Research of cerebral insufficiency improver based on the mechanism of acrolein toxicity on cell growth

• Project/Area Number: 22790169
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Chiba Institute of Science
• Principal Investigator: TOMITORI Hideyuki 千葉科学大学, 薬学部, 准教授 (30337381)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 生理活性物質 / 脳・神経 / バイオマーカー / 臨床化学 / 細胞毒性 / 脳梗塞 / ポリアミン / アクロレイン / 脳機能

Research Abstract

Polyamines play important roles in cell proliferation and differentiation. However, acrolein that is highly toxic compound is produced by polyamine oxidation. In this study, we studied on the molecular mechanism of acrolein toxicity on cell growth, and researched candidates for cerebral insufficiency improver based on the mechanism of acrolein toxicity on cell growth. New findings in this study have been described below.

Research Products

• [Journal Article] Augmented glutathione synthesis decreases acrolein toxicity (2012)
  • Author(s): Tomitori, H., Nakamura, M., Sakamoto, A., Terui, Y., Yoshida, M., Igarashi, K., Kashiwagi, K
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 418 Pages: 110-115
• [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., Kashiwagi, K
  • Journal Title: Int. J. Biochem. Cell Biol. Volume: 44 Pages: 412-422
• [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
• [Journal Article] Augmented glutathione synthesis decreases acrolein toxicity (2012)
  • Author(s): Tomitori, H., et al
  • Journal Title: Biochem.Biophys Res.Commun. Volume: 418 Issue: 1 Pages: 110-115
  • DOI: 10.1016/j.bbrc.2011.12.143
  • Peer Reviewed
• [Journal Article] Increase in cell viability by polyamines through stimulation of the synthesis of ppGpp regulatory protein and ω protein of RNA polymerase in Escherichia coli (2012)
  • Author(s): Terui, Y., et al
  • Journal Title: Int.J.Biochem.Cell.Biol. Volume: 44 Issue: 2 Pages: 412-422
  • DOI: 10.1016/j.biocel.2011.11.017
  • 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., Yamanaka, M
  • Journal Title: Chem. Commun.(Camb) Volume: 47 Pages: 10344-10346
• [Journal Article] Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability (2011)
  • Author(s): Hamdan, F. F., Gauthier, J., Araki, Y., Lin, D. T., Yoshizawa, Y., Higashi, K., Park, A. R., Spiegelman, D., Dobrzeniecka, S., Piton, A., Tomitori, H., Daoud, H., Massicotte, C., Henrion, E., Diallo, O.; S2D Group, Shekarabi, M., Marineau, C., Shevell, M.
  • Journal Title: Am. J. Hum. Genet Volume: 88 Pages: 306-316
• [Journal Article] Possible involvement of syntaxin 1A downregulation in the late phase of allodynia induced by peripheral nerve injury (2011)
  • Author(s): Fukushima, T., Takasusuki, T., Tomitori, H., Hori, Y
  • Journal Title: Neuroscience Volume: 175 Pages: 344-357
• [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 Volume: 30 Pages: 339-342
• [Journal Article] Separation of proteins using supramolecular gel electrophoresis (2011)
  • Author(s): Yamamichi, S., et al
  • Journal Title: Chem.Commun.(Camb). Volume: 47 Issue: 37 Pages: 10344-10346
  • DOI: 10.1039/c1cc13826j
  • Peer Reviewed
• [Journal Article] Excess of De Novo Deleterious Mutations in Genes Associated with Glutamatergic Systems in Nonsyndromic Intellectual Disability. (2011)
  • Author(s): Hamdan, F.F., et al.
  • Journal Title: Am.J.Hum.Genet. Volume: 88 Pages: 306-316
  • Peer Reviewed
• [Journal Article] Possible involvement of syntaxin 1A downregulation in the late phase of allodynia induced by peripheral nerve injury. (2011)
  • Author(s): Fukushima, T., et al.
  • Journal Title: Neuroscience Volume: 175 Pages: 344-357
  • 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., et al.
  • Journal Title: Clin.Chim.Acta. Volume: 412 Pages: 339-342
  • 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 Volume: 285 Pages: 28698-28707
• [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., Kashiwado, K., 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 Volume: 211 Pages: 475-479
• [Journal Article] Ribosome modulation factor, an important protein for cell viability encoded by the polyamine modulon. (2010)
  • Author(s): Terui, Y., et al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 28698-26707
  • 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., et al.
  • Journal Title: Atherosclerosis Volume: 211 Pages: 475-479
  • Peer Reviewed
• [Presentation] 大腸菌ポリアミン-アミノ酸アンチポーターCadB及びPotEの構造と機能 (2012)
  • Author(s): 富取秀行
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学、札幌
