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2010 Fiscal Year Final Research Report

Strategy for the personalized medicine of molecular target drug based on the polymorphism information of plasma protein

Research Project

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Project/Area Number 20390161
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionKumamoto University

Principal Investigator

MARUYAMA Toru  Kumamoto University, 薬学部, 教授 (90423657)

Co-Investigator(Renkei-kenkyūsha) OTAGIRI MASAKI  崇城大学, 薬学部, 教授 (80120145)
WATANABE Hiroshi  熊本大学, 薬学部, 講師 (70398220)
Project Period (FY) 2008 – 2010
Keywords血清タンパク質 / α1-酸性糖タンパク質 / 多型情報 / 体内動態 / タンパク結合
Research Abstract

We determined the crystal structures of complexes of the A variant AGP with some drugs. Comparison of our results with the structure of F1*S variant provides important new insights into the mechanism of the drug-binding selectivity of AGP variants. In addition, we explored the mechanism involved in hepatic cellular uptake of AGP. The findings indicate that hemoglobin beta-subunit contributes to the hepatocellular uptake of AGP, and AGP is incorporated via caveolae/lipid rafts pathway.

  • Research Products

    (36 results)

All 2011 2010 2009 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (18 results) Remarks (1 results)

  • [Journal Article] Quantitative analysis of cysteine-34 on the anitioxidative properties of human serum albumin in hemodialysis patients.2011

    • Author(s)
      Anraku M, Takeuchi K, Watanabe H, Kadowaki D, Kitamura K, Tomita K, Kuniyasu A, Suenaga A, Maruyama T, Otagiri M.
    • Journal Title

      J Pharm Sci. in press

    • Peer Reviewed
  • [Journal Article] Structural insights into differences in drug binding selectivity between two forms of human alphal-acid glycoprotein genetic variants, the A and F1*S forms.2011

    • Author(s)
      Nishi K, Ono T, Nakamura T, Fukunaga N, Izumi M, Watanabe H, Suenaga A, Maruyama T, Yamagata Y, Curry S, Otagiri M.
    • Journal Title

      J Biol Chem. in press

    • Peer Reviewed
  • [Journal Article] Fluid resuscitation with hemoglobin-vesicles prevents Escherichia coli growth via complement activation in a hemorrhagic shock rat model.2011

    • Author(s)
      Taguchi K, Ogaki S, Watanabe H, Kadowaki D, Sakai H, Kobayashi K, Horinouchi H, Maruyama T, Otagiri M.
    • Journal Title

      J Pharmacol Exp Ther. 337

      Pages: 201-208

    • Peer Reviewed
  • [Journal Article] Organic anion transporters play an important role in the uptake of p-cresyl sulfate, a uremic toxin, in the kidney.2011

    • Author(s)
      Miyamoto Y, Watanabe H, Noguchi T, Kotani S, Nakajima M, Kadowaki D, Otagiri M, Maruyama T.
    • Journal Title

      Nephrol Dial Transplant. in press

    • Peer Reviewed
  • [Journal Article] Repeated injection of high doses of hemoglobin encapsulated liposomes (hemoglobin-vesicles) induces accelerated blood clearance in a hemorrhagic shock rat model.2011

    • Author(s)
      Taguchi K, Iwao Y, Watanabe H, Kadowaki D, Sakai H, Kobayashi K, Horinouchi H, Maruyama T, Otagiri M.
    • Journal Title

      Drug Metab Dispos. 39

      Pages: 484-489

    • Peer Reviewed
  • [Journal Article] Vitamin D receptor activator reduces oxidative stress in hemodialysis patients with secondary hyperparathyroidism.2011

    • Author(s)
      Tanaka M, Tokunaga K, Komaba H, Itoh K, Matsushita K, Watanabe H, Kadowaki D, Maruyama T, Otagiri M, Fukagawa M.
    • Journal Title

      Ther Apher Dial. 15

      Pages: 129-131

    • Peer Reviewed
  • [Journal Article] Alteration in the pharmacokinetics of hemoglobin-vesicles in a rat model of chronic liver cirrhosis is associated with Kupffer cell phagocyte activity.2011

