Structure and functions of polyamine transport proteins and NMDA receptors

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590066
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Chiba Institute of Science
• Principal Investigator: KASHIWAGI Keiko Chiba Institute of Science, 薬学部, 教授 (80169424)
• Project Period (FY): 2008 – 2010
• Keywords: 生理活性アミン / ポリアミン / 脳・神経 / NMDA受容体 / 輸送 / プトレスシン / スペルミジン / スペルミン

Research Abstract

Polyamines (putrescine, spermidine and spermine) play important roles in cell proliferation and differentiation. In this study, mechanism of polyamine transport and role of polyamines on NMDA receptor activities have been studied. As the results, a spermidine excretion system was newly identified and amino acid residues involved in the activities of polyamine uptake system were identified. Properties of regulatory (R) domains of NMDA receptor were characterized and regulatory sites by spermine in the channel region of NMDA receptor were identified.

Research Products

• [Journal Article] Brain infarction correlates more closely with acrolein than with reactive oxygen species. (2011)
  • Author(s): Saiki, R., Park, H., Ishii, I., Yoshida, M., Nishimura, K., Toida, T., Tatsukawa, H., Kojima, S., Ikeguchi, Y., Pegg, A.E., Kashiwagi, K., Igarashi, K.
  • Journal Title: Biochem.Biophys.Res.Commun. 404 Pages: 1044-1049
  • Peer Reviewed
• [Journal Article] Relationship between metabolic disorders and relative risk values of brain infarction estimated by protein-conjugated acrolein, IL-6 and CRP together with age. (2011)
  • Author(s): Yoshida, M., Mizoi, M., Saiki, R., Kobayashi, E., Saeki, N., Wakui, K., Kusaka, T., Takizawa, H., Kashiwado, K., Suzuki, N., Fukuda, K., Nakamura, T., Watanabe, S., Tada, K., Tomitori, H., Kashiwagi, K., Igarashi, K.
  • Journal Title: Clin.Chim.Acta 412 Pages: 339-342
  • Peer Reviewed
• [Journal Article] Identification and functions of amino acid residues in PotB and PotC involved in spermidine uptake activity. (2010)
  • Author(s): Higashi, K., Sakamaki, Y., Herai, E., Demizu, R., Uemura, T.m Saroj, S.D., Terui, Y., Nishimura, K., Toida, T., Kashiwagi, K., Igarashi, K.
  • Journal Title: J.Biol.Chem. 285 Pages: 39061-39069
  • Peer Reviewed
• [Journal Article] Ribosome modulation factor, an important protein for cell viability encoded by the polyamine modulon. (2010)
  • Author(s): Terui, Y., Tabei, Y., Akiyama, M., Higashi, K., Tomitori, H., Yamamoto, K., Ishihama, A., Igarashi, K., Kashiwagi, K.
  • Journal Title: J.Biol.Chem. 285 Pages: 28698-28707
  • Peer Reviewed
• [Journal Article] Modulation of cellular function by polyamines. (Review article) (2010)
  • Author(s): Igarashi, K., Kashiwagi, K.
  • Journal Title: Int.J.Biochem.Cell Biol. 42 Pages: 39-51
  • Peer Reviewed
• [Journal Article] Correlation between images of silent brain infarction, carotid atherosclerosis and white matter hyperintensity, and plasma levels of acrolein, IL-6 and CRP. (2010)
  • Author(s): Yoshida, M., Higashi, K., Kobayashi, E., Saeki, N., Wakui, K., Kusaka, T., Takizawa, H., Suzuki, N., Fukuda, K., Nakamura, T., Watanabe, S., Tada, K., Machi, Y., Mizoi, M., Toida, T., Kanzaki, T., Tomitori, H., Kashiwagi, K., Igarashi, K.
  • Journal Title: Atherosclerosis 211 Pages: 475-479
  • Peer Reviewed
• [Journal Article] Characteristics of cellular polyamine transport in prokaryotes and eukaryotes. (Review article) (2010)
  • Author(s): Igarashi, K., Kashiwagi, K.
  • Journal Title: Plant Physiol.Biochem. 48 Pages: 506-512
  • Peer Reviewed
• [Journal Article] Intense correlation between protein-conjugated acrolein and primary Sjogren's syndrome. (2010)
  • Author(s): Higashi, K., Yoshida, M., Igarashi, A., Ito, K., Wada, Y., Murakami, S., Kobayashi, D., Nakano, M., Sohda, M., Nakajima, T., Narita, I., Toida, T., Kashiwagi, K., Igarashi, K.
