Molecular analysis of drug intoxication by use of integrated toxicomics

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460862
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Aki Toshihiko 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (60304474)
• 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)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• 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

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.

Free Research Field

法医学、生化学