title: Acrylamide and 2,5-hexanedione induce collapse of neurofilaments in SH-SY5Y human neuroblastoma cells to form perikaryal inclusion bodies.
abstract: Neurofilament accumulations are characteristic of a number of neurological conditions including amyotrophic lateral sclerosis, giant axonal neuropathies and several chemically-induced neuropathies. Although the mechanism(s) leading to neurofilament accumulation are unknown, it is possible that similar processes occur both in disease and in chemically-induced neuropathies. Understanding the mechanism(s) of chemically-induced neurofilament accumulation, which is more amenable to experimental manipulation, may give insight into the neurological diseases they mimic. We have compared the effects of two chemically-dissimilar neurotoxins, 2,5-hexanedione and acrylamide, on neurofilaments in the human neuroblastoma cell line, SH-SY5Y. Both undifferentiated and differentiated SH-SY5Y cells were exposed to 2,5-hexanedione or acrylamide and changes in cytoskeletal organization examined by immunofluorescence and electron microscopy. Although distinct morphological differences have previously been characterized in the neuropathies induced by 2,5-hexanedione and acrylamide in vivo, we have found that both compounds had similar direct effects on neurofilaments in SH-SY5Y cells, inducing formation of perikaryal inclusion bodies. In addition, differentiated SH-SY5Y cells were more sensitive to both 2,5-hexanedione and acrylamide compared with undifferentiated cells. These similar effects of 2,5-hexanedione and acrylamide lend further support that a common mechanism(s) may lead to neurofilament accumulation in these neuropathies. SH-SY5Y cells provide a useful model to investigate further the biochemical basis of neurofilament accumulation.
authors.affiliation: Department of Clinical Neurosciences, Institute of Psychiatry, London, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Hartley
authors.forename: V E
authors.initials: VE
authors.lastname: Anderson
authors.forename: B H
authors.initials: BH
authors.lastname: Anderton
authors.forename: J
authors.initials: J
authors.lastname: Robertson
authors.forename: B H
authors.initials: BH
authors.lastname: Anderson
mesh_terms: D020106:Acrylamide; D000178:Acrylamides / Q000494:pharmacology*; D002454:Cell Differentiation / Q000502:physiology; D003078:Colchicine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D006588:Hexanones / Q000494:pharmacology*; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008854:Microscopy, Electron; D009447:Neuroblastoma / Q000737:chemistry* / Q000201:enzymology / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000032:analysis / Q000187:drug effects* / Q000648:ultrastructure; D009498:Neurotoxins / Q000494:pharmacology*; D014404:Tubulin / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: D000178:Acrylamides; D006588:Hexanones; D016900:Neurofilament Proteins; D009498:Neurotoxins; D014404:Tubulin; C051774:neurofilament protein H; D020106:Acrylamide; C011269:2,5-hexanedione; D007770:L-Lactate Dehydrogenase; D003078:Colchicine