Li Huang-Yuan, Wu Si-Ying, Shi Nian
Department of Occupational and Environmental Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Fuzhou 350004, China.
Toxicol Lett. 2007 Jun 15;171(1-2):87-98. doi: 10.1016/j.toxlet.2007.04.007. Epub 2007 Apr 27.
Activation of transcription factor NF-E2-related factor 2 (Nrf2) is a key initiation step in the cellular protection against a broad range of chemical oxidative stresses. To gain insights into dopaminergic cell responses to pesticides, the present study was conducted to examine the effects of deltamethrin (DM), a prototype of widely used pyrithroid pesticides, on the activation and expression of Nrf2 in PC12 rat adrenal pheochromocytoma cells as a dopaminergic cell model. We found, for the first time, that DM enhanced cellular expression of Nrf2 at the transcriptional and protein levels and activated expression of Nrf2-regulated genes in these cells. In addition, DM exposure caused nuclear accumulation of Nrf2 in association with downstream activation of Nrf2-mediated oxidative response genes, such as heme oxygenase-l (HO-1) and gamma-glutamylcysteine synthetase catalytic heavy subunit (GCSh). Furthermore, when cells were pretreated with N-acetyl cysteine (NAC), a scavenger of reactive oxygen species (ROS), DM-induced Nrf2 signaling was suppressed. These results indicate that ROS is the mediator of nuclear Nrf2 accumulation. Taken together, these data clearly show that DM increases Nrf2 expression and activity and that ROS is one of the mediators of this process.
转录因子NF-E2相关因子2（Nrf2）的激活是细胞抵御多种化学氧化应激的关键起始步骤。为深入了解多巴胺能细胞对农药的反应，本研究以PC12大鼠肾上腺嗜铬细胞瘤细胞作为多巴胺能细胞模型，检测了广泛使用的拟除虫菊酯类农药的原型溴氰菊酯（DM）对Nrf2激活和表达的影响。我们首次发现，DM在转录和蛋白质水平增强了Nrf2的细胞表达，并激活了这些细胞中Nrf2调控基因的表达。此外，DM暴露导致Nrf2在细胞核中积累，并伴随Nrf2介导的氧化反应基因如血红素加氧酶-1（HO-1）和γ-谷氨酰半胱氨酸合成酶催化重亚基（GCSh）的下游激活。此外，当用活性氧（ROS）清除剂N-乙酰半胱氨酸（NAC）预处理细胞时，DM诱导的Nrf2信号传导受到抑制。这些结果表明ROS是细胞核Nrf2积累的介质。综上所述，这些数据清楚地表明DM增加了Nrf2的表达和活性，并且ROS是这一过程的介质之一。
