{"created":"2023-06-19T10:54:59.251959+00:00","id":5469,"links":{},"metadata":{"_buckets":{"deposit":"41977609-c80a-45fd-ad52-55f32a676b84"},"_deposit":{"created_by":17,"id":"5469","owners":[17],"pid":{"revision_id":0,"type":"depid","value":"5469"},"status":"published"},"_oai":{"id":"oai:kobe-c.repo.nii.ac.jp:00005469","sets":["40:1397:1398"]},"author_link":["5860","3194"],"item_10002_biblio_info_30":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-06-20","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"152","bibliographicPageStart":"141","bibliographicVolumeNumber":"64","bibliographic_titles":[{"bibliographic_title":"神戸女学院大学論集"},{"bibliographic_title":"KOBE COLLEGE STUDIES","bibliographic_titleLang":"en"}]}]},"item_10002_description_28":{"attribute_name":"要旨(日）","attribute_value_mlt":[{"subitem_description":"大脳皮質でのアミロイドβ沈着は、アルツハイマー型認知症（AD）の病態と密接に関連している。神経細胞は、異常蛋白質を修復する小胞体にアミロイドβ沈着物を取り込む。異常蛋白質の蓄積によって小胞体ストレスが増加すると、細胞はシャペロン蛋白の誘導などの小胞体ストレス応答（UPR）を惹起して小胞体ストレスに対処する。しかしUPRの惹起が十分でない場合は、アポトーシスによる細胞死に至る。今回我々は、アミロイドβ負荷による神経細胞のUPRがERストレスの対処には不十分であり、AD発症率を低下させる女性ホルモンがUPRを増強して細胞死を抑制するかを、培養細胞モデルを用いて検討した。ラット神経系由来のPC-12細胞に、小胞体ストレス誘発剤であるツニカマイシン、アミロイドβ単量体、または凝集体を負荷すると、小胞体ストレスが増加するとともに、UPRで誘導されるジャペロン蛋白GRP78も増加させた。女性ホルモンの17β-エストラジオールによる前処理は、ツニカマイシン、アミロイドβによるGRP78発現を増強するとともにすると、神経細胞における小胞体ストレスを減少した。また、アポトーシスが誘導されたことにより、ツニカマイシンによるUPRは小胞体ストレスの凌駕には不充分であることがわかる。17β-エストラジオールによる前処理はツニカマイシンによるアポトーシスも減少させた。以上より、大脳皮質におけるアミロイドβ沈着は神経細胞の小胞体ストレスを惹起するが、誘導されるUPRが不十分な場合にはアポトーシスによる細胞死が生じた。女性ホルモンのエストロゲンは、UPRを増強することによってアミロイドβ負荷による小胞体ストレスを軽減し、アポトーシスを抑制する可能性が示された。女性ホルモンは、アミロイドβによる神経細胞の小胞体ストレスを修飾することによって、ADの発症率を低下させていることが示唆された。","subitem_description_type":"Other"}]},"item_10002_description_49":{"attribute_name":"要旨（英）","attribute_value_mlt":[{"subitem_description":"Amyloid β deposits in the cerebral cortex are closely related to the pathogenesis of Alzheimer's disease (AD). Neurons uptake amyloid β deposits into endoplasmic reticulum (ER) where abnormal proteins are repaired. As ER stress caused by the accumulation of abnormal proteins in ER increases, cell respond to the stress by evoking unfolded protein responses (UPR), such as the induction of chaperone proteins. If cells cannot adapt to the stress by UPR, they initiate apoptosis pathway leading to cell death. Therefore, we investigated whether amyloid β elicits ER stress unalbe to be coped with UPR, and whether female hormones, which reduce morbidity of AD in women, prevent neuronal cell death by enhancing UPR in a cell culture model of AD.\nPC-12 cells, derived from rat neuronal tissue, were exposed to an ER stress inducer, tunicamycin (1 μM), amyloid β monomers (5 μM) or aggregates (5 μM). These treatments increased ER stress together with the upregulation of GRP78, a chaperone protein induced by UPR. Pretreatment with a female hormone, 17β-estradiol (0～1 μM), enhanced GRP78 expression dose dependently in tunicamycin or amyloid β treated cells, which coincided with the decrease of ER stress in the cells. Because tunicamycin evoked apoptosis in PC-12, UPR incuced by tunicamycin was not sufficient to overcome ER stress. When the cells were pretreated with 17β-estradiol, it also decreased the apoptosis induced by tunicamycin significantly.\nThese results indicate that amyloid β deposition in the cerebral contex increases the ER stress of neuronal cells. If UPR induced by ER stress is insufficient, neuronal cell death by apoptosis increases. A female hormone, estrogen, augments UPR and reduces the ER stress caused by amyloid β, and many prevent cell death by apoptosis. Therefore, female hormones may reduce the morbidity of AD through the modulation of ES stress in neurons caused by amyloid β deposits.