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Bas i s stud i es on the appropr i ate usage of c l i n i ca I med i c i ne : i so form specificity of the functional interaction between drug metabolizing enzymes and the individual differences

Research Project

Project/Area Number 21590164
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionKyushu University

Principal Investigator

ISHII Yuji  九州大学, 大学院・薬学研究院, 准教授 (90253468)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords薬物代謝 / UDP-グルクロン酸転移酵素 / グルクロン酸抱合 / シトクロムP450 / タンパク質間相互作用
Research Abstract

Interaction between cytochP4so P450 CYPsA4YP3A4) and UDPglucuronosyltransferase(UGT) isoforms in COS cells was evidenced by an analysis using Fluorescence Resonance Energy Transfer. FurtCYPsA4YP3A4 affects the glucuronidation activity catalyzeUGTlAiGT1A7 and 1A3. However, the modifying effecCYPsA4YP3A4 differed between UGT isoforms. In addition, differences were also seen in the effecCYPsA4YP3AUGTlAiGT1A7 variants* 1,* 2 and* 3. Therefore, these results support the hypothesis that the interaction betCYPsA4YP3A4 and UGT is one of the determinants involved in the interindividual difference in glucuronidation. On the other hand, it is also suggested that some of the endogenous and foodderived compounds modulate UGT activity.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (45 results)

All 2012 2011 2010 2009 Other

All Journal Article (8 results) (of which Peer Reviewed: 5 results) Presentation (36 results) Remarks (1 results)

  • [Journal Article] Modulation of UDPglucuronosyltransferase by ProteinProtein Association2010

    • Author(s)
      Ishii Y, Takeda S, Yamada H.
    • Journal Title

      Drug Metab. Rev

      Volume: 42 Pages: 140-153

    • Related Report
      2011 Final Research Report
  • [Journal Article] Activation of Morphine Glucuronidation by Fatty Acyl-CoAs and Its Plasticity : A Comparative Study in Humans and Rodents Including Chimeric Mice Carrying Human Liver2010

    • Author(s)
      Nurrochmad A, Ishii Y, Nakanoh H, Inoue T, Horie T, Sugihara K, Ohta S, Taketomi A, Maehara Y, Yamada H.
    • Journal Title

      Drug Metab. Pharmacokinet.

      Volume: 25 Pages: 262-273

    • NAID

      10027582853

    • Related Report
      2011 Final Research Report
  • [Journal Article] Modulationof UDPglucuronosyltransferase Activity by Endogenous Compounds2010

    • Author(s)
      Ishii Y, Nurrochmad A, Yamada H.
    • Journal Title

      Drug Metab. Pharmacokinet

      Volume: 25 Pages: 134-148

    • Related Report
      2011 Final Research Report
  • [Journal Article] Modulation of UDP-glucuronosyltransferase activity by endogenous compounds2010

    • Author(s)
      Ishii Y, Nurrochmad A, Yamada H
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 25 Pages: 134-148

    • NAID

      10027582269

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of morphine glucuronidation by fatty acyl-CoAs and its plasticity : a comparative study in humans and rodents including chimeric micecarrying human liver.2010

    • Author(s)
      Nurrochmad A, Ishii Y, 他xx名
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 25 Pages: 62-73

    • NAID

      10027582853

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of UDP-glucuronosyltransferase by protein-protein association2010

    • Author(s)
      Ishii Y, 他2名
    • Journal Title

      Drug Metabolism Review 42

      Pages: 140-153

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of UDP-glucuronosyltransferase activity by endogenous compounds2010

    • Author(s)
      Ishii Y, 他2名
    • Journal Title

      Drug Metabolism and Pharmacokinetics (In press)

    • NAID

      10027582269

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of Morphine Glucuronidation by Fatty Acyl-CoAs and Its Plasticity : A Comparative Study in Humans and Rodents Including Chimeric Mice Carrying Human Liver2010

    • Author(s)
      Nurrochmad A, Ishii Y, 他8名
    • Journal Title

      Drug Metabolism and Pharmacokinetics (In press)

    • NAID

      10027582853

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] モノテルペノイドアルコール類によるモルヒネUDP一グルクロン酸転移酵素の阻害2012

    • Author(s)
      飯田直子、石井祐次、宮内優、マッケンジー・ピーター、山田英之
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
    • Related Report
      2011 Final Research Report
  • [Presentation] モノテルペノイドアルコール類によるモルヒネUDP-グルクロン酸転移酵素の阻害2012

    • Author(s)
      飯田直子、石井祐次、宮内優、マッケンジー・ピーター、山田英之
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] 生体内化合物によるUDP一グルクロン酸転移酵素活性の制御2011

