Cytoskeletal effects of acrylamide and 2,5-hexanedione: selective aggregation of vimentin filaments.
Several neurotoxic compounds cause aggregation of neurofilaments in peripheral axons. This may represent a primary action of these chemicals or a secondary response to other cellular damage. To distinguish between these possibilities, the effects of acrylamide and 2,5-hexanedione (2,5-HD) on vimentin were examined in PtK2 cultured cells. Vimentin intermediate filaments were chosen because they are closely related, in structure, to neurofilaments. Effects on other components of the cytoskeleton (cytokeratin filaments, microtubules, and microfilaments) were also determined. Both acrylamide and 2,5-HD caused aggregation of vimentin filaments in a concentration-dependent fashion; these effects occurred at a lower concentration than alterations in other cytoskeletal filaments. The effects of both acrylamide and 2,5-HD were reversible, except at high concentrations of 2,5-HD. Crosslinking of cytoskeletal proteins was also examined. High-molecular-weight proteins with vimentin-like immunoreactivity were detected on blots from cells exposed to high concentrations of 2,5-HD. No crosslinked protein was detected after acrylamide treatment. These results suggest that both acrylamide and 2,5-HD cause a primary collapse of vimentin intermediate filaments in cultured cells. The initial redistribution of vimentin filaments occurred without apparent crosslinking of cytoskeletal proteins. The aggregation of vimentin filaments in cultured cells and of neurofilaments in vivo may share a common molecular mechanism.
Sager
P R
PR
Cellular and Reproductive Toxicology, Environmental Health Center, ICI Americans Inc., Farmington, Connecticut 06032.
D020106:Acrylamide; D000178:Acrylamides / Q000494:pharmacology*; D008841:Actin Cytoskeleton / Q000187:drug effects; D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D006588:Hexanones / Q000494:pharmacology*; D007382:Intermediate Filaments / Q000187:drug effects* / Q000648:ultrastructure; D007633:Keratins / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D000178:Acrylamides; D000199:Actins; D006588:Hexanones; D007659:Ketones; D009498:Neurotoxins; D014404:Tubulin; D014746:Vimentin; D020106:Acrylamide; D007633:Keratins; C011269:2,5-hexanedione