The AhR binds to contain ligands, such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, 3-methylcholantrene, or β-naphthoflavone. The activation mechanism of AhR is not yet fully understood, but it is known that AhR associ...The AhR binds to contain ligands, such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, 3-methylcholantrene, or β-naphthoflavone. The activation mechanism of AhR is not yet fully understood, but it is known that AhR associates with the molecular chaperone HSP90 in the cytoplasm. There are a few reports about the association or dissociation of AhR and HSP90, and which domain of HSP90 binds to AhR. We reported the association and activation mechanisms between HSP90 and AhR-PAS or AhR-bHLH. In the current study, we found that cisplatin inhibits the AhR activation. Although ATP and 17-DMAG have no effect on the dissociation of HSP90 from AhR, some contents of HSP90 were dissociated from AhR in the presence of cisplatin. We could detect the increase of CYP1A in the presence of 3-MC. On the contrary, the induction of CYP1A1 was inhibited in the presence of cisplatin. We couldn’t detect AhR in the HeLa cell soluble fraction in the presence of 50 μM cisplatin. In the presence of MG-132, we could detect AhR. These results suggested that AhR was dissociated from the HSP90 chaperone complex and processed during the protein proteasome degradation system in the presence of cisplatin.展开更多
This project reports on the use of a novel nanomembrane filtering technology to isolate and analyze the bioactivity of microplastic(MP)-containing debris from Lake Ontario water samples.Environmental MPs are a complex...This project reports on the use of a novel nanomembrane filtering technology to isolate and analyze the bioactivity of microplastic(MP)-containing debris from Lake Ontario water samples.Environmental MPs are a complex mixture of polymers and sorbed chemicals that are persistent and can exhibit a wide range of toxic effects.Since human exposure to MPs is unavoidable,it is necessary to characterize their bioactivity to assess potential health risks.This work seeks to quantify MP presence in the nearshore waters of Lake Ontario and begin to characterize the bioactivity of the filtrate containing MPs.We utilized silicon nitride(SiN)nanomembrane technology to isolate debris sized between 8 and 20μm from lake water samples collected at various times and locations.MPs were identified with Nile red staining.Cell-based assays were conducted directly on the filtered debris to test for cell viability,aryl hydrocarbon receptor(AhR)activity,and interleukin 6(IL-6)levels as a measure of proinflammatory response.All samples contained MPs.None of the isolated debris impacted cell viability.However,AhR activity and IL-6 levels varied over time.Additionally,no associations were observed between the amount of plastic and bioactivity.Observed differences in activity are likely due to variations in the physiochemical properties of debris between samples.Our results highlight the need for increased sampling to fully characterize the bioactivity of MPs in human cells and to elucidate the role that sample physiochemical and spatiotemporal properties play in this activity.展开更多
Emerging evidence showed that 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) could induce expression of certain reactivation-associated genes in astrocytes, however, the consequent cellular effects and molecular mechanisms...Emerging evidence showed that 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) could induce expression of certain reactivation-associated genes in astrocytes, however, the consequent cellular effects and molecular mechanisms are still unclear. During the process of astrocyte reactivation, migration is a critical cellular event. In the present study, we employed woundhealing assay and Transwell? motility assay to explore the effects of TCDD on cell migration in primary cultured rat cortical astrocytes. We found that upon TCDD treatments at relative low concentrations(10^(-10) and/or 10^(-9) mol/L), the ability of primary astrocytes to migrate horizontally and vertically was promoted. In line with this cellular effect, the mR NA expression of two promigratory genes, including cell division cycle 42(CDC42) and