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

• Material Type: 博士論文
• 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
• Author/Editor: 高, 裕子
• Author Heading: 高, 裕子 タカシ, ユウコ
• Publication, Distribution, etc.: Elsevier
• Alternative Title: Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis
• Degree grantor/type: 鹿児島大学
• Date Granted: 2021-02-25
• Dissertation Number: 甲総研第582号
• Degree Type: 博士(歯学); Doctor of Philosophy in Dental Science
• Text Language Code: eng
• Subject Heading: Mitochondria; Ferroptosis; Aquaporin; Hydrogen peroxide; Fe2+
• Target Audience: 一般
• Note (General): 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; 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. Yuko Takashi, Kazuo Tomita, Yoshikazu Kuwahara, Mehryar Habibi Roudkenar, Amaneh Mohammadi Roushandeh, Kento Igarashi Taisuke Nagasawa, Yoshihiro Nishitani, Tomoaki Sato Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis Free Radical Biology and Medicine 161, 2020, p.60-70 https://doi.org/10.1016/j.freeradbiomed.2020.09.027
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 鹿児島大学 : 鹿児島大学リポジトリ

Table of Contents

Result_Takashi_Yuko_isk_582 other

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Diss_高_裕子_ISK582_2020 fulltext

Abstract_高_裕子_4517810197_2020 abstract