Transcriptomics

Dataset Information

0

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.fdx1b-/- mutants show a 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. 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.

ORGANISM(S): Danio rerio

PROVIDER: GSE107547 | GEO | 2019/01/21

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2022-01-19 | E-MTAB-10092 | biostudies-arrayexpress
2023-04-19 | GSE179837 | GEO
2016-12-05 | GSE76073 | GEO
| phs001314 | dbGaP
2012-03-21 | E-MEXP-3288 | biostudies-arrayexpress
2022-11-02 | GSE196818 | GEO
2017-12-06 | GSE107715 | GEO
2008-10-11 | GSE9402 | GEO
2008-10-26 | E-GEOD-9402 | biostudies-arrayexpress
2007-06-20 | GSE7978 | GEO