Abstract
Tri-o-cresyl phosphate (TOCP) is a widely used organophosphorus compound, which can cause a neurodegenerative disorder, i.e., organophosphate-induced delayed neurotoxicity (OPIDN). The biochemical events in the initiation of OPIDN were not fully understood except for the essential inhibition of neuropathy target esterase (NTE). NTE, located in endoplasmic reticulum (ER), catalyzes the deacylation of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) to glycerophosphocholine (GPC). The present study aims to study the changes of ER phospholipids profile as well as levels of important intermediates of phospholipid synthesis such as diacylglycerol (DAG) and phosphatidic acid (PA) at the initiation stage of OPIDN. Hens are the most commonly used animal models of OPIDN. The spinal cord phospholipidomic profiles of hens treated by TOCP were studied by using HPLC-MS-MS. The results revealed that TOCP induced an increase of PC, LPC, and sphingomyelin (SM) levels and a decrease of GPC, phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), phosphatidylglycerol (PG), and phosphatidylinositol (PI) levels., Levels of DAG and PA were also decreased. Pretreatment with phenylmethylsulfonyl fluoride (PMSF) 24 h before TOCP administration prevented OPIDN and restored the TOCP-induced changes of phospholipids except GPC. Thus, the disruption of ER phospholipid homeostasis may contribute to the initiation of organophosphate-induced delayed neurotoxicity.
Highlights
Phospholipid bilayers maintain the structure and functionality of all unicellular and multicellular membranes
Phenylmethylsulfonyl fluoride (PMSF) pretreatment prevented the delayed neurotoxicity in hens induced by tri-o-cresyl phosphate (TOCP), NTE activity inhibition was not prevented by PMSF pretreatment compared to that by TOCP alone treatment
OP-induced delayed neurotoxicity (OPIDN) was successfully induced in hens using a single dose of TOCP and pretreatment with PMSF prevented hens from OPIDN
Summary
Phospholipid bilayers maintain the structure and functionality of all unicellular and multicellular membranes. Disruption of ER’s secretory function may play an important role in the initiation of OPIDN. Phospholipidomics is a powerful research tool that can be utilized to investigate phospholipid pathways, which play important roles in cell biology and in specific disease processes. In the current study, to investigate the relationship between ER phospholipid profile and OPIDN, phospholipidomics was employed to characterize ER phospholipid profiles in hens exposed to TOCP with or without pretreatment with PMSF. To our knowledge, this is the first phospholipidomics analysis for OPIDN
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