ログイン
言語:

WEKO3

  • トップ
  • コミュニティ
  • ランキング
AND
To

Field does not validate



インデックスリンク

インデックスツリー

WEKO

One fine body…

アイテム

{"_buckets": {"deposit": "fcae78c2-8a52-4593-8319-bf763427966a"}, "_deposit": {"id": "36496", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "36496"}, "status": "published"}, "_oai": {"id": "oai:tsukuba.repo.nii.ac.jp:00036496"}, "item_5_biblio_info_6": {"attribute_name": "\u66f8\u8a8c\u60c5\u5831", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2015-11", "bibliographicIssueDateType": "Issued"}, "bibliographicPageStart": "73", "bibliographicVolumeNumber": "8", "bibliographic_titles": [{"bibliographic_title": "Molecular Brain"}]}]}, "item_5_creator_3": {"attribute_name": "\u8457\u8005\u5225\u540d", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "\u4fdd\u5742, \u611b"}], "nameIdentifiers": [{"nameIdentifier": "161696", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "70708453", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://nrid.nii.ac.jp/ja/nrid/1000070708453"}, {"nameIdentifier": "0000003410", "nameIdentifierScheme": "\u7b51\u6ce2\u5927\u5b66\u7814\u7a76\u8005\u7dcf\u89a7", "nameIdentifierURI": "http://trios.tsukuba.ac.jp/researcher/0000003410"}]}, {"creatorNames": [{"creatorName": "\u7389\u5ca1, \u6643"}], "nameIdentifiers": [{"nameIdentifier": "32", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "50192183", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://nrid.nii.ac.jp/ja/nrid/1000050192183"}, {"nameIdentifier": "0000001775", "nameIdentifierScheme": "\u7b51\u6ce2\u5927\u5b66\u7814\u7a76\u8005\u7dcf\u89a7", "nameIdentifierURI": "http://trios.tsukuba.ac.jp/researcher/0000001775"}]}]}, "item_5_description_4": {"attribute_name": "\u6284\u9332", "attribute_value_mlt": [{"subitem_description": "Background\n\u03b2-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is a membrane-bound aspartyl protease that initiates amyloid \u03b2-protein (A\u03b2) generation. Aberrant elevation of BACE1 levels in brains of Alzheimer\u2019s disease (AD) patients may involve A\u03b2. In the present study, we used a neuron culture model system to investigate the effects of A\u03b2 on BACE1 expression as well as the underlying mechanisms.\n\nResults\nRat primary cortical neurons were treated with relatively low concentrations (2.5 \u03bcM) of A\u03b242 oligomers (A\u03b2-O) or fibrils (A\u03b2-F) for 2\u20133 days. A\u03b2-O induced a significant increase in protein levels of BACE1, while A\u03b2-F only had a marginal effect. Levels of amyloid precursor protein (APP) and the major \u03b1-secretase, ADAM10, remained unaltered upon treatment with both types of A\u03b2. A\u03b2-O treatment resulted in activation of eIF2\u03b1 and caspase 3 in a time-dependent manner, with no changes in the endoplasmic reticulum (ER) stress marker, GRP78, indicating that a typical ER stress response is not induced under our experimental conditions. Furthermore, A\u03b2-O did not affect BACE1 mRNA expression but augmented the levels of exogenous BACE1 expressed via recombinant adenoviruses, indicating regulation of BACE1 protein expression, not at the transcriptional or translational but the post-translational level. Immunocytochemical analysis revealed that A\u03b2-O causes a significant increase in BACE1 immunoreactivity in neurites (both axons and dendrites), but not soma of neurons; this change appears relevant to the mechanism of A\u03b2-O-induced BACE1 elevation, which may involve impairment of BACE1 trafficking and degradation. In contrast, A\u03b2-O had no effect on APP immunoreactivity.