Proteomische Analyse der Nephrotoxizität im Falle der Cyclosporin A und Tacrolimus Therapie

Wülfrath, Hauke Sebastian

dc.contributor.advisor	Dihazi, Hassan Prof. Dr.
dc.contributor.author	Wülfrath, Hauke Sebastian
dc.date.accessioned	2023-05-03T07:30:11Z
dc.date.available	2023-05-10T00:50:10Z
dc.date.issued	2023-05-03
dc.identifier.uri	http://resolver.sub.uni-goettingen.de/purl?ediss-11858/14651
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-9869
dc.format.extent	130	de
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc	610	de
dc.title	Proteomische Analyse der Nephrotoxizität im Falle der Cyclosporin A und Tacrolimus Therapie	de
dc.type	doctoralThesis	de
dc.contributor.referee	Dihazi, Hassan Prof. Dr.
dc.date.examination	2023-05-03	de
dc.description.abstracteng	Immunosuppressants have made organ transplantation possible as a therapeutic intervention. One of the first and still most important groups of drugs among immunosuppressants are the calcineurin inhibitors, including Cyclosporin A and Tacrolimus. Nephrotoxicity of calcineurin inhibitors as an undesirable drug effect occurs both acutely and chronically. Calcineurin inhibitor nephrotoxicity is often dose-limiting in therapy. Renal fibrosis plays an important role in chronic calcineurin inhibitor nephrotoxicity. Renal fibrosis in general is largely mediated by endoplasmic reticulum stress. Among others, the proteins GRP78, ERP57, and Calreticulin regulate this stress. Cyclosporin A and Tacrolimus exhibit toxic effects on the renal cell lines HK-2 and TK-173 at micromolar concentrations. This toxic effect is manifested by reduced cell viability and increased apoptosis rate of the cells, accompanied by increased expression of ER stress proteins. In this study, for the first time, a proteomic analysis of the nephrotoxicity of calcineurin inhibitors on HK-2 cells was conducted. Regulated signaling pathways were identified that are known to contribute to kidney pathologies and may serve as potential targets for therapeutic interventions to alleviate calcineurin inhibitor nephrotoxicity. The increased expression of ER stress proteins leads to increased tolerance of HK-2 cells to Cyclosporin A and Tacrolimus. At the same time, reduced expression of the same ER stress proteins results in decreased tolerance to calcineurin inhibitors. This suggests a protective effect of ER stress proteins against the toxic effects of calcineurin inhibitors on renal cell lines.	de
dc.contributor.coReferee	Urlaub, Henning Prof. Dr.
dc.subject.eng	calcineurin inhibitor	de
dc.subject.eng	transplantation	de
dc.subject.eng	proteomics	de
dc.subject.eng	endoplasmic reticulum stress	de
dc.identifier.urn	urn:nbn:de:gbv:7-ediss-14651-2
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Medizin (PPN619874732)	de
dc.subject.gokfull	Innere Medizin - Allgemein- und Gesamtdarstellungen (PPN619875747)	de
dc.description.embargoed	2023-05-10	de
dc.identifier.ppn	1844637514
dc.notes.confirmationsent	Confirmation sent 2023-05-03T07:45:02	de

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Human- und Zahnmedizin [2872]

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