EFFECT OF GLUTATHIONE DEPLETION ON NRF2/ARE ACTIVATION BY DELTAMETHRIN IN PC12 CELLS
EFFECT OF GLUTATHIONE DEPLETION ON NRF2/ARE ACTIVATION BY DELTAMETHRIN IN PC12 CELLS
复制标题
谷胱甘肽消耗对 PC12 细胞中溴氰菊酯 Nrf2/Are 激活的影响
DOI：
10.2478/10004-1254-64-2013-2251
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发表时间：
2013-03-01
影响因子：
2.1
通讯作者：
Shi, Nian
中科院分区：
文献类型：
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作者：
Li, Huangyuan;Wu, Siying;Shi, Nian
转录因子NF-E2相关因子2（Nrf 2）对于细胞保护免受化学诱导的氧化应激是重要的。以前，我们已经报道，在PC 12细胞，Nrf 2可以触发溴氰菊酯（DM），一种常用的拟除虫菊酯杀虫剂。DM激活Nrf 2的分子机制尚不清楚。在这里，我们研究了细胞谷胱甘肽（GSH）耗尽对DM激活Nrf 2的影响。我们发现，DM增强Nrf 2在mRNA和蛋白水平的表达，并增加核Nrf 2水平。Nrf 2的激活与其下游靶点的激活相关，如血红素加氧酶-1（HO-1）和谷氨酸半胱氨酸连接酶催化亚基（GCLC）。相反，DL-丁硫氨酸-[S，R]-亚砜亚胺（BSO），一种已知的GSH消耗剂，不增加Nrf 2蛋白表达或引起其核积累。然而，用BSO预处理触发HO-1和GCLC的mRNA表达。此外，BSO预处理抑制DM诱导的Nrf 2上调和激活，并降低DM处理后HO-1和GCLC的mRNA表达。这些数据表明，GSH消耗是不必要的Nrf 2/ARE的激活DM在PC 12细胞中，GCLC和HO-1的表达可以通过其他信号通路增加。
Transcription factor NF-E2-related factor 2 (Nrf2) is important for cell protection against chemical-induced oxidative stress. Previously, we have reported that in PC12 cells, Nrf2 can be triggered by deltamethrin (DM), a commonly used pyrethroid insecticide. Molecular mechanisms behind Nrf2 activation by DM are still unclear. Here we studied the effects of cell glutathione (GSH) depletion on Nrf2 activation by DM. We found that DM enhanced Nrf2 expression at the mRNA and protein levels and increased nuclear Nrf2 levels. Activation of Nrf2 was associated with activation of its, downstream targets, such as heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic subunit (GCLC). In contrast, DL-buthionine-[S,R]-sulfoximine (BSO), a known GSH-depleting agent, did not increase Nrf2 protein expression or cause its nuclear accumulation. However, pre-treatment with BSO triggered mRNA expression of HO-1 and GCLC. Furthermore, BSO pre-treatment suppressed DM-induced Nrf2 upregulation and activation and lowered mRNA expression of HO-1 and GCLC upon DM treatment. These data demonstrate that GSH depletion is not necessary for the activation of Nrf2/ARE by DM in PC12 cells, and that GCLC and HO-1 expression can increase through other signalling pathways.