ヒト肝癌細胞における非環式ジテルペノイド GGA の極性代謝産物の 同定

• Material Type: 文書・図像類
• Title: ヒト肝癌細胞における非環式ジテルペノイド GGA の極性代謝産物の 同定
• Author/Editor: 四童子, 好廣; SHIDOJI, Yoshihiro
• Author Heading: 四童子, 好廣; SHIDOJI, Yoshihiro
• Publication, Distribution, etc.: 長崎県立大学
• Publication Date: 2019-03
• Publication Date (W3CDTF): 2019-03
• Alternative Title: Unequivocal evidence for endogenous geranylgeranoic acid biosynthesized from mevalonate in mammalian cells
• Periodical title: 学長裁量研究成果報告書
• No. or year of volume/issue: 平成30年度 シーボルト校
• Volume: 平成30年度
• Issue: シーボルト校
• Pages: 1-6
• Text Language Code: eng
• Subject Heading: cancer; isoprenoids; mass spectrometry
• Target Audience: 一般
• Note (General): type:Other; Geranylgeranoic acid (GGA) has been reported to induce autophagic cell death via upregulation of lipid-induced unfolded protein response in several human hepatoma-derived cell lines, and its 4,5-didehydro derivative has been developed as a preventive agent against second primary hepatoma in clinical trials. We have previously reported that GGA is a natural diterpenoid synthesized in several medicinal herbs. Here, we provide unequivocal evidence for de novo GGA biosynthesis in mammals. First, with normal male Wistar rats, the levels of GGA in liver were found to be far greater than those in other organs analyzed. Second, we demonstrated the metabolic GGA labeling from the 13C-labeled mevalonolactone in the human hepatoma-derived cell line HuH-7. Isotopomer spectral analysis revealed that approximately 80% of the cellular GGA was newly synthesized from mevalonate (MVA) in 12 h and the acid picked up pre-existing farnesyl diphosphate and geranylgeranyl diphosphate, suggesting that GGA is derived from farnesyl diphosphate and geranylgeranyl diphosphate through the MVA pathway. Third, zaragozic acid A, a squalene synthase inhibitor, induced dose-dependent upregulation of endogenous GGA content in HuH-7 cells and their concomitant cell death. These results strongly suggest that a cancer-preventive GGA is biosynthesized via the MVA pathway in mammals.; カラー図版あり; identifier:http://reposit.sun.ac.jp/dspace/handle/10561/1628
• Format (IMT): application/pdf
• Source: http://reposit.sun.ac.jp/dspace/bitstream/10561/1628/1/H30%e3%82%b7%20shidoji.pdf
• Access Restrictions: 限定公開
• 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): 長崎県立大学 : 長崎県立大学学術リポジトリ