Basic study for treatment of Japanese type of Cystinuria by peptidomimetic drugs

• Project/Area Number: 22790789
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Osaka University
• Principal Investigator: NAGAMORI Shushi 大阪大学, 大学院・医学系研究科, 助教 (90467572)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: トランスポーター / シスチン尿症 / 遺伝病 / ペプチドミメティック薬 / 病態モデル / 輸送体 / 腎臓 / タンパク質相互作用 / cell-free病態モデル

Research Abstract

Cystinuria is an inherited disorder of renal reabsorption of cystine and dibasic amino acids by dysfunction of the transporter. It results in nephrollthalasis of cystine and leads to kidney failure. 80% of Japanese patients have the same mutation P482L at the C terminal of the cystine transporter. In this study, we have revealed the mechanism for the dysfunction of the mutant transporter in vitro and in vivo. This opens the door for treatment of the disease in the future.

Research Products

• [Journal Article] Prognostic Significance of L-type Amino Acid Transporter 1 Expression in Surgically Resected Pancreatic Cancer (2012)
  • Author(s): Kaira K., Sunose Y., Arakawa K., Ogawa T., Sunaga N., Shimizu K., TominagaH., Oriuchi N., Itoh H., Nagamori. S., Kanai Y., Segawa A., Furuya M., Mori M., Oyama T., Takeyoshi I.
  • Journal Title: Br J Cancer Volume: (in press)
  • Peer Reviewed
• [Journal Article] Linkage of N-cadherin to Multiple Cytoskeletal Elements Revealed by a Proteomic Approach in Hippocampal Neurons (2012)
  • Author(s): Tanaka H., Takafuji K., Taguchi A., Wiriyasermkul P., Ohgaki R., Nagamori S., Suh P-G., Kanai Y.
  • Journal Title: Neurochem Int Volume: (in press)
  • Peer Reviewed
• [Journal Article] Transport of 3-fluoro-L-α-methyl tyrosine by tumor-upregulated amino acid transporter LAT1 : a cause of the tumor uptake in PET (2012)
  • Author(s): Wiriyasermkul, P. Nagamori S, Tominaga H, Oriuchi N, Kaira K, Nakao H, Kitashoji T, Ohgaki R. Tanaka H, Endou H, Endo K, Sakurai H and Kanai Y
  • Journal Title: J Nucl Med Volume: (in press)
  • Peer Reviewed
• [Journal Article] Pathogenic GLUT9 Mutations Causing Renal Hypouricemia Type 2(RHUC2) (2011)
  • Author(s): Kawamura Y, Matsuo H, Chiba T, Nagamori S, Nakayama A, Inoue H, Utsumi Y, Oda T, Nishiyama J, Kanai Y, Shinomiya N
  • Journal Title: Nucleosides Nucleotides Nucleic Acids Volume: 30 Pages: 1105-11
  • Peer Reviewed
• [Journal Article] Pathogenic GLUT9 mutations causing renal hypouricemiatype 2 (RHUC2) (2011)
  • Author(s): Kawamura Y, Matsuo H, Chiba T, Nagamori S, Nakayama A, Inoue H, Utsumi Y, Oda T, Nishiyama J, Kanai Y, 外1名
  • Journal Title: Nucleosides Nucleotides Nucleic Acids
  • Peer Reviewed
• [Journal Article] Inhibition of L-type Amino Acid Transporter 1 Has Antitumor Activity in Non-small Cell Lung Cancer (2010)
  • Author(s): Imai H., Kaira K., Oriuchi N., Shimizu K., Tominaga H., Yanagitani N., Sunaga N., Ishizuka T., Nagamori S., Promchan K., Nakajima T., Yamamoto N., Mori M., Kanai Y.
  • Journal Title: Anticancer Res Volume: 30 Pages: 4819-28
  • Peer Reviewed
• [Journal Article] A novel transporter of SLC22 family specifically transports prostaglandins and co-localizes with 15-hydroxyprostaglandin dehydrogenase in renal proximal tubules (2010)
