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| 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.
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| 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.
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| 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 |
| |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| 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 |
| GSM430342 |
Neuroblastoma SH-SY5Y cells_cloneG_stably transfected with RNAi against DJ-1_replicate2 |
| GSM430343 |
Neuroblastoma SH-SY5Y cells_cloneH_scramble control_replicate1 |
| GSM430344 |
Neuroblastoma SH-SY5Y cells_cloneH_scramble control_replicate2 |
| GSM430345 |
Neuroblastoma SH-SY5Y cells_cloneM_scramble control_replicate1 |
| GSM430346 |
Neuroblastoma SH-SY5Y cells_cloneM_scramble control_replicate2 |
|
| Relations |
| BioProject |
PRJNA119215 |
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