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砷代谢产物影响神经丝蛋白和tau基因的表达:一项关于砷神经毒性机制的体外研究。

Arsenic metabolites affect expression of the neurofilament and tau genes: an in-vitro study into the mechanism of arsenic neurotoxicity.

作者信息

Vahidnia A, van der Straaten R J H M, Romijn F, van Pelt J, van der Voet G B, de Wolff F A

机构信息

Department of Clinical Pharmacy and Toxicology, L1-p, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.

出版信息

Toxicol In Vitro. 2007 Sep;21(6):1104-12. doi: 10.1016/j.tiv.2007.04.007. Epub 2007 Apr 27.

Abstract

Neurological studies indicate that the central (CNS) and peripheral nervous system (PNS) may be affected by arsenic (As). As-exposed patients show significantly lower nerve conduction velocities (NCVs) in their peripheral nerves in comparison to healthy subjects. As may play a role in the disruption of neuroskeletal integrity, but the mechanisms by which it exerts a toxic effect on the peripheral and central nervous system are still unclear. In the present study, we examined the neurotoxic effects of various arsenic metabolites (iAs(III), iAs(V), MMA(V) and DMA(V)) on two different cell lines derived from the peripheral (ST-8814) and central (SK-N-SH) nervous system. The effects of the arsenic metabolites were examined on the relative quantification levels of the cytoskeletal genes, neurofilament-light (NEFL), neurofilament-medium (NEF3), neurofilament-heavy (NEFH) and microtubule-associated protein-tau (MAPT), using real-time PCR. Our results show that iAs(III) and iAs(V) have no significant effects on either cell lines. On the other hand, MMA(V) and DMA(V) cause significant changes in expression levels of NEF3 and NEFL genes, while the expression level of the NEFH gene is significantly increased in both cell lines.

摘要

神经学研究表明,中枢神经系统(CNS)和周围神经系统(PNS)可能会受到砷(As)的影响。与健康受试者相比,接触砷的患者外周神经的神经传导速度(NCV)明显较低。砷可能在神经骨骼完整性破坏中起作用,但其对周围和中枢神经系统产生毒性作用的机制仍不清楚。在本研究中,我们检测了各种砷代谢物(亚砷酸盐(III)、砷酸盐(V)、一甲基砷(V)和二甲基砷(V))对源自周围神经系统(ST-8814)和中枢神经系统(SK-N-SH)的两种不同细胞系的神经毒性作用。使用实时聚合酶链反应检测了砷代谢物对细胞骨架基因神经丝轻链(NEFL)、神经丝中链(NEF3)、神经丝重链(NEFH)和微管相关蛋白tau(MAPT)相对定量水平的影响。我们的结果表明,亚砷酸盐(III)和砷酸盐(V)对两种细胞系均无显著影响。另一方面,一甲基砷(V)和二甲基砷(V)导致NEF3和NEFL基因表达水平发生显著变化,而NEFH基因的表达水平在两种细胞系中均显著增加。

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