Identification and assessment of the molecular targets of lead and acrylamide using a novel proteomic system coupled with bioinformatic analysis

The identification of biomarkers that can be used to assess toxicity is an important scientific goal. The discovery of these biomarkers would speed drug development and improve toxicological evaluation of chemical exposure. Protein interactions are fundamental to biological processes and biomarkers that identify the state of these processes are needed. Acrylamide and lead produce neurological dysfunction, including biochemical and electrophysiological effects. Protein-protein interactions that are sensitive to these compounds can be used as biomarkers for acrylamide and lead toxicity.; Proteomics provides a powerful approach for detecting protein-protein interactions. Here, a two-hybrid proteomic technology was modified to develop biomarkers for acrylamide and lead toxicity. Eight acrylamide sensitive protein interactions and four lead sensitive protein interactions were identified from a set of aproximately 500,000 two-hybrid protein pairs. Computational tools were used to analyze the identified proteins and screen for high confidence biomarkers. High confidence biomarkers for acrylamide were mitochondrial COX subunit 2 and vacuolar ATP synthase 16 kDa proteolipid subunit. Triosephosphate isomerase was identified as a biomarker for lead. Networks containing the identified biomakers were generated using protein domain, GO annotation and protein interaction data. Acrylamide effected networks were protein synthesis, mitochondrial electron transport and vacuolar proton transport processes. Lead effected networks included protein synthesis, mitochondrial proton translocation processes and glycolysis. The coupling of two-hybrid and bioinformatic analysis identified high confidence arylamide and lead toxicity biomarkers and the processes they function in.