Physiological role of polyamines and regulation of their cellular contents

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590088
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Chiba Institute of Science
• Principal Investigator: KASHIWAGI Keiko 千葉科学大学, 薬学部, 教授 (80169424)
• Co-Investigator(Renkei-kenkyūsha): TOMITORI Hideyuki 元千葉科学大学, 薬学部, 准教授 (30337381) ; TERUI Yusuke 千葉科学大学, 薬学部, 准教授 (60433687)
• Project Period (FY): 2011 – 2013
• Keywords: 生理活性アミン / ポリアミン / アクロレイン / 脳・神経 / NMDA受容体 / プトレスシン輸送 / 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. The physiological role of polyamines and regulation of their cellular contents were examined. 1) Five genes were identified as members of "polyamine modulon", whose expression is enhanced by polyamines at the level of translation, and were involved in maintenance of cell viability in Escherichia coli. 2) For elucidation of the role of polyamines on neural functions, spermine and ifenprodil binding sites on R domains of NMDA receptors were identified and the structural change of R domains by binding of these compounds were elucidated. Acrolein, a polyamine metabolite, was found to be involved in neurodegeneration after stroke. Mechanisms of cell toxicity of acrolein were examined. 4) Physiological role of two putrescine transport systems were clarified in E. coli.

Research Products

• [Journal Article] Distinction between mild cognitive impairment and Alzhemer's disease by CSF amyloidβ40 andβ42, and protein-conjugated acrolein (2014)
  • Author(s): Mizoi, M., Yoshida, M., Saiki, R., Waragai, M., Uemura, K., Akatsu, H., Kashiwagi, K., and Igarashi, K
  • Journal Title: Clin. Chim. Acta Volume: 430 Pages: 150-155
  • Peer Reviewed
• [Journal Article] Properties of putrescine uptake by PotFGHI and PuuP and their physiological significance in Escherichia coli (2014)
  • Author(s): Terui, Y., Saroj, S. D., Sakamoto, A., Yoshida, T., Higashi, K., Kurihara, S., Suzuki, H., Toida, T., Kashiwagi, K., and Igarashi, K
  • Journal Title: Amino Acids Volume: 46 Pages: 661-670
  • Peer Reviewed
• [Journal Article] Acrolein stimulates the synthesis of IL-6 and CRP in thrombosis model mice and cultured cells (2013)
  • Author(s): Saiki, R., Hayashi, D., Ikuo, Y., Nishimura, K., Ishii, I., Kobayashi, K., Chiba, K., Toida, T., Kashiwagi, K., and Igarashi, K
  • Journal Title: J. Neurochem Volume: 127 Pages: 652-659
  • Peer Reviewed
• [Journal Article] Prediction of the interaction between spermidine and G-G mismatch containing acceptor stem in tRNA^<Ile>: Molecular modeling, density functional theory, and molecular dynamics study (2013)
  • Author(s): Hayashi, Y., Sugiyama, H., Suganami, A., Higashi, K., Kashiwagi, K., Igarashi, K., and Kawauchi, S
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 441 (4) Pages: 999-1004
  • Peer Reviewed
• [Journal Article] Expression, purification, crystallization, and preliminary crystallographic analysis of spermidine acetyltransferase from Escherichia coli (2013)
  • Author(s): Niiyama, M., Sugiyama, S., Hirose, M., Ishikawa, S., Tomitori, H., Higashi, K., Yamashita, T., Adachi, H., Takano, K., Murakami, S., Murata, M., Inoue, T., Mori, Y., Kashiwagi, K., Matsumura, H., and Igarashi, K
  • Journal Title: Acta Crystallogr Volume: F69 Pages: 884-887
