Effects of acute and chronic ethanol administration on ribosomal protein synthesis in mouse brain and liver

Kuriyama, Kinya; Sze, Paul Y.; Rauscher, Gregory E.

doi:10.1016/0024-3205(71)90016-6

Cited by 87 publications

(10 citation statements)

References 20 publications

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“…A slight increase was also seen with 100 mg/dl, but this was not statistically significant. This difference be tween the effects of acute and chronic ex posure to ethanol on protein synthesis has been previously reported by Kuriyama et al [8] who found that whereas hepatocytes from mice which were fed ethanol acutely showed a 53% depression of l4C-leucine incorporation into ribosomal protein (blood ethanol, 220 mg%), feeding over 14 days resulted in an enhancement to 210% of control values (blood ethanol, 240 mg%). The increases in protein syn thesis which we have quantitated were not merely the result of the presence of larger cells in ethanol-containing cultures as an increased incorporation was evident even when the data were expressed as incorpo ration of radioactivity per femtolitre of cell volume.…”

Section: Discussionsupporting

confidence: 59%

Effects of Ethanol on Cell Volume and Protein Synthesis in a Human Lymphoblastoid Cell Line (Raji)

Okany¹,

Bond²,

Wickramasinghe³

1983

Acta Haematol

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A human lymphoblastoid cell line (Raji) developed macrocytosis after 5–7 days when cultured in the presence of 100, 250 and 500 mg ethanol/dl. The degree of macrocytosis was least with 100 mg/dl and greatest with 500 mg/dl. The macrocytosis was associated with a proportionate increase in the total protein content per cell, was reversed after culture in the absence of ethanol and was uninfluenced by the supplementation of the culture medium with 50 μg folic or folinic acids per millilitre. Ethanol also caused a substantial prolongation of the cell doubling time at concentrations of 250 and 500 mg/dl (but not 100 mg/dl) and this was associated with some increase in the proportion of non-viable cells in the cultures. Furthermore, ethanol increased the incorporation of ³H-leucine into protein per femtolitre of cell volume. It is proposed that the etha-nol-induced macrocytosis may have developed as a consequence of the stimulation of the rate of protein synthesis within a normal or prolonged cell cycle.

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Section: Discussionsupporting

confidence: 59%

Effects of Ethanol on Cell Volume and Protein Synthesis in a Human Lymphoblastoid Cell Line (Raji)

Okany¹,

Bond²,

Wickramasinghe³

1983

Acta Haematol

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“…In contrast to the decreased receptor synthesis, amino acid incorporation into the total cellular protein pool was not altered in cells from ethanol-fed animals. Work from other laboratories on the effect of ethanol administration on protein synthesis in vitro in hepatocytes, as well as in isolated microsomes from mice and rats, likewise did not find ethanol-induced alterations in incorporation of amino acids into the total protein pool (25,26). We do not know at this time whether defects in post-transcriptional processing by the mRNA for the ASGP-R are present in alcohol-fed animals; however, the fact that message level was decreased to a similar extent as was receptor synthesis would indicate that the decreased receptor mRNA levels alone could explain the decreased in vitro synthesis of the receptor.…”

