title: 2,5-Hexanedione neuropathy is associated with the covalent crosslinking of neurofilament proteins.
abstract: Protein composition in different segments along nerves from rats intoxicated with 2,5-hexanedione (HD) was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by immunoblotting, using monoclonal antibodies specific for each of the three neurofilament polypeptide components (H, M, and L). Comparison with nerve protein extracts from normal (control) rats revealed a disappearance of the largest neurofilament polypeptide (H), accompanied by accumulation of higher-molecular-weight products that were immunoreactive with H-specific antibodies. Both the extent of this crosslinking and its localization in particular portions of peripheral nerves showed a correlation with HD dosage and with the known progression of ultrastructural features during HD-induced neuropathy. Similar changes were not detected for the M and L neurofilament components.
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006588:Hexanones / Q000494:pharmacology*; D007381:Intermediate Filament Proteins / Q000302:isolation & purification / Q000378:metabolism*; D007659:Ketones / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D006588:Hexanones; D007381:Intermediate Filament Proteins; D007659:Ketones; C011269:2,5-hexanedione