Involvement of vimentin in neurite outgrowth damage induced by fipronil in SH-SY5Y cells.
Fipronil, a phenylpyrazole insecticide, is more selective in its potency towards insects than humans and is thus commonly used. In this study, we demonstrated that exposure to fipronil may pose a human health risk. We observed in vitro the shortening of neurite outgrowths of SH-SY5Y neuroblastoma cells upon treatment with fipronil, even at a non-cytotoxic concentration. Fipronil induced apoptosis involving caspase-6, which is an apoptotic effector highly implicated in neurodegenerative diseases. Moreover, at a concentration that did not induce apoptosis, mitochondrial dysfunction and autophagic vacuole formation were detected. Interestingly using proteomics, we identified vimentin to be dramatically expressed by SH-SY5Y cells as a response to fipronil treatment. Not only did the expression of total vimentin increase, different isoforms were observed, indicating alterations in post-translational modifications. Vimentin was localized at the neurite outgrowth, possibly to repair the damage in cellular structure. However at high concentrations of fipronil, vimentin was found in less defined fibrils, in bridge-like formation, and dense surrounding vacuoles. In all, our results indicate that vimentin plays an important role in fipronil-induced neurotoxicity in SH-SY5Y cells.
Environmental Toxicology Program, Chulabhorn Graduate Institute, Bangkok, Thailand.
Theetat
T
Ruangjaroon
Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand.
Daranee
D
Chokchaichamnankit
Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand.
Chantragan
C
Srisomsap
Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand; Applied Biological Sciences Program, Chulabhorn Graduate Institute, Bangkok, Thailand.
Jisnuson
J
Svasti
Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand. Electronic address: nilubol@cri.or.th.
N Monique
NM
Paricharttanakul
D017209:Apoptosis / Q000187:drug effects; D053178:Caspase 6 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000071446:Neuronal Outgrowth / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020033:Protein Isoforms / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011720:Pyrazoles / Q000633:toxicity*; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014746:Vimentin / Q000819:agonists / Q000235:genetics* / Q000378:metabolism
D007306:Insecticides; D020033:Protein Isoforms; D011720:Pyrazoles; D014746:Vimentin; C505514:CASP6 protein, human; D053178:Caspase 6; C082360:fipronil
Apoptosis; Autophagy; Fipronil; Neurite outgrowth damage; Neuron; Vimentin