Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis Revealed by Proteomic and Transcriptomic Analyses of the Striata in Two Mouse Models of Parkinson’s Disease

Department of Molecular and Medical Pharmacology, Human Genetics, Laboratory of NeuroImaging, Department of Neurology, and Surgery, David Geffen School of Medicine at University of California-Los Angeles (UCLA), Los Angeles, California 90095, USA.
Journal of Proteome Research (Impact Factor: 4.25). 03/2008; 7(2):666-77. DOI: 10.1021/pr070546l
Source: PubMed


The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson's disease (PD) are not completely understood. Here, we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 86 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA, following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response, and apoptosis. These results constitute one of the largest descriptive data sets integrating protein and transcript changes for these neurotoxin models with many similar end point phenotypes but distinct mechanisms.

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Available from: Wei-Jun Qian, Jan 09, 2014
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    • "Mitochondria have fundamental roles in many cellular processes, including energy metabolism via the oxidative phosphorylation system, the Kreb's cycle, and β-oxidation of free fatty acids [22,23]. Critical steps for heme biosynthesis, ketone body formation and urea degradation takes place in the mitochondria [24-26]. Recent evidence implicates mitochondrial involvement in cellular signaling pathways through modulation of intracellular calcium stores, production of reactive species, and the interaction of nitric oxide on mitochondrial functions, such as respiration and biogenesis [7,27]. "
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    • "To corroborate our results, as well as to detect potentially important genes common to the response to OS in different tissues, we performed a meta-analysis of microarray studies that explored transcriptional changes upon OS (Edwards et al. 2004; Tomita et al. 2006, 2007; Wang et al. 2007, 2009; Chin et al. 2008; Olesen et al. 2008; Patel et al. 2008; Sforza 2008) using the LOLA database and analysis software ( (Cahan et al. 2005). "
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    • "Despite the fact that several gene expression studies focused on PD have been performed (5–14), no database has been developed to allow full-scale meta-analysis of microarray data related to PD. "
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