{"created":"2024-03-15T03:11:33.622714+00:00","id":2001329,"links":{},"metadata":{"_buckets":{"deposit":"848eecb0-e9db-4763-b062-81379eadf656"},"_deposit":{"created_by":10,"id":"2001329","owners":[10],"pid":{"revision_id":0,"type":"depid","value":"2001329"},"status":"published"},"_oai":{"id":"oai:repository.lib.tottori-u.ac.jp:02001329","sets":["1:9","2:12","23:34:1710471377862:1710471383343"]},"author_link":["4730","4931","4742","2430","2712","4288","04712"],"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2024-02-21","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicNumberOfPages":"11","bibliographicPageEnd":"51","bibliographicPageStart":"41","bibliographicVolumeNumber":"67","bibliographic_titles":[{"bibliographic_title":"Yonago Acta Medica","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background: Doxorubicin (Dox) is effective against different types of cancers, but it poses cardiotoxic side effects, frequently resulting in irreversible heart failure. However, the complexities surrounding this cardiotoxicity, especially at sublethal dosages, remain to be fully elucidated. We investigated early cellular disruptions in response to sublethal Dox, with a specific emphasis on the role of phosphorylated calcium/calmodulin-dependent protein kinase II (CaMKII) in initiating mitochondrial dysfunction. Methods: This study utilized the H9c2 cardiomyocyte model to identify a sublethal concentration of Dox and investigate its impact on mitochondrial health using markers such as mitochondrial membrane potential (MMP), mitophagy initiation, and mitochondrial calcium dynamics. We examined the roles of and interactions between CaMKII, dynamin-related protein 1 (Drp1), and the mitochondrial calcium uniporter (MCU) in Dox-induced mitochondrial disruption using specific inhibitors, such as KN-93, Mdivi-1, and Ru360, respectively. Results: Exposure to a sublethal dose of Dox reduced the MMP red-to-green fluorescence ratio in H9c2 cells by 40.6% compared with vehicle, and increased the proportion of cells undergoing mitophagy from negligible levels compared with vehicle to 62.2%. Mitochondrial calcium levels also increased by 8.7-fold compared with the vehicle group. Notably, the activation of CaMKII, particularly its phosphorylated form, was pivotal in driving these mitochondrial changes, as inhibition using KN-93 restored MMP and decreased mitophagy. However, inhibition of Drp1 and MCU functions had a limited impact on the observed mitochondrial disruptions. Conclusion: Sublethal administration of Dox is closely linked to CaMKII activation through phosphorylation, emphasizing its pivotal role in early mitochondrial disruption. These findings present a promising direction for developing therapeutic strategies that may alleviate the cardiotoxic effects of Dox, potentially increasing its clinical efficacy.","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Tottori University Medical Press","subitem_publisher_language":"en"}]},"item_10001_relation_16":{"attribute_name":"情報源","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"Yonago Acta Medica. 2024, 67(1), 41-51."}]}]},"item_10001_relation_17":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://www.lib.tottori-u.ac.jp/yam/yam/yam67-1/67-1contents.html"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://www.lib.tottori-u.ac.jp/yam/yam/yam67-1/67-1contents.html","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://doi.org/10.33160/yam.2024.02.005"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.33160/yam.2024.02.005","subitem_relation_type_select":"DOI"}}]},"item_10001_rights_15":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"(C)2024 Tottori University Medical Press","subitem_rights_language":"en"}]},"item_10001_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AA00892882","subitem_source_identifier_type":"NCID"}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"13468049","subitem_source_identifier_type":"PISSN"}]},"item_10001_text_33":{"attribute_name":"著者所属（英）","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Division of Pharmacology, Department of Pathophysiological and Therapeutic Sciences, School of Medicine, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Pharmacology, Department of Pathophysiological and Therapeutic Sciences, School of Medicine, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Pharmacology, Department of Pathophysiological and Therapeutic Sciences, School of Medicine, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Pharmacology, Department of Pathophysiological and Therapeutic Sciences, School of Medicine, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Pharmacology, Department of Pathophysiological and Therapeutic Sciences, School of Medicine, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Cardiovascular Medicine and Endocrinology and Metabolism, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Cardiovascular Medicine and Endocrinology and Metabolism, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Cardiovascular Medicine and Endocrinology and Metabolism, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Regenerative Medicine and Therapeutics, Department of Genomic Medicine and Regenerative Therapy, School of Medicine, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Cardiovascular Medicine and Endocrinology and Metabolism, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University"},{"subitem_text_language":"en","subitem_text_value":"Division of Pharmacology, Department of Pathophysiological and Therapeutic Sciences, School of Medicine, Faculty of Medicine, Tottori University"}]},"item_10001_version_type_20":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"15101","affiliationNameIdentifierScheme":"kakenhi"}],"affiliationNames":[{"affiliationName":"鳥取大学","affiliationNameLang":"ja"},{"affiliationName":"Tottori University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Agung,Kurniawan Priyono","creatorNameLang":"en"}],"familyNames":[{"familyName":"Agung","familyNameLang":"en"}],"givenNames":[{"givenName":"Kurniawan 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dose","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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Mitochondrial Responses to Sublethal Doxorubicin in H9c2 Cardiomyocytes: The Role of Phosphorylated CaMKII","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Mitochondrial Responses to Sublethal Doxorubicin in H9c2 Cardiomyocytes: The Role of Phosphorylated CaMKII","subitem_title_language":"en"}]},"item_type_id":"10001","owner":"10","path":["12","9","1710471383343"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-03-21"},"publish_date":"2024-03-21","publish_status":"0","recid":"2001329","relation_version_is_last":true,"title":["Mitochondrial Responses to Sublethal Doxorubicin in H9c2 Cardiomyocytes: The Role of Phosphorylated CaMKII"],"weko_creator_id":"10","weko_shared_id":-1},"updated":"2024-03-15T06:37:51.404196+00:00"}