Study on the serum protein-mediated drug transport in biological membrane interface

• Project/Area Number: 21590054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Sojo University
• Principal Investigator: YAMASAKI Keishi 崇城大学, 薬学部, 准教授 (30435143)
• Co-Investigator(Kenkyū-buntansha): OTAGIRI Masaki 崇城大学, 薬学部, 教授 (80120145)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 膜インターフェイス / 血清アルブミン / 薬物輸送 / α_1-酸性糖タンパク質

Research Abstract

This study was undertaken to evaluate serum protein-mediated drug transport. Through the investigation of the interaction between human serum albumin(HSA) and tissue cells, we explored the specific mechanism that HSA is incorporated and change its conformation so that the bound drug is released. In addition, our data suggests that HSA is incorporated into liver parenchymal cell via clathrin-medicated endocytosis.

Research Products

• [Journal Article] Characterization of the hepatic cellular uptake of α1-acid glycoprotein(AGP), part 1 : a peptide moiety of human AGP is recognized by the hemoglobinβ-chain on mouse liver parenchymal cells (2012)
  • Author(s): Nishi K, Komori H, Kikuchi M, Uehara N, Fukunaga N, Matsumoto K, Watanabe H, Nakajou K, Misumi S, Suenaga A, Maruyama T, Otagiri M
  • Journal Title: J. Pharm. Sci Volume: 101 Pages: 1599-1606
  • Peer Reviewed
• [Journal Article] Human serum albumin-thioredoxin fusion protein with long blood retention property is effective in suppressing lung injury (2011)
  • Author(s): Furukawa M, Tanaka R, Chuang VT, Ishima Y, Taguchi K, Watanabe H, Maruyama T, Otagiri M
  • Journal Title: J. Control. Release Volume: 154 Pages: 189-195
  • Peer Reviewed
• [Journal Article] Update on the pharmacokinetics and redox properties of protein-bound uremic toxins (2011)
  • Author(s): Watanabe H, Miyamoto Y, Otagiri M, Maruyama T.
  • Journal Title: J Pharm Sci Pages: 3682-3695
  • Peer Reviewed
• [Journal Article] Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and IIA in allosteric ligand binding (2011)
  • Author(s): Kaneko K, Chuang VT, Minomo A, Yamasaki K, Bhagavan NV, Maruyama T, Otagiri M
  • Journal Title: IUBMB Life Volume: 63 Pages: 277-285
  • Peer Reviewed
• [Journal Article] Characterization of the hepatic cellular uptake of α_1-acid glycoprotein (AGP), Part 2 : Involvement of the hemoglobin β-chain on plasma membranes in the uptake of human AGP by liver parenchymal cells (2011)
  • Author(s): 小森久和
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 101 Issue: 4 Pages: 1607-1615
  • DOI: 10.1002/jps.22804
  • Peer Reviewed
• [Journal Article] Human serum albumin-thioredoxin fusion protein with long blood retention property is effective in suppressing lung injury (2011)
  • Author(s): Furukawa M
  • Journal Title: J.Control.Release Volume: 154 Pages: 185-195
  • Peer Reviewed
• [Journal Article] Update on the pharmacokinetics and redox properties of protein-bound uremic toxins (2011)
  • Author(s): Watanabe H
  • Journal Title: J.Pharm.Sci. Volume: 100 Issue: 9 Pages: 3682-3695
  • DOI: 10.1002/jps.22592
  • Peer Reviewed
• [Journal Article] Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and IIA in allosteric ligand binding. (2011)
  • Author(s): Kaneko K
  • Journal Title: IUBMB Life Volume: 63 Pages: 277-285
  • Peer Reviewed
• [Journal Article] Receptor-mediated uptake of humanα1-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 Volume: 25 Pages: 101-107
  • 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 Volume: 145 Pages: 9-16
  • Peer Reviewed
• [Journal Article] The roles of oligosaccharide moieties in 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 Volume: 25 Pages: 200-207
  • Peer Reviewed
• [Journal Article] Genetically engineered mannosylated-human serum albumin as a versatile carrier for liver-selective therapeutics. (2010)
  • Author(s): Hirata K
  • Journal Title: J.Control.Release Volume: 145 Pages: 9-16
  • Peer Reviewed
• [Journal Article] Construction of an expression system for human alpha(1)-acid glycoprotein in E.coli : The roles of oligosaccharide moieties in structural and functional properties. (2010)
  • Author(s): Nishi K
  • Journal Title: Drug Metab.Pharmacokinet. Volume: 25 Pages: 200-207
  • Peer Reviewed
• [Journal Article] Receptor-mediated uptake of human α_1-acid glycoprotein into liver parenchymal cells in mice. (2010)
  • Author(s): Matsumoto K
  • Journal Title: Drug Metab.Pharmacokinet. 25 Pages: 101-107
  • Peer Reviewed
• [Journal Article] Competitive Displacement of Serum Protein Binding of Radiopharmaceuticals with Amino Acid Infusion Investigated with N-Isopropyl-p-123I-Iodoamphetamine (2009)
