Volume 13, Issue 8
Research Article

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

Young‐Eun Cho

Department of Molecular Medicine, Cell and Matrix Biology Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

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Pyong‐Gon Moon

Department of Molecular Medicine, Cell and Matrix Biology Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

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Jeong‐Eun Lee

Department of Molecular Medicine, Cell and Matrix Biology Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

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Thoudam S. K. Singh

Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

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Wonku Kang

College of Pharmacy, Yeungnam University, Kyoungbuk, Republic of Korea

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Hyun‐Chul Lee

D&P Biotech, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

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Myung‐Hoon Lee

D&P Biotech, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

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Sang‐Hyun Kim

Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

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Moon‐Chang Baek

Corresponding Author

Department of Molecular Medicine, Cell and Matrix Biology Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

Correspondence: Professor Moon‐Chang Baek, Department of Molecular Medicine, School of Medicine, Kyungpook National University, 101 Dongin‐dong 2 Ga, Jung‐Gu, Daegu, 700‐422, Republic of Korea

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Fax: +82‐53‐420‐4944

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First published: 16 January 2013
Citations: 25

Colour Online:: See the article online to view Figs. 3 and 6 in colour.

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.

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