Post-transcriptional regulation of mRNA associated with DJ-1 in sporadic Parkinson disease.
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.
Blackinton
Jeff
J
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States.
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
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001921:Brain / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009245:NADH Dehydrogenase / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D000071617:Protein Deglycase DJ-1; D054648:Protein Phosphatase 2 / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D051151:Selenoprotein W / Q000235:genetics; D051025:bcl-Associated Death Protein / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C494819:BAD protein, human; D047908:Intracellular Signaling Peptides and Proteins; C490666:MAPK8IP1 protein, human; D015513:Oncogene Proteins; C517192:PPP2R2C protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C495240:SELENOW protein, human; D051151:Selenoprotein W; D051025:bcl-Associated Death Protein; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D009245:NADH Dehydrogenase; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D054648:Protein Phosphatase 2