アクション |
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OMCL_310534.pdf (2.1 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-02-19 | |||||
タイトル | ||||||
タイトル | Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Colocalization | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Culture conditions | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | DNA damages | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | DNA double strand breaks | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Galactosidases | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Human diploid fibroblasts | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Hypoxic cells | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Life span | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Normal human fibroblast | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Phosphoinositide 3-kinase | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Phosphorylated histone | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Replicative senescence | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Telomeres | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Wortmannin | |||||
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 | |||||
著者 |
Suzuki, Masatoshi
× Suzuki, Masatoshi× Suzuki, Keiji× Kodama, Seiji× Yamashita, Shunichi× Watanabe, Masami |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Foci of phosphorylated histone H2AX and ATM are the surrogate markers of DNA double strand breaks. We previously reported that the residual foci increased their size after irradiation, which amplifies DNA damage signals. Here, we addressed whether amplification of DNA damage signal is involved in replicative senescence of normal human diploid fibroblasts. Large phosphorylated H2AX foci (>1.5 μm diameter) were specifically detected in presenescent cells. The frequency of cells with large foci was well correlated with that of cells positive for senescence-associated β-galactosidase staining. Hypoxic cell culture condition extended replicative life span of normal human fibroblast, and we found that the formation of large foci delayed in those cells. Our immuno-FISH analysis revealed that large foci partially localized at telomeres in senescent cells. Importantly, large foci of phosphorylated H2AX were always colocalized with phosphorylated ATM foci. Furthermore, Ser15-phosphorylated p53 showed colocalization with the large foci. Since the treatment of senescent cells with phosphoinositide 3-kinase inhibitor, wortmannin, suppressed p53 phosphorylation, it is suggested that amplification of DNA damage signaling sustains persistent activation of ATM-p53 pathway, which is essential for replicative senescence. | |||||
書誌情報 |
Oxidative Medicine and Cellular Longevity 巻 2012, p. 310534, 発行日 2012 |
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出版者 | ||||||
出版者 | Hindawi Publishing Corporation | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 19420900 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 19420994 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1155/2012/310534 | |||||
権利 | ||||||
権利情報 | © 2012 Masatoshi Suzuki et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Oxidative Medicine and Cellular Longevity, 2012, 310534; 2012 |