Observational Study
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World J Gastroenterol. Jul 14, 2014; 20(26): 8681-8690
Published online Jul 14, 2014. doi: 10.3748/wjg.v20.i26.8681
Expression of P450 and nuclear receptors in normal and end-stage Chinese livers
Hong Chen, Zhong-Yang Shen, Wang Xu, Tie-Yan Fan, Jun Li, Yuan-Fu Lu, Ming-Liang Cheng, Jie Liu
Hong Chen, Zhong-Yang Shen, Wang Xu, Tie-Yan Fan, Jun Li, The Institute of Organ Transplantation, The General Hospital of Chinese People’s Armed Police Forces, Beijing 100039, China
Yuan-Fu Lu, Jie Liu, Department of Pharmacology, Kay Lab for Basic Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi 563003, Guizhou Province, China
Ming-Liang Cheng, Department of Infectious Diseases, Guiyang Medical College Hospital, Guiyang 550004, Guizhou Province, China
Author contributions: Chen H, Shen ZY, Cheng ML and Liu J designed the experiments; Chen H, Xu W, Fan TY and Li J collected samples and performed the experiments; Lu YF performed RT-PCR analysis; Cheng ML contributed reagents/analytic tools; Chen H and Liu J analyzed the data and wrote the manuscript.
Supported by Grants from the Chinese 863 project, No. 2012AA022409; and Guizhou Science and Technology Foundation, No. 2009-70019
Correspondence to: Dr. Zhong-Yang Shen, The Institute of Organ Transplantation, The General Hospital of Chinese People’s Armed Police Forces, No. 69 Yong-Ding Road, Beijing 100039, China. zhongyangshen@gmail.com
Telephone: +86-10-57976839 Fax: +86-10-68242910
Received: January 9, 2014
Revised: February 19, 2014
Accepted: April 8, 2014
Published online: July 14, 2014
Processing time: 179 Days and 17.1 Hours
Abstract

AIM: To investigate the expression of P450 enzyme genes by using end-stage liver disease samples and trimmed normal Chinese donor livers.

METHODS: The end-stage liver disease samples [n = 93, including hepatocellular carcinoma (HCC), peri-HCC tissue, hepatitis B virus cirrhosis, alcoholic cirrhosis, and severe cirrhosis] and trimmed normal Chinese donor livers (n = 35) from The Institute of Organ Transplantation in Beijing, China. Total RNA was extracted, purified, and subjected to real-time RT-PCR analysis.

RESULTS: For cytochrome P450 enzymes 1 (CYP1) family, the expression of CYP1A2 was decreased 90% in HCC, 80% in alcoholic cirrhosis, and 65% in severe cirrhosis. For CYP2 family, the expression of CAR was decreased 50% in HCC, but increased 50% in peri-HCC tissues. Similar decreases (about 50%) of CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 were observed in HCC, as compared to peri-HCC tissues and normal livers. CYP2C19 were decreased in all end-stage liver diseases and CYP2E1 also decreased in alcoholic cirrhosis and severe cirrhosis. For CYP3 family, the expression of PXR was decreased 60% in HCC, together with decreases in CYP3A4, CYP3A5, and CYP3A7. In contrast, the expression of CYP3A7 was slightly increased in HBV cirrhosis. The expression of CYP4A11 was decreased 85% in HCC, 7% in alcoholic cirrhosis and severe liver cirrhosis, along with decreases in PPARα. The 93 end-stage livers had much higher inter-individual variations in gene expression than 35 normal livers.

CONCLUSION: The expression of CYP enzyme genes and corresponding nuclear receptors was generally decreased in end-stage liver diseases, and significant differences in gene expression were evident between peri-HCC and HCC.

Keywords: Cytochrome P450; Nuclear receptors; mRNA expression; End-stage livers; Chinese donor livers; Hepatocellular carcinoma

Core tip: This study examined the expression of P450 enzyme (CYP) genes in end-stage liver diseases, including hepatocellular carcinoma (HCC), peri-HCC tissue, hepatitis B virus cirrhosis, alcoholic cirrhosis, and severe cirrhosis, and compared to normal donor livers by real-time RT-PCR analysis. The 93 end-stage livers had much higher inter-individual variations in gene expression than 35 normal livers. In general, the end-stage livers had decreased expression of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7 and CYP4A11, as well as their corresponding nuclear receptor AhR, CAR, PXR, and PPARα. HCC had dramatic decreases in CYP gene expression and nuclear receptors compared with peri-HCC tissues.