1. Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice.
- Author
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Coughlan, Christina, Walker, Douglas I., Lohr, Kelly M., Richardson, Jason R., Saba, Laura M., Caudle, W. Michael, Fritz, Kristofer S., and Roede, James R.
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DISEASE risk factors , *ACADEMIC medical centers , *ANIMAL experimentation , *HIGH performance liquid chromatography , *MICE , *PARKINSON'S disease , *PESTICIDES , *RESEARCH funding , *STATISTICS , *WESTERN immunoblotting , *PROTEOMICS , *DATA analysis , *OXIDATIVE stress , *DATA analysis software - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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