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PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENIC EXPOSURES
Citation:
ORTIZ, P. A., K. WALLACE, AND W. M. WINNIK. PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENIC EXPOSURES. Presented at Genetics and Environmental Mutagenesis Society (GEMS), Research Triangle Park, NC, October 06, 2008.
Impact/Purpose:
The purpose of the study is to identify global protein-level changes associated with exposure to the individual trivalent arsenicals which may provide information crucial to the understanding of key molecular events underlying their toxicity.
Description:
Chronic exposure to arsenic has been associated with human cancers of the bladder, kidney, lung, liver, and skin. Inorganic arsenic is biotransformed in a stepwise manner via both a reduction and then an oxidative methylation step in which arsenic cycles between +5 and +3 oxidation states. To identify global protein-level changes associated with exposure to the individual trivalent arsenicals, a comparative proteome analysis of human urothelial cells (UROtsa) has been performed. UROtsa cells have been shown not to biotransform arsenic, making them a good model system for study. UROtsa cells treated with 1 mM of arsenite (AsIII), monomethylarsonous acid (MMAIII), dimethylarsinous acid (DMAIII) and 5 mM arsenite for 24h were examined by a 2D difference gel electrophoresis (DIGE) approach and proteins were identified by nanospray-liquid chromatography-tandem mass spectrometry (LC-MSMS) analysis. Exposure to MMAIII showed the most significant changes in the protein expression profiles, exhibiting fifty-seven differentially expressed proteins, including thioredoxin reductase, transgelin, aconitase, cofilin and glyceraldehyde-3-phosphate dehydrogenase. Western blots of a subset of these proteins are being performed to validate the LC-MSMS results. Understanding the effects of these trivalent arsenicals on protein expression may provide information crucial to the understanding of key molecular events underlying their toxicity.