Regulatory mechanisms of sterol transporters under pathophysiological conditions

• Project/Area Number: 21790143
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: TAKADA Tappei The University of Tokyo, 医学部附属病院, 助教 (90376468)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 発現制御 / 薬理学 / 生理学 / 脂質 / トランスポーター

Research Abstract

Niemann-Pick C1-like 1 (NPC1L1) is known to contribute to the cholesterol absorption in the small intestine and liver and is believed to be a pharmacological target of ezetimibe. As a result of the present study, we succeeded in the construction of human NPC1L1 promoter-driven adenovirus for the expression of human NPC1L1. In addition, it was demonstrated that L-FABP is involved in the positive regulation of the expression of NPC1L1 protein in a post-transcriptional manner. These results would be important to understand the relationship between the pathogenesis of obesity-related diseases and sterol transporters.

Research Products

• [Journal Article] Human NPC1L1 expression is positively regulated by PPARα. (2011)
  • Author(s): Iwayanagi Y, Takada T, Tomura F, Yamanashi Y, Terada T, Inui K, Suzuki H.
  • Journal Title: Pharm Res. 28(2) Pages: 405-412
  • Peer Reviewed
• [Journal Article] Itraconazole-induced cholestasis : involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4. (2011)
  • Author(s): Yoshikado T, Takada T, Yamamoto T, Yamaji H, Ito K, Santa T, Yokota H, Yatomi Y, Yoshida H, Goto J, Tsuji S, Suzuki H.
  • Journal Title: Mol Pharmacol. 79(2) Pages: 241-250
  • Peer Reviewed
• [Journal Article] Human NPC1L1 expression is positively regulated by PPARα (2011)
  • Author(s): Iwayanagi Y, et al.
  • Journal Title: Pharm Res Volume: 28(2) Pages: 405-12
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of membrane transport of vitamin E. (2010)
  • Author(s): Takada T, Suzuki H.
  • Journal Title: Mol Nutr Food Res. 54(5) Pages: 616-622
  • Peer Reviewed
• [Journal Article] In-vitro characterization of the six clustered variants of NPC1L1 observed in cholesterol low absorbers. (2009)
  • Author(s): Yamanashi Y, Takada T, Suzuki H.
  • Journal Title: Pharmacogenet Genomics. 19(11) Pages: 884-892
  • Peer Reviewed
• [Presentation] Transportsome in biliary cholesterol secretion (2011)
  • Author(s): 高田龍平、山梨義英、鈴木洋史
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] 脂質異常症治療薬の薬効標的分子NPC1L1による脂溶性物質輸送 (2010)
  • Author(s): 高田龍平
  • Organizer: 第54回日本薬学会関東支部大会
  • Place of Presentation: 東京
  • Year and Date: 2010-10-02
• [Presentation] コレステロール胆汁分泌におけるABCG5/G8とNPC2の機能連関 (2010)
  • Author(s): 高田龍平、山梨義英、吉門崇、鈴木洋史
  • Organizer: BMB2010
  • Place of Presentation: 神戸
• [Presentation] NPC1L1, a pharmacological target of dyslipidemia (2010)
  • Author(s): 高田龍平、山梨義英、鈴木洋史
  • Organizer: 第25回日本薬物動態学会年会
  • Place of Presentation: 大宮
• [Presentation] Effect of ticlopidine on MDR3/ABCB4-mediated biliary secretion of phospholipids (2010)
  • Author(s): 吉門崇、高田龍平、伊藤晃成、三田智文、鈴木洋史
  • Organizer: 第25回日本薬物動態学会年会
  • Place of Presentation: 大宮
• [Presentation] MDR3/ABCB4阻害を介したイトラコナゾール誘発性胆汁うっ滞 (2010)
  • Author(s): 吉門崇、高田龍平、山本武人、山道寛子、伊藤晃成、三田智文、鈴木洋史
  • Organizer: 第5回トランスポーター研究会
  • Place of Presentation: 東京
• [Presentation] コレステロールトランスポーターNPC1L1によるビタミンEの消化管吸収 (2010)
  • Author(s): 高田龍平、成島和哉、山梨義英、小西健太郎、鈴木洋史
  • Organizer: 日本ビタミン学会第62回大会
  • Place of Presentation: 盛岡
