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

• Material Type: 博士論文
• ISSN: 0006-291X
• Title: Paraquat toxicity is attenuated by 4-phenylbutyrate-induced phosphorylation of ERK2 via PI3K in A549 cells
• Volume: 503 2
• Author/Editor: 保科, 千里
• Publication Date: 2018-09
• Publication Date (W3CDTF): 2018-09
• Periodical title: Biochemical and biophysical research communications
• Degree grantor/type: 旭川医科大学
• Date Granted: 2018-12-25
• Date Granted (W3CDTF): 2018-12-25
• Dissertation Number: 乙第476号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 乙第476号
• Text Language Code: eng
• Subject Heading: 4-Phenylbutyrate; A549 cell; Akt; ERK; PI3K; Paraquat
• Note (General): 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
• Persistent ID (NDL): info:ndljp/pid/11239116; https://dl.ndl.go.jp/pid/11239116
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 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
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2019-02-03T04:35:56+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20181225_O476
• Data Provider (Database): 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