Biomarkers for ischemia and renal faiure

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659062
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• 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)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 1-メチルアデノシン / 修飾核酸 / 急性虚血 / 腎機能障害 / 酸化ストレス

Research Abstract

Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases including acute kidney injury and chronic kidney disease. Its early detection is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we demonstrate oxidative stress induces direct conformational change in tRNA structure and the change promotes subsequent tRNA fragmentation. Such tRNA changes occur much earlier than DNA damage. By various types of tissue damage model (ischemic reperfusion, toxic injury), the circulating tRNA-derivative levels are increased and the increase is more rapid than the known damage markers. In humans, the circulating tRNA-derivatives also increase under renal ischemia conditions. It also correlates with mortality in the general population (n=1,033 for 6.7 year follow up) . Therefore, tRNA damage reflects early oxidative stress damage and its detection is a useful tool for identifying organ damages and forming a clinical prognosis.

Research Products

• [Journal Article] Conformational Change in tRNA is an Early Indicator of Acute Cellular Damage with Prognostic Significance (2014)
  • Author(s): Mishima E., Inoue C., Saigusa D., Inoue R., Ito K., Ito S., Tomioka Y., Itoh K. and Abe T.
  • Journal Title: J . Am. Soc. Nephrol. Volume: pii : ASN (Epub ahead of print) Pages: 2013091001
  • Peer Reviewed
• [Journal Article] Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA (2013)
  • Author(s): Akiyama Y., Kikuchi K., Saigusa D., Suzuki T., Takeuchi Y., Mishima E., Yamamoto Y., Ishida A., Sugawara D., Shima H., Toyohara T., Suzuki C., Souma T., Moriguchi T., Tomioka Y., Ito S. and AbeT.
  • Journal Title: Plos One Volume: 8 Pages: e66518
  • DOI: 10.1371/journal.pone.0066518
  • Peer Reviewed
• [Journal Article] Mutation of the Mg^<2+> Transporter SLC41A1 Results in a Nephronophthisis-Like Phenotype (2013)
  • Author(s): Hurd TW, Edgar A. Otto EA, Mishima E, Gee HY, Inoue H., Inazu M., Yamada H., Halbritter J., Seki, G., Konishi M., Zhou W., Yamane T., Murakami S., Caridi G., Ghiggeri G., AbeT. and Hildebrandt F.
  • Journal Title: J . Am. Soc. Nephrol. Volume: 24 Pages: 967-977
  • DOI: 10.1681/ASN.2012101034
  • Peer Reviewed
• [Presentation] CE-MSを用いた透析患者の病態に特有な尿毒症物質の同定 (2013)
  • Author(s): 秋山泰利
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2013-05-12
• [Presentation] エリスロポエチン産生を増強させる化合物群の探索と同定(その1) (2013)
  • Author(s): 佐原利人
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2013-05-12
• [Presentation] エリスロポエチン産生を増強させる化合物群の探索と同定(その2) (2013)
  • Author(s): 鈴木雄介
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2013-05-12
• [Presentation] tRNAの挙動検知はDNAダメージよりも早期の虚血組織障害マーカーとなる (2013)
  • Author(s): 三島英換
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2013-05-10
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~takaabe/
• [Patent(Industrial Property Rights)] 腎機能障害の予防又は改善剤 (2013)
  • Inventor(s): 阿部 高明
  • Industrial Property Rights Holder: 阿部 高明
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-209539
  • Filing Date: 2013-10-04
• [Patent(Industrial Property Rights)] エリスロポエチン産生促進剤 (2013)
  • Inventor(s): 阿部 高明
  • Industrial Property Rights Holder: 阿部 高明
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: JP2013/006916
  • Filing Date: 2013-11-25
  • Overseas