  • Journal Title: Clin.Chim.Acta 411 Pages: 359-363
  • Peer Reviewed
• [Journal Article] Identification of acrolein-conjugated protein in plasma of patients with brain infarction. (2010)
  • Author(s): Yoshida, M., Higashi, K., Jin, L., Machi, Y., Suzuki, T., Masuda, A., Dohmae, N., Suganami, A., Tamura, Y., Nishimura, K., Toida, T., Tomitori, H., Kashiwagi, K., Igarashi, K.
  • Journal Title: Biochem.Biophys.Res.Commun. 391 Pages: 1234-1239
  • Peer Reviewed
• [Journal Article] Polyamine-modulon in yeast-stimulation of COX4 synthesis by spermidine at the level of translation. (2009)
  • Author(s): Uemura, T., Higashi, K., Takigawa, M., Toida, T., Kashiwagi, K., Igarashi, K.
  • Journal Title: Int.J.Biochem.Cell Biol. 41 Pages: 2538-2545
  • Peer Reviewed
• [Journal Article] Neuroprotection by tosyl-polyamine derivatives through the inhibition of ionotropic glutamate receptors. (2009)
  • Author(s): Masuko, T., Namiki, R., Nemoto, Y., Miyake, M., Kizawa, Y., Suzuki, T., Kashiwagi, K., Igarashi, K., Kusama, T.
  • Journal Title: J.Pharmacol.Exp.Ther. 331 Pages: 522-530
  • Peer Reviewed
• [Journal Article] Intense correlation between brain infarction and protein-conjugated acrolein. (2009)
  • Author(s): Saiki, R., Nishimura, K., Ishii, I., Omura, T., Okuyama, S., Kashiwagi, K., Igarashi, K.
  • Journal Title: Stroke 40 Pages: 3356-3361
  • Peer Reviewed
• [Journal Article] Acrolein, IL-6 and CRP as markers of silent brain infarction. (2009)
  • Author(s): Yoshida, M., Tomitori, H., Machi, Y., Katagiri, D., Ueda, S., Horiguchi, K., Kobayashi, E., Saeki, N., Nishimura, K., Ishii, I., Kashiwagi, K., Igarashi, K.
  • Journal Title: Atherosclerosis 203 Pages: 557-562
  • Peer Reviewed
• [Journal Article] Acrolein toxicity : comparison with reactive oxygen species. (2009)
  • Author(s): Yoshida, M., Tomitori, H., Machi, Y., Hagihara, M., Higashi, K., Goda, H., Ohya, T., Niitsu, M., Kashiwagi, K., Igarashi, K.
  • Journal Title: Biochem.Biophys.Res.Commun. 378 Pages: 313-318
  • Peer Reviewed
• [Journal Article] Identification of proteins whose synthesis is preferentially enhanced by polyamines at the level of translation in mammalian cells. (2009)
  • Author(s): Nishimura, K., Okudaira, H., Ochiai, E., Higashi, K., Kaneko, M., Ishii, I., Nishimura, T., Dohmae, N., Kashiwagi, K., Igarashi, K.
  • Journal Title: Int.J.Biochem.Cell Biol. 41 Pages: 2251-2261
  • Peer Reviewed
• [Journal Article] Enhancement of the synthesis of RpoE and StpA by polyamines at the level of translation in Escherichia coli under heat shock conditions. (2009)
  • Author(s): Terui, Y., Higashi, K., Tabei, Y., Tomitori, H., Yamamoto, K., Ishihama, A., Igarashi, K., Kashiwagi, K.
  • Journal Title: J.Bacteriol. 191 Pages: 5348-5357
  • Peer Reviewed
• [Journal Article] Selective structural change by spermidine in the bulged-out region of double-stranded RNA and its effect on RNA function. (2008)
  • Author(s): Higashi, K., Terui, Y., Suganami, A., Tamura, Y., Nishimura, K., Kashiwagi, K., Igarashi, K.
  • Journal Title: J.Biol.Chem. 283 Pages: 32989-32994
  • Peer Reviewed
• [Journal Article] Differential effects of linear and cyclic polyamines on NMDA receptor activities. (2008)
  • Author(s): Masuko, T., Miyake, M., Kusama-Eguchi, K., Koike, T., Kimura, E., Kizawa, Y., Kashiwagi, K., Igarashi, K., Kusama, T.
