Stimulation of protein synthesis in isolated pancreatic acini from chronically ethanol-fed rats is due to alterations in post-transcriptional regulation.
In an earlier study, we reported that isolation of acini from the pancreas of rats fed ethanol chronically, led to a 2- to 3-fold increase in the rate of protein synthesis compared to acini from rats fed the control diet. In the present study, we wanted to investigate whether the enhanced rate of protein synthesis was due to an increased rate of degranulation, 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 the secretory proteins in vivo with [3H]leucine followed by determination of their fate in the intact tissue as well as in the subsequently isolated acini. The recovery of the label in isolated acini as a fraction of that incorporated into the tissue was similar for control and ethanol-fed groups, suggesting that ethanol feeding had no effect on the rate of degranulation during the isolation of acini. The rate of incorporation of [3H]uridine into total RNA was about 70% higher in acini from the ethanol-fed group as compared to the control group, suggesting a higher rate of transcription. However, the steady-state level of mRNA for trypsinogen, a representative digestive enzyme mRNA, showed only a moderate increase of 20% in acini from the ethanol-fed group compared 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.
Ponnappa
B C
BC
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, PA.
Dodge
G R
GR
Dudkowski
B
B
Hoek
J B
JB
Iozzo
R V
RV
Rubin
E
E
D000818:Animals; D002919:Chymotrypsinogen / Q000032:analysis; D000431:Ethanol / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D007930:Leucine / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D017393:RNA Editing; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D014529:Uridine / Q000378:metabolism
D012333:RNA, Messenger; D014316:Tritium; D000431:Ethanol; D012313:RNA; D002919:Chymotrypsinogen; D007930:Leucine; D014529:Uridine