Effect of Chronic Ethanol Consumption on Respiratory and Glycolytic Activities of Rat Periportal and Perivenous Hepatocytes

Baio, Debra L.; Czyz, Craig N.; Horn, Cynthia G. Van; Ivester, Priscilla; Cunningham, Carol C.

doi:10.1006/abbi.1997.0514

Cited by 23 publications

(18 citation statements)

References 29 publications

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“…Moreover, the glycolysis inhibition with IAA in ethanol-perfused livers induced only a slight decrease (-4%) in the ATP content. Beside of previous works observing the ethanol-induced decrease of lactate and/or pyruvate excretion which demonstrated decrease in the glycolytic activity in ethanol-perfused liver isolated from fed rats [4] and in isolated hepatocytes from ethanol-fed rats [5,6], the present work clearly evidenced that ethanol highly diminished the glycolytic ATP production. Hence, ATP production is mainly mitochondrial in the presence of ethanol.…”

Section: Discussionsupporting

confidence: 72%

“…Since hepatic glycogenolysis occurs in the presence of ethanol as demonstrated in isolated hepatocytes [3], subsequent glycolysis could then supply some ATP until all the stored carbohydrates are oxidated. However, in fed rats the glycolytic ATP production has been reported to be diminished in isolated livers perfused with ethanol [4] and in isolated hepatocytes from ethanol-fed rats [5,6]. Hence, ATP production in the presence of ethanol might be mainly mitochondrial and the observed increase in its rate [1] at the new steady state might reflect an increase in ATP consumption in the whole liver, since at a steady state the net ATP consumption rate equals the net ATP synthesis.…”

Section: Introductionmentioning

confidence: 99%

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Some processes of energy saving and expenditure occurring during ethanol perfusion in the isolated liver of fed rats; a Nuclear Magnetic Resonance study.

et al. 2004

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BackgroundIn the isolated liver of fed rats, a 10 mM ethanol perfusion rapidly induced a rapid 25% decrease in the total ATP content, the new steady state resulting from both synthesis and consumption. The in situ rate of mitochondrial ATP synthesis without activation of the respiration was increased by 27%, implying an increased energy demand. An attempt to identify the ethanol-induced ATP-consuming pathways was performed using 31P and 13C Nuclear Magnetic Resonance.ResultsEthanol (i) transiently increased sn-glycerol-3-phosphate formation whereas glycogenolysis was continuously maintained; (ii) decreased the glycolytic ATP supply and (iii) diminished the intracellular pH in a dose-dependent manner in a slight extend. Although the cytosolic oxidation of ethanol largely generated H+ (and NADH), intracellular pHi was maintained by (i) the large and passive excretion of cellular acetic acid arising from ethanol oxidation (evidenced by exogenous acetate administration), without energetic cost or (ii) proton extrusion via the Na+-HCO3- symport (implying the indirect activation of the Na+-K+-ATPase pump and thus an energy use), demonstrated during the addition of their specific inhibitors SITS and ouabaïn, respectively.ConclusionVarious cellular mechanisms diminish the cytosolic concentration of H+ and NADH produced by ethanol oxidation, such as (i) the large but transient contribution of the dihydroxyacetone phosphate / sn-glycerol-3-phosphate shuttle between cytosol and mitochondria, mainly implicated in the redox state and (ii) the major participation of acetic acid in passive proton extrusion out of the cell. These processes are not ATP-consuming and the latter is a cellular way to save some energy. Their starting in conjunction with the increase in mitochondrial ATP synthesis in ethanol-perfused whole liver was however insufficient to alleviate either the inhibition of glycolytic ATP synthesis and/or the implication of Na+-HCO3- symport and Na+-K+-ATPase in the pHi homeostasis, energy-consuming carriers.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Some processes of energy saving and expenditure occurring during ethanol perfusion in the isolated liver of fed rats; a Nuclear Magnetic Resonance study.

et al. 2004

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“…These studies add to previous work using liver tissue that found chronic alcohol consumption can interfere with the glycolytic pathway (Baio et al, 1998;Van Horn et al, 2001). The altered metabolism of H] d-glucose in hepatocytes demonstrates that alcohol consumption can effectively lesion phase 1 of glycolysis between glucose and GAPDH (Hara et al, 2006).…”

Section: Reduced Glycolysismentioning

confidence: 47%

Proteomic Analysis Demonstrates Adolescent Vulnerability to Lasting Hippocampal Changes Following Chronic Alcohol Consumption