    • Author(s)
      安貴愛、石井祐次、西村嘉雄、山田英之
    • Organizer
      第28回日本薬学会九州支部大会
    • Place of Presentation
      福岡
    • Year and Date
      2011-12-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 生体内化合物によるUDP-グルクロン酸転移酵素活性の制御2011

    • Author(s)
      安貴愛、石井祐次、西村嘉雄、山田英之
    • Organizer
      第28回日本薬学会九州支部大会
    • Place of Presentation
      福岡
    • Year and Date
      2011-12-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 異種薬物代謝酵素間相互作用による代謝制御:UDP-glucuronosyltransferase1A9および2B7によるcytochrome P450 3A4活性の調節2011

    • Author(s)
      宮内優、石井祐次、追崎俊也、永田清、山添康、Peter I.Mackenzie、山田英之
    • Organizer
      第28回日本薬学会九州支部大会
    • Place of Presentation
      福岡
    • Year and Date
      2011-12-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Ariel Nurrochmad, Yoshio Nishimura, Kie An, Naoko Iida, Hideyuki Yamada, Alteration in UDPGlucuronosyltransferase Function by Endogenous Substances with Low Molecular Weight2011

    • Author(s)
      Yuji Ishii
    • Organizer
      26th Annual Meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      Hiroshima
    • Year and Date
      2011-11-18
    • Related Report
      2011 Final Research Report
  • [Presentation] Alteration in UDP-Glucuronosyltransferase Function by Endogenous Substances with Low Molecular Weight2011

    • Author(s)
      Yuji Ishii, Arief Nurrochmad, Yoshio Nishimura, Kie An, Naoko Iida, Hideyuki Yamada
    • Organizer
      26th Annual meeting of Japanese Society for the study of Xenobiotics
    • Place of Presentation
      広島(招待講演)
    • Year and Date
      2011-11-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] Toshiya Oizaki, Yasushi Yamazoe, Kiyoshi Nagata, Peter I. Mackenzie, HideyukiYamada, Hetero-Oligomerization of UDP-Glucuronosyltransferases and CytochroP4so450 3A4 : Analysis by Fluorescence Resonance Energy Transfer(FRET) and Modulation of CYPsA43A4 acti2011

    • Author(s)
      Yuu Miyauchi, Yuji Ishii
    • Organizer
      26th Annual Meeting oSociety for the Study of Xenobiotics
    • Place of Presentation
      Hiroshima
    • Year and Date
      2011-11-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Yuu Miyauchi, Toshiya Oizaki, Shin-ichi Ikushiro, Yasushi Yamazoe, Kiyoshi Nagata, Peter I. Mackenzie and Hideyuki Yamada, Effect of Cytochrome P4so 3A4 on the Functionof UDP-Glucuronosyltransferase 1A3 : Alteration of Affinity toward UDP-Glucuronic Acid2011

    • Author(s)
      Kousuke Kinoshita, Yuji Ishii
    • Organizer
      26th Annual Meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      Hiroshima
    • Year and Date
      2011-11-16
    • Related Report
      2011 Final Research Report
  • [Presentation] and Hideyuki Yamada, Inhibitory Effect of AdenineRelated Compounds on UDPGlucuronosyltransferase Activity in Human Liver Microsomes2011

    • Author(s)
      Kie An, Yoshio Nishimura, Yuji Ishii
    • Organizer
      26th Annual Meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      Hiroshima
    • Year and Date
      2011-11-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Hetero-Oligomerization of UDP-Glucuronosyltransferases and Cytochrome P450 3A4 : Analysis by Fluorescence Resonance Energy Transfer (FRET) and Modulation of CYP3A4 activity by UGTs2011

    • Author(s)
      Yuu Miyauchi, Yuji Ishii, Toshiya Oizaki, Yasushi Yamazoe, Kiyoshi Nagata, Peter I.Mackenzie, Hideyuki Yamada
    • Organizer
      26th Annual meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      広島
    • Year and Date
      2011-11-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Effect of Cytochrome P450 3A4 on the Function of UDP-Glucuronosyltransferase 1A3 : Alteration of Affinity toward UDP-Glucuronic acid2011

    • Author(s)
      Kousuke Kinoshita, Yuji Ishii, Yuu Miyauchi, Toshiya Oizaki, Shin-ichi Ikushiro, Yasushi Yamazoe, Kiyoshi Nagata, Peter I.Mackenzie, Hideyuki Yamada
    • Organizer
      26th Annual meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      広島
    • Year and Date
      2011-11-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Inhibitory Effect of Adenine-Related Compounds on UDP-Glucuronosyltransferase Activity in Human Liver Microsomes2011

    • Author(s)
      Kie An, Yoshio Nishimura, Yuji Ishii, Hideyuki Yamada
    • Organizer
      26th Annual meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      広島
    • Year and Date
      2011-11-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] 麻薬の代謝とその変動要因2011

