Effects of ethanol on membrane lipids III. Quantitative changes in lipid and fatty acid composition of nonpolar and polar lipids of mouse total liver, mitochondria and microsomes following ethanol feeding

Miceli, Joseph N.; Ferrell, William J.

doi:10.1007/bf02531839

Cited by 43 publications

(9 citation statements)

References 22 publications

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“…It is not found in any other mammalian membrane. Previous studies on phospholipid composition of mitochondria from chronic alcoholic rats, while indicating changes in phospholipid composition (30)(31)(32)(33), appear contradictory. Our own initial study of phospholipid composition indicates that a major change is in the fatty acid composition of cardiolipin.…”

Section: Resultsmentioning

confidence: 87%

Membranes and phospholipids of liver mitochondria from chronic alcoholic rats are resistant to membrane disordering by alcohol.

Waring¹,

Rottenberg²,

Ohnishi³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

135

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Using the spin probe 5-doxylstearic acid, we studied the structural perturbations of rat liver mitochondrial membranes produced by exposure to ethanol in vitro and by chronic ethanol feeding. The addition of ethanol in vitro to mitochondria from control animals appears to "fluidize" the membranes, as evidenced by a pronounced decrease in the order parameter. By contrast, in membranes from rats fed ethanol chronically, there was no effect on the order parameter. This resistance of the mitochondrial membranes from chronically intoxicated animals to the fluidizing effect of ethanol probably results from a change in the composition of the phospholipids, because the same differential response to ethanol was observed upon using vesicles of mitochondrial phospholipids extracted from control and chronically treated rats. In the presence of 0.025-0.1 M ethanol, a range that prevails in the blood of chronic alcoholics, the order parameter of mitochondrial membranes from rats fed ethanol was comparable to that of control membranes without ethanol in vitro. Analysis of extracted mitochondrial phospholipids showed that the cardiolipin from ethanol-fed animals had fatty acyl residues that are more saturated than those of controls. These findings point to the underlying molecular mechanism for our previous observation that mitochondria from chronic alcoholic rats are more resistant to uncoupling by ethanol at physiological temperature [Rottenberg, H Chronic ethanol ingestion by rats produces striking structural (1, 2) and functional (3, 4) aberrations of liver mitochondria. Although these changes are commonly ascribed to a damaging effect of chronic alcoholism on hepatic metabolism, we have recently suggested (5) that they might reflect an adaptation of the mitochondrial membranes to the presence of ethanol. In mitochondria from rats treated chronically with ethanol, respiration and ATPase activities are lower and more resistant to the stimulating effect of ethanol at physiological temperature (5). This latter effect is probably the result of the "fluidizing" effect ofethanol on phospholipid membranes (6). The resistance to the effect of ethanol in mitochondria from chronically intoxicated animals might result from a change in the membrane structure, as suggested by the shifts of the breaks in Arrhenius plots of both respiration and ATPase to higher temperatures, and by the lowering of the energy of activation of these membrane enzymes. We, therefore, sought to detect such structural changes by direct physical measurements in intact membranes and in their isolated lipids to discover whether the membranes become more "rigid" or more resistant to the fluidizing effect ofethanol, as suggested by our previous study (5). We employed the nitroxide spin labels 5-doxyl-and 12-doxylstearic acid as probes ofthe membrane lipid environment (7). The distribution of molecular orientations of the probe in the membrane is commonly expressed in terms of a calculated order parameter (8). Our EPR measurements with these probes directly ...

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Section: Resultsmentioning

confidence: 87%

Membranes and phospholipids of liver mitochondria from chronic alcoholic rats are resistant to membrane disordering by alcohol.

Waring¹,

Rottenberg²,

Ohnishi³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

135

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“…Therefore, although the 40-50% increase in 18:1 n-9 is indicative of lipogenesis enhanced by etha nol [ 15], or of increased delta-9 desaturation of 18:0, TG accumulation did not occur. Lack of a signifant increase in liver TG after ethanol feeding has been reported previously in mice fed a basal diet [ 12] and in mice and rats fed a liquid diet containing ethanol [13,14] in which 18:2n-6 was present at 2-3% instead of the 15-20% typically provided by the liquid diets used in studies in which eth anol-induced fatty liver occurs. Increased di etary 18:2n-6 would possibly have been asso ciated with increased liver TG in the etha nol-fed hamsters [16].…”

Section: Discussionmentioning

confidence: 89%

Long-Term Ethanol Consumption in the Hamster: Effects on Tissue Lipids, Fatty Acids and Erythrocyte Hemolysis

Cunnane¹,

McAdoo²,

Horrobin³

1987

Ann Nutr Metab

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Male Golden Syrian hamsters at 1 year of age were given a basal diet and either distilled water or 10% absolute ethanol in distilled water to drink for 1 year in order to determine the influence of prolonged ethanol intake on tissue long chain fatty acid, lipid composition and erythrocyte hemolysis in response to osmotic stress. Total lipids were extracted from liver, heart, plasma and erythrocytes. Individual lipid fractions were quantitated and the percentage fatty acid composition of the lipid fractions analyzed by gas-liquid chromatography. Although no significant changes in tissue lipid content or erythrocyte hemolysis were attributable to ethanol intake, fatty acid changes were marked in the ethanolfed hamsters. The primary fatty acid changes were increased oleic acid (40–50%) and decreased linoleic acid (25–60%) which were observed in all tissues. Arachidonic acid was decreased only in triacylglycerol fractions. The results suggest that in the hamster long-term voluntary ethanol intake alters specific long chain fatty acids, but that erythrocyte membrane integrity and tissue lipid composition were not compromised.

