論文

査読有り
2014年10月

Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
  • Eikan Mishima
  • ,
  • Chisako Inoue
  • ,
  • Daisuke Saigusa
  • ,
  • Ryusuke Inoue
  • ,
  • Koki Ito
  • ,
  • Yusuke Suzuki
  • ,
  • Daisuke Jinno
  • ,
  • Yuri Tsukui
  • ,
  • Yosuke Akamatsu
  • ,
  • Masatake Araki
  • ,
  • Kimi Araki
  • ,
  • Ritsuko Shimizu
  • ,
  • Haruka Shinke
  • ,
  • Takehiro Suzuki
  • ,
  • Yoichi Takeuchi
  • ,
  • Hisato Shima
  • ,
  • Yasutoshi Akiyama
  • ,
  • Takafumi Toyohara
  • ,
  • Chitose Suzuki
  • ,
  • Yoshikatu Saiki
  • ,
  • Teiji Tominaga
  • ,
  • Shigehito Miyagi
  • ,
  • Naoki Kawagisihi
  • ,
  • Tomoyoshi Soga
  • ,
  • Takayoshi Ohkubo
  • ,
  • Kenichi Yamamura
  • ,
  • Yutaka Imai
  • ,
  • Satohiro Masuda
  • ,
  • Venkata Sabbisetti
  • ,
  • Takaharu Ichimura
  • ,
  • David B. Mount
  • ,
  • Joseph V. Bonventre
  • ,
  • Sadayoshi Ito
  • ,
  • Yoshihisa Tomioka
  • ,
  • Kunihiko Itoh
  • ,
  • Takaaki Abe

25
10
開始ページ
2316
終了ページ
2326
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1681/ASN.2013091001
出版者・発行元
AMER SOC NEPHROLOGY

Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis.

Web of Science ® 被引用回数 : 59

リンク情報
DOI
https://doi.org/10.1681/ASN.2013091001
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24833129
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000342403800020&DestApp=WOS_CPL

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