    • Author(s)
      石井祐次,山田英之
    • Organizer
      日本法中毒学会第30年会
    • Place of Presentation
      長崎
    • Year and Date
      2011-06-10
    • Related Report
      2011 Final Research Report
  • [Presentation] Yuu Miyauchi, Hideyuki Yamada, Protein猶rotein Interaction of Cytochrome P450 and UDP宥lucuronosyltransferase2011

    • Author(s)
      Yuji Ishii
    • Organizer
      Alteration of P450 activity by UGT. 4th Asian猶acific ISSX meeting
    • Place of Presentation
      Tainan, Taiwan
    • Year and Date
      2011-04-24
    • Related Report
      2011 Final Research Report
  • [Presentation] Protein-Protein Interaction of Cytochrome P450 and UDP-Glucuronosyltransferase : Alteration of P450 activity by UGT2011

    • Author(s)
      Yuji Ishii, Yuu Miyauchi, Hideyuki Yamada
    • Organizer
      4th Asian-Pacific ISSX meeting 2011
    • Place of Presentation
      Tainan, Taiwan(招待講演)
    • Year and Date
      2011-04-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] アデニン関連化合物によるUDP一グルクロン酸転移酵素活性の阻害作用:界面活性剤およびpore-forming peptideアラメチシン処理での比較2011

    • Author(s)
      安貴愛、西村嘉雄、石井祐次、山田英之
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Related Report
      2011 Final Research Report
  • [Presentation] 麻薬の代謝とその変動要因2011

    • Author(s)
      石井祐次, 山田英之
    • Organizer
      日本法中毒学会第30年会
    • Place of Presentation
      長崎(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] UDP一グルクロン酸転移酵素1A7の遺伝的多型と触媒活性:シトクロムP4450 3A4共発現による影響2010

    • Author(s)
      古葉弘樹、石井祐次、追崎俊也、竹田修三、生城真一、永田清、山添康、Peter I. Mackenzie、山田英之
    • Organizer
      第27回日本薬学会九州支部大会
    • Place of Presentation
      長崎
    • Year and Date
      2010-12-11
    • Related Report
      2011 Final Research Report
  • [Presentation] UDP-グルクロン酸転移酵素1A7の遺伝的多型と触媒活性:シトクロムP450 3A4 共発現による影響2010

    • Author(s)
      古葉弘樹、石井祐次、追崎俊也、竹田修三、生城真一、永田清、山添康、Peter I.Mackenzie、山田英之
    • Organizer
      第27回日本薬学会九州支部大会
    • Place of Presentation
      長崎市
    • Year and Date
      2010-12-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] Protein-protein association of cytochrome P450 and UDP-glucuronosyltransferase : Its relevance to enzyme function2010

    • Author(s)
      Yuji Ishii
    • Organizer
      25th Annual meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      大宮市(招待講演)
    • Year and Date
      2010-10-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Modulation of cytochrome P450 activity by UDP-glucuronosyltransferase : major human UGT isoforms, UGT2B7, 1A1, 1A6 and 1A9 enhance CYP3A4-catalyzed oxidation.2010

    • Author(s)
      Yuu Miyauchi, Yuji Ishii, Hideyuki Yamada, Japanese Society for the Study of Xenobiotics
    • Organizer
      25th Annual meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      大宮市
    • Year and Date
      2010-10-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Comparison of catalytic properties between human UDP-glucuronosyltransferase 1A7^*3, an allelic variant and its wild-type 1A7^*12010

    • Author(s)
      Hiroki Koba, Yuji Ishii, Toshiya Oizaki, Arief Nurrochmad, Shin-ichi Ikushiro, Yasushi Yamazoe, Kiyoshi Nagata, Peter I.Mackenzie, Hideyuki Yamada
    • Organizer
      25th Amnual meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      大宮市
    • Year and Date
      2010-10-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Protein-rotein Association of Cytochrome P4so and UDP宥lucuronosyltransferase : Its Relevance to Enzyme Function2010

    • Author(s)
      Yuji Ishii
    • Organizer
      25th Annual meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      Ohmiya, Saitama
    • Year and Date
      2010-10-08
    • Related Report
      2011 Final Research Report
  • [Presentation] Toshiya Oizaki, Arielf Nurrochmad, Shin-ichi Ikushiro, Yasushi Yamazoe, Kiyoshi Nagata, Peter I. Mackenzie and Hideyuki Yamada, Comparison ofCatalytic Properties BetweenHuman UDPGlucuronosyltransferase 1A7* 3, an Allelic Variant, and its Wild-type 1A7* 12010

