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Long‐Term Ethanol Consumption Selectively Impairs Ganglioside Pathway in Rat Brain
Author(s) -
Ghosh Pradeep,
Ender Ingo,
Hale Eric A.
Publication year - 1998
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1998.tb03902.x
Subject(s) - ganglioside , term (time) , ethanol , consumption (sociology) , neuroscience , chemistry , biology , biochemistry , physics , philosophy , quantum mechanics , aesthetics
Gangliosides are sialo‐glycosphingolipids that play important roles in the interaction of cells with their environment and are thus involved in the regulation of many cellular events. Sialic acid residues are important for the conformation of a glycomolecule, their structural stability and their functions. Although decreased brain ganglioside sialic acid has been previously reported as a result of chronic ethanol treatment in rats, no reports are available on the sialylation of specific gangliosides and/or the mechanism leading to depletion of their sialic acid residues. Therefore, in this investigation, we have examined the effects of chronic ethanol treatment on (1) incorporation of [4,5‐ 3 H] N ‐acetylmannosamine (ManNAc) into specific rat brain gangliosides, GD 3 , GD 1a , GT 1a , and GT 1b ; and (2) enzymatic activities of brain sialyltransferase and sialidase at specific subcellular levels. The experiments were done in male Wistar rats pair‐fed with either ethanol or control liquid diets for a period of 8 weeks. The rats were intracerebroventriculatly injected with labeled ManNAc (30 μCi/rat) and killed after 90 min. Radioactivity was determined in respective ganglioside bands separated on a thin layer chromatography system. Specific activities of sialyftansferase and sialidase were assessed using GM, and GD, as substrates, respectively. The results showed significant decreases of 57.7% ( p < 0.001) and 68.9% ( p < 0.001), respectively, in the labeled ManNAc incorporation into GD 3 and GD 1a fractions in rats of the ethanol group, compared with rats of the control group. No significant changes were noted in the incorporation of labeled ManNAc into GT 1a or GT 1b ganglioside fractions between the ethanol and control groups. Concomitantly, compared with control rats, a decrease of 18.9% ( p < 0.05), 20.6% ( p < 0.05), and 15.8% ( p < 0.001) was found in the sialyltransferase activity, respectively, at the whole brain, and brain Golgi and synaptosomal levels. However, dramatic increases of 32.4% ( p < 0.05), 105% ( p < 0.001), and 150% ( p < 0.001) in sialidase activity were found, respectively, at the whole brain and brain cytosol and synaptosomal fractions of rat treated chronically with ethanol. Thus, we conclude that the deleterious actions of ethanol on the sialylation of rat brain gangliosides is specific, and the reduced sialic acid label found in GD 3 and GD 1a in this study is mainly due to increased activity of brain sialidase. Furthermore, the study reaffirms our tenet that, regardless of whether it is the liver or the brain, glycosylation cascade is one of the main target of the deleterious attacks of ethanol.