Comparative proteomic analysis of carbonylated proteins from the striatum and cortex of pesticide-treated mice

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. © 2015 christina coughlan et al.