Proteomics is the study of protein expression at a global level for a specific cell type, tissue or organ. A primary objective of Proteomics is the identification of differentially expressed proteins after experimental treatment, environmental contaminant exposure or in human disease. Understanding global changes in gene expression at the protein level will be a useful tool for experimental biology, can implicate new targets or pathways for therapeutics, and will provide new markers for environmental toxicology. Proteomics is accomplished by combining protein separation like 2D gel electrophoresis and identification technologies such as mass spectrometry (MS) in a sequential and automated fashion. It is also important to use complementry power of expression technologies like proteomics and cDNA microarray inresearch problem areas. Several such proteomics studies have been completed. In one study, effects of acute dioxin treatment on protein expression in liver have revealed changes in the NFkB pathway involving altered distribution of activating kinases and inhibitory proteins. In another study, subacute treatment with the metabolic enzyme inducer, phenobarbital, have shown alterations in over 60 proteins by proteomic analysis using a subcellular fractionation strategy. When compared with cDNA microarray analysis of the same tissue, many of the same changes in gene expression occurred at the message and protein level while important differences, particularly in nuclear proteins, were noted by proteomics. In other work with arensic transformed cells, results showed alterations in growth control genes at the mRNA and protein level, particularly indicating a relationship with c-myc overexpression and aresenic expsoure with increased cell proliferation. These collective studies demonstrate the value of global protein analysis in pointing to key pathways altered in response to toxicant exposure as well as the value of performing parallel cDNA microarray analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES010017-03
Application #
6681819
Study Section
(LMC)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Waters, Michael; Stasiewicz, Stanley; Merrick, B Alex et al. (2008) CEBS--Chemical Effects in Biological Systems: a public data repository integrating study design and toxicity data with microarray and proteomics data. Nucleic Acids Res 36:D892-900
Merrick, B Alex (2008) The plasma proteome, adductome and idiosyncratic toxicity in toxicoproteomics research. Brief Funct Genomic Proteomic 7:35-49
Liu, Jie; Xie, Yaxiong; Ducharme, Danica M K et al. (2006) Global gene expression associated with hepatocarcinogenesis in adult male mice induced by in utero arsenic exposure. Environ Health Perspect 114:404-11
Liu, Jie; Xie, Yaxiong; Merrick, B Alex et al. (2006) Transplacental arsenic plus postnatal 12-O-teradecanoyl phorbol-13-acetate exposures associated with hepatocarcinogenesis induce similar aberrant gene expression patterns in male and female mouse liver. Toxicol Appl Pharmacol 213:216-23
Xirasagar, Sandhya; Gustafson, Scott F; Huang, Cheng-Cheng et al. (2006) Chemical effects in biological systems (CEBS) object model for toxicology data, SysTox-OM: design and application. Bioinformatics 22:874-82
Merrick, B Alex (2006) Toxicoproteomics in liver injury and inflammation. Ann N Y Acad Sci 1076:707-17
Merrick, B Alex; Bruno, Maribel E; Madenspacher, Jennifer H et al. (2006) Alterations in the rat serum proteome during liver injury from acetaminophen exposure. J Pharmacol Exp Ther 318:792-802
Fannin, Rick D; Auman, J Todd; Bruno, Maribel E et al. (2005) Differential gene expression profiling in whole blood during acute systemic inflammation in lipopolysaccharide-treated rats. Physiol Genomics 21:92-104
Merrick, B Alex; Madenspacher, Jennifer H (2005) Complementary gene and protein expression studies and integrative approaches in toxicogenomics. Toxicol Appl Pharmacol 207:189-94
Fostel, Jennifer; Choi, Danielle; Zwickl, Craig et al. (2005) Chemical effects in biological systems--data dictionary (CEBS-DD): a compendium of terms for the capture and integration of biological study design description, conventional phenotypes, and 'omics data. Toxicol Sci 88:585-601

Showing the most recent 10 out of 19 publications