0000000000714761

AUTHOR

Elke Schaeffeler

showing 5 related works from this author

Variability in human hepatic MRP4 expression: influence of cholestasis and genotype

2007

The multidrug resistance protein 4 (MRP4) is an efflux transporter involved in the transport of endogenous substrates and xenobiotics. We measured MRP4 mRNA and protein expression in human livers and found a 38- and 45-fold variability, respectively. We sequenced 2 kb of the 5'-flanking region, all exons and intron/exon boundaries of the MRP4 gene in 95 patients and identified 74 genetic variants including 10 non-synonymous variations, seven of them being located in highly conserved regions. None of the detected polymorphisms was significantly associated with changes in the MRP4 mRNA or protein expression. Immunofluorescence microscopy indicated that none of the non-synonymous variations af…

AdultMaleGenotypeProtein ConformationBiologyPolymorphism Single NucleotideExonCholestasisTerminology as TopicGenotypeGenetic variationGeneticsmedicineHumansRNA MessengerGeneCellular localizationPharmacologyMessenger RNACholestasisPolymorphism GeneticReverse Transcriptase Polymerase Chain ReactionIntronGenetic VariationDNAmedicine.diseaseImmunohistochemistryMolecular biologyIntronsGene Expression RegulationHaplotypesLiverMicroscopy FluorescenceMolecular MedicineFemaleMultidrug Resistance-Associated ProteinsThe Pharmacogenomics Journal
researchProduct

Designer Thiopurine-analogues for Optimised Immunosuppression in Inflammatory Bowel Diseases.

2015

Background and Aims: The clinical use of azathioprine and 6-mercaptopurine is limited by their delayed onset of action and potential side effects such as myelosuppression and hepatotoxicity. As these drugs specifically target the Vav1/Rac1 signalling pathway in T lamina propria lymphocytes via their metabolite 6-thio-GTP, we studied expression and optimised suppression of this pathway in inflammatory bowel diseases [IBD]. Methods: Rac1 and Vav1 expressions were analysed in mucosal immune cells in IBD patients. Targeted molecular modelling of the 6-thio-GTP molecule was performed to optimise Rac1 blockade; 44 modified designer thiopurine-analogues were tested for apoptosis induction, potenti…

0301 basic medicinerac1 GTP-Binding Proteinmedicine.medical_treatmentT-LymphocytesAzathioprineApoptosisInflammatory bowel diseaseDesigner Drugs03 medical and health sciences0302 clinical medicineImmune systemIntestinal mucosamedicineHumansIntestinal MucosaProto-Oncogene Proteins c-vavLamina propriaThiopurine methyltransferasebiologybusiness.industryMercaptopurineGastroenterologyImmunosuppressionGeneral Medicinemedicine.diseaseInflammatory Bowel Diseases030104 developmental biologymedicine.anatomical_structureApoptosisCase-Control StudiesDrug DesignImmunologybiology.protein030211 gastroenterology & hepatologybusinessBiomarkersImmunosuppressive Agentsmedicine.drugSignal TransductionJournal of Crohn'scolitis
researchProduct

Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes: implications for atherosclerosis.

2016

The first ATP-competitive p38α MAPK/MAPK14 inhibitor with excellent in vivo efficacy and selectivity, skepinone-L, is now available. We investigated the impact of selective p38α MAPK/MAPK14 inhibition on enzymatically modified LDL (eLDL) stimulated human monocytes with its implications for atherosclerosis. Among the different p38 MAPK isoforms, p38α/MAPK14 was the predominantly expressed and activated isoform in isolated human peripheral blood monocytes. Moreover, eLDL colocalized with macrophages positive for p38α MAPK/MAPK14 in human carotid endarterectomy specimens. Using the human leukemia cell line THP-1 and/or primary monocyte-derived macrophages, skepinone-L inhibited eLDL-induced ac…

0301 basic medicineAdultMaleChemokineMAP Kinase Signaling Systemp38 mitogen-activated protein kinasesCD36CCL4Dibenzocycloheptenes030204 cardiovascular system & hematologyBiochemistryGene Expression Regulation EnzymologicMonocytesMitogen-Activated Protein Kinase 1403 medical and health sciences0302 clinical medicineCell Line TumorGeneticsHumansInterleukin 8Molecular BiologyFoam cellMAPK14AgedAged 80 and overCaspase 7biologyChemistryCaspase 3Cholesterol LDLAtherosclerosisMolecular biology030104 developmental biologyBiochemistryMitogen-activated protein kinasebiology.proteinFemaleBiotechnologyFASEB journal : official publication of the Federation of American Societies for Experimental Biology
researchProduct

Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner

2016

ABSTRACT Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wil…

0301 basic medicineMaleCancer Researchmedicine.medical_specialtyHeterozygoteNitric Oxide Synthase Type IIIOffspringBiology03 medical and health sciencesGenomic ImprintingMiceSex FactorsEnosInternal medicineFetal programmingmedicineAnimalsEpigeneticsMolecular BiologyGeneFatty liverWild typeHeterozygote advantageDNA Methylationmedicine.diseasebiology.organism_classificationFatty LiverMice Inbred C57BL030104 developmental biologyEndocrinologyPhenotypeKnockout mouseeNOSCarbohydrate MetabolismFemaleEpigeneticsInstitut für ErnährungswissenschaftmetabolismResearch Paper
researchProduct

Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner

2016

Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mi…

researchProduct