  • Author(s): Shiraya K., Hirata T., Hatano R., Nagamori S., Wiriyasermkul P., Jutabha P., Matsubara M., Muto S., Tanaka H., Asano S., Anzai N., Endou H., Yamada A., Sakurai H., Kanai Y.
  • Journal Title: J Biol Chem Volume: 285 Pages: 22141-51
  • Peer Reviewed
• [Journal Article] A novel transporter of SLC22 family specifically transports prostaglandins and co-localizes with 15-hydroxyprostaglandin dehydrogenase in renal proximaltubules. (2010)
  • Author(s): Shiraya K, Hirata T, Hatano R, Nagamori S, Wiriyasermkul P, Jutabha P, Matsubara M, Muto S, Tanaka H, Asano S, Anzai N, Endou H, Yamada A, Sakurai H, Kanai Y.
  • Journal Title: J Biol Chem. Volume: 285 Pages: 22141-22151
  • Peer Reviewed
• [Journal Article] Inhibition of L-type Amino Acid Transporter 1 Has Antitumor Activity in Non-small Cell Lung Cancer. (2010)
  • Author(s): Imai H., Kaira K., Oriuchi N., Shimizu K., Tominaga H., Yanagitani N., Sunaga N., Ishizuka T., Nagamori S., Promchan K., Nakajima T., Yamamoto N., Mori M., Kanai Y.
  • Journal Title: Anticancer Res Volume: 30 Pages: 4819-4828
  • Peer Reviewed
• [Presentation] Comprehensive and comparative quantification of epithelial cell membrane transporters between wild type and diabetic model mice (2012)
  • Author(s): Nagamori S, Takafuji K, Nishiyama S and Kanai Y
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-16
• [Presentation] Establishment of a human-disease model mouse for Japanese-type cystinuria (2012)
  • Author(s): Kawamoto Y, Nagamori S, Wiriyasermkul P, Iio K, Kanai Y
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] Functional coupling between a Na+-dependent anion transporter SMCT2 and a urate-anion exchanger URAT1 through a scaffold protein PDZK1 (2012)
  • Author(s): Nagamori S, Umemura Y, Wiriyasermkul P, Nakagomi S, Nishinaka Y, Takafuji K, Ohgaki R、Toru Kimura and Kanai Y
  • Organizer: 第一回多階層生体機能学HD Physiology国際シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2012-01-21
• [Presentation] Functional coupling between a Na^+-dependent anion transporter SMCT2 and a urate-anion exchanger URAT1 through a scaffold protein PDZK1 (2012)
  • Author(s): Nagamori S, Umemura Y, Wiriyasermkul P, Nakagomi S, Nishinaka Y, Takafuji K, Ohgaki R、Toru Kimura, Kanai Y
  • Organizer: 第一回多階層生体機能学HD Physiology国際シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2012-01-21
• [Presentation] 比較定量オミックス技術を用いた新規アニオントランスポーターOatn1の生体における機能の解析 (2011)
  • Author(s): 永森收志、平田拓、Pattama Wiriyasermkul、他3名、金井好克
  • Organizer: 第33回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 岡山
  • Year and Date: 2011-11-25
• [Presentation] 足場タンパク質PDZK1上におけるNa+依存アニオン輸送体SMCT2と尿酸-アニオン交換体URAT1の機能共役 (2011)
  • Author(s): 永森收志、梅村康浩、Pattama Wiriyasermkul、中込咲綾、西中由美子、他三名、金井好克
  • Organizer: 2011年度生理研研究会上皮細胞の恒常性維持機構におけるイオン・物質輸送の新しい分子生理
  • Place of Presentation: 岡崎
  • Year and Date: 2011-11-22
• [Presentation] 足場タンパク質PDZK1上におけるNa^+依存アニオン輸送体SMCT2と尿酸-アニオン交換体URAT1の機能共役 (2011)
  • Author(s): 永森牧志、梅村康浩、Pattama Wiriyasermkul,中込咲綾、酉中由美子, 他三名、金井好克
