{"_buckets": {"deposit": "2f687a23-5760-43e0-9740-7450b5c73375"}, "_deposit": {"id": "7195", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "7195"}, "status": "published"}, "_oai": {"id": "oai:soar-ir.repo.nii.ac.jp:00007195", "sets": ["849"]}, "author_link": ["17462", "17463", "17464", "17465", "17466"], "item_1628147817048": {"attribute_name": "出版タイプ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_970fb48d4fbd8a85", "subitem_version_type": "VoR"}]}, "item_6_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2011-08-11", "bibliographicIssueDateType": "Issued"}, "bibliographicPageEnd": "2170", "bibliographicPageStart": "2157", "bibliographicVolumeNumber": "17", "bibliographic_titles": [{"bibliographic_title": "MOLECULAR VISION"}]}]}, "item_6_description_19": {"attribute_name": "内容記述", "attribute_value_mlt": [{"subitem_description": "信州大学博士（医学）・学位論文・平成24年3月28日授与（乙第21144号）・中村朋子", "subitem_description_type": "Other"}]}, "item_6_description_20": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Purpose: The transcriptional regulator, nuclear factor-kappa B (NF-kappa B)/Rel family are involved in neuronal cell death and survival. Previously, we reported that NF-kappa Bp50-deficient (p50-deficient) mice exhibit many features resembling human normal tension glaucoma (NTG). The developmental mechanism of human NTG is not clearly understood, and a radical curative treatment has yet to be established. Our aim is to elucidate the signal cascade which mediates the spontaneous optic neuropathy in p50-deficient mice as a model of NTG. Methods: To demonstrate the expression and activation of pro-apoptotic factors, which mediate the death of retinal ganglion cells (RGCs) in p50-deficient mice, western blot (WB) and luciferase reporter assays with retinas from p50-deficient and wild type mice, and cultured RGC-5 cells were performed. Furthermore, we tested the neuroprotective effects of chemical reagents (memantine, lomerizine, and tacrolimus) against N-methyl-D-aspartate (NMDA)-susceptible RGC damage according to in vitro experiments with RGC-5 cells. To elucidate the NF-kappa B-mediated death signaling, the effects of chemical reagents on spontaneous optic neuropathy were examined by histopathological studies. Results: WB experiments and luciferase reporter assays showed that NF-kappa B-inducible BCL2-associated X protein (Bax) and a pro-apoptotic factor, activated caspase 3 were expressed in the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Further, the constitutively active cleaved forms of calcineurin (CaN), which have been reported to lead to apoptosis, were detected in the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Pre-treatment with tacrolimus markedly protected RGC-5 cells from NMDA-induced neurotoxicity, and then both spontaneous RGC death and degenerative changes to the optic nerve in p50-deficient mice were significantly reduced by the chronic administration of tacrolimus. The experiments with cultured RGC-5 cells supported the results of histological examinations with p50-deficient mice, suggesting that CaN activation leads to NF-kappa B-induced Bax activation and caspase 3 activation, and mediates spontaneous optic neuropathy in p50-deficient mice. Conclusions: Research findings show that the chronic administration of tacrolimus significantly reduces spontaneous optic neuropathy in p50-deficient mice. We demonstrated a potential CaN signal cascade, which spontaneously induces age-dependent RGC death and degenerative optic nerve changes in p50-deficient mice.", "subitem_description_type": "Abstract"}]}, "item_6_description_30": {"attribute_name": "資源タイプ（コンテンツの種類）", "attribute_value_mlt": [{"subitem_description": "Article", "subitem_description_type": "Other"}]}, "item_6_description_5": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "MOLECULAR VISION. 17:2157-2170 (2011)", "subitem_description_type": "Other"}]}, "item_6_link_3": {"attribute_name": "信州大学研究者総覧へのリンク", "attribute_value_mlt": [{"subitem_link_text": "Murata, Toshinori", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.jpApONfU.html"}]}, "item_6_link_67": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000293884200003"}]}, "item_6_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "MOLECULAR VISION"}]}, "item_6_relation_51": {"attribute_name": "異版である", "attribute_value_mlt": [{"subitem_relation_type": "isVersionOf", "subitem_relation_type_id": {"subitem_relation_type_id_text": "http://www.molvis.org/molvis/v17/a234", "subitem_relation_type_select": "URI"}}]}, "item_6_select_64": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_6_source_id_35": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1090-0535", "subitem_source_identifier_type": "ISSN"}]}, "item_6_source_id_39": {"attribute_name": "NII ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1090-0535", "subitem_source_identifier_type": "ISSN"}]}, "item_6_source_id_40": {"attribute_name": "書誌レコードID", "attribute_value_mlt": [{"subitem_source_identifier": "AA12037116", "subitem_source_identifier_type": "NCID"}]}, "item_6_text_70": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "RETINAL GANGLION-CELLS; GLUTAMATE-INDUCED NEUROTOXICITY; TRANSCRIPTION FACTOR; INTRAOCULAR-PRESSURE; OPTIC NEUROPATHIES; INDUCED APOPTOSIS; RAT RETINA; GLAUCOMA; NEURONS; FK506"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Nakamura-Yanagidaira,  Tomoko"}], "nameIdentifiers": [{"nameIdentifier": "17462", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Takahashi,  Yasuko"}], "nameIdentifiers": [{"nameIdentifier": "17463", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Sano,  Kenji"}], "nameIdentifiers": [{"nameIdentifier": "17464", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Murata,  Toshinori"}], "nameIdentifiers": [{"nameIdentifier": "17465", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hayashi,  Takuma"}], "nameIdentifiers": [{"nameIdentifier": "17466", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2015-09-25"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "H23Otsu21144_nakamura.pdf", "filesize": [{"value": "1.1 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 1100000.0, "url": {"label": "H23Otsu21144_nakamura.pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/7195/files/H23Otsu21144_nakamura.pdf"}, "version_id": "8cb44f8f-2fa8-4e34-9d92-3d04e09359be"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Development of spontaneous neuropathy in NF-kappa Bp50-deficient mice by calcineurin-signal involving impaired NF-kappa B activation", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Development of spontaneous neuropathy in NF-kappa Bp50-deficient mice by calcineurin-signal involving impaired NF-kappa B activation", "subitem_title_language": "en"}]}, "item_type_id": "6", "owner": "1", "path": ["849"], "permalink_uri": "http://hdl.handle.net/10091/16029", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2012-10-03"}, "publish_date": "2012-10-03", "publish_status": "0", "recid": "7195", "relation": {}, "relation_version_is_last": true, "title": ["Development of spontaneous neuropathy in NF-kappa Bp50-deficient mice by calcineurin-signal involving impaired NF-kappa B activation"], "weko_shared_id": -1}