Melatonin prevents calcineurin-activated the nuclear translocation of nuclear factor of activated T-cells in human neuroblastoma SH-SY5Y cells undergoing hydrogen peroxide-induced cell death.

The interaction between the activation of protein phosphatase, calcineurin (CaN), and the dephosphorylation and nuclear translocation of nuclear factor of activated T-cells (NFAT), a transcriptional factor in the immune system, has attracted interest as a key factor responsible for the cell death process. In this study, the effects of melatonin on the interaction between CaN and NFAT signaling during oxidative stress-induced cell death were investigated. Human neuroblastoma SH-SY5Y cells were treated with the non-radical reactive oxygen species hydrogen peroxide (H2O2). Cells were treated with 200 µM H2O2 for the indicated time. Some H2O2-treated cells were pretreated with melatonin for 1 h. Control cells were treated with the same concentration of ethanol used to dilute melatonin. H2O2-induced cell death promoted increases in reactive oxygen species (ROS) production and the nuclear translocation of NFAT, which were related to increased levels the active, cleaved form of CaN (32.5 kDa). In addition, pretreatment of H2O2-treated cells with melatonin decreased cell death, ROS production, the levels of the active-cleaved form of CaN and the nuclear translocation of NFAT. Based on these findings, melatonin may exert its neuroprotective effects on oxidative damage-induced cell death by inhibiting CaN-activated the nuclear translocation of NFAT.