Effect of carbamate esters on neurite outgrowth in differentiating human SK-N-SH neuroblastoma cells.
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.
Chang
Ping-An
PA
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.
Wu
Yi-Jun
YJ
Li
Wei
W
Leng
Xin-Fu
XF
D000109:Acetylcholine / Q000378:metabolism; D000448:Aldicarb / Q000494:pharmacology*; D012721:Carbaryl / Q000494:pharmacology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D009447:Neuroblastoma / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism
D007306:Insecticides; D016900:Neurofilament Proteins; C051774:neurofilament protein H; D000448:Aldicarb; D000109:Acetylcholine; D012721:Carbaryl