Mechanisms of female-specific expression of drug-metabolizing enzyme CYP3A : comparison between human and mouse

• Project/Area Number: 20590140
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: University of Toyama
• Principal Investigator: SAKUMA Tsutomu University of Toyama, 大学院・医学薬学研究部(薬学), 准教授 (30250468)
• Co-Investigator(Kenkyū-buntansha): NEMOTO Nobuo 富山大学, 大学院・医学薬学研究部(薬学), 教授 (10085631) ; KAWASAKI Yuki 富山大学, 大学院・医学薬学研究部(薬学), 助教 (30432107)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 薬物代謝酵素 / CYP3A / 発現制御 / 性差 / マウス / シトクロムP450 / 性特異性

Research Abstract

To clarify the molecular mechanisms of female-dominant expression of drug-metabolizing enzyme CYP3As in the liver, we analyzed the mechanisms of female-specific expression of mouse Cyp3a41 gene. Our results indicated that HNF4α plays an important role in the transcriptional activation of the Cyp3a41 gene, and a sex difference in chromatin structure may contribute to the female-specific expression of Cyp3a41 in the livers of mice.

Research Products

• [Journal Article] Hepatocyte nuclear factor 4 alpha regulates expression of the mouse female-specific Cyp3a41 gene in the liver. (2011)
  • Author(s): Bhadhprasit W., Sakuma T., Kawasaki Y., Nemoto N.
  • Journal Title: Drug Metab. Dispos. 39 Pages: 490-497
  • Peer Reviewed
• [Journal Article] Cellular glutathione content modulates the effect of andrographolide on β-naphthoflavone-induced CYP1A1 mRNA expression in mouse hepatocytes (2011)
  • Author(s): Kondo S., Chatuphonprasert W., Jaruchotikamol A., Sakuma T., Nemoto N.
  • Journal Title: Toxicology 280 Pages: 18-23
  • Peer Reviewed
• [Journal Article] Hepatocyte nuclear factor 4 alpha regulates expression of the mouse female-specific Cyp3a41 gene in the liver (2011)
  • Author(s): Bhadhprasit W., et al.
  • Journal Title: Drug Metab. Dispos. Volume: 39 Pages: 490-497
  • Peer Reviewed
• [Journal Article] Potent modification of inducible CYP1A1 expression by flavonoids. (2010)
  • Author(s): Chatuphonprasert W., Kondo S., Jarukamjorn K., Kawasaki Y., Sakuma T., Nemoto N.
  • Journal Title: Biol.Pharm.Bull. 33 Pages: 1698-1703
  • NAID: 130000402364
  • Peer Reviewed
• [Journal Article] Regulatory xenobiotic responsive elements in the distal 5'-flanking region of the mouse Cypla2 gene required for transcriptional activation by 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. (2010)
  • Author(s): Kawasaki Y., Sakuma T., Goto Y., Nemoto N.
  • Journal Title: Drug Metab.Dispos. 38 Pages: 1640-1643
  • Peer Reviewed
• [Journal Article] Gender-associated modulation of inducible CYP1A1 expression by andrographolide in mouse liver. (2010)
  • Author(s): Jarukamjorn K., Kondo S., Chatuphonprasert W., Sakuma T., Kawasaki Y., Nemoto N.
  • Journal Title: Eur.J.Pharm.Sci. 39 Pages: 394-401
  • Peer Reviewed
• [Journal Article] Gender-associated modulation of inducible CYP1A1 expression by andrographolide in mouse liver (2010)
  • Author(s): Jarukamjorn K., et al
  • Journal Title: Eur. J. Pharm. Sci. Volume: 39 Pages: 394-401
  • Peer Reviewed
• [Journal Article] Alteration of acetaminophen-induced cytotoxicity in mouse hepatocytes during primary culture. (2009)
  • Author(s): Jaruchotikamol A, Takase A, Ito S, Kawasaki Y., Kondo S, Sakuma T., Nemoto N.
  • Journal Title: J.Health Sci. 55 Pages: 767-776
  • NAID: 130000127965
  • Peer Reviewed
• [Journal Article] Alteration of acetaminophen-induced cytotoxicity in mouse hepatocytes during primary culture (2009)
  • Author(s): Jaruchotikamol A, et al.
  • Journal Title: J.Health Sci. 55 Pages: 767-776
  • Peer Reviewed
• [Journal Article] Sex differences of drug-metabolizing enzyme : female predominant expression of human and mouse cytochrome P450 3A isoforms (2009)