    • Author(s)
      Taguchi K, Miyasato M, Watanabe H, Sakai H, Tsuchida E, Horinouchi H, Kobayashi K, Maruyama T, Otagiri M.
    • Journal Title

      J Pharm Sci. 100

      Pages: 775-783

    • Peer Reviewed
  • [Journal Article] Superior plasma retention of a cross-linked human serum albumin dimer in nephrotic rats as a new type of plasma expander.2010

    • Author(s)
      Taguchi K, Urata Y, Anraku M, Watanabe H, Kawai K, Komatsu T, Tsuchida E, Maruyama T, Otagiri M.
    • Journal Title

      Drug Metab Dispos. 38

      Pages: 2124-2129

    • Peer Reviewed
  • [Journal Article] Hepatically-metabolized and -excreted artificial oxygen carrier, hemoglobin-vesicles, can be safely used under conditions of hepatic impairment.2010

    • Author(s)
      Taguchi K, Miyasato M, Ujihira H, Watanabe H, Kadowaki D, Sakai H, Tsuchida E, Horinouchi H, Kobayashi K, Maruyama T, Otagiri M.
    • Journal Title

      Toxicol Appl Pharmacol. 248

      Pages: 234241

    • Peer Reviewed
  • [Journal Article] Albumin fusion of thioredoxin-the production and evaluation of its biological activity for potential therapeutic applications.2010

    • Author(s)
      Ikuta S, Chuang VTG, Ishima Y, Nakajou K, Furukawa M, Watanabe H, Maruyama T, Otagiri M.
    • Journal Title

      J Control Release. 147

      Pages: 17-23

    • Peer Reviewed
  • [Journal Article] Genetically engineered mannosylated-human serum albumin as a versatile carrier for liver-selective therapeutics.2010

    • Author(s)
      Hirata K, Maruyama T, Watanabe H, Maeda H, Nakajou K, Iwao Y, Ishima Y, Katsumi H, Hashida M, Otagiri M.
    • Journal Title

      J Control Release. 145

      Pages: 9-16

    • Peer Reviewed
  • [Journal Article] The uremic solute indoxyl sulfate acts as an antioxidant against superoxide anion radicals under normal-physiological conditions.2010

    • Author(s)
      Miyamoto Y, Iwao Y, Tasaki Y, Sato K, Ishima Y, Watanabe H, Kadowaki D, Maruyama T, Otagiri M.
    • Journal Title

      FEBS Lett. 584

      Pages: 2816-2820

    • Peer Reviewed
  • [Journal Article] Construction of an expression system for human?acid glycoprotein in E.coli : the role of oligosaccharide moieties on structural and functional properties.2010

    • Author(s)
      Nishi K, Fukunaga N, Ono T, Akuta T, Yumita N, Watanabe H, Kadowaki D, Suenaga A, Maruyama T, Otagiri M.
    • Journal Title

      Drug Metab Pharmacokinet. 25

      Pages: 200-207

    • Peer Reviewed
  • [Journal Article] Receptor-mediated uptake of human?acid glycoprotein into liver parenchymal cells in mice.2010

    • Author(s)
      Matsumoto K, Nishi K, Kikuchi M, Watanabe H, Nakajou K, Komori H, Kadowaki D, Suenaga A, Maruyama T, Otagiri M.
    • Journal Title

      Drug Metab Pharmacokinet. 25

      Pages: 101-107

    • Peer Reviewed
  • [Journal Article] Hemoglobin vesicles, polyethylene glycol (PEG) ylated liposomes developed as a red blood cell substitute, do not induce the accelerated blood clearance phenomenon in mice.2009

    • Author(s)
      Taguchi K, Urata Y, Anraku M, Watanabe H, Kadowaki D, Sakai H, Horinouchi H, Kobayashi K, Tsuchida E, Maruyama T, Otagiri M.
    • Journal Title

      Drug Metab Dispos. 37

      Pages: 2197-2203

    • Peer Reviewed
  • [Journal Article] Pharmacokinetic study of enclosed hemoglobin and outer lipid component after the administration of hemoglobin-vesicles as an artificial oxygen carrier.2009