matrix metalloproteinase 2(MMP2)was induced by TCDD treatment. Dioxin exerts its toxic effects mainly through aryl hydrocarbon receptor(AhR) pathway. So the role of AhR pathway in the pro-migratory effects of TCDD was examined using an AhR antagonist, CH223191. We found that application of CH223191 significantly reversed the pro-migratory effects of TCDD. Interestingly, the basal ability of horizontal migration as well as basal levels of CDC42 and MMP2 expression were dramatically reduced suggesting a possible physiological role of AhR in maintaining the endogenous migration ability of the primary astrocytes. These findings support the notion that dioxin promotes astrocyte reactivation at molecular and cellular levels.展开更多
To evaluate the protective effects of Glycyrrhiza polysaccharide（GPS） against 2,3,7,8-tetrachlorodibenzo-p-dioxin（TCDD）-induced hepatotoxicity in Jian carp,the fish were fed diets containing GPS at doses of 0.1,0....To evaluate the protective effects of Glycyrrhiza polysaccharide（GPS） against 2,3,7,8-tetrachlorodibenzo-p-dioxin（TCDD）-induced hepatotoxicity in Jian carp,the fish were fed diets containing GPS at doses of 0.1,0.5 and 1.0 g/kg for 60 days before an intraperitoneal injection of 0.6 μg/kg TCDD at a volume of 0.05 mL/10 g body weight.At 72 hr post-injection,blood and liver samples were taken for biochemical analysis and the fish liver samples were used for the preparation of pathological slices.The results showed that increases in alanine aminotransferase（GPT）,aspartate aminotransferase（GOT）,lactate dehydrogenase（LDH）,and alkaline phosphatase（AKP） in serum induced by TCDD were significantly inhibited by pre-treatment with 1.0 g/kg GPS.Following the 1.0 g/kg GPS pre-treatment,total protein（TP）,albumin（Alb）,catalase（CAT）,glutathione peroxidase（GPx）,total antioxidant capacity（T-AOC） and superoxide dismutase（SOD） activities in liver tissue increased significantly,malondialdehyde（MDA） formation（P ＆lt; 0.05 or P ＆lt; 0.01） was significantly inhibited,and the expression of cytochrome P4501A（CYP1A）,aryl hydrocarbon receptor 2（AHR2） and aryl hydrocarbon receptor nuclear translocator 2（ARNT2） mRNA（P ＆lt; 0.05） was significantly enhanced.Histological observations on fish liver were obtained by preparing paraffin tissue sections via HE staining,and the results showed that histological changes were obviously reduced by 0.5 and 1.0 g/kg GPS.GPS significantly reduced liver tissue damage caused by TCDD.Overall,these results proved the hepatoprotective effect of GPS in protecting against fish liver injury induced by TCDD,and supported the use of GPS（1.0 g/kg） as a hepatoprotective and antioxidant agent in fish.展开更多
文摘The AhR binds to contain ligands, such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, 3-methylcholantrene, or β-naphthoflavone. The activation mechanism of AhR is not yet fully understood, but it is known that AhR associates with the molecular chaperone HSP90 in the cytoplasm. There are a few reports about the association or dissociation of AhR and HSP90, and which domain of HSP90 binds to AhR. We reported the association and activation mechanisms between HSP90 and AhR-PAS or AhR-bHLH. In the current study, we found that cisplatin inhibits the AhR activation. Although ATP and 17-DMAG have no effect on the dissociation of HSP90 from AhR, some contents of HSP90 were dissociated from AhR in the presence of cisplatin. We could detect the increase of CYP1A in the presence of 3-MC. On the contrary, the induction of CYP1A1 was inhibited in the presence of cisplatin. We couldn’t detect AhR in the HeLa cell soluble fraction in the presence of 50 μM cisplatin. In the presence of MG-132, we could detect AhR. These results suggested that AhR was dissociated from the HSP90 chaperone complex and processed during the protein proteasome degradation system in the presence of cisplatin.
基金supported by the National Natural Science Foundation of China(No.82101690)the Natural Science Foundation of Jiangxi Province,China(No.20224BAB216029).
基金supported by the National Institute of Environmental Health Sciences(NIEHS R01 ES021492)the University of Rochester Toxicology Training Program(NIEHS T32 ES007026)the University of Rochester Environmental Health Sciences Center(NIEHS P30 ES001247).
