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PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENICAL EXPOSURES (SOT 2008)
Citation:
ORTIZ, P. A., K. WALLACE, AND W. M. WINNIK. PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENICAL EXPOSURES (SOT 2008). Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
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.
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 μM of arsenite (AsIII), monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII) 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 64 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.