Role of ALADIN in human adrenocortical cells for oxidative stress response and steroidogenesis

PloS One
Ramona JühlenK Koehler


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.


Apr 14, 2016·European Journal of Human Genetics : EJHG·Valeria NofriniCristina Mecucci
Dec 14, 2016·Nucleic Acids Research·Thomas W KirbyRobert E London
Jan 27, 2018·Current Opinion in Endocrinology, Diabetes, and Obesity·Satoshi Narumi
Aug 5, 2017·Molecular Biology of the Cell·Sara CarvalhalEric R Griffis
Apr 11, 2017·Hormone Research in Pædiatrics·Maria Candida Barisson Villares FragosoBerenice Bilharinho Mendonca
Oct 20, 2017·The Journal of Endocrinology·Eirini MeimaridouL A Metherell
Dec 15, 2017·European Journal of Endocrinology·Florence Roucher-BoulezMichel Pugeat
Oct 27, 2018·Histochemistry and Cell Biology·Ramona Jühlen, Birthe Fahrenkrog
Aug 23, 2019·Journal of Endocrinological Investigation·R PolatT Guran
Jan 16, 2020·Journal of Endocrinological Investigation·V VezzoliM Bonomi
Jan 25, 2018·Biology Open·Ramona JühlenK Koehler


Feb 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T KawamotoH Imura
May 22, 1998·Molecular Biology of the Cell·C X CaiThomas Linsenmayer
Dec 23, 1998·Endocrine Reviews·A J Clark, A Weber
Mar 14, 2000·Archives of Medical Research·C Tsigos
Nov 4, 2000·Nature Genetics·A Tullio-PeletS Lyonnet
Feb 13, 2001·Human Molecular Genetics·K HandschugA Huebner
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Salvatore AlesciMonika Ehrhart-Bornstein
Aug 28, 2002·The Journal of Cell Biology·Janet M CronshawMichael J Matunis
Nov 28, 2002·Biological Chemistry·Matthias BureikRita Bernhardt
May 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Janet M Cronshaw, Michael J Matunis
Oct 27, 2004·Nature Cell Biology·Gwénaël RabutJan Ellenberg
Jan 29, 2005·The Biochemical Journal·Nodar SurguladzeJames R Connor
Feb 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Makito HiranoSatoshi Ueno
Apr 13, 2006·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Manuela KrumbholzA Huebner
Feb 6, 2007·The Journal of Biological Chemistry·Ulrich RassStephen C West
Sep 1, 2007·Molecular Endocrinology·Mabrouka DoghmanEnzo Lalli
Mar 28, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Cindy CaiThomas Linsenmayer
Oct 7, 2008·The Journal of Biological Chemistry·Ulrich RassStephen C West
Jan 23, 2009·Journal of Molecular Endocrinology·Edson F NogueiraW E Rainey
Feb 10, 2009·Journal of Cellular Physiology·Urska MatkovicLuisa Barzon
Aug 26, 2009·Biochemical and Biophysical Research Communications·Yusuke YamazumiTetsu Akiyama
Sep 29, 2009·Biochemical and Biophysical Research Communications·B KindA Huebner
Dec 23, 2009·Methods : a Companion to Methods in Enzymology·Stephen A Bustin
Mar 30, 2010·Biochimica Et Biophysica Acta·Ahmed A Alkhateeb, James R Connor
May 26, 2010·European Journal of Pediatrics·Tatjana MilenkovicA Huebner
Aug 14, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·B KindA Huebner
Jan 19, 2012·Nature Reviews. Molecular Cell Biology·Claudio Hetz
Jan 24, 2012·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·T WangW E Rainey
Jan 15, 2013·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·K KoehlerA Huebner
Nov 1, 2013·Nature Methods·Stephen A BustinJo Vandesompele
Dec 24, 2013·Nature·Percy TumbaleR Scott Williams

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