  • Journal Title: Neurochem.Int. 53 Pages: 38-44
  • Peer Reviewed
• [Journal Article] Binding of spermine and ifenprodil to a purified, soluble regulatory domain of the N-methyl-D-aspartate receptor. (2008)
  • Author(s): Han, X., Tomitori, H., Mizuno, S., Higashi, K., Full, C., Fukiwake, T., Terui, Y., Leewanich, P., Nishimura, K., Toida, T., Williams, K., Kashiwagi, K., Igarashi, K.
  • Journal Title: J.Neurochem. 107 Pages: 1566-1577
  • Peer Reviewed
• [Journal Article] The pore region of N-methyl-D-aspartate receptors differentially influences stimulation and block by spermine. (2008)
  • Author(s): Jin, L., Miyazaki, M., Mizuno, S., Takigawa, M., Hirose, T., Nishimura, K., Toida, T., Williams, K., Kashiwagi, K., Igarashi, K.
  • Journal Title: J.Pharmacol.Exp.Ther. 327 Pages: 68-77
  • Peer Reviewed
• [Journal Article] Selective structural change of bulged-out region of double-stranded RNA containing bulged nucleotides by spermidine. (2008)
  • Author(s): Higashi, K., Terui, Y., Inomata, E., Katagiri, D., Nomura, Y., Someya, T., Nishimura, K., Kashiwagi, K., Kawai, G., Igarashi, K.
  • Journal Title: Biochem.Biophys.Res.Commun. 370 Pages: 572-577
  • Peer Reviewed
• [Journal Article] Identification of a spermidine excretion protein complex (MdtJI) in Escherichia coli. (2008)
  • Author(s): Higashi, K., Ishigure, H., Demizu, R., Uemura, T., Nishino, K., Yamaguchi, A., Kashiwagi, K., Igarashi, K.
  • Journal Title: J.Bacteriol. 190 Pages: 872-878
  • Peer Reviewed
• [Presentation] NMDA受容体調節領域NRIRとNR2BRの構造と機能 (2011)
  • Author(s): 吉沢祐樹, 水野聡美, 富取秀行, 韓霞, 益子崇, 菅波晃子, 田村裕, 東恭平, 斎木遼太郎, 西村和洋, 戸井田敏彦, 柏木敬子, 五十嵐一衛
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡
  • Year and Date: 2011-03-30
• [Presentation] スペルミジン輸送活性に関与するPotB及びPotCのアミノ酸残基の同定とその機能 (2011)
  • Author(s): 柏木敬子, 酒巻善春, 東恭平, 戸来江美子, 出水理砂, 植村武, Sunil D. Saroj, 照井祐介, 西村和洋, 戸井田敏彦, 五十嵐一衛
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡
  • Year and Date: 2011-03-30
• [Presentation] 無症候性脳梗塞,頸部動脈硬化及び大脳白質病変の画像とアクロレイン,IL・6及びCRPの血漿レベルとの相関 (2010)
  • Author(s): 柏木敬子, 吉田円, 東恭平, 小林英一, 佐伯直勝, 町佳樹, 溝井睦美, 戸井田敏彦, 神崎哲人, 富取秀行, 五十嵐一衛
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-12-08
• [Presentation] Identification and functions of amino acid residues in PotB and PotC involved in spermidine uptake activity. (2010)
  • Author(s): Higashi K., Sakamaki Y., Herai E., Demizu R., Uemura T., Saroj S. D., Zenda R., Terui Y., Nishimura K., Toida T., Kashiwagi K., Igarashi K.
  • Organizer: 2nd International Conference on the Role of Polyamines and their Analogs in Cancer and other Diseases
  • Place of Presentation: Rome, Italy
  • Year and Date: 2010-12-04
• [Presentation] Polyamine modulation in Escherichia coli, yeast and mammalian cells. (2010)
  • Author(s): Kashiwagi K., Terui Y., Uemura T., Higashi K., Okudaira H., Ochiai E., Akiyama M., Tomitori H., Nishimura K., Toida T., Igarashi K.
  • Organizer: 2nd International Conference on the Role of Polyamines and their Analogs in Cancer and other Diseases
  • Place of Presentation: Rome, Italy
  • Year and Date: 2010-12-03
• [Presentation] Correlation between images of silent brain infarction, carotid atherosclerosis and white matter hyperintensity, and plasma levels of acrolein, IL-6 and CRP. (2010)
  • Author(s): Kashiwagi K., Yoshida M., Higashi K., Kobayashi E., Saeki N., Machi Y., Mizoi M., Toida T., Kanzaki T., Tomitori, H. Igarashi K.
