The role of mitogen-activated protein kinases in ethanol-induced damage was investigated in SK-N-SH neuroblastoma cells. Ethanol was shown to induce apoptotic cell death and cell cycle arrest, characterized by increased caspase-3 activity, DNA fragmentation, nuclear disruption, and G1 arrest of cell cycle. In addition, ethanol induced a lasting increase in c-Jun N-terminal protein kinase (JNK) activity and a transient increase in p38 kinase (p38K) activity. JNK or p38K 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 ... More
The role of mitogen-activated protein kinases in ethanol-induced damage was investigated in SK-N-SH neuroblastoma cells. Ethanol was shown to induce apoptotic cell death and cell cycle arrest, characterized by increased caspase-3 activity, DNA fragmentation, nuclear disruption, and G1 arrest of cell cycle. In addition, ethanol induced a lasting increase in c-Jun N-terminal protein kinase (JNK) activity and a transient increase in p38 kinase (p38K) activity. JNK or p38K 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 stimulating p53-related cell cycle arrest possibly through activation of the JNK-related cell death pathway.
