Protein and Ribonucleic Acid Metabolism in Brains of Mice Following Chronic Alcohol Consumption*

Abstract

In these proceedings there has been a great deal about the effects of alcohol on biogenic amine metabolism and the possible role of biogenic amine condensation products in alcoholism. There has been little mention of how alcohol affects macromolecules, and indeed the literature is scanty in this problem area. The present report will deal with alterations in brain protein and nucleic acid metabolism as a function of chronic alcohol ingestion in the C57BL/6J mouse. Much of what will be discussed has appeared in press or soon will be.'-4 C57BL/6J male mice, a strain that prefers alcohol over water, were used in all these studies. The experimental animals received 10% (v/v) ethanol in water as their only drinking fluid, and their age-matched controls received only water. Unless otherwise indicated, l a t e r was substituted for the alcohol solution 24 hours before the mice were sacrificed. All animals were provided with laboratory chow, and under these conditions no infections, debility, or mortality were observed in either group even for periods extending to nine months. The alcoholdrinking animals were slightly heavier and had larger livers than the controls, but no differences in brain weights were observed between the two groups. When alcohol was removed, no signs of withdrawal reaction were noted. Subcellular fractionation and other biochemical procedures are given el~ewherel-~ and will not be repeated here.In FIGURE 1, the pH 5 enzyme content of brain is presented as a function of duration of alcohol consumption. This fraction is obtained from the cell sap and includes among other ingredients the initial components of the protein-synthesizing system, namely aminoacyl tRNA synthetases, tRNAs, and the transferases. The results show no differences between the fractions obtained after one or three days of alcohol consumption and fractions from controls. However, alcoholimbibing mice showed a slight decrease of the pH 5 enzyme content at 10 days; this decrease continued with duration of alcohol consumption, so that animals that had consumed alcohol for 46 days had about half as much pH 5 enzyme as controls.Brain ribosomes isolated from animals that had imbibed alcohol for 10 days were incubated in the presence of UJ4C leucine, pH 5 enzyme fraction, and various cofactors and ions. Comparisons were made at various time points with the same fractions obtained from control mice. The data in FIGURE 2 show a significant decrease in incorporation of UJ4C leucine in ribosomal protein of the fractions obtained from brains of alcohol-treated animals. A similar inhibition was noted when fractions were obtained from mice that had imbibed alcohol for 46 days.To determine whether inhibition in protein synthesis involves the pH 5 enzyme fraction, the ribosomes, or both, crossover experiments were performed. The results indicate no marked increase in leucine incorporation when ribosomes from control animals were substituted for ribosomes of ethanol-treated mice (FIGURE 3 ) . A substantial enhancement of incorporation occurred when ...

Distinct methylation patterns in histone H3 at Lys-4 and Lys-9 correlate with up- & down-regulation of genes by ethanol in hepatocytes

“…Posttranslational modifications of histone amino-termini, such as acetylation, phosphorylation and methylation are in most cases correlated with functional organization of chromosomes and chromatin dynamics (Kohlmaier et al, 2004;Jenuwein and Allis, 2001;Wilkins, 2005). An in vivo study on cell morphology reported that the size and shape of alcohol fed hepatocytes were reduced substantially relative to untreated cells (Noble and Tewari, 1973). Initially, it was reported that chromosomes of chronic alcohol treated hepatocytes have highly condensed and altered nonhistone nuclear proteins that may contribute as epigenetic signals (Mahadev and Vemuri, 1998;Park et al, 2003).…”

Maternal ethanol consumption and synaptic membrane glycoproteins in offspring

“…Thus, altered activity of any of the enzymes or substrates involved in the addition of the carbohydrate constituents to the polypeptide backbones could result in an abnormal synthesis o f fucosylated SPM glycoproteins. Nonetheless, it should be noted that the effects observed in the present study are not directly due to the depressant effect of ethanol (or acetaldehyde) on protein synthesis [Tewari and Noble, 1971;Noble and Tewari, 1973;Renis et al, 19751 or on glycoprotein synthesis or secretion [Sorrell et al, 1977;Sorrell and Tuma, 1978;Tuma and Sorrell, 19811. Whereas the presence of ethanol (or acetaldehyde) in vitro or in vivo reportedly has the mentioned effects, little information is available about protein or glycoprotein synthesis one or more weeks aftcr the last exposure to ethanol.…”

Abstinence Improves Cerebral Perfusion and Brain Volume in Alcoholic Neurotoxicity without Wernicke-Korsakoff Syndrome

“…How brain volume is restored by abstinence re mains uncertain. Increases in blood flow and blood volume are certainly one factor, but other possibili ties include regeneration of attenuated neuronal processes and reversal of inhibited protein syn thesis (Noble and Tewari, 1973;Te wari et aI. , 1978;Walker et aI.…”