Mechanisms of neuronal adaptation to ethanol. Ethanol induces Hsc70 gene transcription in NG108-15 neuroblastoma x glioma cells.

摘要: The mechanisms underlying neuronal adaptation to ethanol are poorly understood but appear involve alterations in cellular membrane structure and/or function. Using a two-dimensional gel analysis, we have recently identified Hsc70 as an ethanol-responsive gene (Miles, M.F. (1989) Neurology 39, (Suppl. 1), 425). is constitutive member of the 70-kDa stress protein family which plays important role trafficking and coated vesicle processing. Thus, modulation by could produce widespread changes functioning. Here, report detailed study on regulation NG108-15 neuroblastoma x glioma cells. Northern Western blot analyses showed that concentrations observed actively drinking alcoholics caused induction mRNA protein. Increases were seen early 4 h after exposure ethanol. In comparison with ethanol, propanol butanol proportionally greater increases mRNA. This consistent known anesthetic intoxicating potencies these aliphatic alcohols suggested lipophilicity, rather than osmotic effect, was critical for Hsc70. Induction resulted, at least part, from increased transcription determined nuclear runoff studies. Stable transfection analysis revealed cis-acting element proximal 2500 base pairs promoter. Regulation 50-200 mM appeared be specific change expression typical response since no highly inducible protein, Hsp70, concentrations. These results suggest ethanol-induced may development tolerance dependence alcoholics.