Integrative analysis of proteomic and transcriptomic data for identification of pathways related to simvastatin-induced hepatotoxicity

Title
Integrative analysis of proteomic and transcriptomic data for identification of pathways related to simvastatin-induced hepatotoxicity
Author(s)
강원구조영은[조영은]문평곤[문평곤]이정은[이정은]Singh TSK[Singh TSK]이현철[이현철]이명훈[이명훈]김상현[김상현]백문창[백문창]
Keywords
ACETAMINOPHEN-INDUCED HEPATOTOXICITY; STATIN-INDUCED MYOPATHY; FATTY-ACID SYNTHASE; GENE-EXPRESSION; APOLIPOPROTEIN-B; HEPG2 CELLS; MESSENGER-RNA; LIVER-INJURY; MICE; METABOLISM
Issue Date
201304
Publisher
WILEY-BLACKWELL
Citation
PROTEOMICS, v.13, no.8, pp.1257 - 1275
Abstract
Hepatocytes are used widely as a cell model for investigation of xenobiotic metabolism and the toxic mechanism of drugs. Simvastatin is the first statin drug used extensively in clinical practice for control of elevated cholesterol or hypercholesterolemia. However, it has also been reported to cause adverse effects in liver due to cellular damage. In this study, for proteomic and transcriptomic analysis, rat primary hepatocytes were exposed to simvastatin at IC20 concentration for 24 h. Among a total of 607 differentially expressed proteins, 61 upregulated and 29 downregulated proteins have been identified in the simvastatin-treated group. At the mRNA level, results of transcriptomic analysis revealed 206 upregulated and 41 downregulated genes in the simvastatin-treated group. Based on results of transcriptomic and proteomic analysis, NRF2-mediated oxidative stress response, xenobiotics by metabolism of cytochrome P450, fatty acid metabolism, bile metabolism, and urea cycle and inflammation metabolism pathways were focused using IPA software. Genes (FASN, UGT2B, ALDH1A1, CYP1A2, GSTA2, HAP90, IL-6, IL-1, FABP4, and ABC11) and proteins (FASN, CYP2D1, UG2TB, ALDH1A1, GSTA2, HSP90, FABP4, and ABCB11) related to several important pathways were confirmed by real-time PCR andWestern blot analysis, respectively. This study will provide new insight into the potential toxic pathways induced by simvastatin.
URI
http://hdl.handle.net/YU.REPOSITORY/26058http://dx.doi.org/10.1002/pmic.201200368
ISSN
1615-9853
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약학대학 > 약학부 > Articles
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