{"created":"2023-07-27T06:58:42.813949+00:00","id":57652,"links":{},"metadata":{"_buckets":{"deposit":"1194f9c2-01d3-493e-bc9a-a7e45545df91"},"_deposit":{"created_by":18,"id":"57652","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"57652"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00057652","sets":["2812:2813:2833"]},"author_link":["97886","20160"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2002-03-25","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"1998 – 2000","bibliographic_titles":[{"bibliographic_title":"平成12(2000)年度 科学研究費補助金 基盤研究(B) 研究成果報告書概要"},{"bibliographic_title":"2000 Fiscal Year Final Research 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":"虚血環境下における遺伝子発現の制御は、脳血管障害の遺伝子治療を考える上で必須のテクノロジーである。その第一歩として、脳虚血におけるheat shock protein(HSP)72によるストレス応答を、レポーター遺伝子およびそれを導入したトランスジェニックマウスを用いて検討した。この虚血レポーターのin-vitroにおける発現を確認するため、次にSV40の核移行シグナルを付けたHSPプロモーター遺伝子と、βgalactosidase遺伝子(lacZ)とを組み合わせたレポーター遺伝子を導入したtransgenic mouseの作成を試みた。このマウスを用いて、片側頸動脈閉塞および再潅流を行うと、虚血ストレスによるレポーター遺伝子の発現が見られ、核の青染が起こることが確認された。また、申請者らは、中枢神経系で神経細胞に比してアストログリアが環境変化に極めて強いことに注目し、ラット培養アストロサイトを低酸素ストレスに暴露する系を用い、新規小胞体ストレス蛋白ORP150、SERP1のクローニングに成功した。ストレス応答の場で、神経細胞がこれらストレス蛋白の発現に乏しい事実から、小胞体の機能不全としての神経細胞死を提唱してきた。小胞体の機能不全を救済することが神経細胞死を救うと言うこの研究を発展させ、ORP150のレポーター遺伝子を作成すべく、現在プロモーター領域の同定を行っている。\nストレス蛋白のプロモーターを用いたレポーター遺伝子のtransfection系やそれを導入したトランスジェニックマウス虚血ストレス応答の解析に有用であることが示唆された。またそれらはストレス応答の簡便な定量化、可視化も可能ることで脳虚血の研究に役立つと考えられ、また治療に関しても今後新たな可能性を提示するものと考えられる。","subitem_description_type":"Abstract"},{"subitem_description":"An integral component of the cellular response to environmental challenge is expression, usually by de novo protein synthesis, of stress-associated polypeptides, such as heat shock proteins (induced by high temperature), glucose-regulated proteins (GRPs ; induced by glucose deprivation), and oxygen-regulated proteins (induced by oxygen deprivation). These biosynthetic responses are well preserved from prokaryotes to mammals, and have been hypothesized to contribute importantly to maintenance of cellular homeostasis as cellular adaptation to altered environmental conditions is under way.\nAstrocytes are strategically positioned to exert cytoprotective effects on neurons, the latter known for their vulnerability to changes in the local environment. Such neuro-protective and even neuro-trophic properties of astrocytes have been suggested in the setting of trauma, inflammation, and ischemic insults. To analyze specific mechanisms through which astrocytes mediate these effects, we analyzed polypeptides made by astrocytes exposed to hypoxia, an important component of the ischemic milieu. Our studies have identified a novel 150 kDa protein, ORP150. This endoplasmic reticulum (ER)-associated chaperone has been shown to contribute importantly to the viability of several cultured cell lines under conditions of oxygen deprivation.In view of the susceptibility of neurons to ischemic stress, we hypothesized that such vulnerability might be due, at least in part, to limited expression of ORP15O.In contrast, the resistance of astrocytes to ischemic stress might result from abundant ORP150 expression.\nOxygen-regulated protein 150 kDa (ORP150) is a novel endoplasmic reticulum-associated chaperone induced by oxygen deprivation/ischemia. Although ORP15O was modestly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes. Cultured neurons overexpressing ORP150 were resistant to hypoxemic stress, whereas astrocytes with inhibited ORP15O expression were more vulnerable. Mice with targeted neuronal overexpression of ORP150 displayed smaller strokes compared with controls. Neurons with increased ORP150 demonstrated suppressed caspase-3-like activity and enhanced elaboration of neurotrophic BDNF under hypoxia. These data indicate that ORP150 is an integral participant in ischemic cytoprotective pathways.","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:10480215, 研究期間(年度):1998 – 2000","subitem_description_type":"Other"},{"subitem_description":"出典：「脳虚血における細胞のストレス応答の可視化とその制御」研究成果報告書　課題番号10480215\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/ja/report/KAKENHI-PROJECT-10480215/104802152000kenkyu_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":"金沢大学医学部","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00063922","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/ja/search/?kw=90283746"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/search/?kw=90283746","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-10480215/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-10480215/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-10480215/104802152000kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-10480215/104802152000kenkyu_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":"2021-10-15"}],"displaytype":"detail","filename":"ME-PR-OGAWA-S-kaken 2002-2p.pdf","filesize":[{"value":"106.5 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-OGAWA-S-kaken 2002-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/57652/files/ME-PR-OGAWA-S-kaken 2002-2p.pdf"},"version_id":"534567b2-e1a8-4e7d-a097-ae77079a9785"}]},"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":"脳虚血における細胞のストレス応答の可視化とその制御","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"脳虚血における細胞のストレス応答の可視化とその制御"},{"subitem_title":"Visualization and regulation of ischemia-induced stress response in brain.","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2833"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-10-15"},"publish_date":"2021-10-15","publish_status":"0","recid":"57652","relation_version_is_last":true,"title":["脳虚血における細胞のストレス応答の可視化とその制御"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:43:26.992426+00:00"}