  • Author(s): Sakuma T, et al.
  • Journal Title: J.Health Sci. 55 Pages: 325-337
  • NAID: 130000127906
  • Peer Reviewed
• [Journal Article] Forkhead box A2-mediated regulation of female-predominant expression of the mouse Cyp2b9 gene. (2008)
  • Author(s): Hashita T., Sakuma T., Akada M., Nakajima A., Yamahara H., Ito S., Takesako H., Nemoto N.
  • Journal Title: Drug Metab.Dispos. 36 Pages: 1080-1087
  • Peer Reviewed
• [Journal Article] Synergism of glucocorticoid hormone with growth hormone for female-specific mouse Cyp3a44 gene expression. (2008)
  • Author(s): Sakuma T., Bhadhprasit W., Hashita T., Nemoto N.
  • Journal Title: Drug Metab.Dispos. 36 Pages: 878-884
  • Peer Reviewed
• [Journal Article] Synergism of glucocorticoid hormone with growth hormone for female-specific mouse Cyp3a44 gene expression (2008)
  • Author(s): Sakuma, T., et al.
  • Journal Title: Drug Metab. Dispos. 36 Pages: 878-884
  • Peer Reviewed
• [Journal Article] Forkhead box A2-mediated regulation of female-predominant expression of the mouse Cyp2b9 gene (2008)
  • Author(s): Hashita, T., et al.
  • Journal Title: Drug Metab. Dispos 36 Pages: 1080-1087
  • Peer Reviewed
• [Presentation] マウスCyp3a41遺伝子構造とHNF4αによる性特異的発現 (2010)
  • Author(s): 佐久間勉, 池松怜美, Bhadhprasit Wattanaporn, 河崎優希, 根本信雄
  • Organizer: 日本薬学会北陸支部第122回例会
  • Place of Presentation: 金沢
  • Year and Date: 2010-11-21
• [Presentation] メスマウス肝でのCyp3a41遺伝子発現におけるクロマチン構造とHNF4αの役割 (2010)
  • Author(s): 佐久間勉, 池松怜美, Bhadhprasit Wattanaporn, 河崎優希, 近藤佐千子, 根本信雄
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 東京
• [Presentation] Cyp3a41遺伝子メス特異的発現の調節機構 (2010)
  • Author(s): 佐久間勉, Bhadhprasit Wattanaporn, 河崎優希, 近藤佐千子, 根本信雄
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] Regulatory XREs in distal 5'-flanking region of the mouse Cypla2 gene for transcriptional activation by 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. (2010)
  • Author(s): Kawasaki Y., Yuma Goto, Sakuma T., Nemoto N.
  • Organizer: 18th International Symposium on Microsomes and Drug Oxidations
  • Place of Presentation: Beijing
• [Presentation] Role of hepatocyte nuclear factor 4 alpha and chromatin structure in the regulation of female-specific Cyp3a41 gene expression. (2010)
  • Author(s): Sakuma T., Bhadhprasit W., Kawasaki Y., Nemoto N.
  • Organizer: 18th International Symposium on Microsomes and Drug Oxidations
  • Place of Presentation: Beijing
• [Presentation] Role of hepatocyte nuclear factor 4 alpha and chromatin structure in the regulation of female-specific Cyp3a41 gene expression (2010)
  • Author(s): Tsutomu Sakuma, et al.
  • Organizer: 18th International Symposium on Microsomes and Drug Oxidations
  • Place of Presentation: Beijing
• [Presentation] グルココルチコイドによるCyp3a41遺伝子の発現調節機構:Glucocoeticoid receptorおよびHepatocyte nuclear factor-4αの役割 (2009)
  • Author(s): Bhadhprasit Wattanaporn, 佐久間勉, 河崎優希, 根本信雄
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] Glucocorticoid-mediated induction of mouse Cyp3a41 gene expression ; involvement of glucocorticoid receptor and hepatocyte nuclear factor 4 alpha (2008)
  • Author(s): Bhadhprasit Wattanaporn, 佐久間勉, 根本信雄
  • Organizer: 第23回日本薬物動態学会年会
  • Place of Presentation: 熊本
• [Presentation] メス優位に発現するマウスCyp3a41遺伝子転写過程におけるHNF4αの役割 (2008)
  • Author(s): 根本信雄, 古澤裕之,上野真一, 佐久間勉
  • Organizer: 第15回肝細胞研究会
  • Place of Presentation: 静岡
• [Presentation] マウスCyp3a41の性特異的発現におけるHNF4αの役割 (2008)
  • Author(s): 古澤之裕, 佐久間勉, 上野真一, Bhadhprasit Wattanaporn, 坡下真大, 根本信雄
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
• [Presentation] グルココルチコイドによるCyp3a41遺伝子の調節機構:C/EBPの役割 (2008)
  • Author(s): Bhadhprasit Wattanaporn, 佐久間勉, 赤田真美, 根本信雄
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