title: Changes in beclin-1 and micro-calpain expression in tri-ortho-cresyl phosphate-induced delayed neuropathy.
abstract: Tri-ortho-cresyl phosphate (TOCP) can cause toxic neuropathy known as organophosphate-induced delayed neuropathy (OPIDN), which is pathologically characterized by the swollen axon containing aggregations of neurofilaments, microtubules, and multivesicular vesicles. Autophagy is a self-degradative process which plays a housekeeping role in removing misfolded proteins and damaged organelles. The current study was designed to investigate the possible roles of autophagy in the pathogenesis of OPIDN. Adult hens were treated with a dose of 750mg/kg TOCP by gavage, or injected subcutaneously with 60mg/kg phenylmethanesulfonyl fluoride (PMSF) dissolved in DMSO 24h earlier and subsequently treated with TOCP, then sacrificed on the time-points of 0, 1, 5, 10, and 21 days after dosing of TOCP respectively. The levels of beclin-1 and μ-calpain in tibial nerves and spinal cords were determined by immunoblotting. The results showed that in both tissues TOCP increased the expression of μ-calpain while decreased that of beclin-1. When given before TOCP administration, PMSF pretreatment could protect hens against the delayed neuropathy. In the meantime, pretreatment with PMSF reduced calpain expression below basal and increased beclin-1 expression above basal in tibial nerve, whereas it simply returned calpain and beclin-1 expression to their basal levels in spinal cord. In conclusion, the intoxication of TOCP was associated with a significant change of beclin-1 in hen nervous tissues, which suggested that disruption of autophagy-regulated machinery in neurons might be involved in the pathogenesis of OPIDN.
authors.affiliation: Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Fuyong
authors.initials: F
authors.lastname: Song
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Han
authors.forename: Tao
authors.initials: T
authors.lastname: Zeng
authors.forename: Cuili
authors.initials: C
authors.lastname: Zhang
authors.forename: Chaoshuang
authors.initials: C
authors.lastname: Zou
authors.forename: Keqin
authors.initials: K
authors.lastname: Xie
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000071186:Beclin-1; D002154:Calpain / Q000378:metabolism*; D002645:Chickens; D005260:Female; D008565:Membrane Proteins / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism; D013979:Tibial Nerve / Q000378:metabolism; D014317:Tritolyl Phosphates / Q000633:toxicity*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D014317:Tritolyl Phosphates; D010664:Phenylmethylsulfonyl Fluoride; D002154:Calpain; C449002:mu-calpain; C025541:tri-o-cresyl phosphate