{"created":"2023-07-25T08:14:41.532060+00:00","id":15809,"links":{},"metadata":{"_buckets":{"deposit":"dd34012a-8f4c-48c1-8042-f91332fe2e91"},"_deposit":{"created_by":18,"id":"15809","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"15809"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:00015809","sets":["57:86"]},"author_link":["139315"],"item_5_date_6":{"attribute_name":"作成日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2021-02-09","subitem_date_issued_type":"Collected"}]},"item_5_date_granted_54":{"attribute_name":"学位授与年月日 ","attribute_value_mlt":[{"subitem_dategranted":"2021-02-25"}]},"item_5_degree_grantor_53":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"鹿児島大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"17701","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_42":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(歯学)","subitem_degreename_language":"ja"},{"subitem_degreename":"Doctor of Philosophy in Dental Science","subitem_degreename_language":"en"}]},"item_5_description_17":{"attribute_name":"ファイル（説明）","attribute_value_mlt":[{"subitem_description":"博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_4":{"attribute_name":"要約(Abstract)","attribute_value_mlt":[{"subitem_description":"Most anti-cancer agents and radiotherapy exert their therapeutic effects via the production of free radicals. Ferroptosis is a recently described cell death process that is accompanied by iron-dependent lipid peroxidation. Hydrogen peroxide (H2O2) has been reported to induce cell death. However, it remains controversial whether H2O2-induced cell death is ferroptosis. In the present study, we aimed to elucidate the involvement of mitochondria in H2O2-induced ferroptosis and examined the molecules that regulate ferroptosis. We found that one mechanism underlying H2O2-induced cell death is ferroptosis, which occurs soon after H2O2 treatment (within 3 h after H2O2 treatment). We also investigated the involvement of mitochondria in H2O2-induced ferroptosis using mitochondrial DNA-depleted ρ0 cells because ρ0 cells produce more lipid peroxidation, hydroxyl radicals (•OH), and are more sensitive to H2O2 treatment. We found that ρ0 cells contain high Fe2+ levels that lead to •OH production by H2O2. Further, we observed that aquaporin (AQP) 3, 5, and 8 bind nicotinamide-adenine dinucleotide phosphate oxidase 2 and regulate the permeability of extracellular H2O2, thereby contributing to ferroptosis. Additionally, the role of mitochondria in ferroptosis was investigated using mitochondrial transfer in ρ0 cells. When mitochondria were transferred into ρ0 cells, the cells exhibited no sensitivity to H2O2-induced cytotoxicity because of decreased Fe2+ levels. Moreover, mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQP expression. Our findings also revealed the involvement of AQP and PHB2 in ferroptosis. Our results indicate that H2O2 treatment enhances AQP expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2, and thus, is a promising modality for effective cancer treatment.\n\nYuko Takashi, Kazuo Tomita, Yoshikazu Kuwahara, Mehryar Habibi Roudkenar, Amaneh Mohammadi Roushandeh, Kento Igarashi Taisuke Nagasawa, Yoshihiro Nishitani, Tomoaki Sato\nMitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis\nFree Radical Biology and Medicine 161, 2020, p.60-70\nhttps://doi.org/10.1016/j.freeradbiomed.2020.09.027","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_dissertation_number_55":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲総研第582号"}]},"item_5_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier","subitem_publisher_language":"en"},{"subitem_publisher":"鹿児島大学","subitem_publisher_language":"ja"},{"subitem_publisher":"カゴシマ ダイガク","subitem_publisher_language":"ja-Kana"}]},"item_5_subject_15":{"attribute_name":"NDC","attribute_value_mlt":[{"subitem_subject":"490","subitem_subject_scheme":"NDC"}]},"item_5_text_44":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_text_value":"【指導教員:西谷佳浩】"}]},"item_5_text_47":{"attribute_name":"date.appl","attribute_value_mlt":[{"subitem_text_value":"【学位申請日】2020-12-02"}]},"item_5_version_type_14":{"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":[{"creatorNames":[{"creatorName":"高, 裕子","creatorNameLang":"ja"},{"creatorName":"タカシ, ユウコ","creatorNameLang":"ja-Kana"},{"creatorName":"Takashi, Yuko","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-10-22"}],"displaytype":"detail","filename":"Diss_高_裕子_ISK582_2020.pdf","filesize":[{"value":"1.6 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Diss_高_裕子_ISK582_2020","objectType":"fulltext","url":"https://ir.kagoshima-u.ac.jp/record/15809/files/Diss_高_裕子_ISK582_2020.pdf"},"version_id":"402c9a9d-152d-4552-8d0d-6f2440e725d1"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-09-07"}],"displaytype":"detail","filename":"Abstract_高_裕子_4517810197_2020.pdf","filesize":[{"value":"87.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Abstract_高_裕子_4517810197_2020","objectType":"abstract","url":"https://ir.kagoshima-u.ac.jp/record/15809/files/Abstract_高_裕子_4517810197_2020.pdf"},"version_id":"1b2ff5ee-995e-4cf4-8ea3-8865f8b1fbb3"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-04-09"}],"displaytype":"detail","filename":"Result_Takashi_Yuko_isk_582.pdf","filesize":[{"value":"193.7 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Result_Takashi_Yuko_isk_582","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/15809/files/Result_Takashi_Yuko_isk_582.pdf"},"version_id":"d3106adb-076c-4e3a-af95-0369faa5c1a6"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-04-09"}],"displaytype":"detail","filename":"Comments_Takashi_Yuko_isk_582.pdf","filesize":[{"value":"91.1 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Comments_Takashi_Yuko_isk_582","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/15809/files/Comments_Takashi_Yuko_isk_582.pdf"},"version_id":"e7cd012b-4679-4d65-af64-abef198d8f37"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Mitochondria","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Ferroptosis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Aquaporin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Hydrogen peroxide","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Fe2+","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":"Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis","subitem_title_language":"en"},{"subitem_title":"ミトコンドリア機能障害は過酸化水素の膜透過性とフェロトーシスを制御するアクアポリンの発現を促進させる","subitem_title_language":"ja"}]},"item_type_id":"5","owner":"18","path":["86"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-04-09"},"publish_date":"2021-04-09","publish_status":"0","recid":"15809","relation_version_is_last":true,"title":["Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2024-01-09T01:58:58.015829+00:00"}