Document Detail


Analysis of secreted proteins as an in vitro model for discovery of liver toxicity markers.
MedLine Citation:
PMID:  20822094     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Despite the wealth of sequence data and new technologies that can scan large portions of the transcriptome or proteome in a single experiment, attempts to identify human biomarkers of toxicity have been met with limited success. We have adapted an in vitro model system to identify proteins secreted by a human hepatoma-derived cell line (HepG2/C3A) in response to toxicant exposure. Using quantitative proteomics, we can find alterations in the abundance of proteins at the source of damage-liver cells-that are likely to be present in blood samples of exposed animals. In a proof of concept experiment, conditioned medium from cells exposed to ethanol was subjected to quantitative mass spectral analysis after abundant proteins were immunodepleted. Eighty-seven proteins were identified with almost half changing in abundance. Some of these were only identified in the highest treatment condition and presumably result from the release of intracellular proteins into the medium when the cell membrane is disrupted upon cell death. However, the majority of the identified proteins reflect known consequences of ethanol exposure or alcoholism. The analysis of proteins found in conditioned medium after exposure to toxicants appears to be a useful system for the expedited discovery of potential human biomarkers.
Authors:
John A Lewis; William E Dennis; Jennifer Hadix; David A Jackson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-09-21
Journal Detail:
Title:  Journal of proteome research     Volume:  9     ISSN:  1535-3907     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5794-802     Citation Subset:  IM    
Affiliation:
U.S. Army Center for Environmental Health Research, Fort Detrick, MD 21702, USA. john.a.lewis1@us.army.mil
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