Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
+44 1223 790975
ISSN: 0974-276X
+44 1223 790975
Karen L Leach
Safety Prediction, Pfizer Global Research and Development,
Pfizer, Inc, Groton, Connecticut
Tanzania
Research Article
Assessing Hepatoxicants based on High-throughput Quantitative SILAC
Proteomics and Causal Biological Networks
Author(s): Ahmed Enayetallah, Sashi Nadanaciva, Paul Ajuh, Cristina Vazquez Martin, Amy Wheat, Angus Lamond, Daniel Ziemek and Karen L LeachAhmed Enayetallah, Sashi Nadanaciva, Paul Ajuh, Cristina Vazquez Martin, Amy Wheat, Angus Lamond, Daniel Ziemek and Karen L Leach
Drug-induced liver injury can result in the termination of compounds in preclinical development, as well as withdrawal of marketed drugs. Identification of the signaling pathways and proteins involved in injury is an important step towards establishing assays that could be utilized to identify potential hepatotoxicants early in the drug discovery process. In this study we used high throughput quantitative mass spectrometry proteomics involving Stable Isotope Labeling with Amino acids in Cell culture (SILAC) leveraged by a recently developed systems biology approach (Causal Reasoning Engine, CRE) to investigate the effects of hepatotoxic compounds on the cellular proteome of HepG2 cells. Cells were treated with various concentrations of nefazadone, nimesulide, nomifensine, or glafenine, all of which cause hepatotoxicity in humans. Buspirone and rosiglitazone were used as comparator com.. View More»
DOI:
10.4172/jpb.1000352