Role of ALADIN in human adrenocortical cells for oxidative stress response and steroidogenesis
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Triple A syndrome is caused by mutations in AAAS encoding the protein ALADIN. We investigated the role of ALADIN in the human adrenocortical cell line NCI-H295R1 by either over-expression or down-regulation of ALADIN. Our findings indicate that AAAS knock-down induces a down-regulation of genes coding for type II microsomal cytochrome P450 hydroxylases CYP17A1 and CYP21A2 and their electron donor enzyme cytochrome P450 oxidoreductase, thereby decreasing biosynthesis of precursor metabolites required for glucocorticoid and androgen production. Furthermore we demonstrate that ALADIN deficiency leads to increased susceptibility to oxidative stress and alteration in redox homeostasis after paraquat treatment. Finally, we show significantly impaired nuclear import of DNA ligase 1, aprataxin and ferritin heavy chain 1 in ALADIN knock-down cells. We conclude that down-regulating ALADIN results in decreased oxidative stress response leading to alteration in steroidogenesis, highlighting our knock-down cell model as an important in-vitro tool for studying the adrenal phenotype in triple A syndrome.
Editor(s)
Tsuji, Yoshiaki
Date Issued
2015-04-13
Date Acceptance
2015-03-04
Citation
PLoS ONE, 2015, 10 (4)
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS ONE
Volume
10
Issue
4
Copyright Statement
© 2015 Jühlen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/25867024
PII: PONE-D-14-57334
Subjects
AAAS
APRATAXIN
FERRITIN
GENE-EXPRESSION
GLUCOCORTICOID DEFICIENCY
Multidisciplinary Sciences
NUCLEAR-PORE COMPLEX
PUBLICATION
Science & Technology
Science & Technology - Other Topics
TRANSLOCATION
TRIPLE-A-SYNDROME
WD-REPEAT PROTEIN
Publication Status
Published
Coverage Spatial
United States
Article Number
e0124582
Date Publish Online
2015-04-13