School of Public Health, Fudan University, 130 DongAn Road, Shanghai 200032, PR China; School of Public Health/MOE Key Lab for Public Safety, Fudan University, Shanghai 200032, PR China.
Chem Biol Interact. 2013 Nov 25;206(2):248-55. doi: 10.1016/j.cbi.2013.09.010. Epub 2013 Sep 21.
Paraquat (PQ) is one of the most widely used herbicides in the world. Although available evidence indicates that people exposed to PQ have a higher risk of developing Parkinson's disease, adverse effects of PQ on neural progenitor cells have not been investigated yet. In this study, we investigated the in vitro effect of PQ on immortalized human embryonic neural progenitor cells (hNPCs) by treating them with various concentrations of PQ (0, 0.1, 1, 10 and 100 μM) for 24h. We show that PQ treatment reduces the cell viability and proliferation and induces reactive oxygen species (ROS) production in a dose-dependent manner. In addition, apoptosis induced by PQ was significantly increased at a concentration of as low as 1 μM. To illustrate the underlying molecular mechanisms, we examined the caspase-3 activity, intracellular calcium level, the NF-κB activity, as well as expression of p21, p53 and metallothionein-III mRNA. PQ significantly increased caspase-3 activity at the concentration of 100 μM. Similarly, PQ triggered intracellular Ca(2+) releases and activation of NF-κB was observed after exposure of hNPCs at low concentrations of PQ (1 μM). Meanwhile, p53 and p21 mRNA transcripts were significantly up-regulated at 10 μM and 1 μM of PQ, respectively. MT-III mRNA and protein expression was significantly up-regulated at 1 μM of PQ and reached peak at 10 μM. These results suggest that PQ could reduce viability of hNPCs by inducing oxidative stress and apoptosis.
百草枯（PQ）是世界上使用最广泛的除草剂之一。尽管现有证据表明，接触 PQ 的人患帕金森病的风险更高，但 PQ 对神经祖细胞的不良影响尚未得到研究。在这项研究中，我们通过用不同浓度的 PQ（0、0.1、1、10 和 100μM）处理人永生化胚胎神经祖细胞（hNPCs）24 小时，研究了 PQ 在体外对 hNPCs 的影响。结果表明，PQ 处理以剂量依赖性方式降低细胞活力和增殖，并诱导活性氧（ROS）的产生。此外，低至 1μM 的 PQ 浓度即可显著增加凋亡。为了说明潜在的分子机制，我们检查了 caspase-3 活性、细胞内钙水平、NF-κB 活性以及 p21、p53 和金属硫蛋白-III mRNA 的表达。在 100μM 的浓度下，PQ 显著增加了 caspase-3 活性。同样，在 hNPCs 暴露于低浓度 PQ（1μM）后，观察到细胞内 Ca(2+)释放和 NF-κB 的激活。同时，在 10μM 和 1μM 的 PQ 下，p53 和 p21 mRNA 转录物分别显著上调。在 1μM 的 PQ 下，MT-III mRNA 和蛋白表达显著上调，并在 10μM 时达到峰值。这些结果表明，PQ 可通过诱导氧化应激和细胞凋亡来降低 hNPCs 的活力。
