CYP3 phylogenomics: evidence for positive selection of CYP3A4 and CYP3A7

Qiu, Huan; Taudien, Stefan; Herlyn, Holger; Schmitz, Juergen; Zhou, Yuan; Chen, Guopei; Roberto, Roberta; Rocchi, Mariano; Platzer, Matthias; Wojnowski, Leszek

doi:10.1097/fpc.0b013e3282f313f8

Cited by 40 publications

(58 citation statements)

References 62 publications

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“…Mammalian species have more CYP3A genes than fish, as a result of more recent local gene duplications (Thomas 2007, Qiu et al 2008. Zebrafish CYP3A65 (Tseng et al 2005) and human CYP3A4, CYP3A5, and CYP3A7 (Maruyama et al 2007) show similar induction patterns in the liver.…”

Section: Cyp1b1 (Jansson Et Al 2000)mentioning

confidence: 79%

“…Zebrafish CYP3A65 only produced 4-OHE 2 metabolites, when supplemented with cytochrome b 5 , while mammalian CYP3As do produce 4-OHE 2 regardless of whether cytochrome b 5 is present (Lee et al 2003). Although the mammalian CYP3A subfamily is phylogenetically clustered together with other vertebrate CYP3As, the CYP3A genes from the Actinopterygii class of ray-finned fishes, of which zebrafish are a member, cluster with fish CYP3B, CYP3C, and CYP3D genes (Qiu et al 2008). As such, fish CYP3As share less of a common evolutionary history with mammalian CYP3As than they do with fish CYP3Bs, CYP3Cs, and CYP3Ds.…”

Section: Cyp1b1 (Jansson Et Al 2000)mentioning

confidence: 99%

“…The CYP3A subfamily includes multiple genes in mammals; humans have four CYP3As (Qiu et al 2008). Most fish contain only one or two CYP3As; zebrafish (Danio rerio) have a single CYP3A gene, CYP3A65 (Qiu et al 2008). The CYP1 family contains more subfamilies in non-mammalian vertebrates.…”

Section: Introductionmentioning

confidence: 99%

“…Mammalian CYP enzymes are critical for E 2 metabolism, including those belonging to the CYP1A, CYP1B, and CYP3A subfamilies; yet, there are distinct differences in the CYP1 and CYP3 families across vertebrates. The CYP3A subfamily includes multiple genes in mammals; humans have four CYP3As (Qiu et al 2008). Most fish contain only one or two CYP3As; zebrafish (Danio rerio) have a single CYP3A gene, CYP3A65 (Qiu et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Cytochrome P450-mediated 17β-estradiol metabolism in zebrafish (Danio rerio)

Scornaienchi

Thornton²,

Willett³

et al. 2010

Journal of Endocrinology

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Cytochrome P4501 (CYP1) and CYP3A proteins are primarily responsible for the metabolism of 17b-estradiol (E 2 ) in mammals. We have cloned and heterologously expressed CYP1A, CYP1B1, CYP1C1, CYP1C2, CYP1D1, and CYP3A65 from zebrafish (Danio rerio) to determine the CYP-mediated metabolism of E 2 in a non-mammalian species. Constructs of each CYP cDNA were created using a leader sequence from the bacterial ompA gene to allow appropriate expression in Escherichia coli without 5 0 modification of the gene. Membrane vesicles were purified, and functional CYP protein was verified using carbon monoxide difference spectra and fluorescent catalytic assays with the substrates 7-ethoxyresorufin and 7-benzyloxy-4-(trifluoromethyl)-coumarin. Rates of in vitro E 2 metabolism into 4-hydroxyE 2 (4-OHE 2 ), 2-hydroxyE 2 (2-OHE 2 ), and 16a-hydroxyE 1 (16a-OHE 1 ) metabolites were determined by gas chromatography/mass spectrometry. The 2-OHE 2 metabolite was produced by all CYPs tested, while 4-OHE 2 was only detected following incubation with CYP1A, CYP1B1, CYP1C1, and CYP1C2. The 16a-OHE 1 metabolite was only produced by CYP1A. The highest rates of E 2 metabolism were from CYP1A and CYP1C1, followed by CYP1C2. CYP1B1, CYP1D1, and CYP3A65 had low rates of E 2 metabolism. E 2 metabolism by zebrafish CYP1A, CYP1C1, and CYP1C2 produced similar ratios of 4-OHE 2 to 2-OHE 2 as previous studies with mammalian CYP1As. CYP1B1 formed the highest ratio of 4-OHE 2 to 2-OHE 2 metabolites. Contrary to mammals, these results suggest that fish CYP1A and CYP1C proteins are primarily responsible for E 2 metabolism, with only minor contributions from CYP3A65 and CYP1B1. Similar to mammals, 2-OHE 2 is the predominant metabolite from CYP-mediated E 2 metabolism in fish, suggesting that all vertebrate species produce the same major E 2 metabolite.

