Probing ROS signaling with small molecules

2013 Fiscal Year Final Research Report

• Project Area: Signaling functions of reactive oxygen species
• Project/Area Number: 20117006
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: ARIMOTO HIROKAZU 東北大学, 生命科学研究科, 教授 (60262789)
• Project Period (FY): 2008-11-13 – 2013-03-31
• Keywords: 活性酸素 / 化学プローブ / 一酸化窒素 / ８－ニトロcGMP / オートファジー

Research Abstract

8-Nitro-cGMP is a novel mediator of active oxygen and nitric oxide. In this program, isotopically labeled 8- nitro-cGMP was synthesized to examine its metabolic fate in cells. It was reduced to 8-amino-cGMP first, and then converted to intact cGMP in cells. The latter transformation from 8-amino-cGMP required LPS-treatment of cells. We also prepared fluorescent nitroguanosine probes to obtain insight into the intracellular localization of 8-nitro-cGMP. The lysosomal localization of the fluorescent probes prompted us to examine the roles of 8-nitro-cGMP in autophagy induction. 8-Nitro-cGMP accelerated the autophagic clearance of intracellular group A Streptococcus (GAS). Interestingly, the surface of intracellular GAS was modified by S-guanylation, and the level of the modification showed a robust relationship with GAS ubiquitination suggesting that S-guanylation. These results may suggest that 8-nitro-cGMP works as a tag for selective transport of bacteria to autophagosomes.

Research Products

• [Journal Article] Endogenous Nitrated Nucleotide Is a Key Mediator of Autophagy and Innate Defense against Bacteria (2013)
  • Author(s): Ito, C.; Saito, Y.; Nozawa, T.; Fujii, S.; Sawa, T.; Inoue, H.; Matsunaga, T.; Khan S.; Akashi, S.; Hashimoto, R.; Aikawa, C.; Takahashi, E.; Sagara, H.; Komatsu, M.; Tanaka, K.; Akaike, T.; Nakagawa, I.; Arimoto, H.
  • Journal Title: Molecular Cell Volume: 52 Pages: 794-804
  • DOI: 10.1016/j.molcel.2013.10.024
  • Peer Reviewed
• [Journal Article] Fluorescent probes for live cell imaging of endogenous guanine nitration (2013)
  • Author(s): Saito, Y.; Ito, C.; Fujii, S.; Sawa, T.; Akaike, T.; Arimoto, H.
  • Journal Title: ChemBioChem Volume: 14 Pages: 1068-1071
  • DOI: 10.1002/cbic.201300129
  • Peer Reviewed
• [Journal Article] Nitric oxide promotes recycling of 8-nitro-cGMP, a cytoprotective mediator, into intact cGMP in cells (2012)
  • Author(s): Saito, Y.; Sawa, T.; Yoshitake, J.; Ito, C.; Fujii, S.; Akaike, T.; Arimoto, H.
  • Journal Title: Molecular BioSystems Volume: 8 Pages: 2009-2015
  • DOI: 10.1039/C2MB25189B
  • Peer Reviewed
• [Journal Article] Regulation of Redox Signaling Involving Chemical Conjugation of Protein Thiols by Nitric Oxide and Electrophiles (2010)
  • Author(s): Sawa T.; Arimoto, H.; Akaike T.
  • Journal Title: Bioconjugate Chemistry Volume: 21 Pages: 1121-1129
  • DOI: 10.1021/bc900396u
  • Peer Reviewed
• [Presentation] Endogenous Nitrated Nucleotide Is a Key Mediator of Autophagy and Innate Defense against Bacteria (2014)
  • Author(s): Arimoto, H
  • Organizer: Gordon Research Conference : Autophagy in Stress Development & Disease
  • Place of Presentation: Lucca, Italy
  • Year and Date: 2014-03-19
• [Presentation] 感染症の制御に向けた化学からのアプローチ (2012)
  • Author(s): 有本博一
  • Organizer: 中西シンポジウム2012
  • Place of Presentation: 慶応義塾大学 (横浜市)
  • Year and Date: 2012-03-25
• [Presentation] 感染症の理解と制御のための化学的アプローチ (2011)
  • Author(s): 有本博一
  • Organizer: 第13回生命化学研究会
  • Place of Presentation: 仙台市ホテル佐勘
  • Year and Date: 2011-01-08
• [Presentation] 感染症の理解と制御のための化学的アプローチ (2010)
  • Author(s): 有本博一
  • Organizer: 第22回万有札幌シンポジウム
  • Place of Presentation: 札幌市さっぽろ芸術文化の館
  • Year and Date: 2010-07-03
• [Remarks]
  • URL: http://www.agri.tohoku.ac.jp/bunseki/ArimotoGroup.html
• [Remarks] ① Molecular Cell(論文掲載誌)2013年12月26日号「8-Nitro-cGMP -A New Player in Antibacterial Autophagy」 報道等(計5件)
• [Remarks] ②科学新聞 2013年12月6日 「細菌を細胞から排除:東北大など「鍵分子」発見」 報道等(計5件)
• [Remarks] ③朝日新聞 2013年12月5日朝刊「細胞内で異物につく分子 東北大・東京医科歯科大が発見」 報道等(計5件)
• [Remarks] ④ 毎日新聞 2013年11月28日朝刊「細胞の細菌排除メカニズムを解明」 報道等(計5件)
• [Remarks] ⑤ 河北新報 2013年11月22日朝刊「細胞侵入細菌に結合 目印役の分子発見」 報道等(計5件)
• [Patent(Industrial Property Rights)] 抗8-ニトロサイクリックグアノシン3',5'-一リン酸抗体 (2011)
  • Inventor(s): 赤池孝章、有本博一、芥 照夫、佐々本一美
  • Industrial Property Rights Holder: 国立大学法人 熊本大学 、国立大学法人名古屋大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 4857431
  • Filing Date: 2011-11-11