\n\nConclusion\nOur results collectively suggest that A\u03b2 oligomers induce BACE1 elevation via a post-translational mechanism involving its altered subcellular distribution in neurons, which possibly triggers a vicious cycle of A\u03b2 generation, thus contributing to the pathogenetic mechanism of AD.", "subitem_description_type": "Abstract"}]}, "item_5_publisher_27": {"attribute_name": "\u51fa\u7248\u8005", "attribute_value_mlt": [{"subitem_publisher": "BioMed Central"}]}, "item_5_relation_10": {"attribute_name": "PubMed\u756a\u53f7", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "26552445", "subitem_relation_type_select": "PMID"}}]}, "item_5_relation_11": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "10.1186/s13041-015-0163-5", "subitem_relation_type_select": "DOI"}}]}, "item_5_rights_12": {"attribute_name": "\u6a29\u5229", "attribute_value_mlt": [{"subitem_rights": "\u00a9 2015 Mamada et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated."}]}, "item_5_select_15": {"attribute_name": "\u8457\u8005\u7248\u30d5\u30e9\u30b0", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_5_source_id_7": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1756-6606", "subitem_source_identifier_type": "ISSN"}]}, "item_5_subject_20": {"attribute_name": "NII\u30b5\u30d6\u30b8\u30a7\u30af\u30c8", "attribute_value_mlt": [{"subitem_subject": "\u533b\u5b66", "subitem_subject_scheme": "Other"}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Mamada, Naomi"}], "nameIdentifiers": [{"nameIdentifier": "124080", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Tanokashira, Daisuke"}], "nameIdentifiers": [{"nameIdentifier": "124081", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hosaka, Ai"}], "nameIdentifiers": [{"nameIdentifier": "124082", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kametani, Fuyuki"}], "nameIdentifiers": [{"nameIdentifier": "124083", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Tamaoka, Akira"}], "nameIdentifiers": [{"nameIdentifier": "124084", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Araki, Wataru"}], "nameIdentifiers": [{"nameIdentifier": "124085", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "\u30d5\u30a1\u30a4\u30eb\u60c5\u5831", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2015-12-28"}], "displaytype": "detail", "download_preview_message": "", "filename": "MB_8.pdf", "filesize": [{"value": "2.0 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_6", "mimetype": "application/pdf", "size": 20000000, "url": {"label": "MB_8", "url": "https://tsukuba.repo.nii.ac.jp/record/36496/files/MB_8.pdf"}, "version_id": "9ef04d42-54a1-4da9-a6f0-33357f50a907"}]}, "item_language": {"attribute_name": "\u8a00\u8a9e", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "\u8cc7\u6e90\u30bf\u30a4\u30d7", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Amyloid \u03b2-protein oligomers upregulate the \u03b2-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons", "item_titles": {"attribute_name": "\u30bf\u30a4\u30c8\u30eb", "attribute_value_mlt": [{"subitem_title": "Amyloid \u03b2-protein oligomers upregulate the \u03b2-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons"}]}, "item_type_id": "5", "owner": "1", "path": ["2780/335", "2780/4852", "3/62/5595/4851"], "permalink_uri": "http://hdl.handle.net/2241/00132094", "pubdate": {"attribute_name": "\u516c\u958b\u65e5", "attribute_name_i18n": "\u516c\u958b\u65e5", "attribute_value": "2015-12-28"}, "publish_date": "2015-12-28", "publish_status": "0", "recid": "36496", "relation": {}, "relation_version_is_last": true, "title": ["Amyloid \u03b2-protein oligomers upregulate the \u03b2-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons"], "weko_shared_id": 5}
  1. 医学医療系 (Faculty of Medicine)
  2. 玉岡 晃 (Tamaoka Akira)
  1. 医学医療系 (Faculty of Medicine)
  2. 保坂 愛 (Hosaka Ai)
  1. コンテンツタイプ (Contents Type)
  2. 雑誌発表論文等 (Journal article, etc.)
  3. M~
  4. Molecular Brain