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Section: Cyp1b1 (Jansson Et Al 2000)mentioning

confidence: 79%

Section: Cyp1b1 (Jansson Et Al 2000)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cytochrome P450-mediated 17β-estradiol metabolism in zebrafish (Danio rerio)

Scornaienchi

Thornton²,

Willett³

et al. 2010

Journal of Endocrinology

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show abstract

“…Unlike the CYP2ABFGST cluster, the CYP3A cluster is conserved well between macaque and human; the location and direction of each orthologous gene in this cluster correspond well in the two species (Qiu et al, 2008). Macaque CYP3A8(4) metabolizes typical human CYP3A4 substrates such as midazolam and nifedipine (Iwasaki et al, 2010;Uno et al, 2010) and is induced by the typical human CYP3A4 inducer, rifampicin (Kim et al, 2010), indicating that CYP3A8(4) has drug-metabolizing enzyme properties similar to human CYP3A4.…”

Section: Estradiol-regulated Drug-metabolizing Enzymes In Macaquementioning

confidence: 99%

Effect of Estradiol on Gene Expression Profile in Cynomolgus Macaque Liver: Implications for Drug-Metabolizing Enzymes

Uno

Kito²

2011

Drug Metab Dispos

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ABSTRACT:Estrogen regulation of gene expression is essential for physiological function of estrogen-responsive tissues, such as mammary glands, ovaries, and the uterus. In the liver, estrogen is responsible for sex-dependent gene expression of drug-metabolizing enzymes in rodents. However, the influence of estrogen on hepatic gene expression has not been fully investigated in primates, including human. Macaque, including cynomolgus macaque, is an important species for comparative studies aimed at understanding human physiology due to its evolutionary closeness to human. To identify estrogen-responsive genes in primate liver, therefore, hepatic gene expression was compared, by microarray analysis, in ovariectomized cynomolgus macaques treated with estradiol or solvent (control). The analysis identified 98 estradiol-responsive genes; 47 and 51 were up-and down-regulated by estradiol, respectively (>2.0-fold, P < 0.05). Expression of drug-metabolizing enzyme genes was also influenced by estradiol treatment; estradiol enhanced expression of GSTM5 (3.8-fold, P < 0.05) and CYP3A8(4) (2.7-fold, P < 0.01), but lowered expression of CYP4F12 (2.2-fold, P < 0.01), as verified by quantitative polymerase chain reaction. In particular, CYP3A8(4), orthologous to human CYP3A4, is an essential drug-metabolizing enzyme in cynomolgus macaque liver. These results suggest that expression of hepatic genes, including drug-metabolizing enzyme genes, is at least partly regulated by estradiol in cynomolgus macaque.

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Species extrapolation for the 21st century

Celander

Goldstone

Denslow

et al. 2010

Enviro Toxic and Chemistry

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Safety factors are used in ecological risk assessments to extrapolate from the toxic responses of laboratory test species to all species representing that group in the environment. More accurate extrapolation of species responses is important. Advances in understanding the mechanistic basis for toxicological responses and identifying molecular response pathways can provide a basis for extrapolation across species and, in part, an explanation for the variability in whole organism responses to toxicants. We highlight potential short- and medium-term development goals to meet our long-term aspiration of truly predictive in silico extrapolation across wildlife species' response to toxicants. A conceptual approach for considering cross-species extrapolation is presented. Critical information is required to establish evidence-based species extrapolation, including identification of critical molecular pathways and regulatory networks that are linked to the biological mode of action and species' homologies. A case study is presented that examines steroidogenesis inhibition in fish after exposure to fadrozole or prochloraz. Similar effects for each compound among fathead minnow, medaka, and zebrafish were attributed to similar inhibitor pharmacokinetic/pharmacodynamic distributions and sequences of cytochrome P45019A1/2 (CYP19A1/2). Rapid advances in homology modeling allow the prediction of interactions of chemicals with enzymes, for example, CYP19 aromatase, which would eventually allow a prediction of potential aromatase toxicity of new compounds across a range of species. Eventually, predictive models will be developed to extrapolate across species, although substantial research is still required. Knowledge gaps requiring research include defining differences in life histories (e.g., reproductive strategies), understanding tissue-specific gene expression, and defining the role of metabolism on toxic responses and how these collectively affect the power of interspecies extrapolation methods.

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CYP3 phylogenomics: evidence for positive selection of CYP3A4 and CYP3A7

Abstract: CYP3A7 and CYP3A4 may have acquired catalytic functions especially important for the evolution of hominoids and humans, respectively.

Cited by 40 publications

References 62 publications

Cytochrome P450-mediated 17β-estradiol metabolism in zebrafish (Danio rerio)

Cytochrome P450-mediated 17β-estradiol metabolism in zebrafish (Danio rerio)

Effect of Estradiol on Gene Expression Profile in Cynomolgus Macaque Liver: Implications for Drug-Metabolizing Enzymes

Species extrapolation for the 21st century

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