  • Year and Date: 2012-03-29
• [Presentation] (2012)
  • Author(s): 坂本明彦
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学、札幌
  • 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
  • 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、大宮
  • Year and Date: 2012-01-26
• [Presentation] 大腸菌ポリアミン-アミノ酸アンチポーターCadB及びPotEの構造と機能 (2012)
  • Author(s): 富取秀行
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] ポリアミンによる大腸菌二成分制御系UvrY及びCprX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
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [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
  • Organizer: 日本ポリアミン学会第3回年会
  • Place of Presentation: 大宮
• [Presentation] 脳梗塞患者における尿中アクロレイン-グルタチオン代謝物3-HPMA(3-ヒドロキシプロピルメルカプツール酸)の低下 (2012)
  • Author(s): 柏木敬
  • Organizer: 日本ポリアミン学会第3回年会
  • Place of Presentation: 大宮
• [Presentation] Isolation and their characteristics of acrolein toxicity decreasing mutants from mouse mammary carcinoma and neuroblastoma cells (2011)
  • Author(s): Tomitori, H.
  • Organizer: 16th World Congress on Advances in Oncology and 14th International Symposium on Molecular Medicine
  • Place of Presentation: Rhodos, Greece
  • Year and Date: 2011-10-06
• [Presentation] 細胞内アクロレイン抱合蛋白質の同定及びアクロレイン抱合の細胞増殖に対する影響 (2011)
  • Author(s): 中村瑞穂
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国際会議場、京都
  • Year and Date: 2011-09-23
• [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
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国際会議場、京都
  • Year and Date: 2011-09-23
• [Presentation] Different mechanisms of the resistance to acrolein toxicity of the acrolein resistant mutants (2011)
  • Author(s): Nakamura, M.
  • Organizer: Gordon research conference on polyamine
  • Place of Presentation: New Hampsher, U.S.
  • Year and Date: 2011-06-23
• [Presentation] 高度高熱菌及び大腸菌ポリアミン取り込み系PotABCDのポリアミン結合蛋白質PotDの基質認識 (2011)
  • Author(s): 金井健
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡、静岡
  • Year and Date: 2011-03-30
• [Presentation] 大腸菌の生存率維持に果たすポリアミンの役割解明 (2011)
  • Author(s): 照井祐介
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡、静岡
  • Year and Date: 2011-03-30
• [Presentation] NMDA受容体調節領域NR1RとNR2BRの構造と機能 (2011)
  • Author(s): 吉沢佑基
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡、静岡
  • Year and Date: 2011-03-30
• [Presentation] 細胞内アクロレイン抱合蛋白質の同定及びアクロレイン抱合の細胞増殖に対する影響 (2011)
  • Author(s): 中村瑞穂
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [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
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] 高度高熱菌及び大腸菌ポリアミン取り込み系PotABCDのポリアミン結合蛋白質PotDの基質認識 (2011)
  • Author(s): 金井健
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] 大腸菌の生存率維持に果たすポリアミンの役割 (2011)
  • Author(s): 照井祐介
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] NMDA受容体調節領域NR1RとNR2BRの構造と機能 (2011)
  • Author(s): 吉沢佑基
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] ポリアミンの微生物の生存率に果たす役割 (2011)
  • Author(s): 秋山真律子
  • Organizer: 日本ポリアミン学会第2回年会
  • Place of Presentation: 宇都宮
• [Presentation] メタボリックシンドロームと血漿蛋白質抱合アクロレイン、IL-6、CRPより求めた脳梗塞リスク値との相関 (2011)
  • Author(s): 柏木敬子
  • Organizer: 日本ポリアミン学会第2回年会
  • Place of Presentation: 宇都宮
• [Presentation] マウス神経芽細胞腫Neuro2aを用いたアクロレイン耐性細胞の樹立と新たな毒性除去機構の解明 (2010)
  • Author(s): 坂本明彦
  • Organizer: BMB2010: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: 神戸ポートアイランド、兵庫
  • Year and Date: 2010-12-08
• [Presentation] Isolation and characterization of an acrolein tolerant mutant of FM3A cells (2010)
  • Author(s): 中村瑞穂
  • 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: 2010-12-02
• [Presentation] Structure and function of CadB and PotE (2010)
  • Author(s): 富取秀行
  • 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: 2010-12-02
• [Presentation] 脳梗塞患者の血漿中に見いだされるアクロレイン抱合蛋白質の分析と同定 (2010)
  • Author(s): 西村和洋
  • 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
• [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
  • Organizer: 第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] マウス神経芽細胞腫Neuro2aを用いたアクロレイン耐性細胞の樹立と新たな毒性除去機構の解明 (2010)
  • Author(s): 坂本明彦
  • 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
• [Presentation] 大腸菌由来スペルミジンアセチルトランスフェラーゼのX線結晶構造解析と変異体解析 (2010)
  • Author(s): 石川沙枝
  • 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
• [Patent(Industrial Property Rights)] 脳卒中・無症候性脳梗塞のスクリーニングの方法 (2009)
  • Inventor(s): 五十嵐一衛、上田志朗、佐伯直勝、柏木敬子、富取秀行
  • Industrial Property Rights Holder: 株式会社アミンファーマ研究所、日油株式会社、株式会社フューエンス
  • Acquisition Date: 2009-12-18