Release of mitochondrial rather than cytosolic enzymes during liver regeneration in ethanol-intoxicated rats

Arch Med Res. 2004 Jul-Aug;35(4):263-70. doi: 10.1016/j.arcmed.2004.04.004.

Abstract

Background: Partial hepatectomy (PH) promoted rapid increase in serum of hepatic enzyme activities localized in mitochondria preferentially to increase enzyme activities from cytosol; low doses of ethanol (EtOH) administered to PH rats expedited return to normality of these elevated serum enzyme activities. The fate of released mitochondrial enzymes from liver was investigated in this study to advance knowledge of the role of mitochondria during priming phase of liver regeneration.

Methods: Catalytic activity of mitochondrial and cytosolic proteins was measured in remnant liver after PH and in elutes of perfused remnant livers from control and ethanol-intoxicated rats.

Results: During the first 24 h of liver regeneration (LR), mitochondrial enzymes--glutamate dehydrogenase, aspartate amino transferase, and malate dehydrogenase--diminished 33-58% in mitochondria, increased 17% in cytosol, and for two enzymes rose 68-86% in perfusates. Cytosolic lactate dehydrogenase decreased transiently in cytosol (24%) and increased only 13% in perfusates. Activity of cytochrome oxidase [corrected] (mitochondrial membrane-attached enzymes) was not modified. Ethanol intoxication after PH produced earlier and slightly higher extrusion of matrix mitochondrial enzyme activities.

Conclusions: Selective increase of mitochondrial membrane permeability appeared as an important event during priming phase of LR after PH, thus sustaining preferential release of mitochondrial proteins outside the organelle in comparison with limited redistribution of cytosolic and mitochondrial membrane proteins. High doses of EtOH delayed LR and re-enforced mobilization of proteins produced by PH probably by enhancing greater mitochondrial membrane permeability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholic Intoxication*
  • Animals
  • Aspartate Aminotransferases / metabolism
  • Cell Fractionation
  • Cytoplasm / enzymology*
  • Ethanol / toxicity*
  • Glutamate Dehydrogenase / metabolism
  • Hepatectomy
  • L-Lactate Dehydrogenase / metabolism
  • Liver Regeneration / physiology*
  • Malate Dehydrogenase / metabolism
  • Male
  • Mitochondria / enzymology*
  • Rats
  • Rats, Wistar
  • Thymidine Kinase / metabolism

Substances

  • Ethanol
  • L-Lactate Dehydrogenase
  • Malate Dehydrogenase
  • Glutamate Dehydrogenase
  • Aspartate Aminotransferases
  • Thymidine Kinase