Pancreatic cholesterol esterase, ES-10, and fatty acid ethyl ester synthase III gene expression are increased in the pancreas and liver but not in the brain or heart with long-term ethanol feeding in rats.
BACKGROUND
Chronic alcohol consumption predisposes susceptible individuals to both acute and chronic pancreatitis.


OBJECTIVE
Our hypothesis was that alcohol increases the risk of pancreatitis by disrupting defense mechanisms and/or enhancing injury-associated pathways through altered gene expression. Hence, we studied the expression of pancreatic genes in rats chronically exposed to ethanol.


METHODS
Male Wistar rats were pair-fed liquid diets without and with ethanol for 4 weeks. Total RNA was extracted from rat pancreas and other organs. The mRNA expression patterns among pancreatic samples from ethanol-fed rats and controls were compared with use of mRNA differential display. The differentially expressed cDNA tags were isolated, cloned, and sequenced.


RESULTS
One cDNA tag that was overexpressed in the pancreas showed 99% sequence homology to a rat pancreatic cholesterol esterase mRNA (CEL; Enzyme Commission number [EC] 3.1.1.13). The differential expression was confirmed by realtime PCR. Gene expression was also increased in the liver but not in the heart or brain of the alcohol-fed rats. Because CEL has fatty acid ethyl ester (FAEE)-generating activity and FAEEs play a major role in acute alcoholic pancreatitis, we determined the expression of other genes encoding for FAEE-generating enzymes and showed similar organ-specific expression patterns.


CONCLUSIONS
Our results demonstrate that chronic ethanol consumption induced expression of FAEE-related genes in the pancreas and liver. This upregulation may be a central mechanism leading to acinar cell injury.
Pfützer
Roland H
RH
Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Tadic
Stasa D
SD
Li
Ha-Sheng
HS
Thompson
Bryan S
BS
Zhang
Ji-Ying
JY
Ford
Michael E
ME
Eagon
Patricia K
PK
Whitcomb
David C
DC
D000217:Acyltransferases / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000235:genetics; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D010179:Pancreas / Q000201:enzymology*; D019512:Pancreatitis, Alcoholic / Q000201:enzymology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D002787:Sterol Esterase / Q000235:genetics*
D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D000431:Ethanol; D000217:Acyltransferases; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D002787:Sterol Esterase; C043403:fatty acyl ethyl ester synthase