title: 2,5-hexanedione altered the degradation of low-molecular-weight neurofilament in rat nerve tissues.
abstract: Occupational exposure to n-hexane produces a central-peripheral distal axonopathy, which is characterized by giant axonal swellings filled with neurofilaments (NFs). To investigate the change of NFs degradation and their possible role in n-hexane neuropathy, adult male Wistar rats were administered intraperitoneally at a dosage of 400 mg/kg/day 2,5-hexanedione (2,5-HD) for 4 weeks. The time course of low-molecular-weight neurofilament (NF-L) degradation and autophagy-related protein in rat sciatic nerves and spinal cords was determined by Western blotting. The results demonstrated that the administration of 2,5-HD inhibited NF-L degradation to an undetectable level in sciatic nerves. Furthermore, a significant reduction of NF-L degradation in spinal cords was observed in the early stage of 2,5-HD exposure. In the meantime, 2,5-HD significantly decreased the level of Beclin-1, a key autophagy-regulated protein in sciatic nerves of rats while increased the level of P62, a selective substrate of autophagy degrading pathway, which indicated a dysfunctional autophagy in rat nerve tissues. Collectively, our findings suggested that the inhibition of autophagy by 2,5-HD might be responsible for the reduction of NF-L degradation in rat sciatic nerves, and involved in the pathogenesis of 2,5-HD-induced axonopathy.
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong, 250012, PR China.
authors.forename: Fuyong
authors.initials: F
authors.lastname: Song
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ruirui
authors.initials: R
authors.lastname: Kou
authors.forename: Chaoshuang
authors.initials: C
authors.lastname: Zou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Keqin
authors.initials: K
authors.lastname: Xie
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006586:Hexanes / Q000633:toxicity; D006588:Hexanones / Q000494:pharmacology*; D008297:Male; D008970:Molecular Weight; D009417:Nerve Tissue / Q000187:drug effects* / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
chemical_list: D006586:Hexanes; D006588:Hexanones; D016900:Neurofilament Proteins; C026385:n-hexane; C011269:2,5-hexanedione