Effects of chronic ethanol consumption on the rate of rat liver mitochondrial protein turnover and synthesis (original) (raw)
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Chronic low dose ethanol intake: Biochemical characterization of liver mitochondria in rats
Life Sciences, 2000
Liver mitochondria were isolated from male rats exposed for 2 months to low doses of ethanol (3% v/v in drinking water), a condition not associated with tolerance or dependence. The results show no significant changes in the content of reduced or oxidized glutathione in the liver mitochondria of ethanol treated rats with respect to controls. However, a slight but significant increase in lipid peroxidation, accompanied by an increased content of oxidized proteins, was found in el.hanol exposed animals. Mitochondrial content of cytochrome complexes was not significantly affected by ethanol intake. The specific enzymatic activity of cytochrome oxidase showed, however, a . significant decrease in ethanol-treated rats. The slight mitochondrial alterations found in the liver of rats exposed chronically to low doses of ethanol might represent the beginning of a more extensive damage previously observed in rats exposed to high doses of this substance.
Journal of Clinical Investigation, 1994
Chronic ethanol feeding selectively impairs the translocation of cytosol GSH into the mitochondrial matrix. Since ethanol-induced liver cell injury is preferentially localized in the centrilobular area, we examined the hepatic acinar distribution of mitochondrial GSH transport in ethanol-fed rats. Enriched periportal (PP) and perivenous (PV) hepatocytes from pairand ethanol-fed rats were prepared as well as mitochondria from these cells. The mitochondrial pool size of GSH was decreased in both PP and PV cells from ethanol-fed rats either as expressed per 106 cells or per microliter of mitochondrial matrix volume. The rate of reaccumulation of mitochondrial GSH and the linear relationship of mitochondrial to cytosol GSH from ethanol-fed mitochondria were lower for both PP and PV cells, effects observed more prominently in the PV cells. Mitochondrial functional integrity was lower in both PP and PV ethanol-fed rats, which was associated with decreased cellular ATP levels and mitochondrial membrane potential, effects which were greater in the PV cells. Mitochondrial GSH depletion by ethanol feeding preceded the onset of functional changes in mitochondria, suggesting that mitochondrial GSH is critical in maintaining a functionally competent organelle and that the greater depletion of mitochondrial GSH by ethanol feeding in PV cells could contribute to the pathogenesis of alcoholic liver disease. (J. Clin. Invest. 1994. 94:193-201.)
Life Sciences, 1975
Incorporation of C ly Leucine was determined in vitro or in vivo in isolated mitochondria and microsomas of rat brâin and liver after acute or chronic ethanol administration in vivo. The protein synthess in mitochondrial and microsomal preparation was inhibited respectively by chloramphenicol and cycloeximide, specific inhibitors for the two systems tested. The experimental data demonstrate that the in vitro protein synthesis in both systems, mitochondrial and microsomal, is strongly affected only after chronic treatment which produces significant activation at the mitochondrial and microsomal level in the liver and an inhibition on the same systems of the brain. The data for in vivo protein synthesis instead show strong inhibition after acute administration, except for brain mitochondria, which are practically unaffected, while after chronic treatment no significant alterations are observed .
Mitochondrial remodeling in the liver following chronic alcohol feeding to rats
Free radical biology & medicine, 2017
The feeding of alcohol orally (Lieber-DeCarli diet) to rats has been shown to cause declines in mitochondrial respiration (state III), decreased expression of respiratory complexes, and decreased respiratory control ratios (RCR) in liver mitochondria. These declines and other mitochondrial alterations have led to the hypothesis that alcohol feeding causes "mitochondrial dysfunction" in the liver. If oral alcohol feeding leads to mitochondrial dysfunction, one would predict that increasing alcohol delivery by intragastric (IG) alcohol feeding to rats would cause greater declines in mitochondrial bioenergetics in the liver. In this study, we examined the mitochondrial alterations that occur in rats fed alcohol both orally and intragastrically. Oral alcohol feeding decreased glutamate/malate-, acetaldehyde- and succinate-driven state III respiration, RCR, and expression of respiratory complexes (I, III, IV, V) in liver mitochondria, in agreement with previous results. IG alco...
