Evaluation of Potential Biomarkers for Thioacetamide-induced Hepatotoxicity using siRNA

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Kang, Jin Seok; Yum, Young Na; Han, Eul Sik; Kim, Joo Hwan; Lee, Eun Mi; Ryu, Doug Young; Kim, Young Hee; Yang, Sung Hee; Kim, Seung Hee; Park, Sue Nie
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한국응용약물학회 = The Korean Society of Applied Pharmacology
Biomolecules & Therapeutics 16, 197-202
In our previous publication we compared the gene expression profiles on hepatotoxicants exposure to assess the comparability between in vivo and in vitro test systems. We investigated global gene expression from both mouse liver and mouse hepatic cell line treated with thioacetamide (TAA) and identified several common genes. In this study, we selected genes to validate them as potential biomarkers for hepatotoxicity on the relevance of in vitro and in vivo system. Three up-regulated, aquaporin 8 (Aqp8), glutathione peroxidase 1 (Gpx1), succinate-CoA ligase, GDP-forming, alpha subunit (Suclg1) and two down-regulated, DnaJ (Hsp40) homolog subfamily C member 5 (Dnajc5) and tumor protein D52 (Tpd52) genes were tested for their effects in vitro. For characterization of gene function, short interfering RNA (siRNA) for each gene was synthesized and transfected in mouse hepatic cell line, BNL CL.2. Cell viability, mRNA expression level and morphological alterations were investigated. We confirmed siRNA transfection against selected five genes induced down-regulation of respective mRNA expression. siRNA transfection in general decreased cell viability in different degrees and induced morphological changes such as membrane thickening and alterations of intracellular structures. This suggests that these genes could be associated with TAA-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity for better understanding of its mechanism.
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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