Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism

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dc.authoridTeoman Akçay / 0000-0002-8252-7089
dc.authorscopusidTeoman Akçay / 23968688000
dc.authorwosidTeoman Akçay / AFG-8460-2022
dc.contributor.authorWeger, Meltem
dc.contributor.authorWeger, Benjamin D.
dc.contributor.authorGoerling, Benjamin
dc.contributor.authorPoschet, Gernot
dc.contributor.authorYıldız, Melek
dc.contributor.authorHell, Ruediger
dc.contributor.authorLuy, Burkhard
dc.contributor.authorAkçay, Teoman
dc.contributor.authorGüran, Tülay
dc.contributor.authorDickmeis, Thomas
dc.contributor.authorMueller, Ferenc
dc.contributor.authorKrone, Nils
dc.date.accessioned2020-08-30T20:07:18Z
dc.date.available2020-08-30T20:07:18Z
dc.date.issued2018
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.description.abstractBackground: Deficient glucocorticoid biosynthesis leading to adrenal insufficiency is life-threatening and is associated with significant co-morbidities. The affected pathways underlying the pathophysiology of co-morbidities due to glucocorticoid deficiency remain poorly understood and require further investigation. Methods: To explore the pathophysiological processes related to glucocorticoid deficiency, we have performed global transcriptional, post-transcriptional and metabolic profiling of a cortisol-deficient zebrafish mutant with a disrupted ferredoxin (fdx1b) system. Findings: fdx1b(-/-) mutants show pervasive reprogramming of metabolism, in particular of glutamine-dependent pathways such as glutathione metabolism, and exhibit changes of oxidative stress markers. The glucocorticoid-dependent post-transcriptional regulation of key enzymes involved in de novo purine synthesis was also affected in this mutant. Moreover, fdx1b(-/-) mutants exhibit crucial features of primary adrenal insufficiency, and mirror metabolic changes detected in primary adrenal insufficiency patients. Interpretation: Our study provides a detailed map of metabolic changes induced by glucocorticoid deficiency as a consequence of a disrupted ferredoxin system in an animal model of adrenal insufficiency. This improved pathophysiological understanding of global glucocorticoid deficiency informs on more targeted translational studies in humans suffering from conditions associated with glucocorticoid deficiency. (C) 2018 The Authors. Published by Elsevier B.V.en_US
dc.description.sponsorshipMarie Curie Intra-European FellowshipsEuropean Union (EU) [PIEF-GA-2013-625827]; HGF-programme BIFTM; Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [ZUK 40/2010-3009262]; BBSRCBiotechnology and Biological Sciences Research Council (BBSRC) [BB/L010488/1]en_US
dc.description.sponsorshipMarie Curie Intra-European Fellowships for Career Development (PIEF-GA-2013-625827, MISTRAL; to MW), HGF-programme BIFTM (to TD, BG, BL), Deutsche Forschungsgemeinschaft (grant ZUK 40/2010-3009262; to RH and GP) and BBSRC (BB/L010488/1; to FM). The funders had no role in study design, data collection, data analysis, interpretation, or writing of the report.en_US
dc.identifier.citationWeger, M., Weger, B. D., Görling, B., Poschet, G., Yildiz, M., Hell, R., … Krone, N. (2018). Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism. EBioMedicine, 36, 376–389. https://doi.org/10.1016/j.ebiom.2018.09.024en_US
dc.identifier.doi10.1016/j.ebiom.2018.09.024en_US
dc.identifier.endpage389en_US
dc.identifier.issn2352-3964en_US
dc.identifier.pmid30266295en_US
dc.identifier.scopus2-s2.0-85053871272en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage376en_US
dc.identifier.urihttps://doi.org/10.1016/j.ebiom.2018.09.024
dc.identifier.urihttps://hdl.handle.net/20.500.12713/736
dc.identifier.volume36en_US
dc.identifier.wosWOS:000447685300042en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorAkçay, Teomanen_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofEbiomedicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectZebrafishen_US
dc.subjectFerredoxinen_US
dc.subjectAdrenal Insufficiencyen_US
dc.subjectOxidative Stressen_US
dc.subjectPurine Metabolismen_US
dc.titleGlucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolismen_US
dc.typeArticleen_US

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