Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism
Yükleniyor...
Dosyalar
Tarih
2018
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
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. (C) 2018 The Authors. Published by Elsevier B.V.
Açıklama
Anahtar Kelimeler
Zebrafish, Ferredoxin, Adrenal Insufficiency, Oxidative Stress, Purine Metabolism
Kaynak
Ebiomedicine
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
36
Sayı
Künye
Weger, 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.2018.09.024
