STIMULATION OF PROTEIN-SYNTHESIS IN ISOLATED PANCREATIC ACINI FROM CHRONICALLY ETHANOL-FED RATS IS DUE TO ALTERATIONS IN POSTTRANSCRIPTIONAL REGULATION

In an earlier study, we reported that isolation of acini from the panc reas of rats fed ethanol chronically, led to a 2- to 3-fold increase i n the rate of protein synthesis compared to acini from rats fed the co ntrol diet. In the present study, we wanted to investigate whether the enhanced rate of protein synthesis was due to an increased rate of de granulation, reflecting a stimulation of cellular signal transduction processes, and/or to changes at the level of transcription/translation . The rate of degranulation was monitored by initially prelabelling th e secretory proteins in vivo with [H-3]leucine followed by determinati on of their fate in the intact tissue as well as in the subsequently i solated acini. The recovery of the label in isolated acini as a fracti on of that incorporated into the tissue was similar for control and et hanol-fed groups, suggesting that ethanol feeding had no effect on the rate of degranulation during the isolation of acini. The rate of inco rporation of [H-3]uridine into total RNA was about 70% higher in acini from the ethanol-fed group as compared to the control group, suggesti ng a higher rate of transcription. However, the steady-state level of mRNA for trypsinogen, a representative digestive enzyme mRNA, showed o nly a moderate increase of 20% in acini from the ethanol-fed group com pared to those from the intact tissue. These results suggest that the increased rate of protein synthesis in isolated acini from ethanol-fed rat pancreas is primarily due to post-transcriptional modifications.