Rapid upregulation of the arginine-sensitive amino acid transporter TA1/LAT1/CD98 light chain in response to carbon tetrachloride-induced injury has been demonstrated in previous studies. LAT1 is suggested to have an adaptive role in response to liver injury, yet the underlying downstream mechanisms remain to be elucidated. These studies will focus on the changes in expression of LAT1 and its downstream markers in response to (and comparison with) carbon tetrachloride exposure and amino acid availability. Genes that are found to be differentially expressed may be biomarkers for predicting toxicity. Microarray gene analysis coupled with bioinformatics will be used to identify gene sets of interest. Selected genes will be verified for differential expression using Western blotting, Northern blotting, proteomics, immunoprecipitation and PCR techniques. This proposal aims to test the hypothesis that alterations in gene expression observed at early time points after toxicant exposure will include many genes that respond to other environmental exposures and stresses including nutrient availability and viral infection. It is predicted that genes involved in oxidant and metabolic stress responses, such as LAT1, will be central in adaptation following liver injury.
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