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“…Chronic ethanol increased the levels of 2,4-dienoyl-CoA reductase and ⌬ 3 ,⌬ 2 -enoyl-CoA isomerase, which are enzymes involved in the cis-trans isomerization of ␤-oxidation intermediates and required for ␤-oxidation to continue (49,50). Linoleic and oleic acid are increased in liver mitochondria by chronic ethanol feeding (51)(52)(53), but whether these fatty acids act via a "peroxisome proliferator-activated receptor ␣-like" mechanism to increase the levels of these key proteins involved in ␤-oxidation of unsaturated fatty acids in liver is currently not known.…”

Section: Fig 4 Chronic Ethanol Consumption Decreases the Levels Of mentioning

confidence: 99%

Modification of the Mitochondrial Proteome in Response to the Stress of Ethanol-dependent Hepatotoxicity

Venkatraman

Landar

Davis

et al. 2004

Journal of Biological Chemistry

160

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Mitochondria are particularly susceptible to increased formation of reactive oxygen and nitrogen species in the cell that can occur in response to pathological and xenobiotic stimuli. Proteomics can give insights into both mechanism of pathology and adaptation to stress. Herein we report the use of proteomics to evaluate alterations in the levels of mitochondrial proteins following chronic ethanol exposure in an animal model. Forty-three proteins showed differential expression, 13 increased and 30 decreased, as a consequence of chronic ethanol. Of these proteins, 25 were not previously known to be affected by chronic ethanol emphasizing the power of proteomic approaches in revealing global responses to stress. Both nuclear and mitochondrially encoded gene products of the oxidative phosphorylation complexes in mitochondria from ethanol-fed rats were decreased suggesting an assembly defect in this integrated metabolic pathway. Moreover mtDNA damage was increased by ethanol demonstrating that the effects of ethanol consumption extend beyond the proteome to encompass mtDNA. Taken together, we have demonstrated that chronic ethanol consumption extends to a modification of the mitochondrial proteome far broader than realized previously. These data also suggest that the response of mitochondria to stress may not involve non-discriminate changes in the proteome but is restricted to those metabolic pathways that have a direct role in a specific pathology.Chronic ethanol consumption causes liver damage by a complex process thought to involve oxidative and nitrosative stress, hypoxia, up-regulation of proinflammatory cytokines, and defects in energy metabolism (1-3). As both a source for the formation and target of modifications mediated by reactive oxygen and nitrogen species, the mitochondrion is recognized as a site critical in the cellular stress response induced by chronic ethanol exposure. Increased mitochondrial production of reactive oxygen species (4 -6), oxidation of mitochondrial proteins (7-10), depressed oxidative phosphorylation activity (11-13), and disrupted fatty acid metabolism (14 -16) occur following consumption of alcohol, indicating that ethanol induces significant changes in mitochondria physiology. These responses are also accompanied by a profound increase in the sensitivity of the respiratory chain to inhibition by NO, which we propose plays a key role in contributing to the hypoxia associated with ethanol-dependent hepatotoxicity (17). While mechanisms responsible for ethanol-induced mitochondrial dysfunction have been investigated, the impact of chronic ethanol consumption on the overall content of mitochondrial proteins, the "mitochondrial proteome," has not been studied. Earlier studies by Cunningham and colleagues (18,19) have demonstrated that ethanol consumption decreases the synthesis of the 13 mitochondrially encoded proteins that comprise respiratory complexes I, III, and IV and the ATP synthase. It is proposed that the inhibition of mitochondrial protein synthesis following chronic etha...

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Effects of ethanol on membrane lipids III. Quantitative changes in lipid and fatty acid composition of nonpolar and polar lipids of mouse total liver, mitochondria and microsomes following ethanol feeding

Cited by 43 publications

References 22 publications

Membranes and phospholipids of liver mitochondria from chronic alcoholic rats are resistant to membrane disordering by alcohol.

Membranes and phospholipids of liver mitochondria from chronic alcoholic rats are resistant to membrane disordering by alcohol.

Long-Term Ethanol Consumption in the Hamster: Effects on Tissue Lipids, Fatty Acids and Erythrocyte Hemolysis

Modification of the Mitochondrial Proteome in Response to the Stress of Ethanol-dependent Hepatotoxicity

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