title: Correlation between adenosine triphosphate content and apoptosis in liver of rats treated with alcohol.
abstract: BACKGROUND
  Chronic alcohol consumption depresses adenosine triphosphate (ATP) synthesis and induces mitochondrial DNA (Mt-DNA) deletion. ATP content in cells may play a critical role in inducing cell death, apoptosis, or necrosis. However, it is unknown which type of cell death occurs in alcoholic liver disease. In this study, the deletions of hepatic Mt-DNA, hepatic ATP content, and the number of single-stranded DNA (ss-DNA) of hepatocytes in rats treated with ethanol were determined to elucidate the relationship among Mt-DNA deletion, ATP synthesis, and/or hepatic apoptosis.
  
  
  METHODS
  Sixteen male Wistar rats were fed with a liquid diet containing 36% ethanol (E group) or liquid diet without ethanol (C group) for 5 weeks. Hepatic ATP content was measured and the deletions of Mt-DNA encoding complexes I, IV, and V were determined in fresh liver tissue, and ss-DNA was stained in paraffin sections.
  
  
  RESULTS
  Fatty change was observed in the E group, but not in the C group. Hepatic ATP content in the E group was 0.44 micromol/g of liver, which was significantly lower than that in the C group (0.84 micromol/g of liver). However, no deletion of Mt-DNA encoding complexes I, IV, and V was detected in either the E or the C group. ss-DNA staining was clearly observed in the nuclei of hepatocytes in both groups. The number of ss-DNA-positive hepatocytes in the E group was 5.6 +/- 1.8/10,000 hepatocytes, which was significantly less than that in the C group: 20.6 +/- 4.8/10,000 hepatocytes. There was a positive correlation between hepatic ATP contents and the number of ss-DNA-positive cells.
  
  
  CONCLUSIONS
  The results suggest that mitochondrial function, at least in part ATP synthesis, was depressed before the damage of Mt-DNA by chronic ethanol consumption. Chronic ethanol consumption may not be responsible for the apoptosis of hepatocytes.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukumura
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Tsuchishima
authors.forename: Shujiro
authors.initials: S
authors.lastname: Takase
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002872:Chromosome Deletion; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D000431:Ethanol / Q000633:toxicity; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000235:genetics* / Q000473:pathology; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004272:DNA, Mitochondrial; C021983:complex V (mitochondrial oxidative phosphorylation system); D000431:Ethanol; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D025261:Mitochondrial Proton-Translocating ATPases; D042967:Electron Transport Complex I