{"created":"2024-10-28T05:40:12.370900+00:00","id":2004787,"links":{},"metadata":{"_buckets":{"deposit":"6455b49c-d765-487e-8d49-3956d9a6a179"},"_deposit":{"created_by":7,"id":"2004787","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2004787"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02004787","sets":["1713853213384:1713853296295:1716267878536:1716268699858"]},"author_link":["1117","865","1586","1582","323","866","223"],"item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_alternative_title":"筋萎縮関連ユビキチンリガーゼCbl-bの発現調節における酸化ストレスの重要性","subitem_alternative_title_language":"ja"},{"subitem_alternative_title":"ROS induced Cbl-b expression in rat L6 cells","subitem_alternative_title_language":"en"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018-06-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"6","bibliographicPageEnd":"C731","bibliographicPageStart":"C721","bibliographicVolumeNumber":"314","bibliographic_titles":[{"bibliographic_title":"The American Journal of Physiology. Cell Physiology","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume (Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T. Mol Cell Biol 29: 4798–4811, 2009). However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed that the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression. In L6 myotubes, the assessment of redox status revealed that oxidized glutathione was increased under microgravity conditions, and simulated microgravity caused a burst of ROS, implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROS generation activated the ERK1/2 early-growth response protein (Egr)1/2-Cbl-b signaling pathway, an established contributing pathway to muscle volume loss. Interestingly, antioxidant treatments such as N-acetylcysteine and TEMPOL, but not catalase, blocked the clinorotation-mediated activation of ERK1/2. The increased ROS induced transcriptional activity of Egr1 and/or Egr2 to stimulate Cbl-b expression through the ERK1/2 pathway in L6 myoblasts, since treatment with Egr1/2 siRNA and an ERK1/2 inhibitor significantly suppressed clinorotation-induced Cbl-b and Egr expression, respectively. Promoter and gel mobility shift assays revealed that Cbl-b was upregulated via an Egr consensus oxidative responsive element at −110 to −60 bp of the Cbl-b promoter. Together, this indicates that under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass through Cbl-b expression activated by the ERK-Egr signaling pathway.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"The American Physiological Society","subitem_publisher_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"03636143","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"15221563","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"AA00521122","subitem_source_identifier_type":"NCID"}]},"item_10001_version_type_20":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_be7fb7dd8ff6fe43","subitem_version_type":"NA"}]},"item_1714461018643":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第3146号"}]},"item_1714461102074":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（栄養学）","subitem_degreename_language":"ja"}]},"item_1714461118377":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2018-03-23"}]},"item_1714461137393":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"徳島大学"}]}]},"item_1715043197608":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access"}]},"item_1718868208704":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"内容要旨・審査要旨・論文本文の公開\n本論文は, 著者Takayuki Uchidaの学位論文として提出され, 学位審査・授与の対象となっている。\n学位授与者所属 : 徳島大学大学院栄養生命科学教育部（人間栄養科学専攻）"}]},"item_1718868303842":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲栄第255号"}]},"item_1722929371688":{"attribute_name":"出版社版DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_language":"ja","subitem_relation_name_text":"10.1152/ajpcell.00184.2017"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1152/ajpcell.00184.2017","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"337953"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"内田, 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cells","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"ubquitin ligase Cbl-b","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"unloading-mediated muscle atrophy","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Reactive oxygen species up-regulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Reactive oxygen species up-regulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle 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