Acetaldehyde inhibition of protein synthesis in isolated rat pancreatic acini.
Exposure of isolated dispersed pancreatic acini to increasing concentrations of ethanol (5 to 500 mM) or acetaldehyde (0.5 to 100 mM) produced a progressive inhibition of [3H]leucine incorporation into both "cellular" (those remaining in the cell) and "secretory" (those released into the medium) proteins. Whereas 500 mM ethanol caused 90-95% inhibition in the synthesis of "cellular" and "secretory" proteins, the concentration of acetaldehyde needed to produce a similar inhibition was found to be 50 mM. All subsequent experiments were performed with 12.5 mM acetaldehyde, a concentration that consistently inhibited acinar protein synthesis by about 50%. The acetaldehyde-mediated inhibition of acinar protein synthesis was partially normalized when this metabolite was removed after 30 min during a 90-min incubation period. In the presence of acetaldehyde, the secretion of 3H-pulse-labeled proteins, but not amylase, trypsinogen, or chymotrypsinogen, was greatly depressed. Acetaldehyde also caused a marked reduction in [3H]uridine incorporation into acinar RNA. The entry of [3H]uridine, [3H]leucine, and [3H]aminoisobutyric acid into isolated acini was found to be slightly (15-25%) decreased by acetaldehyde. It is concluded that acetaldehyde exerts a direct toxic effect on isolated dispersed pancreatic acini as evidenced by diminution of both protein and RNA synthesis and decreased secretion of the newly synthesized proteins. This inhibitory effect of acetaldehyde could be partially reversed.
A P
AP
Majumdar
M J
MJ
Haiman
B A
BA
Zylbert
H T
HT
Billy
G D
GD
Vesenka
M C
MC
Geokas
D000079:Acetaldehyde / Q000494:pharmacology*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002469:Cell Separation; D002919:Chymotrypsinogen / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium; D014362:Trypsinogen / Q000378:metabolism
D000621:Aminoisobutyric Acids; D014316:Tritium; C100049:2-aminoisobutyric acid; D014362:Trypsinogen; D002919:Chymotrypsinogen; D000681:Amylases; D007930:Leucine; D000079:Acetaldehyde