  • Peer Reviewed
• [Journal Article] Spermidine is required for morphogenesis in the human pathogenic fungus, Penicillium marneffei (2013)
  • Author(s): Kummasook, A., Cooper, C. R. Jr., Sakamoto, A., Terui, Y., Kashiwagi, K., and Vanittanakorn, N
  • Journal Title: Fungal Genet. Biol Volume: 58-59 Pages: 25-32
  • Peer Reviewed
• [Journal Article] Role of polyamines at the G1/S boundary and G2/M phase of the cell cycle (2013)
  • Author(s): Yamashita, T., Nishimura, K., Saiki, R., Okudaira, H., Tome, M., Higashi, K., Nakamura, M., Terui, Y., Fujiwara, K., Kashiwagi, K., and Igarashi, K
  • Journal Title: Int. J. Biochem. Cell Biol Volume: 45 Pages: 1042-1050
  • Peer Reviewed
• [Journal Article] In vitro and in vivo evaluation of polymethylene tetraamine derivatives as NMDA receptor channel blockers (2013)
  • Author(s): Saiki, R., Yoshizawa, Y., Minarini, A., Milelli, A., Marchetti, C., Tumiatti, V., Toida, T., Kashiwagi, K., and Igarashi, K
  • Journal Title: Bioorg. Med. Chem. Lett Volume: 23 Pages: 3901-3904
  • Peer Reviewed
• [Journal Article] Synthesis and evaluation of pyrrole polyamide-2'-deoxyguanosine 5'-phosphate hybrid (2013)
  • Author(s): Kawashima, E., Nakanishi, Y., Terui, Y., Tomitori, H., Kashiwagi, K., Ohba, Y., and Kamaike, K
  • Journal Title: Nucleosides, Nucleotides Nucleic Acids Volume: 32 Pages: 196-205
  • Peer Reviewed
• [Journal Article] Inactivation of GAPDH as one mechanism of acrolein toxicity (2013)
  • Author(s): Nakamura, M., Tomitori, H., Suzuki, T., Sakamoto, A., Terui, Y., Saiki, R., Dohmae, N., Igarashi, K., and Kashiwagi, K
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 430 Pages: 1265-1271
  • Peer Reviewed
• [Journal Article] Enhanced biofilm formation and/or cell viability by polyamines through stimulation of response regulators UvrY and CpxR in the two-component signal transducing systems, and ribosome recycling factor (2012)
  • Author(s): Sakamoto, A., Terui, Y., Yamamoto, T., Kasahara, T., Nakamura, M., Tomitori, H., Yamamoto, K., Michael, A. J., Igarashi, K., and Kashiwagi, K
  • Journal Title: Int. J. Biochem. Cell Biol Volume: 44 Pages: 1877-1886
  • Peer Reviewed
• [Journal Article] Structural change of R domain heterodimer of NMDA receptor GluN1 and GluN2B through binding of spermine and ifenprodil (2012)
  • Author(s): Tomitori, H., Suganami, A., Saiki, R., Mizuno, S., Yoshizawa, Y., Masuko, T., Tamura, Y., Nishimura, K., Toida, T., Williams, K., Kashiwagi, K., and Igarashi, K
  • Journal Title: J. Pharmacol. Exp. Ther Volume: 343 Pages: 82-90
  • Peer Reviewed
• [Journal Article] Increased protein-conjugated acrolein and amyloid-β40/42 ratio in plasma of patients with mild cognitive impairment and Alzheimer's disease (2012)
  • Author(s): Waragai, M., Yoshida, M., Mizoi, M., Saiki, R., Kashiwagi, K., Takagi, K., Arai, H., Tashiro, J., Hashimoto, M., Iwai, N., Uemura, K., and Igarashi, K
  • Journal Title: J. Alzheimer's Dis Volume: 32 Pages: 33-411
  • Peer Reviewed
• [Journal Article] Inverse correlation between stroke and urinary 3-hydroxypropyl mercapturic acid, an acrolein-glutathione metabolite (2012)
  • Author(s): Yoshida, M., Mikami, T., Higashi, K., Saiki, R., Mizoi, M., Fukuda, K., Nakamura, T., Ishii, I., Nishimura, K., Toida, T., Tomitori, H., Kashiwagi, K., and Igarashi, K
