{"created":"2023-05-15T14:36:21.535757+00:00","id":46813,"links":{},"metadata":{"_buckets":{"deposit":"6718bdea-1578-4c9e-a32d-7fe256bb0273"},"_deposit":{"created_by":1,"id":"46813","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"46813"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00046813","sets":["1"]},"author_link":["466990","466998","466995","466997","467000","467001","466992","466999","466991","466987","466989","466993","466996","466988","466994"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2014-07","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4","bibliographicPageEnd":"1504","bibliographicPageStart":"1498","bibliographicVolumeNumber":"450","bibliographic_titles":[{"bibliographic_title":"Biochemical and Biophysical Research Communications"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"In a previous study, we reported that some tetradentate zinc(II) chelators inhibit p53 through the denaturation of its zinc-requiring structure but a chelator, Bispicen, a potent inhibitor of in vitro apopto- sis, failed to show any efficient radioprotective effect against irradiated mice because the toxicity of the chelator to mice. The unsuitability of using tetradentate chelators as radioprotectors prompted us to undertake a more extensive search for p53-inhibiting agents that are weaker zinc(II) chelators and therefore less toxic. Here, we show that an 8-hydroxyquinoline (8HQ) derivative, AS-2, suppresses p53-dependent apoptosis through a transcription-independent mechanism. A mechanistic study using cells with different p53 characteristics revealed that the suppressive effect of AS-2 on apoptosis is specifically mediated through p53. In addition, AS-2 was less effective in preventing p53-mediated transcription-dependent events than pifithrin-l (PFTl), an inhibitor of transcription-independent apoptosis by p53. Fluorescence visualization of the extranuclear distribution of AS-2 also supports that it is ineffective on the transcription-dependent pathway. Further investigations revealed that AS-2 suppressed mitochondrial apoptotic events, such as the mitochondrial release of intermembrane proteins and the loss of mitochondrial membrane potential, although AS-2 resulted in an increase in the mitochondrial translocation of p53 as opposed to the decrease of cytosolic p53, and did not affect the apoptotic interaction of p53 with Bcl-2. AS-2 also protected mice that had been exposed to a lethal dose of ionizing radiation. Our findings indicate that some types of bidentate 8HQ chelators could serve as radioprotectors with no substantial toxicity in vivo.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"ELSEVIER"}]},"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":"Morita, Akinori"}],"nameIdentifiers":[{"nameIdentifier":"466987","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ariyasu, Shinya"}],"nameIdentifiers":[{"nameIdentifier":"466988","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王, 冰"}],"nameIdentifiers":[{"nameIdentifier":"466989","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Asanuma, Tetsuo"}],"nameIdentifiers":[{"nameIdentifier":"466990","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Onoda, Takayoshi"}],"nameIdentifiers":[{"nameIdentifier":"466991","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sawa, Akiko"}],"nameIdentifiers":[{"nameIdentifier":"466992","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"田中, 薫"}],"nameIdentifiers":[{"nameIdentifier":"466993","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Takahashi, Ippei"}],"nameIdentifiers":[{"nameIdentifier":"466994","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Togami, Shotaro"}],"nameIdentifiers":[{"nameIdentifier":"466995","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"根井, 充"}],"nameIdentifiers":[{"nameIdentifier":"466996","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Inaba, Toshiya"}],"nameIdentifiers":[{"nameIdentifier":"466997","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Aoki, Shin"}],"nameIdentifiers":[{"nameIdentifier":"466998","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王 冰","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"466999","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"田中 薫","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"467000","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"根井 充","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"467001","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"AS-2, a novel inhibitor of p53-dependent apoptosis, prevents apoptotic mitochondrial dysfunction in a transcription-independent manner and protects mice from a lethal dose of ionizing radiation","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"AS-2, a novel inhibitor of p53-dependent apoptosis, prevents apoptotic mitochondrial dysfunction in a transcription-independent manner and protects mice from a lethal dose of ionizing radiation"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2014-09-01"},"publish_date":"2014-09-01","publish_status":"0","recid":"46813","relation_version_is_last":true,"title":["AS-2, a novel inhibitor of p53-dependent apoptosis, prevents apoptotic mitochondrial dysfunction in a transcription-independent manner and protects mice from a lethal dose of ionizing radiation"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T23:47:18.348489+00:00"}