WEKO3
アイテム
{"_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"], "permalink_uri": "https://repo.qst.go.jp/records/46813", "pubdate": {"attribute_name": "公開日", "attribute_value": "2014-09-01"}, "publish_date": "2014-09-01", "publish_status": "0", "recid": "46813", "relation": {}, "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_shared_id": -1}
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
https://repo.qst.go.jp/records/46813
https://repo.qst.go.jp/records/468132e24f335-733e-44e4-b13e-57ef743d9c1a
Item type | 学術雑誌論文 / Journal Article(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2014-09-01 | |||||
タイトル | ||||||
タイトル | 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 | |||||
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 |
Morita, Akinori
× Morita, Akinori× Ariyasu, Shinya× 王, 冰× Asanuma, Tetsuo× Onoda, Takayoshi× Sawa, Akiko× 田中, 薫× Takahashi, Ippei× Togami, Shotaro× 根井, 充× Inaba, Toshiya× Aoki, Shin× 王 冰× 田中 薫× 根井 充 |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
書誌情報 |
Biochemical and Biophysical Research Communications 巻 450, 号 4, p. 1498-1504, 発行日 2014-07 |
|||||
出版者 | ||||||
出版者 | ELSEVIER |