School of Public Health/Key Laboratory for Public Health Safety of MOE/WHO Collaborating Center for Occupational Health (Shanghai), Fudan University , Shanghai , PR China.
Toxicol Mech Methods. 2012 May;22(4):309-14. doi: 10.3109/15376516.2012.657260. Epub 2012 Feb 23.
Chlorpyrifos (CPF) is one of the organophosphorus pesticides widely used around the world, especially in China. Acetylcholinesterase inhibition is the main effect of organophosphorus insecticides exposure. Studies showed that CPF may also interfere with the metabolism of monoamine transmitters. To investigate the effects of CPF on dopaminergic pathway, the dopamine content, gene expression of catechol-O-methyl- transferase (COMT), vesicular monoamine transporter-2 (VMAT-2), and monoamine oxidase (MAO) and its activity in PC12 cells exposed to CPF was determined. Results showed that cell viability was decreased and total dopamine concentration was increased with CPF administration in a dose-dependent pattern. Gene of MAO was significantly downregulated in PC12 cells, while genes of COMT and VMAT-2 in PC12 cells did not show any change after CPF exposure. The MAO activity was decreased following incubation exposed to CPF. These results suggest that CPF may interfere with dopaminergic pathway through inhibition on gene and protein expression of MAO in vitro.
毒死蜱（CPF）是一种在世界各地广泛使用的有机磷农药，特别是在中国。乙酰胆碱酯酶抑制是有机磷杀虫剂暴露的主要作用。研究表明，CPF 还可能干扰单胺递质的代谢。为了研究 CPF 对多巴胺能通路的影响，测定了 CPF 处理的 PC12 细胞中的多巴胺含量、儿茶酚-O-甲基转移酶（COMT）、囊泡单胺转运体-2（VMAT-2）和单胺氧化酶（MAO）的基因表达及其活性。结果表明，随着 CPF 给药剂量的增加，细胞活力降低，总多巴胺浓度增加。MAO 基因在 PC12 细胞中显著下调，而 CPF 暴露后 PC12 细胞中的 COMT 和 VMAT-2 基因没有变化。孵育暴露于 CPF 后 MAO 活性降低。这些结果表明，CPF 可能通过体外抑制 MAO 的基因和蛋白表达干扰多巴胺能通路。
