Sterol regulatory element binding protein 1 trans-activates 25-hydroxy vitamin D3 24-hydroxylase gene expression in renal proximal tubular cells

• 資料種別: 博士論文
• タイトル: Sterol regulatory element binding protein 1 trans-activates 25-hydroxy vitamin D3 24-hydroxylase gene expression in renal proximal tubular cells
• 著者・編者: Kagawa, Tomohiro; Kozai, Mina; Masuda, Masashi; Harada, Nagakatsu; Nakahashi, Otoki; Tajiri, Mari; Yoshikawa, Ryouhei; Nakao, Mari; Takei, Yuichiro; Iwano, Masayuki; Takeda, Eiji; Taketani, Yutaka; Yamamoto, Hironori
• 著者標目: Kagawa, Tomohiro; Kozai, Mina; Masuda, Masashi; Harada, Nagakatsu; Nakahashi, Otoki; Tajiri, Mari; Yoshikawa, Ryouhei; Nakao, Mari; Takei, Yuichiro; Iwano, Masayuki; Takeda, Eiji; Taketani, Yutaka; Yamamoto, Hironori
• 出版事項: Elsevier
• 出版年月日等: 2018-04-17
• 出版年（W3CDTF）: 2018-04-17
• 並列タイトル等: ステロール応答領域結合タンパク質1は腎近位尿細管細胞において25-水酸化ビタミンD3 24-水酸化酵素遺伝子の転写を活性化する
• タイトル（掲載誌）: Biochemical and Biophysical Research Communications
• 巻号年月日等（掲載誌）: 500 2
• 掲載巻: 500
• 掲載号: 2
• 掲載ページ: 275-282
• ISSN（掲載誌）: ISSN : 0006-291X
• 授与機関名: 徳島大学
• 授与年月日: 2018-09-27
• 報告番号: 甲第3221号
• 学位: 博士（栄養学）
• 本文の言語コード: eng
• 件名標目: CYP24A1; SREBP1; Thyroid hormone; Transcriptional regulation; Vitamin D
• 対象利用者: 一般
• 一般注記: The physiological activity of the steroid derived hormone vitamin D is regulated by several enzymatic steps. Both 25-hydroxy vitamin D3 1a-hydroxylase (CYP27B1) and 25-hydroxyvitamin D3 24-hydroxylase (CYP24A1) modulate blood levels of 1,25-dihydroxyvitamin D3, an activated form of vitamin D. We previously demonstrated that CYP27B1 expression was trans-activated by sterol regulatory element binding protein 1 (SREBP1), although whether SREBP1 also regulates CYP24A1 transcription was unclear. Here we investigated the ability of SREBP1 to affect CYP24A1 transcription. In a luciferase reporter assay, mouse and human CYP24A1 promoter activity was strongly activated by SREBP1 in opossum kidney proximal tubular cells (OK-P). Three putative SREs (pSREs) were found in the mouse Cyp24a1 gene promoter and the SREBP1 protein showed specific binding to the pSRE1 element in EMSAs. Site-directed mutagenesis of the pSRE1 element strongly decreased SREBP1-mediated Cyp24a1 gene transcription. Moreover, siRNA-mediated SREBP1 knock-down repressed CYP24A1 expression in human renal proximal tubular epithelial cells (HKC-8). In animal studies, mice given various doses of thyroid hormone (T3) showed dose-dependent reductions in renal Srebp1c and Cyp24a1 mRNA levels. Taken together, our results suggest that SREBP1 trans-activates CYP24A1 expression through SREBP binding elements present in the promoter.
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.1016/j.bbrc.2018.04.058
• 連携機関・データベース: 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
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ

目次

https://repo.lib.tokushima-u.ac.jp/files/public/11/112883/20181218160133499275/k3221_abstract_review.pdf fulltext

https://repo.lib.tokushima-u.ac.jp/files/public/11/112883/2018121816013410831/k3221_fulltext.pdf fulltext