title: Activation of lysosomal degradative pathway in spinal cord tissues of carbon disulfide-treated rats.
abstract: Chronic exposure to carbon disulfide (CS₂) can induce polyneuropathy in occupational worker and experimental animals, but underlying mechanism for CS₂ neuropathy is currently unknown. In the present study, male Wistar rats were randomly divided into three experimental groups and one control group. The rats in experimental groups were treated with CS₂ by gavage at dosages of 200, 400 and 600 mg/kg/day respectively, six times per week for 6 weeks. The formation of autophagosomes and lysosomes in motor neurons of rat spinal cord was observed by transmission electron microscopy, the level of autophagy-related proteins, lysosome-associated membrane protein 1 (LAMP-1), and cathepsin B in spinal cord tissues was determined by Western blot analysis, and the activity of cathepsin B was measured by fluorescence assay. The results demonstrated that the number of lysosomes in motor neurons was markedly increased in CS₂-treated rats. In the meantime, the administration of CS₂ significantly increased the level of microtubule-associated protein light chain 3-II (LC3-II), Atg1, UVRAG and LAMP-1 in rat spinal cord. Furthermore, the content and activity of cathepsin B in rat spinal cord also showed a significant elevation. Taken together, this study suggested that CS₂ intoxication was associated with the activation of lysosomal degradative machinery, which might play a protective role against CS₂-induced neuronal damage.
authors.affiliation: Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China; Linyi Center for Disease Control and Prevention, Beijing Road, Linyi, Shandong 276001, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Anji
authors.initials: A
authors.lastname: Yi
authors.affiliation: Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Kou
authors.affiliation: Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Xie
authors.affiliation: Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China. Electronic address: fysong3707@sdu.edu.cn.
authors.forename: Fuyong
authors.initials: F
authors.lastname: Song
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002246:Carbon Disulfide / Q000378:metabolism* / Q000633:toxicity; D002401:Cathepsin B / Q000032:analysis / Q000378:metabolism; D005684:Gait / Q000187:drug effects; D015151:Immunoblotting; D051907:Lysosomal Membrane Proteins / Q000032:analysis / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D011897:Random Allocation; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism* / Q000648:ultrastructure; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D002246:Carbon Disulfide; D002401:Cathepsin B; D051907:Lysosomal Membrane Proteins; D008869:Microtubule-Associated Proteins; C489117:Lamp1 protein, rat; D052118:Lysosomal-Associated Membrane Protein 1
keywords: Carbon disulfide (CS(2)); Lysosomal degradative pathway; Toxic neuropathy