Ethanol‐induced cell cycle arrest and apoptosis is mediated by sp1‐dependent expression of p75NTR in neuroblastoma cells

The p75NTR is known to play multiple roles in the regulation of neuronal survival, development, and cell apoptosis. Alcohol consumption has multiple effects in the central nervous system. However, there is little information concerning the effect of alcohol exposure on the molecular and cellular mechanisms involved in the neuronal cell function. In this study, we examined the effect of ethanol on p75NTR expression in neuroblastoma cell lines, SK‐N‐SH and SH‐SY5Y. Western blot analysis showed that ethanol significantly increased the expression of p75NTR. Ethanol also increased DNA binding activity but not mRNA and protein levels of sp1, and inhibition of sp1 activity by mythramycine or siRNA suppressed ethanol‐induced p75NTR expression. In addition, the present data showed that CK2 and ERK may negatively regulate ethanol‐induced p75NTR expression via sp1. We also showed that G1 cell cycle arrest and apoptosis induced by ethanol were mediated by p53‐independent induction of p21. Furthermore, inhibition of p75NTR expression by siRNA suppressed ethanol‐induced p21 expression, cell cycle arrest, and apoptosis. Taken together, our results indicate that ethanol increases p75NTR expression via sp1 and subsequently induced p21‐dependent and p53‐independent cell cycle arrest and apoptosis in neuroblastoma cells, and provide more insight into the mechanism of ethanol‐induced damage on brain.