Li H Y, Wu S Y, Ma Q, Shi N
Department of Occupational and Environmental Health, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Fuzhou, China.
Toxicol Ind Health. 2011 Aug;27(7):579-90. doi: 10.1177/0748233710393400. Epub 2011 Mar 11.
The transcription factor NF-E2-related factor 2 (Nrf2) plays a critical role in the mammalian response to chemical and oxidative stress through induction of phase II detoxification enzymes and oxidative stress response proteins. We reported that Nrf2 expression was activated by deltamethrin (DM), a prototype of the widely used Parathyroid pesticides, in PC12 cells. However, no study has examined Nrf2 nuclear translocation and free radical production, two hallmarks of oxidative stress, in the mammalian brain in vivo. To this end, we examined translocation of Nrf2 and production of free radicals in rat brain exposed to DM. Indeed, DM initiated nuclear translocation of Nrf2 in a dose-dependent manner. Furthermore, Nrf2 translocation was accompanied by the expression of heme oxygenase-1 gene, an Nrf2-regulated gene linked to free radical production. Deltamethrin exposure promoted free radical formation in rat brain and reactive oxygen species generation in PC12 cells. Translocation of Nrf2 may be a response to DM-dependent induction of free radicals and DM may act as a mammalian neurotoxin by initiating oxidative stress.
转录因子NF-E2相关因子2（Nrf2）通过诱导II相解毒酶和氧化应激反应蛋白，在哺乳动物对化学和氧化应激的反应中起关键作用。我们报道，广泛使用的拟除虫菊酯类杀虫剂的原型溴氰菊酯（DM）可激活PC12细胞中的Nrf2表达。然而，尚无研究在体内哺乳动物大脑中检测Nrf2核转位和自由基产生这两个氧化应激的标志。为此，我们检测了暴露于DM的大鼠脑中Nrf2的转位和自由基的产生。事实上，DM以剂量依赖性方式引发Nrf2的核转位。此外，Nrf2转位伴随着血红素加氧酶-1基因的表达，该基因是与自由基产生相关的Nrf2调节基因。溴氰菊酯暴露促进大鼠脑中自由基形成和PC12细胞中活性氧生成。Nrf2转位可能是对DM依赖性自由基诱导的反应，并且DM可能通过引发氧化应激而作为哺乳动物神经毒素。
