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

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Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism. / Weger, Meltem; Weger, Benjamin D.; Görling, Benjamin; Poschet, Gernot; Yildiz, Melek; Hell, Rüdiger; Luy, Burkhard; Akcay, Teoman; Güran, Tülay; Dickmeis, Thomas; Müller, Ferenc; Krone, Nils.

In: EBioMedicine, Vol. 36, 10.2018, p. 376-389.

Research output: Contribution to journalArticle

Harvard

Weger, M, Weger, BD, Görling, B, Poschet, G, Yildiz, M, Hell, R, Luy, B, Akcay, T, Güran, T, Dickmeis, T, Müller, F & Krone, N 2018, 'Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism', EBioMedicine, vol. 36, pp. 376-389. https://doi.org/10.1016/j.ebiom.2018.09.024

APA

Weger, M., Weger, B. D., Görling, B., Poschet, G., Yildiz, M., Hell, R., Luy, B., Akcay, T., Güran, T., Dickmeis, T., Müller, F., & 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.2018.09.024

Vancouver

Author

Weger, Meltem ; Weger, Benjamin D. ; Görling, Benjamin ; Poschet, Gernot ; Yildiz, Melek ; Hell, Rüdiger ; Luy, Burkhard ; Akcay, Teoman ; Güran, Tülay ; Dickmeis, Thomas ; Müller, Ferenc ; Krone, Nils. / Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism. In: EBioMedicine. 2018 ; Vol. 36. pp. 376-389.

Bibtex

@article{a5f2ee027ae64f30b34a3810e8ee15e8,
title = "Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism",
abstract = "Background: 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.Fund: Marie Curie Intra-European Fellowships for Career Development, HGF-programme BIFTM, Deutsche Forschungsgemeinschaft, BBSRC",
keywords = "zebrafish, ferrodoxin, adrenal insufficiency, oxidative stress, purine metabolism",
author = "Meltem Weger and Weger, {Benjamin D.} and Benjamin G{\"o}rling and Gernot Poschet and Melek Yildiz and R{\"u}diger Hell and Burkhard Luy and Teoman Akcay and T{\"u}lay G{\"u}ran and Thomas Dickmeis and Ferenc M{\"u}ller and Nils Krone",
year = "2018",
month = oct
doi = "10.1016/j.ebiom.2018.09.024",
language = "English",
volume = "36",
pages = "376--389",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism

AU - Weger, Meltem

AU - Weger, Benjamin D.

AU - Görling, Benjamin

AU - Poschet, Gernot

AU - Yildiz, Melek

AU - Hell, Rüdiger

AU - Luy, Burkhard

AU - Akcay, Teoman

AU - Güran, Tülay

AU - Dickmeis, Thomas

AU - Müller, Ferenc

AU - Krone, Nils

PY - 2018/10

Y1 - 2018/10

N2 - Background: 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.Fund: Marie Curie Intra-European Fellowships for Career Development, HGF-programme BIFTM, Deutsche Forschungsgemeinschaft, BBSRC

AB - Background: 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.Fund: Marie Curie Intra-European Fellowships for Career Development, HGF-programme BIFTM, Deutsche Forschungsgemeinschaft, BBSRC

KW - zebrafish

KW - ferrodoxin

KW - adrenal insufficiency

KW - oxidative stress

KW - purine metabolism

U2 - 10.1016/j.ebiom.2018.09.024

DO - 10.1016/j.ebiom.2018.09.024

M3 - Article

C2 - 30266295

VL - 36

SP - 376

EP - 389

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -