Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice

• Type of Material: Article
• Authors: Christina Coughlan, University of Colorado; Douglas I. Walker, Emory University; Kelly M. Lohr, Emory University; Jason R. Richardson, Rutgers University; Laura M. Saba, University of Colorado; William Caudle, Emory University; Kristofer S. Fritz, University of Colorado; James R. Roede, University of Colorado
• Language: English
• Date: 2015
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Christina Coughlan et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1155/2015/812532
• Title of Journal or Parent Work: Parkinson's Disease
• ISSN: 2090-8083
• Volume: 2015
• Start Page: 1
• End Page: 11
• Grant/Funding Information: The work presented here was supported by grants from the National Institutes of Health, NIH/NIEHS R00 ES022266 (J. R. Roede), R01 ES021800 (J. R. Richardson), P30 ES019776 (W. M. Caudle), and NIH/NIAAA R01 AA022146 (K. S. Fritz).
• Research Categories: Environmental Sciences; Health Sciences, Pharmacy

Abstract

Epidemiological studies indicate exposures to the herbicide paraquat (PQ) and fungicide maneb (MB) are associated with increased risk of Parkinson's disease (PD). Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg), MB (30 mg/kg), or the combination of PQ and MB (PQMB). Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration.