Microarray analysis of gene expression in the liver during the urinary ethanol cycle in rats fed ethanol intragastrically at a constant rate.

Abstract

The regulation of gene expression in the liver of ethanol fed rats was studied using microarray analysis. The changes in gene expression were compared between pair-fed controls and rats fed ethanol intragastrically at a constant rate for 1 month. The rats fed ethanol were sacrificed at low and high urinary ethanol levels (UAL) during the UAL cycle in order to compare the effects of high and low blood alcohol levels (BAL). The results of the microarray analysis indicated that the pattern of gene expression was very different when the controls, high UAL, and low UAL livers were compared. Many of the gene expression changes reflected nonparenchymal cell alterations such as neuroendocrine or muscle related gene expression. When the results of protein levels and gene expression were compared for individual genes, correlations were variable indicating that post-translational factors modified the effects of the changes in gene expression. This was further emphasized by the fact that activation of proteins by phosphorylation as the result of signaling kinase cascades, was not reflected in the microarray analysis results. For instance, the importance of blood alcohol levels at the time that the assays were performed, profoundly changed the gene expression, protein level, and protein phosphorylation level profiles.