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 hr. 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.

中文翻译：

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褪黑激素阻止钙调神经磷酸酶激活的人神经母细胞瘤 SH-SY5Y 细胞中激活的 T 细胞核因子的核转位，该细胞经历过氧化氢诱导的细胞死亡

蛋白磷酸酶、钙调神经磷酸酶 (CaN) 的激活与活化 T 细胞 (NFAT)（免疫系统中的一种转录因子）的核因子的去磷酸化和核易位之间的相互作用引起了人们的兴趣，它是导致细胞死亡过程。在这项研究中，研究了褪黑激素对氧化应激诱导的细胞死亡过程中 CaN 和 NFAT 信号之间相互作用的影响。用非自由基活性氧类过氧化氢 (H2O2) 处理人神经母细胞瘤 SH-SY5Y 细胞。细胞用 200 µM H2O2 处理指定的时间。一些 H2O2 处理的细胞用褪黑激素预处理 1 小时。对照细胞用与稀释褪黑激素相同浓度的乙醇处理。H2O2 诱导的细胞死亡促进了活性氧 (ROS) 产生的增加和 NFAT 的核易位，这与 CaN (32.5 kDa) 的活性裂解形式的水平增加有关。此外，用褪黑激素预处理 H2O2 处理的细胞可减少细胞死亡、ROS 产生、CaN 活性裂解形式的水平和 NFAT 的核易位。基于这些发现，褪黑激素可能通过抑制 CaN 激活的 NFAT 核易位，对氧化损伤诱导的细胞死亡发挥神经保护作用。活性裂解形式的 CaN 和 NFAT 的核易位的水平。基于这些发现，褪黑激素可能通过抑制 CaN 激活的 NFAT 核易位，对氧化损伤诱导的细胞死亡发挥神经保护作用。活性裂解形式的 CaN 和 NFAT 的核易位的水平。基于这些发现，褪黑激素可能通过抑制 CaN 激活的 NFAT 核易位，对氧化损伤诱导的细胞死亡发挥神经保护作用。