Amyloid β-protein oligomers upregulate the β-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons

http://hdl.handle.net/2241/00132094
9d1348c0-5b7b-441a-9d35-f45e147bd695
プレビュー
名前 / ファイル ライセンス Actions
MB_8.pdf MB_8 (2.0 MB)
license.icon
item type Journal Article(1)
公開日 2015-12-28
タイトル
タイトル Amyloid β-protein oligomers upregulate the β-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons
言語
言語 eng
資源タイプ
タイプ journal article
著者 Mamada, Naomi

× Mamada, Naomi

WEKO 124080

Mamada, Naomi

Search repository
Tanokashira, Daisuke

× Tanokashira, Daisuke

WEKO 124081

Tanokashira, Daisuke

Search repository
Hosaka, Ai

× Hosaka, Ai

WEKO 124082

Hosaka, Ai

Search repository
Kametani, Fuyuki

× Kametani, Fuyuki

WEKO 124083

Kametani, Fuyuki

Search repository
Tamaoka, Akira

× Tamaoka, Akira

WEKO 124084

Tamaoka, Akira

Search repository
Araki, Wataru

× Araki, Wataru

WEKO 124085

Araki, Wataru

Search repository
著者別名 保坂, 愛

× 保坂, 愛

WEKO 161696
e-Rad 70708453
筑波大学研究者総覧 0000003410

保坂, 愛

Search repository
玉岡, 晃

× 玉岡, 晃

WEKO 32
e-Rad 50192183
筑波大学研究者総覧 0000001775

玉岡, 晃

Search repository
抄録
内容記述 Background
β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is a membrane-bound aspartyl protease that initiates amyloid β-protein (Aβ) generation. Aberrant elevation of BACE1 levels in brains of Alzheimer’s disease (AD) patients may involve Aβ. In the present study, we used a neuron culture model system to investigate the effects of Aβ on BACE1 expression as well as the underlying mechanisms.

Results
Rat primary cortical neurons were treated with relatively low concentrations (2.5 μM) of Aβ42 oligomers (Aβ-O) or fibrils (Aβ-F) for 2–3 days. Aβ-O induced a significant increase in protein levels of BACE1, while Aβ-F only had a marginal effect. Levels of amyloid precursor protein (APP) and the major α-secretase, ADAM10, remained unaltered upon treatment with both types of Aβ. Aβ-O treatment resulted in activation of eIF2α and caspase 3 in a time-dependent manner, with no changes in the endoplasmic reticulum (ER) stress marker, GRP78, indicating that a typical ER stress response is not induced under our experimental conditions. Furthermore, Aβ-O did not affect BACE1 mRNA expression but augmented the levels of exogenous BACE1 expressed via recombinant adenoviruses, indicating regulation of BACE1 protein expression, not at the transcriptional or translational but the post-translational level. Immunocytochemical analysis revealed that Aβ-O causes a significant increase in BACE1 immunoreactivity in neurites (both axons and dendrites), but not soma of neurons; this change appears relevant to the mechanism of Aβ-O-induced BACE1 elevation, which may involve impairment of BACE1 trafficking and degradation. In contrast, Aβ-O had no effect on APP immunoreactivity.

Conclusion
Our results collectively suggest that Aβ oligomers induce BACE1 elevation via a post-translational mechanism involving its altered subcellular distribution in neurons, which possibly triggers a vicious cycle of Aβ generation, thus contributing to the pathogenetic mechanism of AD.
書誌情報 Molecular Brain

巻 8, p. 73, 発行日 2015-11
ISSN
収録物識別子 1756-6606
PubMed番号
関連識別子
関連識別子 26552445
DOI
関連識別子
関連識別子 10.1186/s13041-015-0163-5
権利
権利情報 © 2015 Mamada et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
著者版フラグ
値 publisher
出版者
出版者 BioMed Central
Back
0
views
See details
Views

Versions

Ver.1 2021-03-01 14:48:38.794926
Show All versions

Share

Mendeley CiteULike Twitter Facebook Print Addthis

Cite as

Export

OAI-PMH
  • OAI-PMH JPCOAR
  • OAI-PMH DublinCore
  • OAI-PMH DDI
Other Formats
  • JSON
  • BIBTEX

Confirm


Powered by CERN Data Centre & Invenio


Powered by CERN Data Centre & Invenio