Regulation of intestinal expression of proton-coupled folate transporter and its relevance to folate malabsorption in alcohol consumption.

• Project/Area Number: 20590163
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kinjo Gakuin University
• Principal Investigator: HAYASHI Yayoi Kinjo Gakuin University, 薬学部, 教授 (00117847)
• Co-Investigator(Kenkyū-buntansha): INOUE Katsuhisa 名古屋市立大学, 大学院・薬学研究科, 准教授 (50315892) ; HATAKEYAMA Mai 金城学院大学, 薬学部, 助教 (20454340)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 葉酸 / メトトレキセート / トランスポーター / PCFT / 転写活性化因子 / 転写抑制因子 / エタノール / フラボノイド / hPCFT / 消化管吸収 / 転写因子 / 発現制御 / フラボノイド類

Research Abstract

Chronic alcohol consumption have been suspected to cause malabsorption of folates by decreaseing the function of folate transporter(s) in small intestine. Therefore, we examined the effects of ethanol and several flavonoids on the function of proton-coupled folate transporter (PCFT). Pretreatment of Caco-2 cells with myricetin, which is included in wines, caused inhibition of the uptake of folate mediated by PCFT, but not with ethanol. We also examined human PCFT promoter activity with several transcriptional factors to elucidate transcriptional regulation mechanism involved in intestinal PCFT expression. It was found that KLF4 is a major nuclear factor involved in the activation of PCFT promoter, and the KLF4-induced activation is likely to be synergistically regulated by HNF4α, CDX2 and C/EBPα.

Research Products

• [Journal Article] Molecular and functional characteristics of proton-coupled folate transporter. (2009)
  • Author(s): Hiroaki Yuasa, Katsuhisa Inoue, Yayoi Hayashi
  • Journal Title: J.Pharm.Sci. 98 Pages: 1608-1616
  • Peer Reviewed
• [Journal Article] プロトン/葉酸共輸送担体の発現制御に関わる転写因子の検索 (2009)
  • Author(s): 湯浅博昭,高橋絢子,太田欣哉,井上勝央,畠山舞,林弥生
  • Journal Title: 薬剤学 69
• [Journal Article] Functional characterization of PCFT/HCP1 as the molecular entity of the carrier-mediated intestinal folate transport system in the rat model. (2008)
  • Author(s): Katsuhisa Inoue, Yasuhiro Nakai, Sayaka Ueda, Shunsuke Kamigaso, Kinya Ohta, Mai Hatakeyama, Yayoi Hayashi, Masaki Otagiri, Hiroaki Yuasa
  • Journal Title: Am.J.Physiol. 294
  • Peer Reviewed
• [Presentation] PCFTを介する葉酸類の輸送に対するフラボノイド類の影響 (2011)
  • Author(s): 西嶋千尋,畠山舞,林弥生,太田欣哉,井上勝央,湯浅博昭
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-29
• [Presentation] Effects of flavonoids on proton-coupled folate transporter. (2010)
  • Author(s): Hiroaki Yuasa, Chihiro Nishijima, Mai Hatakeyama, Yayoi Hayashi, Kinya Ohta, Katsuhisa Inoue
  • Organizer: Pharmaceutical Sciences World Congress 2010 (4th)
  • Place of Presentation: New Orleans, Louisiana, U.S.A.
  • Year and Date: 2010-11-16
• [Presentation] PCFTの転写調節におけるKLF4とHNF-4αの関与 (2010)
  • Author(s): 畠山舞, 太田欣哉, 井上勝央, 林弥生, 湯浅博昭
  • Organizer: 第25回日本薬物動態学会年会
  • Place of Presentation: 埼玉
  • Year and Date: 2010-10-09
• [Presentation] PCFTの転写調節におけるKLF4とHNF-4αの関与 (2010)
  • Author(s): 畠山舞,太田欣哉,井上勝央,林弥生,湯浅博昭
  • Organizer: 第25回日本薬物動態学会年会
  • Place of Presentation: さいたま
  • Year and Date: 2010-10-08
• [Presentation] Caco-2細胞における葉酸類の取り込みに対するエタノール及びフラボノイド類の影響 (2010)
  • Author(s): 西嶋千尋,畠山舞,林弥生,太田欣哉,井上勝央,湯浅博昭
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] Effects of flavonoids on proton-coupled folate transporter. (2010)
  • Author(s): Yuasa, H., Nishijima, C., Hatakeyama, M., Hayashi, Y., Ohta, K., Inoue, K.
  • Organizer: Pharmaceutical Sciences World Congress 2010 (4th)
  • Place of Presentation: New Orleans, Louisiana, U.S.A
• [Presentation] プロトン/葉酸共輸送担体の発現制御に関わる転写因子の検索 (2009)
  • Author(s): 湯浅博昭,高橋絢子,太田欣哉,井上勝央,畠山舞,林弥生
  • Organizer: 日本薬剤学会第24年会
  • Place of Presentation: 静岡
  • Year and Date: 2009-05-23
• [Presentation] 小腸に存在する転写因子による葉酸/H^+共輸送担体(PCFT)の発現制御 (2008)
  • Author(s): 高橋絢子,畠山舞,林弥生,太田欣哉,井上勝央,湯浅博昭
  • Organizer: 第23回日本薬物動態学会年会
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-30
• [Presentation] Regulation of the expression of proton-coupled folate transporter (PCFT) by transcription factors in the small intestine (2008)
  • Author(s): Ayako Takahashi, et al.
  • Organizer: 第23回日本薬物動態学会年会
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-30
• [Presentation] Functional characteristics of human proton-coupled folate transporter/heme carrier protein 1 (hPCFT/HCP1) heterologously expressed in mammalian cells. (2008)
  • Author(s): Misato Sugiura, Katsuhisa Inoue, Yasuhiro Nakai, Naoki Abe, Kinya Ohta, Mai Hatakeyama, Yayoi Hayashi, Hiroaki Yuasa
  • Organizer: Pan-Pacific International Partnership Conference on Pharmaceutical and Life Sciences (The 4th US-Japan Joint Conference)
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2008-02-22
• [Remarks] ホームページ等
  • URL: http://www.phar.nagoya-cu.ac.jp/hp/yzg/index.html