| Project/Area Number |
24659062
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
ABE Takaaki 東北大学, 医工学研究科, 教授 (80292209)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| 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 / 腎不全物質 / メタボローム解析 / LC/MS/MS |
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| 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.
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