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Expression of genes involved in xenobiotic metabolism and transport in end-stage liver disease: up-regulation of ABCC4 and CYP1B1

Kurzawski, Mateusz, Dziedziejko, Violetta, Post, Mariola, Wójcicki, Maciej, Urasińska, Elżbieta, Miętkiewski, Janusz, Droździk, Marek·2012·Pharmacological Reports
DOI 10.1016/s1734-1140(12)70888-5
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Abstract

Background Expression of drug-metabolizing enzymes and drug transporters in liver is mainly regulated by a system of nuclear receptors. The aim of the current study was to investigate the expression of nuclear receptors, as well as these enzymes and transporters, in liver samples from patients suffering from end-stage liver disease of various etiologies (HCV infection, alcohol liver disease, and primary sclerosis cholangitis). Methods Gene expression was measured using quantitative real-time PCR with surgical specimens from livers of patients with end-stage liver disease, and non-tumoral liver tissue that served as control. Results Our study confirmed that the expression of most phase I enzymes is suppressed in end-stage liver disease, and is correlated with a decrease in NR1I2 and NR1I3, the main regulators of xenobiotic metabolism. While mRNA levels of phase II enzymes were generally unchanged, some ABC transporters were up-regulated. The most spectacular increases in expression were observed with ABCC4 (MRP4) - at the mRNA level, and CYP1B1 - at both the mRNA and protein levels. We also demonstrated that IL-6 can induce CYP1B1 expression independently of CYP1A1, in a human hepatocellular liver carcinoma cell line. Conclusions As CYP1B1 is an enzyme which converts various substrates into carcinogenous metabolites, its overexpression in liver may be one of the factors increasing the risk of hepatic cancers in patients with liver disease. CYP1A1 and CYP1B1 are often referred…

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  • ABCC4 is highly expressed in the liver and localized to the basolateral hepatocyte membrane, where it mediates transport of molecules into the bloodstream.

    “ABCC4 is highly expressed in the liver and is localized to the basolateral hepatocyte membrane, where it mediates the transport of molecules into the bloodstream51,89,90.”

    From ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver (2025) · cites this paper as [90]

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Metadata

Authors
Kurzawski, M., Dziedziejko, V., Post, M., Wójcicki, M., Urasińska, E., Miętkiewski, J., & Droździk, M.
Venue
Pharmacological Reports
Publisher
Springer Science and Business Media LLC
Published
2012-07
Volume
64
Issue
4
Pages
927-939
ISSN
1734-1140
DOI
10.1016/s1734-1140(12)70888-5
Cited by
52
References
0
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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