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.

Abstract

INTRODUCTION:

Chronic alcohol consumption predisposes susceptible individuals to both acute and chronic pancreatitis.

AIMS:

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.

METHODOLOGY:

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.

CONCLUSION:

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.

• Authors: Roland H Pfützer, Stasa D Tadic, Ha-Sheng Li, Bryan S Thompson, Ji-Ying Zhang, Michael E Ford, Patricia K Eagon, David C Whitcomb
• Journal: Pancreas (Pancreas) Vol. 25 Issue 1 Pg. 101-6 (Jul 2002) ISSN: 0885-3177 [Print] United States
• PMID: 12131779 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Central Nervous System Depressants
• RNA, Messenger
• Ethanol
• Acyltransferases
• Carboxylic Ester Hydrolases
• Carboxylesterase
• Sterol Esterase
• fatty acyl ethyl ester synthase

Topics

• Acyltransferases (genetics)
• Animals
• Base Sequence
• Brain (enzymology)
• Carboxylesterase
• Carboxylic Ester Hydrolases (genetics)
• Central Nervous System Depressants (pharmacology)
• Ethanol (pharmacology)
• Gene Expression Profiling
• Gene Expression Regulation, Enzymologic
• Liver (enzymology)
• Male
• Molecular Sequence Data
• Myocardium (enzymology)
• Pancreas (enzymology)
• Pancreatitis, Alcoholic (enzymology, physiopathology)
• RNA, Messenger (isolation & purification)
• Rats
• Rats, Wistar
• Sterol Esterase (genetics)