  • Journal Title: Clin. Chim. Acta Volume: 413 Pages: 753-759
  • Peer Reviewed
• [Journal Article] Increase in cell viability by polyamines through stimulation of the synthesis of ppGpp regulatory protein andωprotein of RNA polymerase in Escherichia coli (2012)
  • Author(s): Terui, Y., Akiyama, M., Sakamoto, A., Tomitori, H., Yamamoto, K., Ishihama, A., Igarashi, K., and Kashiwagi, K
  • Journal Title: Int. J. Biochem. Cell Biol Volume: 44 Pages: 412-422
  • Peer Reviewed
• [Journal Article] Augmented glutathione synthesis decreases acrolein toxicity (2012)
  • Author(s): Tomitori, H., Nakamura, M., Sakamoto, A., Terui, Y., Yoshida, M., Igarashi, K., and Kashiwagi, K
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 418 Pages: 110-115
  • Peer Reviewed
• [Journal Article] Structure and function of polyamine-amino acid antiporters CadB and PotE in Escherichia coli (2012)
  • Author(s): Tomitori, H., Kashiwagi, K., and Igarashi, K
  • Journal Title: Amino Acids Volume: 42 Pages: 733-740
  • Peer Reviewed
• [Journal Article] Antagonism of NMDA receptors by butanesulfonyl-homospermine guanidine and neuroprotective effects in in vitro and in vivo (2012)
  • Author(s): Masuko, T., Suzuki, T., Miyake, M., Kusama-Eguchi, K., Kizawa, Y., Tomono, K., Kashiwagi, K., Igarashi, K., Kusama, T
  • Journal Title: Neurosci Lett Volume: 506 Pages: 251-255
  • Peer Reviewed
• [Journal Article] Separation of proteins using supramolecular gel electrophoresis (2011)
  • Author(s): Yamamichi, S., Jinno, Y., Haraya, N., Oyoshi, T., Tomitori, H., Kashiwagi, K., and Yamanaka, M
  • Journal Title: Chem. Commun Volume: 47 Pages: 10344-10346
  • Peer Reviewed
• [Journal Article] Protein-conjugated acrolein as a biochemical marker of brain infarction (2011)
  • Author(s): Igarashi, K., and Kashiwagi, K
  • Journal Title: Mol. Nutr. Food Res Volume: 55 Pages: 1332-1341
  • Peer Reviewed
• [Journal Article] Characterization of genes for polyamine modulon (2011)
  • Author(s): Igarashi, K., and Kashiwagi, K
  • Journal Title: Methods Mol. Biol Volume: 720 Pages: 51-65
  • Peer Reviewed
• [Journal Article] Identification and assays of polyamine transport systems in Escherichia coli and Saccharomyces cerevisiae (2011)
  • Author(s): Kashiwagi, K., and Igarashi, K
  • Journal Title: Methods Mol. Biol Volume: 720 Pages: 295-308
  • Peer Reviewed
• [Journal Article] Use of polyamine metabolites as markers for stroke and renal failure (2011)
  • Author(s): Igarashi, K., and Kashiwagi, K
  • Journal Title: Methods Mol. Biol Volume: 720 Pages: 395-408
  • Peer Reviewed
• [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., and Igarashi, K
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 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., and Igarashi, K
  • Journal Title: Clin. Chim. Acta Volume: 412 Pages: 339-342
  • Peer Reviewed
• [Presentation] 酸化ストレス下におけるポリアミンモジュロンの生理的役割解明 (2014)
  • Author(s): 山本拓, 吉田健人, 照井祐介, 坂本明彦, 山本兼由, 石浜明, 鈴木秀之, 五十嵐一衛, 柏木敬子
  • Organizer: 日本ポリアミン学会第5回年会
  • Place of Presentation: 銚子・千葉科学大学
  • Year and Date: 2014-01-23
• [Presentation] アクロレイン耐性細胞Neuro2a-ATD-2の毒性解除機構の解明 (2014)
  • Author(s): 中村瑞穂, 坂本明彦, 照井祐介, 富取秀行, 斎木遼太郎, 吉田円, 五十嵐一衛, 柏木敬子
  • Organizer: 日本ポリアミン学会第5回年会
  • Place of Presentation: 銚子・千葉科学大学