    • Author(s)
      Hiroki Koba, Yuji Ishii
    • Organizer
      25th Annual Meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      Ohmiya, Saitama
    • Year and Date
      2010-10-07
    • Related Report
      2011 Final Research Report
  • [Presentation] UGT-CYP Protein Interactions : Role of Conjugating Enzymes in Modulating Oxidative Enzyme Activity. American Society for Pharmacology and Experimental2010

    • Author(s)
      Yuji Ishii
    • Organizer
      Therapeutics 2010 Annual Meeting at Experimental Biology
    • Place of Presentation
      Anaheim, California, U. S. A.
    • Year and Date
      2010-04-28
    • Related Report
      2011 Final Research Report
  • [Presentation] UGT-CYP protein interactions : role of conjugating enzymes in modulating oxidative enzyme activity2010

    • Author(s)
      Yuji Ishii
    • Organizer
      ASPET 2010 Annual Meeting at EB2010
    • Place of Presentation
      米国カリフォルニア州アナハイム(招待講演)
    • Year and Date
      2010-04-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] UDP宥lucuronosyltransferase1A7* 3の触媒活性2010

    • Author(s)
      古葉弘樹,互遜,追崎俊也, Arielf Nurrochmad, I. Mackenzie,生城真一, Peter山田英之,ヒト
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Related Report
      2011 Final Research Report
  • [Presentation] ACTIVATION OF MORPHINE GLUCURONIDATION BY FATTY ACYL-COA : ENHANCED INCORPORATION OF UDP-GLUCURONIC ACID I NTO THE ENDOPLASMIC RETICULUM2009

    • Author(s)
      Ishii Y, Nurrochmad, A, 他3名
    • Organizer
      24th Annual meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      京都市
    • Year and Date
      2009-11-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] Arielf Nurrochmad, Akinobu Taketomi, Yoshihiko Maehara and Hideyuki Yamada, Activation of Morphine Glucuronidation by Fatty Acyl-CoA : Enhanced Incorporation of UDPGlucuronic Acid into the Endoplasmic Reticulum2009

    • Author(s)
      Yuji Ishii
    • Organizer
      24th Annual Meeting of Japanese Society for the Study of Xenobiotics
    • Place of Presentation
      Kyoto
    • Year and Date
      2009-11-26
    • Related Report
      2011 Final Research Report
  • [Presentation] 脂肪酸アシルCoAによるモルヒネグルクロン酸抱合の活性化2009

    • Author(s)
      石井祐次
    • Organizer
      UGT研究会2009
    • Place of Presentation
      静岡
    • Year and Date
      2009-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] Alteration of UDP宥lucuronosyltransferase Activity by CytochromeP4so0 3A42009

    • Author(s)
      Yuji Ishii
    • Organizer
      Environmental Stimuli and Biological Responses
    • Place of Presentation
      Fukuoka
    • Year and Date
      2009-06-26
    • Related Report
      2011 Final Research Report
  • [Presentation] Arielf Nurrochmad,山田英之,脂肪酸および脂肪酸CoAがモルヒネグルクロン酸抱合活性に及ぼす影響2009

    • Author(s)
      石井祐次
    • Organizer
      日本法中毒学会第28年会
    • Place of Presentation
      金沢
    • Year and Date
      2009-06-12
    • Related Report
      2011 Final Research Report
  • [Presentation] 脂肪酸および脂肪酸CoAがモルヒネグルクロン酸抱合活性に及ぼす影響2009

    • Author(s)
      石井祐次, Arief Nurrochmad, 山田英之
    • Organizer
      日本法中毒学会第28年会
    • Place of Presentation
      金沢市
    • Year and Date
      2009-06-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cytochrome P450 3A4 enhances UDP-glucuronosyltransferase 1A9-catalyzed glucuronidation of SN-38, an active metabolite of irinotecan2009

    • Author(s)
      Ishii Y, Iwamoto Y., 他10名
    • Organizer
      The 3rd Asian-Pacific Regional ISSX Meeting
    • Place of Presentation
      タイ王国バンコク市
    • Year and Date
      2009-05-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] Yuki Iwamoto, Toshiya Oizaki, Arielf Nurrochmad, Yoshio Nishimura, Shin' ichi Ikushiro, Futoshi Taura, Satoshi Morimoto, Kiyoshi Nagata, Yasushi Yamazoe, Peter I. Mackenzie, Hideyuki Yamada. CytochromeP4so0 3A4 Enhances2009

    • Author(s)
      Yuji Ishii
    • Organizer
      UDP-lucuronosyltransferase 1A9-Catalyzed Glucuronidation of SN-s88, an Active Metabolite of Irinotecan. Abstract of papers,# 150, The 3rd Asian-Pacific Regional ISSX Meeting
    • Place of Presentation
      Bangkok, Thailand, Drug Metab
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.kyushu-u.ac.jp

    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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