Some Implications of Alcohol-Induced Lipid Changes

Barboriak, Joseph J.; Menahan, Lawrence A.

doi:10.1007/978-1-4615-7743-0_3

Cited by 2 publications

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References 159 publications

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“…In addition to the well-known physiological and psychological impacts on the nervous system,6 the various biological effects of ETOH studied include for example the pathogenesis of fatty cell injury via lipid peroxidation,1° changes in biomembrane structure and function,'> and alterations of lipoprotein metabolism relevant to cardiovascular disease. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] The last has caused a great deal of concern about the chronic intake of moderate amounts of alcohol in lowering LDL-cholesterol12 and in raising HDL-cholesterol, plasma triglyceride and systolic blood pressure. 133 l4 Recently, acute administration of ETOH was shown to inhibit platelet aggregation and thrombus formation in a rabbit m0de1.l~ In this laboratory, exposure of monocyte-like U937 cells to ETOH resulted in depression of tissue factor activity and its activation induced by bacterial endotoxin.…”

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confidence: 99%

Mechanism by which ethanol inhibits phosphatidylcholine biosynthesis in human leukemic monocyte‐like U937 cells

Chu

1994

Cell Biochemistry & Function

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A previous study showing that ethanol (ETOH) blocked [3H]choline incorporation into phosphatidylcholine (PC) suggested an inhibition of PC biosynthesis in human leukemic monocyte-like U937 cells. The mechanism of the inhibitory action of ETOH was investigated. Cells were pulsed with [3H]choline for 30 min and chased in the presence or absence of ETOH for up to 6 h. PC biosynthesis was inhibited drastically within 1 h after exposure to ETOH which increased intracellular cAMP appreciably. After a 3-h treatment, ETOH significantly inhibited both choline kinase (CK) and the cytosolic CTP: cholinephosphate cytidylyltransferase (CT). The inactivated CT was no longer stimulated by exogenous phosphatidylglycerol (PG). There was no evidence for redistribution of CT activity between cytosol and microsomes. When cells were exposed to 8-Bromo-cAMP ranging from 100 to 300 microM, PC biosynthesis remained unaffected despite the drastically elevated cAMP. These results seem to suggest that the raised cAMP is not a prerequisite for the inhibition of PC biosynthesis in U937 cells. Following pretreatment with protein kinase inhibitors (H-89 and K-252a), PC biosynthesis was decreased significantly and the inhibitory effect of ETOH was potentiated. Taken together, our results suggest that the inhibition of PC biosynthesis and the inhibitory effect of ETOH are independent of the activation of cAMP-dependent protein kinase. Unlike protein kinase inhibitors, pretreatment with tyrosine kinase inhibitors (erbstatin, genistein and tyrphostin 25) resulted in differential effects on PC biosynthesis and on the inhibitory action of ETOH. Genistein stimulated PC biosynthesis by 30 per cent as well as partially preventing/reversing the ETOH action, while tyrphostin 25 produced a synergistic inhibition. The relevance of tyrosine phosphorylation/dephosphorylation to the regulation of PC biosynthesis and ETOH action remains to be established.

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Section: Introductionmentioning

confidence: 99%

Mechanism by which ethanol inhibits phosphatidylcholine biosynthesis in human leukemic monocyte‐like U937 cells

Chu

1994

Cell Biochemistry & Function

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Ethanol inhibits phosphatidylcholine and phosphatidylethanolamine biosynthesis in human leukemic monocyte‐like U937 cells

Chu

Nguyen

1993

Cell Biochemistry & Function

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The effect of ethanol (ETOH) on the incorporation of [14C]oleic acid (18:1) into lipid in human monocyte-like U937 cells was investigated. With increasing time of exposure to ETOH, the percentage of the label distributed into neutral lipid (NL) declined from 35 per cent (3 h) to 10 per cent (24 h) accompanied by increased incorporation into phospholipid (PL). [14C] 18:1 was preferentially incorporated into triglyceride (TG) and phosphatidylcholine (PC), comprising over 65 per cent and 50 per cent of the label associated with NL and PL, respectively. Low concentrations of ETOH (< or = 1.0 per cent; v/v) had no effect. At concentrations greater than 1.5 per cent, there was enhanced incorporation into TG and diacylglycerol (DAG) in a 24-h incubation period, while at 16 h the label in phosphatidylethanolamine (PE) was decreased. The effect of ETOH on the CDP-choline or ethanolamine pathway was examined by monitoring the incorporation of [3H]choline or [14C]ethanolamine into PC or PE, respectively. At low concentrations ETOH had no effect on either choline uptake or the incorporation into PC. Higher concentrations (> or = 1.5 per cent) for 3 and 6 h resulted in a slightly decreased choline uptake, and the reduction (40-50 per cent) of incorporation into PC suggests that the CDP-choline pathway was inhibited. There was a similar inhibition of the incorporation of [14C]ethanolamine into PE. When the cells were incubated for 3 h in the presence of 2 per cent ETOH and with labelled 18:1 and PL-base, the ratios of incorporation (base/18:1) into PC and PE fractions decreased, indicating that the major inhibition lay in blockage of the availability of the base moiety for PL formation. Analysis of the distribution of the label into metabolites revealed that ETOH inhibited the conversion of [14C]ethanolamine into [14C]phosphorylethanolamine. The reduction in incorporation was not due to the enhanced breakdown of base-labelled PL. Our results indicate that ETOH has an inhibitory effect on the CDP-choline or ethanolamine pathway.

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Some Implications of Alcohol-Induced Lipid Changes

Cited by 2 publications

References 159 publications

Mechanism by which ethanol inhibits phosphatidylcholine biosynthesis in human leukemic monocyte‐like U937 cells

Mechanism by which ethanol inhibits phosphatidylcholine biosynthesis in human leukemic monocyte‐like U937 cells

Ethanol inhibits phosphatidylcholine and phosphatidylethanolamine biosynthesis in human leukemic monocyte‐like U937 cells

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