Effects of 2‐methoxyestradiol, a main metabolite of estradiol on Hepatic ABCA1 expression in HepG2 cells

• Material Type: 博士論文
• Title: Effects of 2‐methoxyestradiol, a main metabolite of estradiol on Hepatic ABCA1 expression in HepG2 cells
• Author/Editor: 井端, 智裕
• Author Heading: 井端, 智裕
• Publication Date: 2022-06-29
• Publication Date (W3CDTF): 2022-06-29
• Alternative Title: エストラジオールの主要な代謝産物である2‐メトキシストラジオールはHepG2細胞において肝ABCA1の発現を増加させる
• Degree grantor/type: 香川大学
• Date Granted: 2022-06-29
• Date Granted (W3CDTF): 2022-06-29
• Dissertation Number: 甲第814号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第814号
• Text Language Code: eng
• Alias of Author: Ibata, Tomohiro
• Subject Heading: ABCA1; 2-methoxyestradiol; lipid accumulation; fatty liver; cell signaling
• Target Audience: 一般
• Note (General): ATP-binding cassette transporter A1 (ABCA1) is a key regulator of lipid efflux, and the absence of ABCA1 induces hepatic lipid accumulation, which is one of the major causes of fatty liver. 2-Methoxyestradiol (2-ME2) has been demonstrated to protect against fatty liver. In this study, we investigated the effects of 2-ME2 on the hepatic lipid content and ABCA1 expression. We found that 2-ME2 dose-dependently increased ABCA1 expression, and therefore, the lipid content was significantly decreased in HepG2 cells. 2-ME2 enhanced the ABCA1 promoter activity; however, this effect was reduced after the inhibition of the PI3K pathway. The overexpression of Akt or p110 induced ABCA1 promoter activity, while dominant-negative Akt diminished the ability of 2-ME2 on ABCA1 promoter activity. Further, 2-ME2 stimulated the rapid phosphorylation of Akt and FoxO1 and reduced the nuclear accumulation of FoxO1. Chromatin immunoprecipitation confirmed that FoxO1 bonded to the ABCA1 promoter region. The binding was reduced by 2-ME2, which facilitated ABCA1 gene transcription. Furthermore, mutating FoxO1-binding sites in the ABCA1 promoter region or treatment with FoxO1-specific siRNA disrupted the effect of 2-ME2 on ABCA1 expression. All of our results demonstrated that 2-ME2 might upregulate ABCA1 expression via the PI3K/Akt/FoxO1 pathway, which thus reduces the lipid content in hepatocytes.
• DOI: info:doi/10.3390/nu14020288; https://doi.org/info:doi/10.3390/nu14020288
• Persistent ID (NDL): info:ndljp/pid/12314244; https://dl.ndl.go.jp/pid/12314244
• 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): 2022-08-08T06:02:54+09:00
• Date Created (W3CDTF): 2022-07-07
• Format (IMT): 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): https://kagawa-u.repo.nii.ac.jp/records/9802
• 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