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The role of microtubule on dithiocarbamate cytotoxicity
Author(s) -
Gonzalez-lopez Eugene,
Cheng Shu-Yuan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb227
Subject(s) - mptp , cytotoxicity , chemistry , viability assay , neurotoxin , neurotoxicity , microtubule , dithiocarbamate , microbiology and biotechnology , cell , dopamine transporter , dopaminergic , pharmacology , toxicity , biochemistry , biophysics , dopamine , biology , in vitro , transporter , neuroscience , organic chemistry , gene
Maneb (MB), mancozeb (MZ) and diethyldithiocarbamate (DDC) are fungicides widely used in the United States. These compounds can potentiate the presence of the dopaminergic neurotoxin (MPTP). However, the mechanisms for those effects are not so clear. Dopamine transporter (DAT) is essential for MPTP toxicity by transporting MPP+, the active metabolite of MPTP, into dopaminergic neurons. Preliminary results show that MB and MZ increase the interaction of DAT and alpha‐synuclein followed by accumulating cell surface DAT expression which in turn enhances MPP+ cytotoxicity by increasing MPP+ uptake. The disruption of the interaction of alpha‐synuclein with microtubules has been showed to enhance cell surface recruitment of DAT. The aim of this study is to elucidate the role of microtubules on dithiocarbamate cytotoxicity. Immunocytochemistry for the microtubule network was performed on PC12 cells treated with DDC (75 uM), MB (20 uM) and MZ (20 uM) for 4 hours. The images showed that those dithiocarbamates disturbed the cytoskeleton network, with MZ having shown the most severe depolymerization. Cells pre‐treated with microtubular stabilizer Taxol showed a significant alleviation in cell damage assayed by cell viability MTT assay. These results indicate that these compounds directly influence the microtubules; however, dithiocarbamates might also trigger other toxic mechanism resulting in cell death.