Expression of PXR, CYP3A and MDR1 genes in liver of zebrafish.
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 16alpha-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.
Bresolin
Taise
T
Laboratório de Biomarcadores de Contaminação Aquática e Imunoquímica, Departamento de Bioquímica, CCB, Universidade Federal de Santa Catarina, Florianópolis 88040-900, Brazil.
de Freitas Rebelo
Mauro
M
Celso Dias Bainy
Afonso
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D003022:Clotrimazole / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D000077297:Pregnane X Receptor; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics*; D015027:Zebrafish / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011285:Pregnenolone Carbonitrile; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D003022:Clotrimazole; D009543:Nifedipine