  • Organizer: 2010 International Polyamine Conference, Gotemba, Japan
  • Place of Presentation: 御殿場高原ホテルBU
  • Year and Date: 2010-06-17
• [Presentation] ポリアミンから産生されるアクロレインの脳梗塞巣形成に果たす役割 (2010)
  • Author(s): 斎木遼太郎, 朴恵林, 石井伊都子, 西村和洋, 戸井田敏彦, 辰川英樹, 小嶋聡一, 柏木敬子, 五十嵐一衛
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 就実大学,岡山
  • Year and Date: 2010-03-28
• [Presentation] Binding of spermine and ifenprodil to a regulatory domain (R-domain) of the N-methyl-Daspartate (NMDA) receptor and the role of R-domain on the activity of NMDA receptor. (2009)
  • Author(s): Kashiwagi K., Han X., Mizuno S., Tomitori H., Higashi K., Terui Y., Nishimura K., Toida T., Williams K., Igarashi K.
  • Organizer: 第31回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 大阪大学コンベンションセンター
  • Year and Date: 2009-12-01
• [Presentation] アクロレイン耐性細胞の樹立とそのアクロレイン毒性除去機構 (2009)
  • Author(s): 中村瑞穂, 富取秀行, 照井祐介, 吉田円, 柏木敬子, 五十嵐一衛
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2009-10-23
• [Presentation] Polyamine effect on protein synthesis and its mechanism. (2009)
  • Author(s): Kashiwagi K., Terui Y., Higashi K., Okudaira H., Ochiai E., Tomitori H., Nishimura K., Yamamoto K., Ishihama A., Igarashi K.
  • Organizer: Gordon Research Conference on Polyamines
  • Place of Presentation: Waterville Valley, NH, USA
  • Year and Date: 2009-06-22
• [Presentation] スペルミン及びイフェンプロジルのNMDA受容体調節領域への結合能 (2009)
  • Author(s): 韓霞, 富取秀行, 水野聡美, 東恭平, 吹言睾友秀, 照井祐介, 西村和洋, 戸井田敏彦, 柏木敬子, 五十嵐一衛
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-03-26
• [Presentation] 細胞周期進行におけるポリアミンの役割解析 (2009)
  • Author(s): 柏木敬子, 山下智子, 西村和洋, 奥平宏之, 當銘真悠子, 東恭平, 藤原邦雄, 五十嵐一衛
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-03-26
• [Presentation] 大腸菌スペルミジン優先取り込み系の膜貫通蛋白質PotB及びPotCの性質 (2008)
  • Author(s): 出水梨沙, 東恭平, 酒巻善春, 植村武史, 戸来江美子, 善田理沙, 西村和洋, 柏木敬子, 五十嵐一衛
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2008-12-09
• [Presentation] スペルミンによるNMDA受容体活性促進効果とチャネルブロック作用に影響するチャネル領域の同定 (2008)
  • Author(s): 柏木敬子, 金麗花, 宮崎真紀, 水野聡美, 瀧川美紀, 廣瀬直雄, 西村和洋, 戸井田敏彦, K. Williams, 五十嵐一衛
  • Organizer: 第30回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2008-08-08
• [Book] Methods Mol.Biol. 720(Eds. A.E. Pegg and R.A. Casero, Jr)(Characterization of genes for polyamine modulon. "Polyamines") (2011)
  • Author(s): Igarashi, K., Kashiwagi, K.
  • Total Pages: 523(51-65)
  • Publisher: Humana Press
• [Book] Methods Mol.Biol. 720(Eds. A.E. Pegg and R.A. Casero, Jr)(Identification and assays of polyamine transport systems in Escherichia coli and Saccharomyces cerevisiae. "Polyamines") (2011)
  • Author(s): Kashiwagi, K., Igarashi, K.
  • Total Pages: 523(295-308)
  • Publisher: Humana Press
• [Book] Methods Mol.Biol. 720(Eds. A.E. Pegg and R.A. Casero, Jr)(Use of polyamine metabolites as markers for stroke and renal failure. "Polyamines") (2011)
  • Author(s): Igarashi, K., Kashiwagi, K.
  • Total Pages: 523(395-408)
  • Publisher: Humana Press