Chang Ping-An, Wu Yi-Jun, Li Wei, Leng Xin-Fu
Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, PR China.
Chem Biol Interact. 2006 Jan 5;159(1):65-72. doi: 10.1016/j.cbi.2005.09.005. Epub 2005 Oct 27.
Carbamate esters are widely used as pesticides and can cause neurotoxicity in humans and animals; the exact mechanism is still unclear. In the present investigation, the effects of carbamates at sublethal concentration on neurite outgrowth and cytoskeleton as well as activities of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in differentiating human SK-N-SH neuroblastoma cells were studied. The results showed that 50 microM of either aldicarb or carbaryl significantly decreased neurite length in the retinoic acid-induced differentiation of the neuroblastoma cells, compared to cells treated with vehicle. Western blot analyses revealed that neither carbamate had significant effects on the levels of actin, or total neurofilament high molecular proteins (NF-H). However, increased NF-H phosphorylation was observed following carbamate treatment. These changes may represent a useful in vitro marker of carbamate neurotoxicity within a simple model of neuronal cell differentiation. Furthermore, activity of AChE, but not NTE, was significantly inhibited by aldicarb and carbaryl in differentiating cells, which suggested that cytoskeletal protein changes induced by carbamate esters in differentiating cells was associated with inhibition of AChE but not NTE.
氨基甲酸酯类广泛用作杀虫剂，可导致人和动物神经毒性；确切机制仍不清楚。在本研究中，研究了亚致死浓度的氨基甲酸酯对人SK-N-SH神经母细胞瘤细胞分化过程中神经突生长、细胞骨架以及乙酰胆碱酯酶（AChE）和神经病变靶标酯酶（NTE）活性的影响。结果表明，与用溶媒处理的细胞相比，50微摩尔的涕灭威或西维因在视黄酸诱导的神经母细胞瘤细胞分化中显著降低了神经突长度。蛋白质免疫印迹分析显示，两种氨基甲酸酯对肌动蛋白或总高分子量神经丝蛋白（NF-H）水平均无显著影响。然而，氨基甲酸酯处理后观察到NF-H磷酸化增加。在一个简单的神经元细胞分化模型中，这些变化可能代表氨基甲酸酯神经毒性的一种有用的体外标志物。此外，涕灭威和西维因在分化细胞中显著抑制了AChE的活性，但未抑制NTE的活性，这表明氨基甲酸酯类在分化细胞中诱导的细胞骨架蛋白变化与AChE的抑制有关，而与NTE无关。
