{"created":"2021-03-01T06:11:02.635343+00:00","id":7195,"links":{},"metadata":{"_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":["461:848:849"]},"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_url":"http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=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_source_id_35":{"attribute_name":"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_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Nakamura-Yanagidaira,  Tomoko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Takahashi,  Yasuko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Sano,  Kenji"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Murata,  Toshinori"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Hayashi,  Takuma"}],"nameIdentifiers":[{}]}]},"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","filename":"H23Otsu21144_nakamura.pdf","filesize":[{"value":"1.1 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","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"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2012-10-03"},"publish_date":"2012-10-03","publish_status":"0","recid":"7195","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_creator_id":"1","weko_shared_id":-1},"updated":"2022-12-14T03:54:11.945666+00:00"}