    • Author(s)
      Taguchi K, Urata Y, Anraku M, Maruyama T, Watanabe H, Sakai H, Horinouchi H, Kobayashi K, Tsuchida E, Kai T, Otagiri M.
    • Journal Title

      Drug Metab Dispos. 37

      Pages: 1456-1463

    • Peer Reviewed
  • [Journal Article] A site-directed mutagenesis study of drug-binding selectivity in genetic variants of human alpha (1)-acid glycoprotein.2009

    • Author(s)
      Nishi K, Ueno M, Murakami Y, Fukunaga N, Akuta T, Kadowaki D, Watanabe H, Suenaga A, Maruyama T, Otagiri M.
    • Journal Title

      J Pharm Sci. 98

      Pages: 4316-4326

    • Peer Reviewed
  • [Presentation] 尿毒症物質CMPFの酸化ストレス誘発メカニズム2011

    • Author(s)
      宮本洋平、岩尾康範、米良克美、渡邊博志、門脇大介、異島優、佐藤圭創、小田切優樹、丸山徹
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      ツインメッセ静岡
    • Year and Date
      20110328-20110331
  • [Presentation] 一酸化炭素結合型赤血球による肝CYP保護効果2011

    • Author(s)
      大柿滋、田口和明、渡邊博志、門脇大介、小田切優樹、丸山徹
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡,グランシップ
    • Year and Date
      20110328-20110331
  • [Presentation] 尿毒症物質p-cresyl sulfateの酸化ストレスに及ぼす影響2011

    • Author(s)
      本田大輔、宮本洋平、渡邊博志、門脇大介、丸山徹、小田切優樹
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      ツインメッセ静岡
    • Year and Date
      20110328-20110331
  • [Presentation] α_1-酸性糖タンパク質の薬物結合部位に関する構造生物学的研究2010

    • Author(s)
      和泉実代子、中村照也、小野知実、渡邊博志、山縣ゆり子、小田切優樹、丸山徹
    • Organizer
      第27回日本薬学会九州支部大会
    • Place of Presentation
      長崎大学薬学部
    • Year and Date
      20101211-20101212
  • [Presentation] BLM誘発肺線維症に対するアルブミン-チオレドキシン融合タンパク質の有用性評価2010

    • Author(s)
      田中遼大, 古川真斗, 異島優, 田中健一郎, 水島徹, 渡邊博志, 小田切優樹, 丸山徹
    • Organizer
      第27回日本薬学会九州支部大会
    • Place of Presentation
      長崎大学薬学部
    • Year and Date
      20101211-20101212
  • [Presentation] 一酸化炭素を付加した赤血球は大量出血時における肝チトクロームP450を保護する2010

    • Author(s)
      大柿滋、田口和明、渡邊博志、小田切優樹、丸山徹
    • Organizer
      第27回日本薬学会九州支部大会
    • Place of Presentation
      長崎大学薬学部
    • Year and Date
      20101211-20101212
  • [Presentation] 尿毒症物質CMPFの生体内レドックス特性2010

    • Author(s)
      宮本洋平、岩尾康範、渡邊博志、門脇大介、佐藤圭創、小田切優樹、丸山徹
    • Organizer
      第27回臨床フリーラジカル会議
    • Place of Presentation
      京都,烟川
    • Year and Date
      20101203-20101204
  • [Presentation] 1-acid glycoprotein enhances the expression of hemoglobin scavenge receptor CD163 through the activation of TLR4 signaling2010

    • Author(s)
      Komori H, Watanabe H, Syuto T, Maruyama T, Otagiri M
    • Organizer
      第4回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      東京大学武田先端知ビル
    • Year and Date
      20101127-20101128
  • [Presentation] Involvement of hemoglobin beta-chain on plasma membrane in uptake of human alfal-acid glycoprotein into liver2010

    • Author(s)
      Komori H, Uehara N, Nishi K, Watanabe H, Maruyama T, Otagiri M
    • Organizer
      The Pharmaceutical Sciences World Congress 2010
    • Place of Presentation
      New Orleans
    • Year and Date
      20101114-20101118
  • [Presentation] 出血性ショックモデルラットにおける一酸化炭素結合型赤血球のチトクロームP450の保護効果2010

