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

Bresolin, Taise; Rebelo, Mauro de Freitas; Bainy, Afonso Celso Dias

doi:10.1016/j.cca.2005.04.003

Cited by 86 publications

(64 citation statements)

References 16 publications

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“…Recent molecular phylogenetic studies explored relationships among CYP3 genes between vertebrates (McArthur et al, 2003;Williams et al, 2004), showing that the CYP3s are much more conserved than the CYP2s, undergoing diversification within taxa, yet with the great majority of genes retaining sufficient identity to be classified in the same subfamily. The biochemistry of CYP3As also is broadly similar from fish to mammals (Celander et al, 1996;Hegelund and Celander, 2003;Bresolin et al, 2005). It has been suggested that the CYP3 ancestral line arose in a bilaterian ancestor between 800 and 1100 million years ago (mya) (Nebert and Gonzalez, 1987;Gonzalez, 1990), but there have been no CYP3s described in non-vertebrate species.…”

Section: Introductionmentioning

confidence: 99%

Isolation and phylogeny of novel cytochrome P450 genes from tunicates (Ciona spp.): A CYP3 line in early deuterostomes?

Verslycke

Goldstone

Stegeman

2006

Molecular Phylogenetics and Evolution

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Cytochromes P450 (CYPs) form a gene superfamily involved in the biotransformation of numerous endogenous and exogenous natural and synthetic compounds. In humans, CYP3A4 is regarded as one of the most important CYPs due to its abundance in liver and its capacity to metabolize more than 50% of all clinically used drugs. It has been suggested that all CYP3s arose from a common ancestral gene lineage that diverged between 800 and 1100 million years ago, before the deuterostome-protostome split. While CYP3s are well known in mammals and have been described in lower vertebrates, they have not been reported in non-vertebrate deuterostomes. Members of the genus Ciona belong to the tunicates, whose lineage is thought to be the most basal among the chordates, and from which the vertebrate line diverged. Here we describe the cloning, exon-intron structure, phylogeny, and estimated expression of four novel genes from Ciona intestinalis. We also describe the gene structure and phylogeny of homologous genes in Ciona savignyi. Comparing these genes with other members of the CYP clan 3, show that the Ciona sequences bear remarkable similarity to vertebrate CYP3A genes, and may be an early deuterostome CYP3 line.

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Section: Introductionmentioning

confidence: 99%

Isolation and phylogeny of novel cytochrome P450 genes from tunicates (Ciona spp.): A CYP3 line in early deuterostomes?

Verslycke

Goldstone

Stegeman

2006

Molecular Phylogenetics and Evolution

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“…Similar to mammals, some drugs and endogenous compounds can induce CYP3A gene expression in reptiles, amphibians, and fish. Chemically-induced upregulation of CYP3A expression has been demonstrated in microsomes from alligator liver by phenobarbital and 3-methylcholanthrene [192], in microsomes from a toad epithelial cell line by dexamethasone and corticosterone [193], in Atlantic cod by alkylphenols [194], in rainbow trout and killifish by ketoconazole [195], in adult zebrafish liver by pregnenolone 16α-carbonitrile (but not clotrimazole or nifedipine) [185], and in larval zebrafish foregut by rifampin and dexamethasone [196]. The molecular mechanism of CYP3A induction in the species mentioned above has not been determined.…”

Section: Nr1i Subfamily Members In Non-mammalian Speciesmentioning

confidence: 99%

“…The dominant role of the Xenopus laevis BXRs in regulating early frog development [35,87,89], and of the detection of VDR in early frog embyos [64] and of PXR in larval zebrafish [185], suggests that PXR and VDR may generally be important developmental regulators in non-mammalian vertebrates. Developmental roles of PXR and CAR in mammals have not been described.…”

Section: Nr1i Subfamily Members In Non-mammalian Speciesmentioning

confidence: 99%

Evolution and Function of the NR1I Nuclear Hormone Receptor Subfamily (VDR, PXR, and CAR) with Respect to Metabolism of Xenobiotics and Endogenous Compounds

