title: How does ethanol induce apoptotic cell death of SK-N-SH neuroblastoma cells.
abstract: 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.
authors.affiliation: Department of Public Health Administration, Namseoul University, Chunan, Seoul 331-707, Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Moon
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Kangdong Sacred Heart Hospital, Hallym University, Seoul 134-701, Korea.
authors.forename: Yongil
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Yu
keywords: apoptosis; c-Jun amino-terminal kinases; ethanol; grants-supported paper; mitogen-activated protein kinases; nerve cell; neural regeneration; neuroblastoma cell; neuroregeneration; p38K; p53