\n","subitem_description_type":"Other"}]},"item_10002_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.18878/00005416","subitem_identifier_reg_type":"JaLC"}]},"item_10002_select_43":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"publisher"}]},"item_10002_text_31":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_text_value":"神戸女学院大学研究所"}]},"item_10002_text_47":{"attribute_name":"著者所属","attribute_value_mlt":[{"subitem_text_value":"神戸女学院大学大学院人間科学研究科人間科学専攻博士前期課程"},{"subitem_text_value":"神戸女学院大学人間科学部環境・バイオサイエンス学科教授"}]},"item_10002_text_48":{"attribute_name":"雑誌書誌ID","attribute_value_mlt":[{"subitem_text_value":"AN00085725"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"山本, 智美"},{"creatorName":"ヤマモト, トモミ","creatorNameLang":"ja-Kana"},{"creatorName":"YAMAMOTO, Tomomi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"5860","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"西田, 昌司"},{"creatorName":"ニシダ, マサシ","creatorNameLang":"ja-Kana"},{"creatorName":"NISHIDA, Masashi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"3194","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"1000040283783","nameIdentifierScheme":"CiNii ID","nameIdentifierURI":"http://ci.nii.ac.jp/nrid/1000040283783"},{"nameIdentifier":"40283783","nameIdentifierScheme":"KAKEN-研究者検索","nameIdentifierURI":"https://nrid.nii.ac.jp/ja/nrid/1000040283783/"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-08-02"}],"displaytype":"detail","filename":"201706_178-10.pdf","filesize":[{"value":"954.5 kB"}],"format":"application/pdf","license_note":"神戸女学院大学研究所","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"201706_178-10","url":"https://kobe-c.repo.nii.ac.jp/record/5469/files/201706_178-10.pdf"},"version_id":"cce5d98e-cdea-4843-9995-0c16e057bce6"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"アルツハイマー型認知症","subitem_subject_scheme":"Other"},{"subitem_subject":"アミロイドβ","subitem_subject_scheme":"Other"},{"subitem_subject":"小胞体ストレス応答","subitem_subject_scheme":"Other"},{"subitem_subject":"17β-エストラジオール","subitem_subject_scheme":"Other"},{"subitem_subject":"アポトーシス","subitem_subject_scheme":"Other"},{"subitem_subject":"小胞体ストレス","subitem_subject_scheme":"Other"},{"subitem_subject_scheme":"Other"},{"subitem_subject":"Alzheimer's disease","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"amyloid β","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"unfolded protein responses","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"17β-estradiol","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"apoptosis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"endoplasmic reticulum stress","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"女性ホルモンとアルツハイマー型認知症Ⅱ―アミロイドβ負荷による神経細胞の小胞体ストレスに対する17β-エストラジオールの影響―","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"女性ホルモンとアルツハイマー型認知症Ⅱ―アミロイドβ負荷による神経細胞の小胞体ストレスに対する17β-エストラジオールの影響―"},{"subitem_title":"Female Hormones and Alzheimer's Disease ⅡーThe Effect of 17 β-Estradiol on ER Stress of Neurons Induced by Amiloid βー","subitem_title_language":"en"}]},"item_type_id":"10002","owner":"17","path":["1398"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-08-02"},"publish_date":"2017-08-02","publish_status":"0","recid":"5469","relation_version_is_last":true,"title":["女性ホルモンとアルツハイマー型認知症Ⅱ―アミロイドβ負荷による神経細胞の小胞体ストレスに対する17β-エストラジオールの影響―"],"weko_creator_id":"17","weko_shared_id":-1},"updated":"2023-06-19T11:33:00.983013+00:00"}