Long-term ethanol consumption alters pancreatic gene expression in rats: a possible connection to pancreatic injury.
OBJECTIVE
Long-term ethanol consumption does not cause acute pancreatitis but rather sensitizes the pancreas to subsequent insults. The mechanisms responsible for this sensitization are unknown. To determine whether alterations in pancreatic gene expression might participate in ethanol-mediated sensitization, we performed gene-profiling analysis.


METHODS
Animals were fed ethanol-containing Lieber-DeCarli or control diet (pair-fed). After 8 weeks, pancreatic RNA expression was analyzed using Affimetrix GeneChips. Changes in specific genes were verified using quantitative reverse transcriptase-polymerase chain reaction.


RESULTS
Long-term ethanol feeding caused a significant alteration of pancreatic gene expression. Selection criteria of changes more than 3-fold and P < 0.05 yielded 114 probe sets. Activating transcription factor 3, heat shock protein 70, heat shock protein 27, and mesotrypsinogen were increased, whereas pancreatitis associate protein, folate carrier, and metallothionein were decreased.


CONCLUSIONS
Ethanol had a profound effect on pancreatic gene expression. The genes identified as elevated and reduced in this study may contribute to pancreatic sensitivity to stress. This study indicates for the first time the identities of multiple genes whose expression levels are dramatically influenced by long-term ethanol feeding. The identified genes may help explain the relationship between long-term ethanol abuse and pancreatic disease and lead to possible preventative or therapeutic approaches to ethanol-induced pancreatic disease.
Kubisch
Constanze H
CH
Department of Cancer Biology, MD Anderson Cancer Center, University of Texas, Houston, TX 77230-1429, USA.
Gukovsky
Ilya
I
Lugea
Aurelia
A
Pandol
Stephen J
SJ
Kuick
Rork
R
Misek
David E
DE
Hanash
Samir M
SM
Logsdon
Craig D
CD
D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D019512:Pancreatitis, Alcoholic / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D051700:Activating Transcription Factor 3; D000951:Antigens, Neoplasm; C497108:Atf3 protein, rat; D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D012333:RNA, Messenger; D000431:Ethanol