Gutenberg Open Science: Identification of trichlormethiazide as a Mdr1a/b gene expression enhancer via a dual secretion-based promoter assay

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7429

Full metadata record

DC Field	Value	Language
dc.contributor.author	Schulze, Sarina	-
dc.contributor.author	Reinhardt, Sven	-
dc.contributor.author	Freese, Christian	-
dc.contributor.author	Schmitt, Ulrich	-
dc.contributor.author	Endres, Kristina	-
dc.date.accessioned	2022-07-15T07:40:33Z	-
dc.date.available	2022-07-15T07:40:33Z	-
dc.date.issued	2015	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/7443	-
dc.description.abstract	Transporters of the ATP-binding cassette (ABC) family such as MDR1 play a pivotal role in persistence of brain homeostasis by contributing to the strict permeability properties of the blood-brain barrier. This barrier on one hand compromises treatment of central nervous system diseases by restricting access of drugs; on the other hand, an impaired or altered function of barrier building cells has been described in neurological disorders. The latter might contribute to increased vulnerability of the brain under pathological conditions or even enforce pathogenesis. Here, we present a novel approach for a systematic examination of drug impact on Mdr1 gene expression by establishing a dual reporter gene assay for the murine upstream core promoters of Mdr1a and b. We validated the time-resolved assay in comparison with single reporter gene constructs and applied it to analyze effects of a Food and Drug Administration (FDA)-approved drug library consisting of 627 substances. The chemo-preventive synthetic dithiolethione oltipraz was reidentified with our assay as an already known inducer of Mdr1 gene expression. Together with two newly characterized modifiers - gemcitabine and trichlormethiazide - we prove our findings in a blood-brain barrier culture model as well as in wild-type and Mdr1 knockout mice. In sum, we could demonstrate that our dual reporter gene assay delivers results, which also persist in the living animal and consequently is applicable for further analysis and prediction of Mdr1 regulation in vivo.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin	de
dc.language.iso	eng	de
dc.rights	CC BY-NC-ND	*
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/3.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Identification of trichlormethiazide as a Mdr1a/b gene expression enhancer via a dual secretion-based promoter assay	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7429	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.department	FB 09 Chemie, Pharmazie u. Geowissensch.	de
jgu.organisation.number	2700	-
jgu.organisation.number	7950	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Pharmacology research & perspectives	de
jgu.journal.volume	3	de
jgu.journal.issue	1	de
jgu.pages.alternative	e00109	de
jgu.publisher.year	2015	-
jgu.publisher.name	Wiley	de
jgu.publisher.place	Chichester	de
jgu.publisher.uri	http://dx.doi.org/10.1002/prp2.109	de
jgu.publisher.issn	2052-1707	de
jgu.organisation.place	Mainz	-
jgu.identifier.pmid	25692026	-
jgu.subject.ddccode	610	de
opus.date.modified	2018-09-05T09:12:16Z	-
opus.subject.dfgcode	00-000	-
opus.organisation.string	FB 04: Medizin: Institut für Pathologie	de_DE
opus.organisation.string	FB 04: Medizin: Psychiatrische Klinik und Poliklinik	de_DE
opus.organisation.string	FB 09: Chemie, Pharmazie und Geowissenschaften: Institut für Pharmazie	de_DE
opus.identifier.opusid	51967	-
opus.importsource	pubmed	-
opus.institute.number	0423	-
opus.institute.number	0432	-
opus.institute.number	0908	-
opus.metadataonly	false	-
opus.type.contenttype	Keine	de_DE
opus.type.contenttype	None	en_EN
opus.affiliated	Freese, Christian	-
opus.affiliated	Schmitt, Ulrich	-
opus.affiliated	Endres, Kristina	-
jgu.publisher.doi	10.1002/prp2.109	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)

Files in This Item:

	File	Description	Size	Format
	identification_of_trichlormet-20220713090351432.pdf		549.31 kB	Adobe PDF	View/Open

Show simple item record