Seitz, Tina

[["dc.bibliographiccitation.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.volume","388"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Bokelmann, Kristin"],["dc.contributor.author","Pereira, Joao N. dos Santos"],["dc.contributor.author","Mueller, T."],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Koepsell, Hermann"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.date.accessioned","2018-11-07T10:01:10Z"],["dc.date.available","2018-11-07T10:01:10Z"],["dc.date.issued","2015"],["dc.format.extent","S54"],["dc.identifier.isi","000359539100217"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37958"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","81st Annual Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und Toxikologie-e-V"],["dc.relation.eventlocation","Kiel, GERMANY"],["dc.relation.issn","1432-1912"],["dc.relation.issn","0028-1298"],["dc.title","Does the apparently predictive haplotype Met408-Del420 really exist and how strong it affects OCT1 activity?"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Biological Chemistry"],["dc.bibliographiccitation.volume","398"],["dc.contributor.author","Chen, Jiayin"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Koenig, Joerg"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Chen, Xijing"],["dc.date.accessioned","2018-11-07T10:22:22Z"],["dc.date.available","2018-11-07T10:22:22Z"],["dc.date.issued","2017"],["dc.format.extent","813"],["dc.identifier.doi","10.1515/hsz-2017-0129"],["dc.identifier.isi","000403093600009"],["dc.identifier.pmid","28291733"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42256"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Walter De Gruyter Gmbh"],["dc.relation.issn","1437-4315"],["dc.relation.issn","1431-6730"],["dc.title","Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families (vol 398, pg 237, 2017)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","56"],["dc.bibliographiccitation.journal","Genome Medicine"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Stalmann, Robert"],["dc.contributor.author","Dalila, Nawar"],["dc.contributor.author","Chen, Jiayin"],["dc.contributor.author","Pojar, Sherin"],["dc.contributor.author","Pereira, Joao N. dos Santos"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.date.accessioned","2018-11-07T09:55:48Z"],["dc.date.available","2018-11-07T09:55:48Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: The organic cation transporter OCT1 (SLC22A1) mediates the uptake of vitamin B1, cationic drugs, and xenobiotics into hepatocytes. Nine percent of Caucasians lack or have very low OCT1 activity due to loss-of-function polymorphisms in OCT1 gene. Here we analyzed the global genetic variability in OCT1 to estimate the therapeutic relevance of OCT1 polymorphisms in populations beyond Caucasians and to identify evolutionary patterns of the common loss of OCT1 activity in humans. Methods: We applied massively parallel sequencing to screen for coding polymorphisms in 1,079 unrelated individuals from 53 populations worldwide. The obtained data was combined with the existing 1000 Genomes data comprising an additional 1,092 individuals from 14 populations. The identified OCT1 variants were characterized in vitro regarding their cellular localization and their ability to transport 10 known OCT1 substrates. Both the population genetics data and transport data were used in tandem to generate a world map of loss of OCT1 activity. Results: We identified 16 amino acid substitutions potentially causing loss of OCT1 function and analyzed them together with five amino acid substitutions that were not expected to affect OCT1 function. The variants constituted 16 major alleles and 14 sub-alleles. Six major alleles showed improper subcellular localization leading to substrate-wide loss in activity. Five major alleles showed correct subcellular localization, but substrate-specific loss of activity. Striking differences were observed in the frequency of loss of OCT1 activity worldwide. While most East Asian and Oceanian individuals had completely functional OCT1, 80 % of native South American Indians lacked functional OCT1 alleles. In East Asia and Oceania the average nucleotide diversity of the loss-of-function variants was much lower than that of the variants that do not affect OCT1 function (ratio of 0.03) and was significantly lower than the theoretically expected heterozygosity (Tajima's D=-1.64, P < 0.01). Conclusions: Comprehensive genetic analyses showed strong global variations in the frequency of loss of OCT1 activity with selection pressure for maintaining OCT1 activity in East Asia and Oceania. These results not only enable pharmacogenetically-based optimization of drug treatment worldwide, but may help elucidate the functional role of human OCT1."