Reschly¹,

Krasowski²

2006

CDM

126

130

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The NR1I subfamily of nuclear hormone receptors includes the 1,25-(OH) 2 -vitamin D 3 receptor (VDR; NR1I1), pregnane X receptor (PXR; NR1I2), and constitutive androstane receptor (CAR; NR1I3). PXR and VDR are found in diverse vertebrates from fish to mammals while CAR is restricted to mammals. Current evidence suggests that the CAR gene arose from a duplication of an ancestral PXR gene, and that PXR and VDR arose from duplication of an ancestral gene, represented now by a single gene in the invertebrate Ciona intestinalis. Aside from the high-affinity effects of 1,25-(OH) 2 -vitamin D 3 on VDRs, the NR1I subfamily members are functionally united by the ability to bind potentially toxic endogenous compounds with low affinity and initiate changes in gene expression that lead to enhanced metabolism and elimination (e.g., induction of cytochrome P450 3A4 expression in humans). The detoxification role of VDR seems limited to sensing high concentrations of certain toxic bile salts, such as lithocholic acid, whereas PXR and CAR have the ability to recognize structurally diverse compounds. PXR and CAR show the highest degree of crossspecies variation in the ligand-binding domain of the entire vertebrate nuclear hormone receptor superfamily, suggesting adaptation to species-specific ligands. This review examines the insights that phylogenetic and experimental studies provide into the function of VDR, PXR, and CAR, and how the functions of these receptors have expanded to evolutionary advantage in humans and other animals.

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“…The CYP3A activity and expression are regulated by PXR [13,14]. The PXR is a member of the nuclear hormone receptor superfamily.…”

Section: Discussionmentioning

confidence: 99%

“…In fish, they are regulated by the same receptors as in mammals, namely, through the pregnane X receptor (PXR) [13][14][15]. The CYP3A expression can also be modulated by the constitutive androstane receptor, but the constitutive androstane receptor is restricted to mammals [16,17].…”

Section: Introductionmentioning

confidence: 99%

A microtiter‐plate‐based cytochrome P450 3A activity assay in fish cell lines

Christen

Oggier

Fent

2009

Enviro Toxic and Chemistry

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Abstract-Enzymes belonging to the cytochrome P450 3A (CYP3A) subfamily play an important role in the metabolism of endogenous substances and xenobiotics, including pharmaceuticals. Xenobiotics can alter CYP3A expression and activity, and therefore, changes in CYP3A activity may serve as a biomarker of xenobiotic exposure. To determine changes in CYP3A enzyme activity for environmental risk assessment of xenobiotics including pharmaceuticals, high-throughput assays are needed, but these are missing for fish cells to date. Here, we report on the development of a fluorescent-based CYP3A high-throughput assay for four fish cell lines cultivated in 96-well plates based on 7-benzyloxy-4-trifluoromethylcoumarin as a CYP3A substrate. We show that human CYP3A substrate BFC is catalyzed by fish CYP3A enzymes to a fluorescent product. Its formation is dependent on cell numbers and incubation time. Furthermore, we demonstrate that with this new CYP3A assay induction and inhibition of enzyme activity by pharmaceuticals can be determined. This new cell-based assay is suitable for detection of alteration in CYP3A enzyme activity in largescale experiments for screening of pharmaceuticals occurring in the environment.

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

Cited by 86 publications

References 16 publications

Isolation and phylogeny of novel cytochrome P450 genes from tunicates (Ciona spp.): A CYP3 line in early deuterostomes?

Isolation and phylogeny of novel cytochrome P450 genes from tunicates (Ciona spp.): A CYP3 line in early deuterostomes?

Evolution and Function of the NR1I Nuclear Hormone Receptor Subfamily (VDR, PXR, and CAR) with Respect to Metabolism of Xenobiotics and Endogenous Compounds

A microtiter‐plate‐based cytochrome P450 3A activity assay in fish cell lines

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