Ethanol-responsive gene expression in neural cell cultures.
We have studied the molecular mechanisms underlying neuronal adaptation to chronic ethanol exposure. NG108-15 neuroblastoma cells were used to perform a detailed analysis of ethanol-induced changes in neuronal gene expression. High resolution, quantitative two-dimensional (2-D) gel electrophoresis of in vitro translation products showed both dose-dependent increases and decreases in specific mRNA abundance following treatment with ethanol at concentrations seen in actively drinking alcoholics (50-200 mM). Dose response curves for representative members of the increasing or decreasing response groups had very similar profiles, suggesting that similar mechanisms may regulate members of a response group. Some mRNAs that increased with ethanol treatment appeared identical to species induced by heat shock while other mRNAs were only induced by ethanol. We conclude that chronic ethanol exposure can produce specific coordinate changes in expression of neuronal mRNAs, including some members of the stress protein response. However, the overall pattern of ethanol-responsive gene expression is distinct from the classical heat shock subgroup of stress proteins response. Changes in gene expression and specifically, mechanisms regulating a subset of stress protein expression, could be an important aspect of neuronal adaptation to chronic ethanol seen in alcoholics.
Miles
M F
MF
Department of Neurology, University of California School of Medicine, San Francisco.
Diaz
J E
JE
DeGuzman
V
V
D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D000431:Ethanol