    • Author(s)
      大柿滋、田口和明、渡邊博志、小田切優樹、丸山徹
    • Organizer
      第17回日本血液代替物学会
    • Place of Presentation
      熊本国際交流会館
    • Year and Date
      20101018-20101019
  • [Presentation] X-RAY CRYSTALLOGRAPHIC STUDY OF HUMAN ALPHA1-ACID GLYCOPROTEIN AND DRUG COMPLEX2010

    • Author(s)
      Miyoko Izumi, Tomomi Ono, Teruya Nakamura, Koji Nishi, Hiroshi Watanabe, Toru Maruyama, Yuriko Yamagata, Masaki Otagiri
    • Organizer
      日本薬物動態学会 第25回年会
    • Place of Presentation
      大宮ソニックシティ
    • Year and Date
      20101007-20101009
  • [Presentation] CHARACTERIZATION OF STRUCTURE AND FUNCTION OF HUMAN SERUM ALBUMIN IN PATIENTS WITH LIVER DISEASE2010

    • Author(s)
      Kohei Nagumo, Tsuyoshi Sugimori, Motohiko Tanaka, Yutaka Sasaki, Yu Ishima, Hiroshi Watanabe, Kazuyuki Kubota, Naoyuki Yamada, Masaki Otagiri, Toru Maruyama.
    • Organizer
      日本薬物動態学会 第25回年会
    • Place of Presentation
      大宮ソニックシティ
    • Year and Date
      20101007-20101009
  • [Presentation] IMPROVED THERAPEUTIC EFFECT OF THIOREDOXIN BY FUSION TO HUMAN SERUM ALBUMIN AGAINST BLEOMYCIN-INDUCED PULMONARY FIBROSIS2010

    • Author(s)
      田中遼大, 古川真斗, 異島優, 田中健一郎, 水島徹, 渡邊博志, 小田切優樹, 丸山徹
    • Organizer
      日本薬物動態学会 第25回年会
    • Place of Presentation
      大宮ソニックシティ
    • Year and Date
      20101007-20101009
  • [Presentation] alfal-酸性糖タンパク質によるCD163の発現誘導2010

    • Author(s)
      Komori H, Watanabe H, Syuto T, Maruyama T, Otagiri M
    • Organizer
      第35回西日本薬剤学研究会
    • Place of Presentation
      大分,九重共同研修所
    • Year and Date
      20100917-20100918
  • [Presentation] Hepatic uptake of alfal-acid glycoprotein through hemoglobin beta-chain-mediated endocytic pathway2010

    • Author(s)
      Komori H, Uehara N, Nishi K, Watanabe H, Maruyama T, Otagiri M
    • Organizer
      9^<th> International ISSX meeting
    • Place of Presentation
      Istanbul
    • Year and Date
      20100904-20100908
  • [Presentation] ヒトalfal-酸性糖タンパク質/薬物複合体のX線結晶構造解析2010

    • Author(s)
      和泉実代子、小野知実、中村照也、西弘二、渡邊博志、丸山徹、山縣ゆり子、小田切優樹
    • Organizer
      第25回日本薬剤学会
    • Place of Presentation
      あわぎんホール 徳島県郷土文化会館
    • Year and Date
      20100511-20100514
  • [Presentation] 尿毒症物質CMPFの酸化ストレス誘発機序解明2010

    • Author(s)
      宮本洋平、岩尾康範、渡邊博志、門脇大介、佐藤圭創、小田切優樹、丸山徹
    • Organizer
      第25回日本薬剤学会
    • Place of Presentation
      あわぎんホール 徳島県郷土文化会館
    • Year and Date
      20100511-20100514
  • [Presentation] 一酸化炭素結合型赤血球による肝チトクロームP450の保護効果2010

    • Author(s)
      大柿滋、田口和明、渡邊博志、小田切優樹、丸山徹
    • Organizer
      第25回日本薬剤学会
    • Place of Presentation
      あわぎんホール徳島県郷土文化会館
    • Year and Date
      20100511-20100514
  • [Remarks] ホームページ

    • URL

      http://www.pharm.kumamoto-u.ac.jp/Labs/Yakuzai/

URL: 

Published: 2012-01-26   Modified: 2016-04-21  

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