Alcohol and Alcoholism Advance Access originally published online on June 2, 2006
Alcohol and Alcoholism 2006 41(5):494-504; doi:10.1093/alcalc/agl044
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GLYCOSYLATION IS ALTERED BY ETHANOL IN RAT HIPPOCAMPAL CULTURED NEURONS
1 Section of Cell Biology and Pathology, Center for Investigation, Hospital La Fe, Valencia, Spain and 2 Department of Human Anatomy and Embryology. University of Granada, Spain
* Author to whom correspondence should be addressed at: Sec. Biología y Patología Celular, Centro de Investigación, Hospital Universitario ‘La Fe’, Avda. Campanar 21, E-46009 Valencia, Spain. Tel: +34 96 386 27 00 (ext. 50411); Fax: +34 96 197 30 18; E-mail: renau_jai{at}gva.es
(Received 6 March 2006; first review notified 4 April 2006; in revised form 28 April 2006; accepted 4 May 2006)
Aims: Glycoproteins, such as adhesion molecules and growth factors, participate in the regulation of nervous system development. Ethanol affects the synthesis, intracellular transport, distribution, and secretion of N-glycoproteins in different cell types, including astrocytes and hepatocytes, suggesting alterations in the glycosylation process. We analysed the effect of exposure to low doses of ethanol (30 mm, 7 days) on glycosylation in cultured hippocampal neurons. Methods: Neurons were incubated for short (5 min) and long (90 min) periods with the radioactively labelled carbohydrate precursors 2-deoxy-glucose, N-acetyl-D-mannosamine and mannose. The uptake and metabolism of these precursors, as well as the radioactivity distribution in protein gels, were analysed. The levels of the glucose transporters GLUT1 and GLUT3 were also determined. Results: Ethanol exposure reduces the synthesis of proteins, DNA and RNA and decreased the uptake of mannose, but not of 2-deoxy-glucose and N-acetyl-D-mannosamine, and it increased the protein levels of both glucose transporters. Moreover, it altered the carbohydrate moiety of several proteins. Finally, alcohol treatment results in an increment of cell surface glycoconjugates containing terminal non-reduced mannose. Conclusions: Alcohol-induced alterations in glycosylation of proteins in neurons could be a key mechanism involved in the teratogenic effects of alcohol exposure on brain development.