Arsenic metabolites affect expression of the neurofilament and tau genes: an in-vitro study into the mechanism of arsenic neurotoxicity.
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.
Vahidnia
A
A
Department of Clinical Pharmacy and Toxicology, L1-p, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. a.vahidnia@lumc.nl
van der Straaten
R J H M
RJ
Romijn
F
F
van Pelt
J
J
van der Voet
G B
GB
de Wolff
F A
FA
D001151:Arsenic / Q000633:toxicity*; D020261:Arsenic Poisoning / Q000378:metabolism; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016900:Neurofilament Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics*
C054369:MAPT protein, human; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D016875:tau Proteins; D001151:Arsenic