  • Organizer: 2011年度生理研研究会 上皮細胞の恒常性維持機構におけるイオン・物質輸送の新しい分子生理
  • Place of Presentation: 岡崎
  • Year and Date: 2011-11-22
• [Presentation] Functional coupling of a Na+-dependent anion transporter and a urate-anion exchanger through a scaffold protein (2011)
  • Author(s): Nagamori S, Umemura Y, Wiriyasermkul P, Nakagomi S, Nishinaka Y, Takafuji K, Ohgaki R and Kanai Y
  • Organizer: 第84回日本生化学会大会シンポジウム「生体膜エネルギー変換装置の超分子科学」招待講演
  • Place of Presentation: 京都
  • Year and Date: 2011-09-21
• [Presentation] Functional coupling of a Na^+-dependent anion transporter and a urate-anion exchanger through a scaffold protein (2011)
  • Author(s): Nagamori S, Umemura Y, Wiriyasermkul P, Nakagomi S, Nishinaka Y, Takafuji K, Ohgaki R, Kanai Y
  • Organizer: 第84回日本生化学会大会シンポジウム「生体膜エネルギー変換装置の超分子科学」
  • Place of Presentation: 京都(招待講演)
  • Year and Date: 2011-09-21
• [Presentation] 上皮細胞膜トランスポーターの質量分析による網羅的変動解析手法の確立 (2011)
  • Author(s): 永森收志, 他
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 神奈川県・横浜市
  • Year and Date: 2011-03-22
• [Presentation] The structural requirements of leucine derivatives to be transported by L-type amino acid transporter 1(LAT1) and to activate mammalian target of rapamycin(mTOR) (2010)
  • Author(s): Pattama Wiriyasermkul, 永森收志, 他
  • Organizer: 第118回日本薬理学会近畿部会
  • Place of Presentation: 大阪府・豊中市
  • Year and Date: 2010-11-19
• [Presentation] The structural requirements of leucine derivatives to be transported by L-type amino acid transporter 1 (LAT1) and to activate mammalian target of rapamycin (mTOR) (2010)
  • Author(s): Pattama Wiriyasermkul, 永森收志, 他
  • Organizer: 第118回日本薬理学会近畿部会
  • Place of Presentation: 大阪府・豊中市
  • Year and Date: 2010-11-19
• [Presentation] メタボロミクスを用いた新規有機アニオントランスポーターOatn1の生体内における機能の解析2010年度 (2010)
  • Author(s): 永森收志, 他
  • Organizer: 生理研研究会
  • Place of Presentation: 愛知県・岡崎市
  • Year and Date: 2010-11-04
• [Presentation] メタボロミクスを用いた新規有機アニオントランスポーターOatn1の生体内における機能の解析 (2010)
  • Author(s): 永森收志, 他
  • Organizer: 2010年度生理研研究会
  • Place of Presentation: 愛知県・岡崎市(招待講演)
  • Year and Date: 2010-11-04
• [Presentation] CE-MS based metabolome analysis in knockout mice reveals real physiological substrates of an organic anion transporter(Invited short talk) (2010)
  • Author(s): Nagamori S
  • Organizer: Gordon Research Conference : Membrane Transport Proteins
  • Place of Presentation: 米国・メイン州ビッデフォード
  • Year and Date: 2010-08-17
• [Presentation] CE-MS based metabolome analysis in knockout mice reveals real physiological substrates of an organic anion transporter (2010)
  • Author(s): 永森收志, 他
  • Organizer: Gordon Research Conference : Membrane Transport Proteins
  • Place of Presentation: 米国・メイン州ビッデフォード(Invited short talk)
  • Year and Date: 2010-08-17
• [Presentation] 新規塩基性アミノ酸トランスポーターCAT5の機能と構造の解析から解くトランスポーターの基質輸送に伴った構造変化 (2010)
  • Author(s): 永森收志, 他
  • Organizer: 第117回日本薬理学会近畿部会
  • Place of Presentation: 徳島県・徳島市
  • Year and Date: 2010-07-08
• [Book] 栄養・食品機能とトランスポーター (2011)
  • Author(s): 永森收志
  • Total Pages: 304
  • Publisher: 建帛社
• [Book] トランスポートソーム生体膜輸送機構の全体像に迫る金井好克編 (2011)
  • Author(s): 永森收志
  • Total Pages: 280
  • Publisher: メディカルドゥ