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

被引:73
作者
Blackinton, Jeff [1 ,2 ]
Kumaran, Ravindran [3 ]
van der Brug, Marcel P. [1 ]
Ahmad, Rili [1 ]
Olson, Lars [2 ]
Galter, Dagmar [2 ]
Lees, Andrew [3 ]
Bandopadhyay, Rina [3 ]
Cookson, Mark R. [1 ]
机构
[1] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
[2] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden
[3] UCL, Inst Neurol, Reta Lila Weston Inst Neurol Studies, London WC1N 1PJ, England
关键词
Sporadic Parkinson's disease; Recessive parkinsonism; Translational regulation; Oxidative stress; OXIDATIVE DAMAGE; PROTEIN DJ-1;
D O I
10.1016/j.neulet.2008.12.053
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) Published by Elsevier Ireland Ltd.
引用
收藏
页码:8 / 11
页数:4
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