{"created":"2023-05-15T14:47:34.042387+00:00","id":65221,"links":{},"metadata":{"_buckets":{"deposit":"a295414c-cadb-46b9-8455-b96a021d91b7"},"_deposit":{"created_by":1,"id":"65221","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"65221"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00065221","sets":["10:29"]},"author_link":["642556","642559","642567","642566","642565","642564","642560","642569","642563","642561","642557","642562","642558","642570","642571","642568"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2013-10-20","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"【目的】　p53阻害性の放射線防護剤は、放射線被ばく事故での救命だけでなく、がんの放射線治療や化学療法による正常組織障害軽減が期待されている。我々は、p53阻害活性を有する新たな低分子有機化合物の探索を進め、いくつかの亜鉛キレート化剤をp53依存性アポトーシスの阻害剤として見出した。今回、我々は、先行研究で検討が進んでいた三座以上の配位子でなく、これまで未検討であった二座配位性の亜鉛キレート化剤を中心に放射線防護活性評価を実施し、優れた放射線細胞死抑制効果を示したKH-3（5-chloro-8-quinolinol）の作用機構解析を進めた。\n【方法】　ヒトT細胞白血病細胞株MOLT-4、MOLT-4のp53 shRNA導入ノックダウン株や、p53ノックダウン株にshRNA抵抗性p53を再導入した株等を用いた。KH-3は、10Gyのγ線照射の1時間前に添加し、細胞の生死判定や、p53標的遺伝子の発現をリアルタイムPCR法やイムノブロッテイング法で解析した。また、マウス全身照射試験には、8週齢のICR雌マウスを用いた。\n【結果】　解析の結果、KH-3は、アポトーシスを抑制するp21のmRNA発現、タンパク質発現を亢進させる一方で、アポトーシスを誘導するPUMAのmRNA発現、タンパク質発現は抑制した。また、p53ノックダウン株、およびp53再導入株を用いた感受性比較試験から、KH-3が放射線細胞死抑制効果を発揮するためにはp53が必須であることも明らかとなった。さらに、7.5 Gy全身照射30日後のマウス生存率は、KH-3投与群は50%、非投与群0%であった（p<0.01）。\n【考察】　KH-3は、p53阻害剤ではなくp53転写修飾剤として機能し、p53標的遺伝子の発現を変化させることによって細胞を生存に導く新しいタイプの放射線防護剤である可能性が示唆された。","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"日本放射線影響学会第56回大会","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"高橋, 一平"}],"nameIdentifiers":[{"nameIdentifier":"642556","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"森田, 明典"}],"nameIdentifiers":[{"nameIdentifier":"642557","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"青木, 伸"}],"nameIdentifiers":[{"nameIdentifier":"642558","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"花屋, 賢悟"}],"nameIdentifiers":[{"nameIdentifier":"642559","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"有安, 真也"}],"nameIdentifiers":[{"nameIdentifier":"642560","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王, 冰"}],"nameIdentifiers":[{"nameIdentifier":"642561","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"田中, 薫"}],"nameIdentifiers":[{"nameIdentifier":"642562","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"笹谷, めぐみ"}],"nameIdentifiers":[{"nameIdentifier":"642563","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"谷本, 圭司"}],"nameIdentifiers":[{"nameIdentifier":"642564","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"細井, 義夫"}],"nameIdentifiers":[{"nameIdentifier":"642565","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"永田, 靖"}],"nameIdentifiers":[{"nameIdentifier":"642566","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"稲葉, 俊哉"}],"nameIdentifiers":[{"nameIdentifier":"642567","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王 冰","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"642568","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"田中 薫","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"642569","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"細井 義夫","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"642570","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"稲葉 俊哉","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"642571","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"新規アポトーシス抑制剤KH-3の作用機構解明","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"新規アポトーシス抑制剤KH-3の作用機構解明"}]},"item_type_id":"10005","owner":"1","path":["29"],"pubdate":{"attribute_name":"公開日","attribute_value":"2013-10-23"},"publish_date":"2013-10-23","publish_status":"0","recid":"65221","relation_version_is_last":true,"title":["新規アポトーシス抑制剤KH-3の作用機構解明"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T21:02:36.382753+00:00"}