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Series GSE17204 Query DataSets for GSE17204
Status Public on Apr 16, 2010
Title Parkinson's disease-associated DJ-1 is required for the expression of GDNF receptor Ret in human neuroblastoma cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. To explore DJ-1-mediated transcriptional control in Parkinson’s disease (PD), we generated human neuroblastoma cells with inducible knock-down of DJ-1 expression. We then used functional genomic techniques to identify novel pathways dysregulated by loss of DJ-1 function. Using microarray gene expression profiling, we found that DJ-1 silencing alters the expression of 26 genes, with 10 down-regulated and 16 up-regulated transcripts. Among the down-regulated genes we found Ret, tyrosine kinase receptor for the neurotrophic factor GDNF. Taking advantage of Ingenuity Pathways Analysis, we identified hypoxia inducible factor 1 alpha (Hif1a) as a possible mediator of the interplay between DJ-1 and Ret. We show that Hif1a is stabilized in the absence of DJ-1, and that loss of DJ-1 generates hypoxia and accumulation of free radical species (ROS). Overexpression of wt DJ-1, but not of C106A and L166P mutants deficient in ROS scavenger activity, rescues Ret expression in neuroblastoma cells. These findings reveal novel players in PD pathogenesis and provide evidence for additional pathways involved in DJ-1-mediated neurodegeneration.
Overall design Comparison between DJ-1-silenced human SH-SY5Y neuroblastoma cells and control cells. Two clones were selected for each condition, and each clone was analyzed in duplicate, for a total of 8 samples.
Citation(s) 20395301
Submission date Jul 20, 2009
Last update date Dec 06, 2018
Contact name Paola Roncaglia
Organization name SISSA/ISAS (International School for Advanced Studies)
Department Neurobiology
Street address via Bonomea 265
City Trieste
State/province TS
ZIP/Postal code 34136
Country Italy
Platforms (1)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (8)
GSM430339 Neuroblastoma SH-SY5Y cells_cloneB_stably transfected with RNAi against DJ-1_replicate1
GSM430340 Neuroblastoma SH-SY5Y cells_cloneB_stably transfected with RNAi against DJ-1_replicate2
GSM430341 Neuroblastoma SH-SY5Y cells_cloneG_stably transfected with RNAi against DJ-1_replicate1
BioProject PRJNA119215

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Supplementary file Size Download File type/resource
GSE17204_RAW.tar 17.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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