Section: Discussionmentioning

confidence: 99%

Decreased Binding of Asialoglycoproteins to Hepatocytes from Ethanol-fed Rats

Tworek

Tuma

Casey

1996

Journal of Biological Chemistry

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Chronic ethanol administration alters the process of receptor-mediated endocytosis in isolated rat hepatocytes. Using the asialoglycoprotein receptor (ASGP-R) as a model, we have previously shown decreased binding of asialoglycoproteins to this receptor after as early as 1 week of ethanol administration. In the present study, we further analyzed the mechanism(s) responsible for this impairment by determining the ligand and antibody binding characteristics of the ASGP-R in rats fed ethanol over a 5-week time course. The results presented here demonstrate that ethanol treatment for 4 days significantly impaired total ligand binding without affecting antibody binding. Ethanol administration for a longer period of 1-2 weeks resulted in intermediate impairments in both ligand and antibody binding. After 5 weeks of ethanol exposure, ligand and antibody binding were equally lowered. In contrast to total cellular receptor binding, surface binding of both ligand and antibody were decreased over the entire time course of ethanol administration. Our data indicate that the ASGP-R is initially inactivated during the time course of ethanol exposure and that a redistribution of surface receptors to intracellular compartments occurs. Northern blot analysis showed that there was a significant decrease in receptor mRNA content in the 5-week chronically fed animals but not in the animals fed for 1 week. In addition, after 5 weeks of ethanol feeding, biosynthetic labeling of the ASGP-R was decreased in the ethanol cells, indicating impaired synthesis of the ASGP-R. In summary, an early inactivation of the ASGP-R occurs during ethanol exposure followed by an actual decrease in protein and mRNA content for the receptor.Receptor-mediated endocytosis (RME) 1 is a process common to many cell types including hepatocytes and has been shown to be affected by ethanol administration (1-3). During RME, molecules in the extracellular fluid bind to cell surface receptors and are internalized as receptor-ligand complexes via a clathrin-coated pit/coated vesicle pathway. Within this pathway, the vesicles lose the clathrin coats, form endosomes, and are sorted in the acidic compartment of uncoupling receptor and ligand. Once separated, ligands and receptors can be routed to the lysosomes for degradation or they can be recycled back to the cell surface (4). The hepatic asialoglycoprotein receptor (ASGP-R) is one of the well characterized receptors that undergoes efficient recycling (5). The ASGP-R recognizes glycoproteins with terminal galactose or N-acetylgalactosamine residues and removes these potentially harmful desialylated glycoproteins from the circulation (6). We have previously reported ethanol-induced impairments in the RME process of asialoorosomucoid (ASOR), a representative ligand for the hepatocyte-specific ASGP-R. Impairments in ligand binding, internalization, and degradation were demonstrated in hepatocytes isolated from animals fed ethanol for 5-7 weeks (1). Decreased binding of ASOR by the hepatocytes of ethanol-treated rats appe...

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“…Acute ethanol administration to animals has been reported to inhibit hepatic synthesis of both constituent (46)(47)(48) and export (49)(50)(51)(52) proteins in vivo and in vitro. Other investigators iFERRIN have reported that chronic ethanol administration increases protein synthesis in ribosomes (46) and microsomes (53), whereas acute administration produces opposite effects. In our study, synthesis of total liver protein was significantly enhanced in ethanolfed rats compared to pair-fed controls.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of alcohol-induced accumulation of protein in the liver.

Baraona¹,

Leo²,

Borowsky³

et al. 1977

J. Clin. Invest.

298

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A B S T R A C T Alcohol feeding to rats produced hepatomegaly, associated with enlargement of the hepatocytes. The increase in liver dry weight was accounted for not only by fat but also by protein accumulation, primarily in microsomes and cytosol, with a selective increase in export proteins: concentrations of both immunoreactive albumin and transferrin were augmented in liver microsomes and cytosol of ethanol-fed rats. To investigate the mechanism ofthis protein accumulation, [14C]leucine was injected intravenously and its incorporation into both liver and serum proteins was measured after various time intervals. Rates of synthesis and export were assessed from protein labeling and specific activities of leucyl-tRNA. Synthesis of liver protein and proalbumin were enhanced by chronic ethanol feeding, but this was not associated with a corresponding rise in serum albumin output. Actually, there was a significant retention of the label in liver albumin and transferrin with delayed appearance in the serum of ethanol-fed rats. This indicated that, regardless of the changes in synthesis, the export of protein from the liver into the plasma was impaired. This alteration in export was associated with a decreased amount of polymerized tubulin in the liver of ethanol-treated animals. Thus, both enhanced protein synthesis and defective export contribute to the ethanol-induced accumulation of liver protein, and the decrease in liver microtubules represents a possible site for impairment of protein export.

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Effects of acute and chronic ethanol administration on ribosomal protein synthesis in mouse brain and liver

Cited by 87 publications

References 20 publications

Effects of Ethanol on Cell Volume and Protein Synthesis in a Human Lymphoblastoid Cell Line (Raji)

Effects of Ethanol on Cell Volume and Protein Synthesis in a Human Lymphoblastoid Cell Line (Raji)

Decreased Binding of Asialoglycoproteins to Hepatocytes from Ethanol-fed Rats

Pathogenesis of alcohol-induced accumulation of protein in the liver.

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