  • Author(s): Kuga N, Shikano N, Takamura N, Nishii R, Yamasaki K, Kobayashi M, Nagamachi S, Tamura S, Kawai K
  • Journal Title: J. Nucl. Med Volume: 50 Pages: 1378-1383
  • Peer Reviewed
• [Journal Article] A site-directed mutagenesis study of drug-binding selectivity in genetic variants of humanα1-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 Volume: 98 Pages: 4316-4326
  • Peer Reviewed
• [Journal Article] Competitive Displacement of Serum Protein Binding of Radiopharmaceuticals with Amino Acid Infusion Investigated with N-Isopropyl-p-^<123>I-Iodoamphetamine. (2009)
  • Author(s): Kuga N
  • Journal Title: J.Nucl.Med. 50 Pages: 1378-1383
  • Peer Reviewed
• [Journal Article] A site-directed mutagenesis study of drug-binding selectivity in genetic variants of human α_1-acid glycoprotein. (2009)
  • Author(s): Nishi K
  • Journal Title: J.Pharm.Sci. 98 Pages: 4316-4326
  • Peer Reviewed
• [Presentation] α1-酸性糖タンパク質のヘモグロビンβ鎖介在性肝取り込み機構 (2012)
  • Author(s): 末永綾香
  • Organizer: 日本薬学会137年会
  • Place of Presentation: 北海道大学
  • Year and Date: 2012-03-31
• [Presentation] α_1-酸性糖タンパク質のヘモグロビンβ鎖介在性肝取り込み機構 (2012)
  • Author(s): 末永綾香
  • Organizer: 日本薬学会137年会
  • Place of Presentation: 北海道大学
  • Year and Date: 2012-03-31
• [Presentation] 急性肝障害に対するマンノース付加アルブミンを担体としたクッパー細胞選択的チオール送達の有用性評価 (2012)
  • Author(s): 丸山徹
  • Organizer: 日本薬学会137年会
  • Place of Presentation: 北海道大学
  • Year and Date: 2012-03-30
• [Presentation] 肝疾患患者におけるヒト血清アルブミンの構造及び機能特性 (2010)
  • Author(s): 南雲恒平
  • 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: 2010-11-16
• [Presentation] チオレドキシンとアルブミン融合体の作製と生物活性の評価 (2010)
  • Author(s): 小田切優樹
  • Organizer: 第26回日本DDS学会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2010-06-17
• [Presentation] ヒトα1-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
  • Organizer: 日本薬剤学会第25回年会
  • Place of Presentation: 徳島郷土文化会館
  • Year and Date: 2010-05-14
• [Presentation] ヒトα_1-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
  • Organizer: 日本薬剤学会第25回年会
  • Place of Presentation: 徳島郷土文化会館
  • Year and Date: 2010-05-14
• [Presentation] α1-酸性糖タンパク質のヘモグロビンβ鎖を介した肝実質細胞取り込み機構の解明 (2010)
  • Author(s): 小森久和
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2010-03-27
• [Presentation] α_1-酸性糖タンパク質のヘモグロビンβ鎖を介した肝実質細胞取り込み機構の解明 (2010)
  • Author(s): 小森久和
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2010-03-27
• [Presentation] Involvement of hemoglobinβ-chain mediated endocytic pathway in hepatic uptake of α1-acid glycoprotein (2009)
  • Author(s): Komori H
  • Organizer: 第31回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 大阪大学
  • Year and Date: 2009-11-29
• [Presentation] Involvement of hemoglobin β-chain mediated endocytic pathway in hepatic uptake of α_1-acid glycoprotein. (2009)
  • Author(s): Komori H
  • Organizer: 第31回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 大阪大学
  • Year and Date: 2009-11-29
• [Presentation] α1-酸性糖タンパク質のヘモグロビンβ鎖を介した肝細胞取り込み機構 (2009)
  • Author(s): 小森久和
  • Organizer: 第3回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 九州大学
  • Year and Date: 2009-11-14
• [Presentation] α_1-酸性糖タンパク質のヘモグロビンβ鎖を介した肝細胞取り込み機構 (2009)
  • Author(s): 小森久和
  • Organizer: 第3回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 九州大学
  • Year and Date: 2009-11-14
• [Presentation] In vitro evaluation for antioxidant activities of dietary supplements (2009)
  • Author(s): Yamasaki K
  • Organizer: Asian Federation for Pharmaceutical Sciences
  • Place of Presentation: 九州大学
  • Year and Date: 2009-10-17
• [Presentation] Genetically engineered mannnosylated-human serum albumin as a versatile carrier for liver selective therapeutics (2009)
  • Author(s): Hirata K
  • Organizer: Asian Federation for Pharmaceutical Sciences
  • Place of Presentation: 九州大学
  • Year and Date: 2009-10-17
• [Presentation] In vitro evaluation for antioxidant activities of dietary supplements. (2009)
  • Author(s): Yamasaki K
  • Organizer: Asian Federation for Pharmaceutical Sciences
  • Place of Presentation: 九州大学
  • Year and Date: 2009-10-17
• [Presentation] Genetically engineered mannnosylated-human serum albumin as a versatile carrier for liver selective therapeutics. (2009)
  • Author(s): Hirata K
  • Organizer: Asian Federation for Pharmaceutical Sciences
  • Place of Presentation: 九州大学
  • Year and Date: 2009-10-17
• [Presentation] 組換え型糖鎖付加アルブミンの肝ターゲティング担体としての有用性評価 (2009)
  • Author(s): 平田憲史郎
  • Organizer: 第9回日本NO学会学術集会
  • Place of Presentation: 静岡グランシップ
  • Year and Date: 2009-05-08