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Post-transcriptional regulation of mRNA associated with DJ-1 in sporadic Parkinson disease.

ABSTRACT: Mutations in DJ-1 lead to a monogenic form of early onset recessive parkinsonism. DJ-1 can respond to oxidative stress, which has been proposed to be involved in the pathogenesis of sporadic Parkinson disease (PD). We have recently reported that DJ-1 interacts with mRNA in an oxidation-dependent manner. Here, we confirm interaction of DJ-1 and RNA in human brain using immunoprecipitation followed by quantitative real time PCR. We confirmed previous reports that DJ-1 is more oxidized in cortex from cases of sporadic PD compared to controls. In the same samples, protein and RNA expression was measured for four DJ-1 target genes GPx4, MAPK8IP1, ND2 and ND5. While no alterations in mRNA expression were observed, an increase in protein expression was observed in PD cases for GPx4 and MAPK8IP1. In the same patients, we saw decreased mRNA and protein levels of two mitochondrial targets, ND2 and ND5. These results suggest that these proteins undergo regulation at the post-transcriptional level that may involve translational regulation by DJ-1.

SUBMITTER: Blackinton J

PROVIDER: S-EPMC2640439 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Post-transcriptional regulation of mRNA associated with DJ-1 in sporadic Parkinson disease.

Blackinton Jeff J Kumaran Ravindran R van der Brug Marcel P MP Ahmad Rili R Olson Lars L Galter Dagmar D Lees Andrew A Bandopadhyay Rina R Cookson Mark R MR

Neuroscience letters 20090106 1

Mutations in DJ-1 lead to a monogenic form of early onset recessive parkinsonism. DJ-1 can respond to oxidative stress, which has been proposed to be involved in the pathogenesis of sporadic Parkinson disease (PD). We have recently reported that DJ-1 interacts with mRNA in an oxidation-dependent manner. Here, we confirm interaction of DJ-1 and RNA in human brain using immunoprecipitation followed by quantitative real time PCR. We confirmed previous reports that DJ-1 is more oxidized in cortex fr ...[more]

PMID: 19146923

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Project description:Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. We study changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls (Discovery set?) by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. By applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays, gene expression profiling discriminates patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts were validated by RT-qPCR in an independent cohort of 12 patients and controls (?Validation set). Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention. Analyzed samples include blood samples from 40 PD patients and 20 healthy controls. Of the original 60 samples, one (a control sample) did not pass the microarray hybridization quality controls and was excluded from further analyses. All results of bioinformatics analyses shown in this study refer to this set of 59 samples (reported here).

Dataset Information

Post-transcriptional regulation of mRNA associated with DJ-1 in sporadic Parkinson disease.

Publications

Post-transcriptional regulation of mRNA associated with DJ-1 in sporadic Parkinson disease.

Similar Datasets

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