Relation between 1-metyl adenosinea and rheumatoid arthritis

• Project/Area Number: 26305007
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 海外学術
• Research Field: Medical pharmacy
• Research Institution: Tohoku University
• Principal Investigator: ABE Takaaki 東北大学, 医工学研究科, 教授 (80292209)
• Co-Investigator(Kenkyū-buntansha): 石井 智徳 東北大学, 大学病院, 教授 (10282138) ; 山崎 聡士 広島大学, 大学病院, その他 (30367388) ; 伊藤 邦彦 静岡県立大学, 薬学部, 教授 (90221770)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 酸化ストレス / 1-メチルアデノシン / リウマチ / tRNA / 遷移RNA / 炎症 / 特異抗体 / 修飾核酸 / ミトコンドリア / 虚血

Outline of Final Research Achievements

It is critical to make accurate evaluation of disease activity of rheumatoid arthritis (RA) for a better treatment. We generated a novel method to monitor the stress condition in human by using a monoclonal antibody against mononucleoside 1-methyladenosine (m1A), which is a unique to the eukaryotic tRNA-specific modified nucleoside. By using this antibody, we have demonstrated that the nucleotide become detectable in damaged organs when they are under stresses. The presence of mA1 is also confirmed in synovial tissue and urine form RA patients. Therefore, we hypothesize that ELISA system to measure mA1 can be used for the evaluation of RA disease activity, especially of tissue damage in inflamed joints. We applyed our mA1 ELISA to serum samples of the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS), which is a one of the largest prospective observational study designed to determine and validate biomarkers that predicted disease activity and prognosis in RA.

