| Project/Area Number |
15K19278
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Legal medicine
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| Research Institution | Meikai University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | LINE-1 / ゲノム不安定性 / 乱用薬物 / レトロエレメント / イミプラミン / NR2A / MAPK / レトロトランスポジション / モルヒネ / クエン酸フェンタニル / TLR4 / DSB |
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| Outline of Final Research Achievements |
The human genome consists of interspersed repeats, sequences that mark the long-standing activities and high preservative quality of mobile DNA. Long interspersed element-1 (LINE-1 or L1), a highly active autonomous retrotransposon (RTP), is the most abundant endogenous retroelement in humans accounting for approximately 17% of the human genome, approximately 10% of which are "hot L1" copies primed for jumping within the genome. The aim of this study was to identify the mechanism by which abuse drugs induce L1-RTP. We found that methamphetamine, cocaine, morphine, fentanyl and imipramine induced L1-RTP. Results revealed that imipramine induced L1-RTP in neuronal cell lines. This effect was found to be reverse transcriptase-dependent, but not accompanied by the induction of double-strand breaks. Overall, L1-RTP induced by abuse drugs is a novel type of genomic instability, and analysis of this phenomenon might be a novel approach to elucidate the mechanism of substance-use disorders.
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