• [Presentation] NPC1L1を介した腸管におけるコレステロールとビタミンEの吸収機構-薬剤との相互作用- (2010)
  • Author(s): 高田龍平、成島和哉、山梨義英、小西健太郎、鈴木洋史
  • Organizer: 第64回日本栄養・食糧学会大会
  • Place of Presentation: 徳島
• [Presentation] 胆汁中における分泌型Niemann-Pick C2の機能解析 (2010)
  • Author(s): 山梨義英、高田龍平、吉門崇、鈴木洋史
  • Organizer: 日本薬剤学会第25回年会
  • Place of Presentation: 徳島
• [Presentation] Effect of itraconazole on the biliary secretion of phospholipids in vitro and in vivo (2010)
  • Author(s): Hiroshi Suzuki, Takashi Yoshikado, Takehito Yamamoto, Hiroko Yamaji, Kousei Ito, Tappei Takada
  • Organizer: 3^<rd> FEBS Special Meeting ABC2010 Innsbruck
  • Place of Presentation: Austria
• [Presentation] 胆汁脂質輸送体発現系を用いた薬物誘発性胆汁うっ滞のメカニズム解析 (2009)
  • Author(s): 吉門崇、高田龍平、山本武人、山道寛子、伊藤晃成、三田智文、鈴木洋史
  • Organizer: 第31回胆汁酸研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-07
• [Presentation] 薬物関連トランスポーター山口県性差医療研究会 (2009)
  • Author(s): 高田龍平
  • Organizer: 第5回学術講演会
  • Place of Presentation: 山口
  • Year and Date: 2009-06-28
• [Presentation] 薬物関連トランスポーター (2009)
  • Author(s): 高田龍平
  • Organizer: 山口県性差医療研究会第5回学術講演会
  • Place of Presentation: 山口
  • Year and Date: 2009-06-28
• [Presentation] コレステロールトランスポーターNPC1L1の脂肪酸関連蛋白質群による発現制御 (2009)
  • Author(s): 高田龍平、中村英寛、岩柳有起、山梨義英、鈴木洋史
  • Organizer: 第31回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 大阪
• [Presentation] Transcriptional regulation of NPC1L1 by nuclear receptors Asian Federation for Pharmaceutical Sciences 2009 (2009)
  • Author(s): Tappei Takada, Yuki Iwayanagi, Hiroshi Suzuki
  • Organizer: 1^<st> Fukuoka
  • Place of Presentation: Japan
• [Presentation] Vitamin E transport by a cholesterol importer NPC1L1 XXXVI International Congress of Physiological Sciences Kyoto (2009)
  • Author(s): Tappei Takada, Kazuya Narushima, Yoshihide Yamanashi, Hiroshi Suzuki
  • Place of Presentation: Japan
• [Presentation] Functional analysis of NPC1L1, a cholesterol transporter Bioactive Lipid Molecules and Transporters (2009)
  • Author(s): Hiroshi Suzuki, Yoshihide Yamanashi, Tappei Takada
  • Organizer: The Takeda Science Foundation Symposium on PharmaSciences, 5^<th>
  • Place of Presentation: Tokyo, Japan
• [Presentation] Functional analysis of NPC1L1, a cholesterol transporter (2009)
  • Author(s): Hiroshi Suzuki, et al.
  • Organizer: Bioactive Lipid Molecules and Transporters(The Takeda Science Foundation Symposium on PharmaSciences, 5^<th>)
  • Place of Presentation: Tokyo, JAPAN
• [Presentation] Transcriptional regulation of NPC1L1 by nuclear receptors (2009)
  • Author(s): 高田龍平, et al.
  • Organizer: Asian Federation for Pharmaceutical Sciences 2009, 1^<st>
  • Place of Presentation: Fukuoka, JAPAN
• [Presentation] A cholesterol transporter NPC1L1 is transcriptionally and post-transcriptionally regulated by fatty acid-related factors (2009)
  • Author(s): 高田龍平, 他
  • Organizer: 第31回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 大阪
• [Book] 遺伝子医学MOOK19 (2011)
  • Author(s): 山梨義英、高田龍平、鈴木洋史
  • Publisher: 薬効標的としてのABCタンパク質
• [Book] 薬理と治療38 (2010)
  • Author(s): 山梨義英、高田龍平、吉門崇、正田純一、鈴木洋史
  • Publisher: Niemann-Pick C2はABCG5/G8によるコレステロール排出を促進する
• [Book] ビタミン84(8) (2010)
  • Author(s): 高田龍平、鈴木洋史
  • Publisher: コレステロールトランスポーターNPC1L1によるビタミンEの消化管吸収
• [Book] 活用ライブラリー～機能・輸送基質から創薬・臨床応用まで (2009)
  • Author(s): 高田龍平、鈴木洋史
  • Publisher: NTCP,ASBT,MRP3,BCRPの項 薬物トランスポーター
• [Remarks] ホームページ
  • URL: http://square.umin.ac.jp/~todaiyak/index.html