Studies on Mitochondrial Metabolic Processes in Offspring of Alcoholized Rats — I. Evidence for Altered Activity and Sensitivity to Monoamine Oxidase-Dependent Control by Biogenic Amines of Some Membrane-Bound Enzymes

Abstract

In the liver mitochondrial fraction of the first generation offspring of alcoholized male rats, decreased activities of monoamine oxidase (MAO) types A and B, rotenone-insensitive NADH-cytochrome c-reductase and succinate dehydrogenase were observed. The MAO-dependent inhibition of rotenone-insensitive NADH-cytochrome c-reductase and succinate dehydrogenase by biogenic amines, incubated with the mitochondrial fraction, was altered in the offspring of alcoholized animals as compared with control rats. The sensitivity of these enzymatic activities towards the inhibitory effect of 5-methoxyindol-3-ylacetaldehyde was markedly increased in the offspring of alcoholized male rats. The data obtained suggest the existence of a genetically determined predisposition of the mitochondrial metabolic processes in the offspring of the alcoholized rats to the effects of ethanol and to the toxic effects of acetaldehyde, formed during ethanol metabolism.

Effect of ethanol consumption on the expression of the tyrosine hydroxylase gene in rat brain and adrenals

“…In guinea pigs given small doses of alcohol over a short period, changes in neurons were detected not only in the neocortex but also in the CN [5]. Swollen and shrunken cells and occasional ghost cells were observed in CN of rats receiving alcohol for 1-3 months, while most CN neurons were swollen in rats after 6-12 months of alcohol consumption [3]. As we are aware, changes occurring in dendrites and dendritic spikes of experimentally alcoholized animals have not been studied, although these structures Laboratory of Brain Ultrastructure, Institute of Brain, Russian Academy of Medical Sciences, Moscow play an important role in primary processing of information received by the neuron and in the synaptic mechanisms of brain activity.…”

“…Enzymes, particularly monoamine oxidase, dopamine-I~-hydroxylase, tyrosine hydroxylase, and catecholortho-methyltransferase, play an important role in the regulation of catecholamine metabolism. There is a large body of evidence that the activities of these enzymes are altered during prolonged alcoholization [1,3,5], and some of these changes may be implicated in the development of alcohol dependence [3,[6][7][8].Tyrosine hydroxylase (TH), the key enzyme in catecholamine synthesis, converts the amino acid tyrosine into the dopamine precursor dihydroxyphenylalanine, and alterations in the enzyme activity, particularly if sustained, may strongly determine the function of the catecholamine system, However, the neurochemical nature of shifts in the activity of enzymes involved in catecholamine metabolism during prolonged alcoholization has not been ascertained. These shifts may be caused by changes in the transcriptional activity of genes coding for the enzyme.…”