Laboratory of Molecular Biology, Research and Development 151, Bay Pines VA Healthcare System, Bay Pines, Florida 33744-4125, USA.
J Neurotrauma. 2012 Apr 10;29(6):1188-96. doi: 10.1089/neu.2011.1806. Epub 2012 Apr 2.
Traumatic brain injury (TBI) afflicts approximately 1.4 million people in the United States and TBIs have been labeled a major cause of death and disability on a global scale. Regulatory responses in a variety of neuronal loss conditions have supported the protective involvement of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor. Nrf2 regulates antioxidant enzyme genes, and an increase in Nrf2 expression may counteract oxidative damage that results from TBI. Elevated Nrf2 may ultimately act through the upregulation of downstream target genes such as thioredoxin (Trx) and heat-shock protein-70 (HSP70) and this may reduce neuronal loss. We performed multiple mild biaxial stretch injuries to neuroblastoma cells in culture, and examined the effects of the Nrf2 activator, tert-butylhydroquinone (tBHQ). We also compared the stretch injury to oxidative insult. We confirmed that Trx and HSP70 were upregulated by treatment with tBHQ. We observed that tBHQ protected neurons from either insult, and that this was evident by different measures of cell viability and a decrease in annexin V binding. Neuronal health after insult was improved approximately 50% by tBHQ, indicating that neurons exposed to TBI in vitro can be protected.
创伤性脑损伤（TBI）在美国影响约 140 万人，TBI 已被标记为全球范围内主要的死亡和残疾原因。在各种神经元丧失情况下的监管反应支持核因子（红系衍生 2）样 2（Nrf2）转录因子的保护作用。Nrf2 调节抗氧化酶基因，增加 Nrf2 的表达可能抵消 TBI 引起的氧化损伤。升高的 Nrf2 最终可能通过上调下游靶基因（如硫氧还蛋白（Trx）和热休克蛋白 70（HSP70））起作用，这可能减少神经元丧失。我们对培养中的神经母细胞瘤细胞进行了多次轻度双轴拉伸损伤，并研究了 Nrf2 激活剂叔丁基对苯二酚（tBHQ）的作用。我们还将拉伸损伤与氧化损伤进行了比较。我们证实 tBHQ 通过处理上调了 Trx 和 HSP70。我们观察到 tBHQ 可以保护神经元免受任何一种损伤，这可以通过不同的细胞活力测量和 Annexin V 结合减少来证明。用 tBHQ 处理后，神经元的健康状况大约提高了 50%，表明体外暴露于 TBI 的神经元可以得到保护。
