Tris(1,3-dichloro-2-propyl) phosphate(TDCIPP) is a commonly used organophosphatebased flame retardant and can bio-accumulate in human tissues and organs. As its structure is similar to that of neurotoxic organophospha...Tris(1,3-dichloro-2-propyl) phosphate(TDCIPP) is a commonly used organophosphatebased flame retardant and can bio-accumulate in human tissues and organs. As its structure is similar to that of neurotoxic organophosphate pesticides, the neurotoxicity of TDCIPP has raised widespread concerns. TDCIPP can increase neuronal apoptosis and induce autophagy.However, its regulatory mechanism remains unclear. In this study, we found that the expression upregulation of the DNA Damage-Inducible Transcript 4(DDIT4) protein, which might play essential roles in TDCIPP-induced neuronal autophagy and apoptosis, was observed in TDCIPP-treated differentiated rat PC12 cells. Furthermore, we determined the protective effect of the DDIT4 suppression on the autophagy and apoptosis induced by TDCIPP using Western blot(WB) and Flow cytometry(FACS) analysis. We observed that TDCIPP treatment increased the DDIT4, the autophagy marker Beclin-1, and the microtubule-associated protein light chain 3-II(LC_(3)II) expressions and decreased the mTOR phosphorylation levels. Conversely, the suppression of DDIT4 expression increased the p-mTOR expression and decreased cell autophagy and apoptosis. Collectively, our results revealed the function of DDIT4 in cell death mechanisms triggered by TDCIPP through the m TOR signaling axis in differentiated PC12 cells. Thus, this study provided vital evidence necessary to explain the mechanism of TDCIPP-induced neurotoxicity in differentiated PC12 cells.展开更多
The occurrence,concentrations,and distribution profiles of chlorinated organophosphate esters(Cl-OPEs)were investigated in seventy-one car and road dust samples collected from Basrah,southern Iraq.In addition,estimate...The occurrence,concentrations,and distribution profiles of chlorinated organophosphate esters(Cl-OPEs)were investigated in seventy-one car and road dust samples collected from Basrah,southern Iraq.In addition,estimated daily intakes(EDIs)via dust ingestion were assessed for toddlers,regular adults,and taxi drivers.In car dust samples,the concentrations of S3Cl-OPEs ranged from 4120 to 73200 ng/g(median 11700 ng/g)with tris(1,3-dichloroisopropyl)phosphate(TDCIPP)the predominant compound.In road dust samples,the concentrations of ∑_(3)Cl-OPEs ranged from 269 to 3400 ng/g(median 373 ng/g)and 114e526 ng/g(median 222 ng/g)in urban and rural areas,respectively,with tris(2-chloroisopropyl)phosphate(TCIPP),predominant.Concentrations of Cl-OPEs in urban road dust are significantly higher(P<0.05)than those in rural road dust,suggesting commercial and industrial activity,population density,and heavy traffic may influence the concentrations.The different compositional profiles of Cl-OPEs in car and road dust may be attributed to the physicochemical properties of Cl-OPEs and the pathways through which they can be released into indoor and outdoor environments.EDI values of Cl-OPEs for the Iraqi population via car dust ingestion were in the order:toddlers>taxi drivers>regular adults,exceeding those via road dust by factors of 27 and 40 from urban and rural dust,respectively.For people who work as taxi drivers,EDIs were seven times higher than those of regular adults,implying that people-such as professional drivers-who spend a substantial amount of time in their vehicles may be exposed to hazardous levels of Cl-OPEs.Despite the study showing that the EDIs through dust ingestion for the three population groups were well below the reference dose(RfD)levels,further studies are recommended to assess other pathways,such as inhalation,dietary sources,and dermal absorption.展开更多
基金supported by the National Key Research and Development Program of China (No. 2018YFC1603704)the Tianjin Natural Science Foundation (No. 20JCQNJC00860)。
文摘Tris(1,3-dichloro-2-propyl) phosphate(TDCIPP) is a commonly used organophosphatebased flame retardant and can bio-accumulate in human tissues and organs. As its structure is similar to that of neurotoxic organophosphate pesticides, the neurotoxicity of TDCIPP has raised widespread concerns. TDCIPP can increase neuronal apoptosis and induce autophagy.However, its regulatory mechanism remains unclear. In this study, we found that the expression upregulation of the DNA Damage-Inducible Transcript 4(DDIT4) protein, which might play essential roles in TDCIPP-induced neuronal autophagy and apoptosis, was observed in TDCIPP-treated differentiated rat PC12 cells. Furthermore, we determined the protective effect of the DDIT4 suppression on the autophagy and apoptosis induced by TDCIPP using Western blot(WB) and Flow cytometry(FACS) analysis. We observed that TDCIPP treatment increased the DDIT4, the autophagy marker Beclin-1, and the microtubule-associated protein light chain 3-II(LC_(3)II) expressions and decreased the mTOR phosphorylation levels. Conversely, the suppression of DDIT4 expression increased the p-mTOR expression and decreased cell autophagy and apoptosis. Collectively, our results revealed the function of DDIT4 in cell death mechanisms triggered by TDCIPP through the m TOR signaling axis in differentiated PC12 cells. Thus, this study provided vital evidence necessary to explain the mechanism of TDCIPP-induced neurotoxicity in differentiated PC12 cells.
文摘The occurrence,concentrations,and distribution profiles of chlorinated organophosphate esters(Cl-OPEs)were investigated in seventy-one car and road dust samples collected from Basrah,southern Iraq.In addition,estimated daily intakes(EDIs)via dust ingestion were assessed for toddlers,regular adults,and taxi drivers.In car dust samples,the concentrations of S3Cl-OPEs ranged from 4120 to 73200 ng/g(median 11700 ng/g)with tris(1,3-dichloroisopropyl)phosphate(TDCIPP)the predominant compound.In road dust samples,the concentrations of ∑_(3)Cl-OPEs ranged from 269 to 3400 ng/g(median 373 ng/g)and 114e526 ng/g(median 222 ng/g)in urban and rural areas,respectively,with tris(2-chloroisopropyl)phosphate(TCIPP),predominant.Concentrations of Cl-OPEs in urban road dust are significantly higher(P<0.05)than those in rural road dust,suggesting commercial and industrial activity,population density,and heavy traffic may influence the concentrations.The different compositional profiles of Cl-OPEs in car and road dust may be attributed to the physicochemical properties of Cl-OPEs and the pathways through which they can be released into indoor and outdoor environments.EDI values of Cl-OPEs for the Iraqi population via car dust ingestion were in the order:toddlers>taxi drivers>regular adults,exceeding those via road dust by factors of 27 and 40 from urban and rural dust,respectively.For people who work as taxi drivers,EDIs were seven times higher than those of regular adults,implying that people-such as professional drivers-who spend a substantial amount of time in their vehicles may be exposed to hazardous levels of Cl-OPEs.Despite the study showing that the EDIs through dust ingestion for the three population groups were well below the reference dose(RfD)levels,further studies are recommended to assess other pathways,such as inhalation,dietary sources,and dermal absorption.