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2015"],["dc.identifier.doi","10.1186/s13073-015-0172-0"],["dc.identifier.isi","000357566500001"],["dc.identifier.pmid","26157489"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13466"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36829"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1756-994X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Global genetic analyses reveal strong inter-ethnic variability in the loss of activity of the organic cation transporter OCT1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","S0021925822004148"],["dc.bibliographiccitation.firstpage","101974"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.contributor.author","Meyer, Marleen J."],["dc.contributor.author","Schreier, Pascale C.F."],["dc.contributor.author","Basaran, Mert"],["dc.contributor.author","Vlasova, Stefaniia"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Zdrazil, Barbara"],["dc.contributor.author","Tzvetkov, Mladen V."],["dc.date.accessioned","2022-05-02T08:09:54Z"],["dc.date.available","2022-05-02T08:09:54Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1016/j.jbc.2022.101974"],["dc.identifier.pii","S0021925822004148"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107500"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-561"],["dc.relation.issn","0021-9258"],["dc.title","Amino acids in transmembrane helix 1 confer major functional differences between human and mouse orthologs of the polyspecific membrane transporter OCT1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","868"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Clinical Pharmacology & Therapeutics"],["dc.bibliographiccitation.lastpage","878"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Tzvetkov, Mladen V."],["dc.contributor.author","Matthaei, Johannes"],["dc.contributor.author","Pojar, Sherin"],["dc.contributor.author","Faltraco, Frank"],["dc.contributor.author","Vogler, Sabrina"],["dc.contributor.author","Prukop, Thomas"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.date.accessioned","2020-12-10T14:06:00Z"],["dc.date.available","2020-12-10T14:06:00Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1002/cpt.v103.5"],["dc.identifier.issn","0009-9236"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69742"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Increased Systemic Exposure and Stronger Cardiovascular and Metabolic Adverse Reactions to Fenoterol in Individuals with Heritable OCT1 Deficiency"],["dc.title.alternative","OCT1 deficiency and fenoterol toxicity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1427"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Blood"],["dc.bibliographiccitation.lastpage","1429"],["dc.bibliographiccitation.volume","123"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Bokelmann, Kristin"],["dc.contributor.author","Mueller, Thomas"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Koepsell, Hermann"],["dc.date.accessioned","2018-11-07T09:43:36Z"],["dc.date.available","2018-11-07T09:43:36Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1182/blood-2013-11-535864"],["dc.identifier.isi","000335839300028"],["dc.identifier.pmid","24578499"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34216"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Hematology"],["dc.relation.issn","1528-0020"],["dc.relation.issn","0006-4971"],["dc.title","Does the haplotype Met408-Del420, which was apparently predictive for imatinib efficacy, really exist and how strongly may it affect OCT1 activity?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0189521"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Meyer, Marleen Julia"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.date.accessioned","2019-03-07T13:32:00Z"],["dc.date.available","2019-03-07T13:32:00Z"],["dc.date.issued","2017"],["dc.description.abstract","Ranitidine (Zantac®) is a H2-receptor antagonist commonly used for the treatment of acid-related gastrointestinal diseases. Ranitidine was reported to be a substrate of the organic cation transporters OCT1 and OCT2. The hepatic transporter OCT1 is highly genetically variable. Twelve major alleles confer partial or complete loss of OCT1 activity. The effects of these polymorphisms are highly substrate-specific and therefore difficult to predict. The renal transporter OCT2 has a common polymorphism, Ala270Ser, which was reported to affect OCT2 activity."