| Project/Area Number |
25460862
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Aki Toshihiko 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (60304474)
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| Co-Investigator(Kenkyū-buntansha) |
Koichi Uemura 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30244586)
船越 丈司 東京医科歯科大学, 医歯(薬)学総合研究科, 助教 (40444715)
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| Co-Investigator(Renkei-kenkyūsha) |
Takeshi Funakoshi 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (40444715)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | プロテオミクス / トランスクリプトミクス / 薬毒物 / 細胞死 / パラコート / コカイン / 中毒学 / ミトコンドリア / オートファジー / 肺線維症 / アポトーシス / 心筋障害 |
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| Outline of Final Research Achievements |
To elucidate molecular mechanism of drug toxicity, integrated omics analysis has been performed. Proteomics, transcriptomics, and metabolomics analyzes were used to evaluated the cytotoxicity of ethanol, methamphetamine, and LPS on neuronal, cardiac, and lung cells. Using DNA microarray-based transcriptome analysis, we found that norephedrine induced neuronal cell death through disrupting cholesterol homeostasis. This observation was confirmed by GC-MS-based analysis of cholesterol contents in the cells. In addition, we found that LPS induced extrusion of mitochondria from hepatocytes without loss of plasma membrane integrity. This observation was found by use of MALDI-TOF-MS-based proteomics analysis. Collectively, integrated omics analysis has been proved as efficient and useful method to evaluate the cytotoxicity of drugs.
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