Mass Spectrometric Investigation of Liver Proteins Isolated from 2-Aminoanthracene Exposed Fisher-344 Rats

The toxicity associated with 2-aminoanthracene (2-AA) exposure in Fisher-344 (F-344) rats was investigated using proteomics approach. Twenty four post-weaning 3-4 week old F-344 male rats were fed diets of 0 mg kg-1 diet (control), 50 mg kg-1 diet (low dose), 75 mg kg-1 diet (medium dose) and 100 mg kg-1 diet (high dose) 2-AA for 14 and 28 days. This was followed by total protein extraction from liver tissues. Protein samples were separated using one dimensional gel electrophoresis. The gel digests were analyzed by nano LC/MS/MS with a Waters NanoAcquity HPLC system. Generated data were searched using Mascot and quantified via spectral counting. There seem to be more proteins expressed in the short-term study than the long-term experimental group. Employing DAVID analytical tool showed that proteins expressed seem be involved in carbohydrate, lipid and protein metabolic processes. Some of these processes include; galactose metabolism, fatty acid metabolism, cysteine and methionine metabolism, protein complex biogenesis and mitochondrial structural proteins. Using relationship-bioinformatics analytical tool, SLC2A4 and MAPK3 were found to interact with several proteins identified from the current study. The nature of this interaction is unknown at this point. Understanding the role of SLC2A4 in regulating other proteins as observed in the study will be pursued in future investigations. Combining the current data with other toxicogenomic data from the liver and pancreas will be useful in developing biomarkers due to arylamine toxicity.