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1371/journal.pone.0189521"],["dc.identifier.pmid","29236753"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15028"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57665"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Effects of genetic polymorphisms on the OCT1 and OCT2-mediated uptake of ranitidine"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","237"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biological Chemistry"],["dc.bibliographiccitation.lastpage","249"],["dc.bibliographiccitation.volume","398"],["dc.contributor.author","Chen, Jiayin"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Koenig, Joerg"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Chen, Xijing"],["dc.date.accessioned","2018-11-07T10:28:12Z"],["dc.date.available","2018-11-07T10:28:12Z"],["dc.date.issued","2017"],["dc.description.abstract","Tropane alkaloids and their derivatives are anticholinergic drugs with narrow therapeutic range. Here we characterize the organic cation transporters from the SLC22 (OCT1, OCT2, and OCT3) and the SLC47 families (MATE1 and MATE2-K) as potential mediators of the renal and extra-renal excretion, the two major roads of elimination of these substances. All analyzed compounds inhibited and the quaternary amine derivatives ipratropium and trospium were strongly transported by OCTs and MATEs. Overexpression of OCTs or MATEs in HEK293 cells resulted in an up to 63-fold increase in the uptake of ipratropium (K-m of 0.32 mu m to OCT2 and V-max of 3.34 nmol x mg protein(-1) x min(-1) to MATE1). The transcellular transport of ipratropium was 16-fold higher in OCT2-MATE1 and 10-fold higher in OCT1-MATE1 overexpressing compared to control MDCKII cells. Genetic polymorphisms in OCT1 and OCT2 affected ipratropium uptake and clinically relevant concentration of ondansetron and pyrithiamine inhibited ipratropium uptake via MATEs by more than 90%. This study suggests that OCT1, OCT2 and MATEs may be strongly involved in the renal and extra-renal elimination of ipratropium and other quaternary amine alkaloids. These substances have a notoriously narrow therapeutic range and the drug-drug interactions suggested here should be further critically evaluated in humans."],["dc.identifier.doi","10.1515/hsz-2016-0236"],["dc.identifier.isi","000391201600009"],["dc.identifier.pmid","27676604"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43371"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Walter De Gruyter Gmbh"],["dc.relation.issn","1437-4315"],["dc.relation.issn","1431-6730"],["dc.title","Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","190"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical Pharmacology and Therapeutics"],["dc.bibliographiccitation.lastpage","200"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Matthaei, Johannes"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Tann, Annabelle"],["dc.contributor.author","Prukop, Thomas"],["dc.contributor.author","Tadjerpisheh, Sina"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Tzvetkov, Mladen V."],["dc.date.accessioned","2019-10-10T07:11:32Z"],["dc.date.available","2019-10-10T07:11:32Z"],["dc.date.issued","2019"],["dc.description.abstract","Cycloguanil, the active metabolite of proguanil, acts on malaria schizonts in erythrocytes and hepatocytes. We analyzed the impact of the organic cation transporter OCT1 on hepatocellular uptake and pharmacokinetics of proguanil and cycloguanil. OCT1 transported both proguanil and cycloguanil. Common variants OCT1 3 and OCT1 4 caused a substantial decrease and OCT1 5 and OCT1 6 complete abolishment of proguanil uptake. In 39 healthy subjects, low-activity variants OCT1 3 and OCT1 4 had only minor effects on proguanil pharmacokinetics. However, both, cycloguanil area under the time-concentration curve and the cycloguanil-to-proguanil ratio were significantly dependent on number of these low-functional alleles (P = 0.02 for both). Together, CYP2C19, CYP3A5, OCT1 polymorphisms, and sex accounted for 61% of the variation in the cycloguanil-to-proguanil ratio. Most importantly, in vitro OCT1 inhibition caused a fivefold decrease of intracellular cycloguanil concentrations in primary human hepatocytes. In conclusion, OCT1-mediated uptake is a limiting step in bioactivation of proguanil, and OCT1 polymorphisms may affect proguanil efficacy against hepatic malaria schizonts."],["dc.identifier.doi","10.1002/cpt.1128"],["dc.identifier.pmid","29882324"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62483"],["dc.language.iso","en"],["dc.relation.eissn","1532-6535"],["dc.relation.issn","0009-9236"],["dc.title","OCT1 Deficiency Affects Hepatocellular Concentrations and Pharmacokinetics of Cycloguanil, the Active Metabolite of the Antimalarial Drug Proguanil"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]