title: Reduction of retrograde axonal transport associated-proteins motor proteins, dynein and dynactin in the spinal cord and cerebral cortex of hens by tri-ortho-cresyl phosphate (TOCP).
abstract: Tri-ortho-cresyl phosphate (TOCP) can cause a type of neurotoxicity known as organophosphate-induced delayed neuropathy (OPIDN). The characteristic axonal swelling containing aggregations of neurofilaments, microtubules, and multivesicular vesicles is consistent with a disturbance of axonal transport. We hypothesized that there existed a disturbance of molecular motor in the pathogenesis of OPIDN. In the present study, adult hens were treated with a dosage of 750 mg/kg TOCP by gavage, or pretreated 24h earlier with phenylmethanesulfonyl fluoride (PMSF) and subsequently with TOCP, then sacrificed on the time-points of 0, 1, 5, 10, and 21 days after dosing of TOCP, respectively. The level of kinesin-1, dynein, and dynactin in spinal cords and cerebral cortexes of hens was determined. Immunoblotting analysis showed a progressive decline of dynein and dynactin in spinal cords after dosing TOCP. Furthermore, a significant reduction in dynactin and dynein was observed in cerebral cortexes at several time-points post dosing TOCP. In contrast, no significant changes of kinesin-1 were observed throughout the period of experiment. When given before TOCP administration, PMSF could inhibit TOCP-induced motor protein disruption, while it protected hens against the delayed neuropathy. In conclusion, the reduction of the motor proteins, dynein and dynactin, might be associated with the disruption of retrograde neuronal axonal transport in OPIDN.
authors.affiliation: Institute of Toxicology, Shandong University, Jinan, Shandong, PR China.
authors.forename: Fuyong
authors.initials: F
authors.lastname: Song
authors.forename: Chaoshuang
authors.initials: C
authors.lastname: Zou
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: Keqin
authors.initials: K
authors.lastname: Xie
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000187:drug effects* / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D002645:Chickens; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D000072159:Dynactin Complex; D004398:Dyneins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency*; D005260:Female; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency*; D010755:Organophosphates / Q000633:toxicity*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D016896:Treatment Outcome; D014317:Tritolyl Phosphates / Q000633:toxicity*
chemical_list: D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D010755:Organophosphates; D014317:Tritolyl Phosphates; D004398:Dyneins; C025541:tri-o-cresyl phosphate