Hargreaves

Quinn

Kashem

et al. 2008

Alcoholism Clin & Exp Res

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Background: Excessive teenage alcohol consumption is of great concern because alcohol may adversely alter the developmental trajectory of the brain. The aim of the present study was to assess whether chronic intermittent alcohol intake during the adolescent period alters hippocampal protein expression to a greater extent than during adulthood.Methods: Adolescent [postnatal day (PND) 27] and adult (PND 55) male Wistar rats were given 8 hours daily access to beer (4.44% ethanol v ⁄ v) in addition to ad libitum food and water for 4 weeks. From a large subject pool, subgroups of adolescent and adult rats were selected that displayed equivalent alcohol intake (average of 6.1 g ⁄ kg ⁄ day ethanol). The 4 weeks of alcohol access were followed by a 2-week alcohol-free washout period after which the hippocampus was analyzed using 2-DE proteomics.Results: Beer consumption by the adult group resulted in modest hippocampal changes relative to alcohol naı¨ve adult controls. The only changes observed were an up-regulation of citrate synthase (a precursor to the Krebs cycle) and fatty acid binding protein (which facilitates fatty acid metabolism). In contrast, adolescent rats consuming alcohol showed more widespread hippocampal changes relative to adolescent controls. These included an increase in cytoskeletal protein T-complex protein 1 subunit epsilon (TCP-1) and a decrease in the expression of 10 other proteins, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), triose phosphate isomerise, alpha-enolase, and phosphoglycerate kinase 1 (all involved in glycolysis); glutamate dehydrogenase 1 (an important regulator of glutamate); methylmalonate-semialdehyde dehydrogenase (involved in aldehyde detoxification); ubiquitin carboxyl-terminal hydrolase isozyme L1 (a regulator of protein degradation); and synapsin 2 (involved in synaptogenesis and neurotransmitter release).Conclusions: These results suggest the adolescent hippocampus is more vulnerable to lasting proteomic changes following repeated alcohol exposure. The proteins most affected include those related to glycolysis, glutamate metabolism, neurodegeneration, synaptic function, and cytoskeletal structure.

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“…For example, at a media oxygen concentration of 70 micromolar (approximately 50 torr), there were ethanolrelated increases in cellular respiration of 50% and 70% in perivenous and periportal hepatocytes, respectively (23). There were no significant differences in the respiratory activities between periportal and perivenous hepatocytes isolated either from control or ethanol-fed animals.…”

Section: Interaction Between Ethanol Effects and Oxygen Tension In Inmentioning

confidence: 85%

Chronic ethanol oxygen tension and hepatocyte energy metabolism

Cunningham¹

1999

Front Biosci

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Hepatocytes from ethanol-fed animals, isolated from either whole liver or the periportal or perivenous regions of the lobule, exhibited an ethanol-related decrease in energy state only when they were oxygen deficient. This was accompanied by an ethanol-related decrease in hepatocyte viability. Both periportal and perivenous hepatocytes from ethanol-fed rats demonstrated increased respiration. The observations reported here are consistent with an ethanol-induced increase in oxygen utilization which could render the perivenous region of the lobule relatively oxygen deficient in the intact liver. This oxygen deficit may cause the decreases in energy state and cell viability associated with chronic ethanol consumption. Ethanol-associated loss in hepatocyte viability appeared to correlate better with a decrease in energy state than with an increase in the products of oxidative stress. An investigation of the association between viability and cellular malondialdehyde levels revealed no effects of chronic ethanol consumption on MDA levels in hepatocytes that demonstrated ethanol-related decreases in cell viability. INTRODUCTIONIt is now well established that chronic ethanol consumption alters those systems involved in oxygen utilization in the liver. With the microsomal system there is an increase in the activity of the mono-oxygenase system which utilizes oxygen to metabolize a variety of organic compounds, including ethanol (1).In contrast, the mitochondrial system, which accounts for about 80% of the hepatocyte's respiratory activity (2), is damaged by chronic ethanol consumption (3,4). Ethanol elicits a decrease in the capacity of the mitochondrion to carry out mitochondrial protein synthesis due to alterations in mitochondrial ribosomes which make them less functional (5). This results in a depression in the translation of the 13 polypeptides encoded by the mitochondrial genome. Since all these proteins are integral components of the oxidative phosphorylation system (6) mitochondrial respiration, measured with isolated mitochondria, is decreased. The net result is a decrease in the rate of ATP synthesis, as has been measured with tightly coupled, isolated mitochondria (3).It has been assumed that the ethanol-elicited depression in the rate of ATP synthesis translates to a decrease in the energy state of the liver, but this relationship has not been rigorously established to date. References to hepatic energy state indicate either the levels of ATP in the tissue, or comparisons of ATP concentrations to those of its breakdown products, ADP and P i , as expressed by the phosphorylation potential (7). The studies described in this paper are investigations of the effects of chronic ethanol consumption on the energy state of hepatic tissue. They were implemented as an initial step in evaluating the relationship between changes in mitochondrial function and liver energetics. It is also important to determine the effects of ethanol on hepatic energy state because the viability of the tissue will depend on the avai...

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Effect of Chronic Ethanol Consumption on Respiratory and Glycolytic Activities of Rat Periportal and Perivenous Hepatocytes

Cited by 23 publications

References 29 publications

Some processes of energy saving and expenditure occurring during ethanol perfusion in the isolated liver of fed rats; a Nuclear Magnetic Resonance study.

Some processes of energy saving and expenditure occurring during ethanol perfusion in the isolated liver of fed rats; a Nuclear Magnetic Resonance study.

Proteomic Analysis Demonstrates Adolescent Vulnerability to Lasting Hippocampal Changes Following Chronic Alcohol Consumption

Chronic ethanol oxygen tension and hepatocyte energy metabolism

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