How does ethanol induce apoptotic cell death of SK-N-SH neuroblastoma cells.

A body of evidence suggests that ethanol can lead to damage of neuronal cells. However， the mechanism underlying the ethanol-induced damage of neuronal cells remains unclear. The role of mitogen-activated protein kinases in ethanol-induced damage was investigated in SK-N-SH neuroblastoma cells. 3-[4，5-Dimethylthiazol-2-yl]-2，5-diphenyl tetrazolium bromide cell viability assay， DNA fragmentation detection， and flow cytometric analysis showed that ethanol induced apoptotic cell death and cell cycle arrest， characterized by increased caspase-3 activity， DNA fragmentation， nuclear disruption， and G1 arrest of cell cycle of the SK-N-SH neuroblastoma cells. 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 cells. c-Jun N-terminal protein kinase or p38 kinase inhibitors significantly reduced the ethanol-induced cell death. Ethanol also increased p53 phosphorylation， followed by an increase in p21 tumor suppressor 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 mediates apoptosis of SK-N-SH neuroblastoma cells by activating p53-related cell cycle arrest possibly through activation of the c-Jun N-terminal protein kinase-related cell death pathway.