文摘This project reports on the use of a novel nanomembrane filtering technology to isolate and analyze the bioactivity of microplastic(MP)-containing debris from Lake Ontario water samples.Environmental MPs are a complex mixture of polymers and sorbed chemicals that are persistent and can exhibit a wide range of toxic effects.Since human exposure to MPs is unavoidable,it is necessary to characterize their bioactivity to assess potential health risks.This work seeks to quantify MP presence in the nearshore waters of Lake Ontario and begin to characterize the bioactivity of the filtrate containing MPs.We utilized silicon nitride(SiN)nanomembrane technology to isolate debris sized between 8 and 20μm from lake water samples collected at various times and locations.MPs were identified with Nile red staining.Cell-based assays were conducted directly on the filtered debris to test for cell viability,aryl hydrocarbon receptor(AhR)activity,and interleukin 6(IL-6)levels as a measure of proinflammatory response.All samples contained MPs.None of the isolated debris impacted cell viability.However,AhR activity and IL-6 levels varied over time.Additionally,no associations were observed between the amount of plastic and bioactivity.Observed differences in activity are likely due to variations in the physiochemical properties of debris between samples.Our results highlight the need for increased sampling to fully characterize the bioactivity of MPs in human cells and to elucidate the role that sample physiochemical and spatiotemporal properties play in this activity.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Nos.XDB14030401,XDB14030402)the Natural Science Foundation of China (Nos.21377160,21525730)Tianjin Municipal Science and Technology Commission (No.14JCQNJC11300)
文摘Emerging evidence showed that 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) could induce expression of certain reactivation-associated genes in astrocytes, however, the consequent cellular effects and molecular mechanisms are still unclear. During the process of astrocyte reactivation, migration is a critical cellular event. In the present study, we employed woundhealing assay and Transwell? motility assay to explore the effects of TCDD on cell migration in primary cultured rat cortical astrocytes. We found that upon TCDD treatments at relative low concentrations(10^(-10) and/or 10^(-9) mol/L), the ability of primary astrocytes to migrate horizontally and vertically was promoted. In line with this cellular effect, the mR NA expression of two promigratory genes, including cell division cycle 42(CDC42) and matrix metalloproteinase 2(MMP2)was induced by TCDD treatment. Dioxin exerts its toxic effects mainly through aryl hydrocarbon receptor(AhR) pathway. So the role of AhR pathway in the pro-migratory effects of TCDD was examined using an AhR antagonist, CH223191. We found that application of CH223191 significantly reversed the pro-migratory effects of TCDD. Interestingly, the basal ability of horizontal migration as well as basal levels of CDC42 and MMP2 expression were dramatically reduced suggesting a possible physiological role of AhR in maintaining the endogenous migration ability of the primary astrocytes. These findings support the notion that dioxin promotes astrocyte reactivation at molecular and cellular levels.
基金supported by the National Natural Science Foundation of China(Nos.31202002,31200918)Jiangsu Science and Technology Department(No.BK2012535)the Central Public-Interest Scientific Institution Basal Research Fund(No.2014A08YQ01)
文摘To evaluate the protective effects of Glycyrrhiza polysaccharide（GPS） against 2,3,7,8-tetrachlorodibenzo-p-dioxin（TCDD）-induced hepatotoxicity in Jian carp,the fish were fed diets containing GPS at doses of 0.1,0.5 and 1.0 g/kg for 60 days before an intraperitoneal injection of 0.6 μg/kg TCDD at a volume of 0.05 mL/10 g body weight.At 72 hr post-injection,blood and liver samples were taken for biochemical analysis and the fish liver samples were used for the preparation of pathological slices.The results showed that increases in alanine aminotransferase（GPT）,aspartate aminotransferase（GOT）,lactate dehydrogenase（LDH）,and alkaline phosphatase（AKP） in serum induced by TCDD were significantly inhibited by pre-treatment with 1.0 g/kg GPS.Following the 1.0 g/kg GPS pre-treatment,total protein（TP）,albumin（Alb）,catalase（CAT）,glutathione peroxidase（GPx）,total antioxidant capacity（T-AOC） and superoxide dismutase（SOD） activities in liver tissue increased significantly,malondialdehyde（MDA） formation（P ＆lt; 0.05 or P ＆lt; 0.01） was significantly inhibited,and the expression of cytochrome P4501A（CYP1A）,aryl hydrocarbon receptor 2（AHR2） and aryl hydrocarbon receptor nuclear translocator 2（ARNT2） mRNA（P ＆lt; 0.05） was significantly enhanced.Histological observations on fish liver were obtained by preparing paraffin tissue sections via HE staining,and the results showed that histological changes were obviously reduced by 0.5 and 1.0 g/kg GPS.GPS significantly reduced liver tissue damage caused by TCDD.Overall,these results proved the hepatoprotective effect of GPS in protecting against fish liver injury induced by TCDD,and supported the use of GPS（1.0 g/kg） as a hepatoprotective and antioxidant agent in fish.
