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Mathematical Models in the Description of Pregnane X Receptor (PXR)-Regulated Cytochrome P450 Enzyme Induction

dc.date.accessioned2024-08-26T16:15:39Z
dc.date.available2024-08-26T16:15:39Z
dc.date.issued2018-06-15
dc.identifierdoi:10.17170/kobra-2024082310711
dc.identifier.urihttp://hdl.handle.net/123456789/15987
dc.description.sponsorshipThis work was supported by SVV 260 414, GAUK 110/50/75006, Czech Scientific agency (GACR 17-06841S), and EFSA-CDN (No. CZ.02.1.01/0.0/0.0/16_019/0000841) co-funded by ERDF and project No. 00.265.2015 of the Klaus Tschira Stiftung GmbH.eng
dc.language.isoeng
dc.rightsNamensnennung 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectpregnane X receptoreng
dc.subjectgene regulationeng
dc.subjectmathematical modelseng
dc.subjectsimulationeng
dc.subject.ddc510
dc.subject.ddc600
dc.titleMathematical Models in the Description of Pregnane X Receptor (PXR)-Regulated Cytochrome P450 Enzyme Inductioneng
dc.typeAufsatz
dcterms.abstractThe pregnane X receptor (PXR) is a drug/xenobiotic-activated transcription factor of crucial importance for major cytochrome P450 xenobiotic-metabolizing enzymes (CYP) expression and regulation in the liver and the intestine. One of the major target genes regulated by PXR is the cytochrome P450 enzyme (CYP3A4), which is the most important human drug-metabolizing enzyme. In addition, PXR is supposed to be involved both in basal and/or inducible expression of many other CYPs, such as CYP2B6, CYP2C8, 2C9 and 2C19, CYP3A5, CYP3A7, and CYP2A6. Interestingly, the dynamics of PXR-mediated target genes regulation has not been systematically studied and we have only a few mechanistic mathematical and biologically based models describing gene expression dynamics after PXR activation in cellular models. Furthermore, few indirect mathematical PKPD models for prediction of CYP3A metabolic activity in vivo have been built based on compartmental models with respect to drug–drug interactions or hormonal crosstalk. Importantly, several negative feedback loops have been described in PXR regulation. Although current mathematical models propose these adaptive mechanisms, a comprehensive mathematical model based on sufficient experimental data is still missing. In the current review, we summarize and compare these models and address some issues that should be considered for the improvement of PXR-mediated gene regulation modelling as well as for our better understanding of the quantitative and spatial dynamics of CYPs expression.eng
dcterms.accessRightsopen access
dcterms.creatorTebbens, Erik Jurjen Duintjer
dcterms.creatorAzar, Malek
dcterms.creatorFriedmann, Elfriede
dcterms.creatorLanzendörfer, Martin
dcterms.creatorPávek, Petr
dc.relation.doidoi:10.3390/ijms19061785
dc.relation.projectidproject No. 00.265.2015
dc.subject.swdGenregulationger
dc.subject.swdMathematisches Modellger
dc.subject.swdSimulationger
dc.type.versionpublishedVersion
dcterms.source.identifiereissn:1422-0067
dcterms.source.issueIssue 6
dcterms.source.journalInternational Journal of Molecular Scienceseng
dcterms.source.volumeVolume 19
kup.iskupfalse
dcterms.source.articlenumber1785


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Except where otherwise noted, this item's license is described as Namensnennung 4.0 International