Expression of PXR, CYP3A and MDR1 genes in liver of zebrafish

被引:104
作者
Bresolin, T
Rebelo, MD
Bainy, ACD [1 ]
机构
[1] Univ Fed Santa Catarina, CCB, Dept Bioquim, Lab Biomarcadores Contaminacao Aquat & Imunoquim, BR-88040900 Florianopolis, SC, Brazil
[2] Univ Fed Rio de Janeiro, CCS, IBCCF, BR-21941900 Rio De Janeiro, Brazil
来源
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY | 2005年 / 140卷 / 3-4期
关键词
pregnane X-receptor; cytochrome P4503A; multidrug-resistance; zebrafsh; pregnenolone; 16; alpha-carboninitrile; clotrimazole; nifedipine; PXR; CYP3A; MDR;
D O I
10.1016/j.cca.2005.04.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Pregnane X Receptor (PXR) is a nuclear receptor involved in the transcriptional regulation of drug-metabolizing enzymes and transporters. In mammals, many xenobiotics induce the expression of cytochrome P4503A (CYP3A) and the multiple drug resistance 1 (MDR1) genes via the PXR pathway. Little attention has been given to studies about the identification and biological function of PXR homologues in non-mammalian species. Zebrafish is being widely used and accepted as model for toxicological and pharmacological studies to understand the mechanisms of human diseases and identify conserved signaling pathways. The aim of this study was to evaluate the in vivo expression of PXR, CYP3A and MDR1 genes in liver of zebrafish treated with the synthetic steroid pregnenolone 16 alpha-carboninitrile (PCN), the antimycotic clotrimazole (CTZ) and the antianginal drug nifedipine (NIF). The liver of fish treated with PCN showed a 1.9-fold induction in the PXR followed by 1.8-fold induction in the CYP3A and 1.6-fold induction in the MDR1 mRNA. CTZ and NIF did not affect statistically the expression of PXR, CYP3A and MDR1. The similar pattern of mRNA expression of PXR, CYP3A and MDR1 genes found in fish treated with different PXR inducers suggests that the intrinsic association between these three genes is conserved in zebrafish.. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:403 / 407
页数:5
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