Alcoholism: Clinical and Experimental Research, 1994
The relative concentrations of several subunits of the mitochondrial ciated with the FI (a + p and 7) are not altered in Fo.F,-ATP synthase were determined in mitochondria and submito-mitochondria from ethanol-fed animals. ln contrast, the levels of polypeptides of the FO (ATPase 6 and 8) are chondrial particles prepared from the livers of ethanol-fed and control rats. The polypeptides were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis and the stained gels were significantly de~~eased in these organelles. The data preanalyzed by densitometry for the relative concentrations of the ATP sented in this report provides additional evidence that an synthase subunits. A significant decrease in the relative concentra-ethanol-induced lesion in mitochondria1 protein syntion of the mitochondrial gene product, ATPase subunit 8, was thesis7,8 is responsible for the significant alterations in observed in mitochondria and submitochondrial particles from oxidative phosphorylation found in mitochondria from ethanol-fed animals. The relative concentration of the other mitochondrial encoded ATPase subunit, ATPase 6, was also depressed, ethanol-fed rats. Moreover, this study illustrates a difas confirmed in submitochondrial particles. In contrast, there were ferential effect of chronic ethanol consumption on cytono significant ethanol-related depressions in subunits a, 6, and OSCP plasmic and mitochondria1 protein syntheses of the ATP of the Fa. F, or the adenine nucleotide carrier in intact mitochondria. synthase subunits. These results demonstrate that ethanol consumption causes a decrease in the content of mitochondrial synthesized subunits 6 and 8 whereas no effect is exerted on the concentrations of nuclear gene products of the ATP synthase complex. Likewise, the adenine nucleotide transporter, also a nuclear gene product, is unaffected by ethanol consumption.
Ethanol feeding enhances age-related deterioration of the rat hepatic mitochondrion
American Journal of Physiology-Gastrointestinal and Liver Physiology, 2005
Chronic ethanol feeding damages the hepatic mitochondrion by increasing mitochondrial DNA (mtDNA) oxidation, lowering mtDNA yields and impairing mitochondrial respiration. These effects are also seen during aging. By employing a 21-day chronic feeding regimen, we investigated the effects of ethanol consumption on mtDNA content and mitochondrial respiration in 2-, 12-, and 24-mo-old male rats. Aging resulted in decreased mtDNA content, increased mtDNA damage (as indicated by inhibition of Taq polymerase progression), and a decline in state 3 respiration; effects that were further exacerbated by ethanol feeding. Additionally, ethanol consumption caused an increase in the levels of citrate synthase while not impacting mitochondrial protein content. In conclusion, ethanol and aging combine to cause deterioration in the structural and functional integrity of the hepatic mitochondrion. The additive effects of aging and ethanol feeding may have serious consequences for hepatic energy metab...
Role of mitochondria in hepatotoxicity of ethanol
Biophysics, 2010
The current understanding of the effects of alcohol intoxication on the basic mitochondrial func tions has been presented. Both, the direct toxic effect of ethanol on biological membranes and various cellular systems and the toxicity of acetaldehyde and reactive oxygen species (the products of ethanol oxidation) are discussed, with emphasis on the effect of ethanol on the basic functions of mitochondria and Ca 2+ dependent mitochondrial permeability transition. Based on the available experimental data, it is demonstrated that acute alcohol intoxication causes a global mitochondrial dysfunction in the liver, resulting in considerable distur bance of the whole cellular metabolism. Alcohol poisoning of the liver leads to a decreased ability of cells to withstand oxidative stress, to support the synthesis of vital metabolic intermediates (e.g., methyl groups), as well as to produce urea from ammonia, due to a decreased permeability of the outer membrane and impaired exchange of substrates between the cytoplasm and the mitochondrial matrix. This review emphasizes the role of porin channels of the outer mitochondrial membrane in ethanol mediated disturbances of basic mito chondrial functions and its consequences for the entire cell metabolism in the liver.