Research Products

• [Int'l Joint Research] ハーバード大学/リウマチ科(米国)
• [Journal Article] Evaluation of the impact of gut microbiota on uremic solute accumulation by a Capillary Electrophoresis-Time Of Flight Mass Spectroscopy-based metabolomics approach. (2017)
  • Author(s): Mishima E., Fukuda, Mukawa C, Yuri A, Kanemitsu Y., Matsumoto Y., Akiyama Y., Fukuda N. , Tsukamoto H., Asaji K., Shima H., Kikuchi K., Suzuki C., Suzuki T., Tomioka Y., Soga T., Ito S. and Takaaki Abe T.
  • Journal Title: Kidney International Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF-α and TGF-β1 pathways (2017)
  • Author(s): Shima H., Sasaki K., Suzuki T., Mukawa C., Obara T., Oba Y., Matsuo A., Kobayashi T., Mishima E., Watanabe S., Akiyama Y., Kikuchi K., Matsuhashi T., Oikawa Y., Nannto F., Akiyama Y., Ho H.-J., Chitose Suzuki C., Saigusa D., Masamune A., Tomioka Y., Masaki T., Ito S., Hayashi K. and Takaaki Abe T..
  • Journal Title: Sci Rep. Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage. (2016)
  • Author(s): Suzuki T, Kanno SI, Abe T. et al
  • Journal Title: J Am Soc Nephrol. Volume: 27 Issue: 7 Pages: 1-8
  • DOI: 10.1681/asn.2015060623
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Interactions of crizotinib and gefitinib with organic anion-transporting polypeptides (OATP)1B1, OATP1B3, and OATP2B1: gefitinib shows contradictory interaction with OATP1B3. (2016)
  • Author(s): Sato T., Ito H., Hirata A., Abe T., Mano N. and Yamaguchi H.
  • Journal Title: Xenobiotica Volume: 12 Issue: 1 Pages: 1-6
  • DOI: 10.1080/00498254.2016.1275880
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mitochonic Acid 5 (MA-5), a Derivative of the Plant Hormone Indole-3-Acetic Acid, Improves Survival of Fibroblasts from Patients with Mitochondrial Diseases (2015)
  • Author(s): Suzuki T, Yamaguchi H, Kikusato M, Matsuhashi T, Matsuo A, Sato T, Oba Y, Watanabe S, Minaki D, Saigusa D, Shimbo H, Mori N, Mishima E, Shima H, Akiyama Y, Takeuchi Y, Yuri A, Kikuchi K, Toyohara T, Suzuki C, Kohzuki M, Anzai J, Mano N, Kure S, Yanagisawa T, Tomioka Y, Toyomizu M, Ito S, Osaka H, Hayashi K, Abe T
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 236 Issue: 3 Pages: 225-232
  • DOI: 10.1620/tjem.236.225
  • NAID: 130005083526
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage (2015)
  • Author(s): Suzuki T
  • Journal Title: J Am Soc Nephrol. Volume: 26 Pages: 1-8
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Exonic Mutations in the SLC12A3 Gene Cause Exon Skipping and Premature Termination in Gitelman Syndrome (2015)
  • Author(s): 竹内陽一、三島英換、他12名
  • Journal Title: J Am Soc Nephrol Volume: 26 Issue: 2 Pages: 271-279
  • DOI: 10.1681/asn.2013091013
  • Peer Reviewed
• [Journal Article] Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD. (2015)
  • Author(s): Mishima E.
  • Journal Title: J Am Soc Nephrol. Volume: 26 Pages: 271-279
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Exonic Mutations in the SLC12A3 Gene Cause Exon Skipping and Premature Termination in Gitelman’s Syndrome. (2015)
  • Author(s): Takeuchi Y.
  • Journal Title: J Am Soc Nephrol. Volume: 26 Pages: 271-279
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD (2014)
  • Author(s): Eikan Mishima, Shinji Fukuda, Hisato Shima, Akiyoshi Hirayama, Yasutoshi Akiyama, Yoichi Takeuchi, Noriko N Fukuda, Takehiro Suzuki, Chitose Suzuki, Akinori Yuri, Koichi Kikuchi, Yoshihisa Tomioka, Sadayoshi Ito, Tomoyoshi Soga, and Takaaki Abe
  • Journal Title: J Am Soc Nephrol Volume: 26 Issue: 8 Pages: 1-8
  • DOI: 10.1681/asn.2014060530
  • Peer Reviewed
• [Journal Article] The Kidney and Uremic Toxin Removal: Glomerulus or Tubule? (2014)
  • Author(s): Masereeuw R
  • Journal Title: Semin Nephrol. Volume: 34 Issue: 2 Pages: 191-208
  • DOI: 10.1016/j.semnephrol.2014.02.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Proteomics and Metabolomics as Tools to Unravel Novel Culprits and Mechanisms of Uremic Toxicity: Instrument or Hype? (2014)
  • Author(s): Mullen W.
  • Journal Title: Semin Nephrol. Volume: 34 Issue: 2 Pages: 180-190
  • DOI: 10.1016/j.semnephrol.2014.02.009
  • Peer Reviewed
• [Presentation] 慢性腎臓病(CKD)と腸内細菌叢 (2017)
  • Author(s): 阿部高明
  • Organizer: 第20回日本病態栄養学会年次学術集会
  • Place of Presentation: 京都・京都国際会議場
  • Year and Date: 2017-01-15
  • Invited
• [Presentation] Development of a novel mitochondrial drug, MA-5 (2016)
  • Author(s): 阿部高明
  • Organizer: The 13th Conference of Asian Society for Mitochondrial Research and Medicine
  • Place of Presentation: 東京・TKPガーデンシティ品川
  • Year and Date: 2016-10-31
  • Int'l Joint Research / Invited
• [Presentation] 腸内細菌叢と腎疾患 (2016)
  • Author(s): 阿部高明
  • Organizer: 第46回腎臓学会西部学術大会
  • Place of Presentation: 宮崎・シーガイア コンベンションセンター
  • Year and Date: 2016-10-15
  • Invited
• [Presentation] 尿毒素によるエピジェネティック修飾と腎不全 (2016)
  • Author(s): 阿部高明
  • Organizer: 第61回透析医学会
  • Place of Presentation: 大阪・大阪国際会議場
  • Year and Date: 2016-06-11
  • Invited