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Cytotoxic and cytoprotective signaling pathways mediated by reactive oxygen and nitrogen species

https://repo.qst.go.jp/records/69050
https://repo.qst.go.jp/records/69050
7b93e2f6-d435-48c0-86ed-a6831edbe067
Item type 会議発表用資料 / Presentation(1)
公開日 2007-07-23
タイトル
タイトル Cytotoxic and cytoprotective signaling pathways mediated by reactive oxygen and nitrogen species
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_c94f
資源タイプ conference object
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 Katsube, Takanori

× Katsube, Takanori

WEKO 677699

Katsube, Takanori

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Mori, Masahiko

× Mori, Masahiko

WEKO 677700

Mori, Masahiko

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Tsuji, Hideo

× Tsuji, Hideo

WEKO 677701

Tsuji, Hideo

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Shiomi, Tadahiro

× Shiomi, Tadahiro

WEKO 677702

Shiomi, Tadahiro

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Onoda, Makoto

× Onoda, Makoto

WEKO 677703

Onoda, Makoto

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勝部 孝則

× 勝部 孝則

WEKO 677704

en 勝部 孝則

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森 雅彦

× 森 雅彦

WEKO 677705

en 森 雅彦

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辻 秀雄

× 辻 秀雄

WEKO 677706

en 辻 秀雄

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塩見 忠博

× 塩見 忠博

WEKO 677707

en 塩見 忠博

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小野田 眞

× 小野田 眞

WEKO 677708

en 小野田 眞

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抄録
内容記述タイプ Abstract
内容記述 Reactive oxygen and nitrogen species (RONS) are generated within cells by ionizing radiation via primary ionizing events as well as through secondary amplification systems including metabolic synthesis. Their high reactivities to a variety of macromolecules within cells not only cause dysfunction of the target molecules but also modulate intra- and inter-cellular signal transduction pathways. Hence, RONS are implicated directly and/or indirectly to play a crucial role in biological effects of ionizing radiation. Extensive studies concerning the inflammatory responses have shown that cellular effects of RONS are much complicated and either detrimental or protective, probably depending on the amount, duration, and site of generation as well as the type of species. To elucidate the molecular mechanisms of RONS in both inflammatory and radiation responses, we examined cellular responses to the relatively low concentrations (lower than 0.1 M) of exogenous H2O2 and NO.
A human intestinal epithelial cell line, Caco-2, were grown on permeable supports and exposed to H2O2 and/or NO donors, such as NOC5 and NOC12. A H2O2 treatment induced tyrosine phosphorylation of numerous cellular proteins including ZO-1, E-cadherin, and beta-catenin, components of cell-cell junctions, and exhibited several remarkable features of cell-cell junctional dysfunction, such as an increase in paracellular permeability and disturbance of morphological architecture of cell-cell junctions. On the other hand, a combined treatment with H2O2 and an NO donor suppressed the protein tyrosine phosphorylation and relieved the damage to the cell-cell junction. These findings suggest the presence of two distinct intracellular signalling pathways for detrimental and protective events mediated by H2O2 and NO, respectively. The latter pathway somehow might attenuate the former.
We will also show the latest findings with regard to the effects of H2O2 on radiosensitive mutant cell lines. Targeted disruption of repair genes, such as XRCC4 and Artemis, for DNA double-strand breaks (DSBs) sensitized a human intestinal cancer cell line, HCT116, to ionizing radiation as well as H2O2. Mechanisms underlying DSBs induction by relatively low concentrations of H2O2 (around 0.01-0.04 M) are now under investigation.
会議概要(会議名, 開催地, 会期, 主催者等)
内容記述タイプ Other
内容記述 13th International Congress of Radiation Research
発表年月日
日付 2007-07-12
日付タイプ Issued
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