{"created":"2023-07-27T06:51:25.331567+00:00","id":44841,"links":{},"metadata":{"_buckets":{"deposit":"7dac1cad-3290-42ab-bbc6-b9591fcb2005"},"_deposit":{"created_by":18,"id":"44841","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"44841"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00044841","sets":["2812:2813:2819"]},"author_link":["91","77342"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2015-05-26","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"4p.","bibliographicVolumeNumber":"2012-04-01 - 2015-03-31","bibliographic_titles":[{"bibliographic_title":"平成26(2014)年度 科学研究費補助金 挑戦的萌芽研究 研究成果報告書"},{"bibliographic_title":"2014 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"神経細胞死の機序に関しては不明な点が多い。本研究では熱ショック蛋白であるHsp70.1を中心とした蛋白質-膜脂質間相互作用を検索した。オートファジーに関わる分子連関を検索することで、リソソームの破裂により生じる神経細胞死の全容を究明した。その分子機構には、「calpain-mediated cleavage of carbonylated Hsp70.1」があることを発見した。Hsp70.1の機能がカルボニル化とカルパイン分解によって障害されるため、BMPとの結合が障害され、ASMの機能低下が起きる。その結果スフィンゴミエリンの分解が阻害され膜を安定化するセラミドが減少しリソソームは破裂する。","subitem_description_type":"Abstract"},{"subitem_description":"Using the monkey experimental paradigm, previously we reported that calpain-mediated cleavage of oxidized Hsp70.1 causes neurodegeneration in the hippocampal CA1 sector. However, the molecular mechanisms of the lysosomal destabilization/stabilization have not been elucidated. To elucidate whether regulation of lysosomal ASM could affect the neuronal fate, we analyzed Hsp70.1-BMP binding and ASM activity. We showed that Hsp70.1 being localized at the lysosomal membrane, lysosomal lipid BMP levels, and the lipid binding domain of Hsp70.1 are crucial for Hsp70.1- BMP binding. Calpain activation and a concomitant decrease in the lysosomal membrane localization of Hsp70.1 and BMP levels may diminish Hsp70.1-BMP binding, resulting in decreased ASM activity and lysosomal rupture with leakage of cathepsin B into the cytosol. Regulation of ASM activation in vivo by Hsp70.1-BMP affects lysosomal stability and neuronal survival or death after ischemia/reperfusion.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:24659540, 研究期間(年度):2012-04-01 - 2015-03-31","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「神経細胞死におけるHsp70とその関連蛋白の意義」課題番号24659540\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所））\n（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-24659540/24659540seika/）を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医薬保健研究域医学系","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00051180","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=60181947"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=60181947","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24659540/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24659540/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-24659540/24659540seika/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-24659540/24659540seika/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-06-22"}],"displaytype":"detail","filename":"ME-PR-MINABE-Y-kaken 2015-4p.pdf","filesize":[{"value":"161.3 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-MINABE-Y-kaken 2015-4p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/44841/files/ME-PR-MINABE-Y-kaken 2015-4p.pdf"},"version_id":"abf8fcf1-d7ad-47b6-a2f3-77747af05899"}]},"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":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"神経細胞死におけるHsp70とその関連蛋白の意義","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"神経細胞死におけるHsp70とその関連蛋白の意義"},{"subitem_title":"Role of Hsp70 and its related molecules in neuronal death","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2819"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-06-22"},"publish_date":"2018-06-22","publish_status":"0","recid":"44841","relation_version_is_last":true,"title":["神経細胞死におけるHsp70とその関連蛋白の意義"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T10:43:23.071354+00:00"}