{"created":"2023-07-27T06:58:04.636516+00:00","id":55690,"links":{},"metadata":{"_buckets":{"deposit":"184284de-bf93-42bf-bae3-ffaaa97249cc"},"_deposit":{"created_by":18,"id":"55690","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"55690"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00055690","sets":["2812:2813:2828"]},"author_link":["97886","20160"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2007-12-12","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"4p.","bibliographicVolumeNumber":"2003 – 2005","bibliographic_titles":[{"bibliographic_title":"平成17(2005)年度 科学研究費補助金 基盤研究(A) 研究成果報告書概要"},{"bibliographic_title":"2005 Fiscal Year Final Research Report Summary","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":"1)虚血性神経細胞死\nORP150が小胞体に局在するストレス蛋白として、神経細胞を虚血ストレスから守りうるメカニズムを明らかにするため、スナネズミの遅発性神経細胞死モデルを用いて、ORP150と虚血性神経細胞死の関連について検索した。一過性脳虚血後のスナネズミ海馬CA1領域では虚血負荷後にORP150の発現上昇を認めた。虚血耐性条件ではORP150の上昇は蛋白レベルでも明らかになり、アデノウイルスベクターによるORP150の強制発現によって、神経細胞死が抑止された。以上から、より緩やかに神経細胞死が進む遅発性神経細胞死においても小胞体ストレスの重要性が示された。\n2)マウスにおける小脳発生での検討。\nORP150は、生後4-8日にかけて小脳、特にプルキンエ細胞に強い発現パターンを示した。ORP150を過剰発現させたトランスジェニックマウス(TG)では、プルキンエ細胞に強いORP150の発現を認めるとともに、ORP150ノックアウトヘテロ接合体(KO)では、その発現は明らかに減弱していた。ORP150の強制発現によってこの時期における細胞死が抑制され、逆にORP150ノックアウトマウスでは、神経細胞死が加速された。ORP150は海馬神経においてグルタミン酸による細胞内Ca++上昇を抑え、細胞死を抑制することから小脳発生過程における神経細胞死にも小胞体を介する神経細胞死の関与が示唆される。\n3)コンフォーメーショナル病モデルとしてmegsin transgenic rat(Meg Tg)の解析\nMegsinは東海大学の宮田らによって見いだされた新規serine proteinase inhibitorであり、Meg Tgのヘテロ接合体は、生後4-6ヶ月をピークに、海馬および黒質(SNpc)においてPAS陽性の細胞内沈着を伴って胞死が進む。このMeg Tgの黒質における病変が小胞体依存性の神経細胞死であることを示した。","subitem_description_type":"Abstract"},{"subitem_description":"ORP150 is a novel stress protein localized in the endoplasmic reticulum (ER). To investigate the role of ORP150 in delayed neuronal cell death, we have examined its expression in the gerbil brain after the ischemic insult. The expression of ORP150 antigen, as well as its transcripts, was observed in the CA1 region after the occlusion of the common carotid artery, and this was enhanced by the preconditioning. In cultured neurons, exposure to either hypoxia or glutamate induced the expression of ORP150, and this was also observed by treating the culture with either thapsigargin or breferdin-A, indicating that both glutamate and hypoxia can cause stress in the ER (ER stress). Neurons became more vulnerable to these stresses following treatment of either cycloheximide or the infection with an adenovirus carrying ORP150 antisense structure, In contrast, the overexpression of ORP150 by adenovirus suppressed the neuronal cell death, and this was accompanied by the suppression of the Ca2+ elevation and proteolytic activity induced by glutamate. Further, overexpression of ORP150 in CA1 neurons by the adenovirus carrying ORP150-sense structure suppressed delayed neuronal cell death after ischemia. These date suggest a possible function of ORP150 as an intracellular apparatus, which participates in a protective response in ischemic tolerance.\nSelective loss of dopaminergic neurons is the final common pathway in Parkinson's disease. We discuss the role of ER-stress in neuronal cell death in SNpc by introducing two models. Upregulation of Pael-Receptor in the substantia nigra pars (SNpc) of mice induces endoplasmic reticulum (ER) stress leading to a decrease in tyrosine hydroxylase and death of dopaminergic neurons. The role of ER stress in dopaminergic neuronal vulnerability was highlighted by their enhanced death in mice deficient in the ubiquitin-protein ligase Parkin and the ER chaperone ORP150, suggesting parkin dysfunction result in ER-stress mediated neuronal cell death. Conversely, transgenic rats overexpressing megsin (Tg meg), a newly identified serine protease inhibitor (serpin), demonstrated intraneuronal periodic-acid Schiff (PAS) positive inclusions, which distributed throughout the deeper layers of cerebral cortex, hippocampal CA1, and substantia nigrta. Enhanced ER stress was observed in dopamine neurons in SNpc, accompanied with loss of neuronal viability and motor coordination. In both subregions, PAS-positive inclusions were also positive with megsin. These data suggest that enhanced ER stress causes selective vulnerability in a set of neuronal populations.","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:15200028, 研究期間(年度):2003 – 2005","subitem_description_type":"Other"},{"subitem_description":"出典：「小胞体環境の制御による虚血性神経細胞死の抑止」研究成果報告書　課題番号15200028\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-15200028/152000282005kenkyu_seika_hokoku_gaiyo/)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":"10.24517/00061965","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=90283746"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=90283746","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15200028/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15200028/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-15200028/152000282005kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-15200028/152000282005kenkyu_seika_hokoku_gaiyo/","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":"2021-11-25"}],"displaytype":"detail","filename":"ME-PR-OGAWA-S-kaken 2007-3p.pdf","filesize":[{"value":"119.7 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-OGAWA-S-kaken 2007-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/55690/files/ME-PR-OGAWA-S-kaken 2007-3p.pdf"},"version_id":"bdb5e75e-173b-4132-9d41-1db988d37f6b"}]},"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":"小胞体環境の制御による虚血性神経細胞死の抑止","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"小胞体環境の制御による虚血性神経細胞死の抑止"},{"subitem_title":"Rescue of Neuronal Cell Death by ER-stress protein overexpression","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2828"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-11-25"},"publish_date":"2021-11-25","publish_status":"0","recid":"55690","relation_version_is_last":true,"title":["小胞体環境の制御による虚血性神経細胞死の抑止"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:16:28.005736+00:00"}