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A body of evidence suggests that ethanol can lead to damage of neuronal cel s. However, the me-chanism underlying the ethanol-induced damage of neuronal cel s remains unclear. The role of mi-togen-activated protein kinases in ethanol-induced damage was investigated in SK-N-SH neurob-lastoma cel s. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide cel viability assay, DNA fragmentation detection, and flow cytometric analysis showed that ethanol induced apoptotic cel death and cel cycle arrest, characterized by increased caspase-3 activity, DNA fragmentation, nuclear disruption, and G 1 arrest of cel cycle of the SK-N-SH neuroblastoma cel s. In addition, western blot analysis indicated that ethanol induced a lasting increase in c-Jun N-terminal protein kinase activity and a transient increase in p38 kinase activity of the neuroblastoma cel s. c-Jun N-terminal protein kinase or p38 kinase inhibitors significantly reduced the ethanol-induced cel death. Ethanol also increased p53 phosphorylation, fol owed by an increase in p21 tumor sup-pressor protein and a decrease in phospho-Rb (retinoblastoma) protein, leading to alterations in the expressions and activity of cyclin dependent protein kinases. Our results suggest that ethanol me-diates apoptosis of SK-N-SH neuroblastoma cel s by activating p53-related cel cycle arrest possibly through activation of the c-Jun N-terminal protein kinase-related cel death pathway.
