title: Overexpression of hydroxymethylglutaryl CoA synthase 2 and 2,4-dienoyl-CoA reductase in rat pancreas following chronic alcohol consumption.
abstract: OBJECTIVE
  The mechanism of alcohol-induced pancreatic damage is unclear. The aim of this study was to clarify the effects of chronic alcohol intake on the pancreatic proteome.
  
  
  METHODS
  Rats were fed an alcohol-containing Lieber-DeCarli liquid diet, and the pancreatic proteome was compared with that of pair-fed control rats using agarose 2-dimensional gel electrophoresis followed by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  The expression of 3 proteins was consistently altered in alcohol-fed rats: 1 protein was down-regulated, and 2 proteins were up-regulated. The 2 up-regulated proteins were identified as 2,4-dienoyl-CoA reductase and hydroxymethylglutaryl-CoA synthase (HMGCS2). The combined concentration of malondialdehyde and 4-hydroxyalkenals was significantly greater in alcohol-fed rats. It is noteworthy that the reactivity of anti-4-hydroxy-2-nonenal antibody was significantly higher toward HMGCS2 isolated from alcohol-fed rats. The activity of HMGCS2 was higher in alcohol-fed rats, but the relative increase in enzyme activity in alcohol-fed rats was less than the relative increase in HMGCS2 expression.
  
  
  CONCLUSIONS
  Chronic alcohol consumption results in distinct alterations in the expression of 3 pancreatic proteins. The reactivity of 4-hydroxy-2-nonenal toward one of the up-regulated proteins, HMGCS2, increased markedly following chronic alcohol intake, suggesting that up-regulation of HMGCS2 is connected with alterations of lipid peroxidation induced by alcohol.
authors.affiliation: Clinical Proteomics Research Center, Chiba University Hospital, Chiba University, Chiba, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Eri
authors.initials: E
authors.lastname: Haruta-Satoh
authors.forename: Mako
authors.initials: M
authors.lastname: Yamada
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kado
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology; D002853:Chromatography, Liquid; D004032:Diet; D015180:Electrophoresis, Gel, Two-Dimensional; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000447:Aldehydes; D002492:Central Nervous System Depressants; D020543:Proteome; D000431:Ethanol; D008315:Malondialdehyde; D044925:Oxidoreductases Acting on CH-CH Group Donors; C100153:2,4-dienoyl-CoA reductase; D006904:Hydroxymethylglutaryl-CoA Synthase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal