Microarray Analysis of the Liver at High and Low Blood Alcohol Levels in Rats Fed Ethanol at a Constant Rate for one Month

Abstract

Previous studies have shown that gene expression in the liver of rats fed ethanol differs when controls are compared to rats with low (<100 mg%) and high (>400 mg%) blood alcohol levels (BAL) and when the livers at high BAL are compared with livers at low BAL. To study this problem in more detail, high throughput microanalysis (15,000 rat genes) was done to look for gene expression changes in control, low and high blood alcohol levels. The gene expression changes were very different when the controls, high and low BAL rat livers were compared with each other. Many of the gene expression changes reflected nonparenchymal cell functions such as neuroendocrine or muscle related gene expression. When the results of protein expression and gene expression were compared for individual genes, correlations were variable, indicating that translational or post translational factors modified the effects of the changes in gene expression. This phenomenon was further emphasized by the finding that activation of proteins by phosphorylation as a result of signaling kinase cascades were not reflected in the microanalysis results. For example, phosphorylation activation of ERK1/2, p38 and AKT, which are key proteins in different kinase signaling pathways would not be reflected in the microarray analysis. ERK1/2 phosphorylation was down regulated at high BAL when compared to controls. Phosphorylation of p38 was down regulated equally at both high and low BAL and AKT was upregulated only at low BAL. The results indicate that gene expression at high BAL is profoundly different than at low BAL. Supported by NIH/NIAAA Grant 8116.