Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage
| Autor: | Daisuke Saigusa, Venkata S. Sabbisetti, Yusuke Suzuki, Takafumi Toyohara, Takayoshi Ohkubo, Masatake Araki, Takehiro Suzuki, Yoshikatu Saiki, Yoshihisa Tomioka, Chisako Inoue, David B. Mount, Joseph V. Bonventre, Hisato Shima, Yosuke Akamatsu, Takaharu Ichimura, Ryusuke Inoue, Yuri Tsukui, Yutaka Imai, Tomoyoshi Soga, Eikan Mishima, Takaaki Abe, Daisuke Jinno, Ritsuko Shimizu, Yasutoshi Akiyama, Shigehito Miyagi, Chitose Suzuki, Haruka Shinke, Yoichi Takeuchi, Kimi Araki, Teiji Tominaga, Satohiro Masuda, Kunihiko Itoh, Ken Ichi Yamamura, Koki Ito, Naoki Kawagisihi, Sadayoshi Ito |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Adenosine DNA damage Population Molecular Conformation Apoptosis Oxidative phosphorylation Biology medicine.disease_cause Japan RNA Transfer Up Front Matters Internal medicine medicine Animals Humans Rats Wistar Renal Insufficiency Chronic Fragmentation (cell biology) education Aged Mice Knockout education.field_of_study Renal ischemia RNA General Medicine Acute Kidney Injury Middle Aged Mice Inbred C57BL Oxidative Stress Basic Research Endocrinology Toxic injury Biochemistry Nephrology Case-Control Studies Female Oxidative stress DNA Damage |
| Zdroj: | Journal of the American Society of Nephrology. 25:2316-2326 |
| ISSN: | 1046-6673 |
| DOI: | 10.1681/asn.2013091001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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