title: Identification of differentially expressed proteins related to organophosphorus-induced delayed neuropathy in the brains of hens.
abstract: Some organophosphorus compounds can cause organophosphate-induced delayed neuropathy (OPIDN). Incidents have been documented for decades, however, little is known about which proteins contribute to the initiation, progression and development of OPIDN. In this study, 51 hens were divided into three groups. The tri-ortho-cresyl-phosphate (TOCP) group was treated with 1000 mg kg(-1) TOCP whereas the control group was treated with an equivalent volume of vehicle. The PMSF + TOCP group was treated subcutaneously with 40 mg kg(-1) phenylmethylsulfonyl fluoride (PMSF), followed by 1000 mg kg(-1) TOCP 24 h later. Proteins in the brains of hens were separated by two-dimensional polyacrylamide gel electrophoresis on day 5 after TOCP administration. Mass spectrometry identified eight differentially expressed proteins. Among these proteins, downregulated expression of glutamine synthetase (GS) in the brains of hens after TOCP treatment was further confirmed by real time RT-PCR and ELISA. Moreover, the brains of hens exposed to TOCP exhibited increased levels of glutamate (Glu) and cytosolic calcium concentration ([Ca(2+)](i)), and a decreased level of glutamine (Gln). However, there were no significant differences in GS expression or levels of Glu, Gln, and [Ca(2+)](i) in the brains of hens among the groups on day 21 after TOCP administration. These results indicate that TOCP exposure downregulates GS expression in the brains of hens, and that downregulation of GS is accompanied by increased levels of Glu and [Ca(2+)](i) in the early stage after TOCP administration. It is also suggested that the downregulated expression of GS might be associated with OPIDN through the disruption of homeostasis of the Glu-Gln cycle and [Ca(2+) ](i).
authors: Department of Occupational and Environmental of Health, Dalian Medical University, No. 9 Western Section of Lushun South Road, Dalian, Liaoning, 116044, China.
authors: Ying
authors: Y
authors: Jiang
authors: Xiaohui
authors: X
authors: Liu
authors: Shuangyue
authors: S
authors: Li
authors: Yanning
authors: Y
authors: Zhang
authors: Fengyuan
authors: F
authors: Piao
authors: Xiance
authors: X
authors: Sun
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002645:Chickens; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis*; D005971:Glutamates / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000633:toxicity*; D010664:Phenylmethylsulfonyl Fluoride / Q000008:administration & dosage / Q000627:therapeutic use; D014176:Protein Biosynthesis / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D005971:Glutamates; D009943:Organophosphorus Compounds; D010664:Phenylmethylsulfonyl Fluoride; D005974:Glutamate-Ammonia Ligase; D002118:Calcium
keywords: cytosolic calcium concentration ([Ca2+]i); glutamate-glutamine cycle; glutamine synthetase (GS); organophosphate-induced delayed neuropathy (OPIDN); proteomics; tri-ortho-cresyl-phosphate (TOCP)