Paraquat toxicity is attenuated by 4-phenylbutyrate-induced phosphorylation of ERK2 via PI3K in A549 cells 2

• 資料種別: 博士論文
• ISSN: 0006-291X
• タイトル: Paraquat toxicity is attenuated by 4-phenylbutyrate-induced phosphorylation of ERK2 via PI3K in A549 cells
• 巻次・部編番号: 503 2
• 著者・編者: 保科, 千里
• 出版年月日等: 2018-09
• 出版年（W3CDTF）: 2018-09
• タイトル（掲載誌）: Biochemical and biophysical research communications
• 授与機関名: 旭川医科大学
• 授与年月日: 2018-12-25
• 授与年月日（W3CDTF）: 2018-12-25
• 報告番号: 乙第476号
• 学位: 博士（医学）
• 博論授与番号: 乙第476号
• 本文の言語コード: eng
• 件名標目: 4-Phenylbutyrate; A549 cell; Akt; ERK; PI3K; Paraquat
• 一般注記: Paraquat (PQ) is a widely used herbicide in the world despite being highly toxic to humans. PQ causes fatal damage to multiple organs, especially the lungs. While oxidative stress is the main toxic mechanism of PQ, there is no established standard therapy for PQ poisoning. In this study, we investigated the cytoprotective effect of 4-phenylbutyrate (4PBA) on PQ toxicity in human lung adenocarcinoma A549 cells. Phosphorylation levels of major survival signaling kinases Akt and ERK, as well as expression levels of antioxidant enzymes catalase and superoxide dismutase 2 (SOD2) were examined. The cytoprotective mechanism of 4PBA against PQ was compared with the antioxidant reagent trolox. We demonstrated that both 4PBA and trolox attenuated PQ toxicity, but their mechanisms were different. 4PBA increased ERK2 phosphorylation levels, which could be inhibited by the PI3K inhibitor LY294002. The cytoprotective effect of 4PBA was also inhibited by LY294002. Catalase expression levels were increased by 4PBA, although this increase was not inhibited by LY294002. 4PBA did not increase SOD2 expression. Trolox did not affect phosphorylation of Akt or ERK, or the expression of antioxidant enzymes. These results suggest that 4PBA attenuated PQ cytotoxicity by ERK2 activation via PI3K. Our study may provide new findings for understanding the molecular mechanism underlying cytoprotection by 4PBA, as well as new therapeutic targets for PQ poisoning.; identifier:PMID：29913144; 開始ページ : 809; 終了ページ : 814
• DOI: info:doi/10.1016/j.bbrc.2018.06.080; https://doi.org/info:doi/10.1016/j.bbrc.2018.06.080
• 国立国会図書館永続的識別子: info:ndljp/pid/11239116; https://dl.ndl.go.jp/pid/11239116
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2019-02-03T04:35:56+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20181225_O476
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp