Label-free and iTRAQ proteomics analysis in the liver of zebrafish (Danio rerio) following dietary exposure to the organochlorine pesticide dieldrin

Abstract

The organochlorine dieldrin (DLD) bioaccumulates in lipid-rich tissues and is associated with immunosuppression, altered metabolism, and cancer. The objective of this study was to determine the effect of DLD on the hepatic proteome in zebrafish following dietary treatment as the liver is central to metabolism. Females were fed a control dose or one of three doses of DLD-contaminated food pellets over 21 days. Both label-free and iTRAQ proteomics were conducted as two complementary methods to expand coverage of the proteome. Label-free proteomics quantified 1563 proteins: 6 proteins showed a linear dose-response with DLD. iTRAQ quantified >3500 proteins; 5 proteins were decreased and 34 proteins were increased in abundance within the liver with all three doses. Overall, DLD reduced the abundance of proteins associated with glucose and cholesterol metabolism, lipid oxidation, liver function, and immune-related processes. Few proteins were identified by both methods as being altered (~1%), suggesting that each method detected different subsets of proteins. Protein responses in the liver were largely dependent on dose, however proteins related to liver and organ function, centrosome separation, glucose/energy metabolism, and immune-related pathways were confirmed by each independent technique and were suppressed with DLD exposure. This study identifies proteomic responses that are associated with organochlorine-induced hepatotoxicity. Biological significanceEnvironmental contaminants cause hepatotoxicity because the liver is the major organ for detoxification. The legacy pesticide dieldrin significantly bioaccumulates in tissues, and can affect molecular processes that can lead to liver pathology. LC MS/MS proteomics identified protein networks related to tumors, energy homeostasis, and chromosomal separation as those affected by dietary exposure to dieldrin. We applied two orthogonal mass spectrometry-based methods to more completely survey the liver proteome, strengthening data interpretation. These data improve understanding as to the effects of organochlorine pesticide toxicity in the liver and the study identifies proteome networks that can contribute to adverse outcome pathways for pesticide exposure.