  • Year and Date: 2014-01-23
• [Presentation] Role of polyamines at the G1/S boundary and G2/M phase of the cell cycle (2013)
  • Author(s): Kashiwagi, K., Yamashita, T., Nishimura, K., Saiki, R., Okudaira, H., Tome, M., Higashi, K., Nakamura, M., Terui, Y., Fujiwara, K., Igarashi, K
  • Organizer: 2013 Gordon Research Conference on Polyamines
  • Place of Presentation: Waterville Valley, NH, USA
  • Year and Date: 20130616-20
• [Presentation] 酸化ストレス下における大腸菌のポリアミンの生存率維持の役割 (2013)
  • Author(s): 照井祐介, 坂本明彦, 玉田朗人, 市原朋昌, 山本拓, 山本兼由, 石浜明,五 十嵐一衛, 柏木敬子
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2013-09-13
• [Presentation] 大腸菌プトレスシン輸送蛋白質PotFGHI及びPuuPの生理的意義の解明 (2013)
  • Author(s): 照井祐介, Sunil D. Saroj, 坂本明彦, 吉田健人, 東恭平, 斎木遼太郎, 栗原新, 鈴木秀之, 戸井田敏彦, 柏木敬子, 五十嵐一衛
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2013-03-30
• [Presentation] 大腸菌及び動物細胞におけるポリアミンによる翻訳の効率化機構 (2013)
  • Author(s): 柏木敬子,五十嵐一衛
  • Organizer: シンポジウム「神秘の生理活性物質ポリアミン研究の新展開」日本農芸化学会2013仙台大会
  • Place of Presentation: 東北大学川内キャンパス
  • Year and Date: 2013-03-27
• [Presentation] GAPDHを介したアクロレイン毒性機序の解明 (2013)
  • Author(s): 中村瑞穂, 富取秀行, 鈴木健裕, 照井祐介, 斎木遼太郎, 堂前直, 五十嵐一衛, 柏木敬子
  • Organizer: 日本ポリアミン学会第4回大会
  • Place of Presentation: 松島・ホテル大観荘
  • Year and Date: 2013-01-25
• [Presentation] ポリアミンによるバイオフィルム形成能及び生存率の上昇 (2012)
  • Author(s): 坂本明彦, 照井祐介, 山本拓, 笠原拓馬, 富取秀行, 山本兼由, 石浜明, 五十嵐一衛, 柏木敬子
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: マリンメッセ福岡
  • Year and Date: 2012-12-15
• [Presentation] Structural change of R domain heterodimer of NMDA receptor GluN1 and GluN2B through binding of spermine and ifenprodil (2012)
  • Author(s): Kashiwagi, K., Tomitori, H., Suganami, A., Saiki, R., Mizuno, S., Yoshizawa, Y., Masuko, T., Tamura, Y., Nishimura, K., Toida, T., Williams, K., Igarashi, K
  • Organizer: International Congress on"Polyamines : Biological and Clinical Perspectives"
  • Place of Presentation: Istanbul, Turkey, Istanbul Kültür University
  • Year and Date: 2012-09-03
• [Presentation] ポリアミンによる大腸菌二成分制御系蛋白質UvrY及びCpxR合成促進に基づくバイオフィルム形成上昇 (2012)
  • Author(s): 坂本明彦, 照井祐介, 山本拓, 笠原拓馬, 富取秀行, 山本兼由, 石浜明, 五十嵐一衛, 柏木敬子
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 日北海道大学高等教育推進機構
  • Year and Date: 2012-03-29
• [Presentation] マウス神経芽細胞腫及びマウス乳がん細胞におけるアクロレイン毒性の解毒機構 (2012)
  • Author(s): 富取秀行, 中村瑞穂, 坂本明彦, 照井祐介, 吉田円, 柏木敬子, 五十嵐一衛
  • Organizer: 日本ポリアミン学会第3回年会
  • Place of Presentation: さいたま市民会館おおみや小ホール
  • Year and Date: 2012-01-26
• [Presentation] Structure and functions of R domains of NMDA receptors NR1 and NR2B (2011)
  • Author(s): Kashiwagi, K., Mizuno, S., Tomitori, H., Yoshizawa, Y., Han, X., Higashi, K., Saiki, R., Nishimura, K., Toida, T., Williams, K., Igarashi, K
  • Organizer: 2011 Gordon Research Conference on Polyamines
  • Place of Presentation: Waterville Valley, NH, USA, Waterville Valley Resort
  • Year and Date: 20110620-23
• [Presentation] ポリアミンによるppGppの合成促進及びRpoZ-ppGpp複合体を介したRNA合成調節による大腸菌の生存率上昇. (2011)
  • Author(s): 坂本明彦, 照井祐介, 秋山真律子, 富取秀行, 山本兼由, 石浜明, 五十嵐一衛, 柏木敬子
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2011-09-23
• [Presentation] 原核細胞と真核細胞のポリアミンモジュロン:ポリアミンによる遺伝子発現制御の包括的理解 (2011)
  • Author(s): 柏木敬子, 五十嵐一衛
  • Organizer: 第84回日本生化学会大会シンポジウム「いろいろな生物に見られるポリアミンの多様な機能と代謝」シンポジスト
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2011-09-21