Cytochrome P450 1B1 (CYP1B1) is an enzyme that has a unique tumor-specific pattern of expression ... more Cytochrome P450 1B1 (CYP1B1) is an enzyme that has a unique tumor-specific pattern of expression and is capable of bioactivating a wide range of carcinogenic compounds. We have reported previously that coordinated upregulation of CYP1B1 by inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and the aryl hydrocarbon receptor ligands, may increase bioactivation of promutagens, such as benzo[a]pyrene (BaP) in epithelial cells. Here, we extend those studies by describing a novel mechanism participating in the regulation of CYP1B1 expression, which involves activation of the p38 mitogen-activated protein kinase (p38) and mitogen- and stress-activated protein kinase 1 (MSK1). Using inhibitors of p38 and MSKs, as well as mouse embryonic cells derived from p38α-deficient and MSK1/2 double knockout mice, we show here that TNF-α potentiates CYP1B1 upregulation via the p38/MSK1 kinase cascade. Effects of this inflammatory cytokine on CYP1B1 expression further involve the positive t...
Cyanobacteria are producers of potent and environmentally abundant microcystins, representing an ... more Cyanobacteria are producers of potent and environmentally abundant microcystins, representing an emerging global health issue. In the present study, we investigated the impact of pure microcystins and cyanobacterial biomass on laboratory rats (Wistar albino rats, males, 30 days old) under different exposure scenarios. The rats were fed diets containing fish meat with microcystins in various concentrations and forms (cyanobacterial biomass and isolated microcystins) for 28 days. Although considerable amounts of microcystins (MCs) were administered to the rats, all levels of MCs in the liver were close to the detection limit (3-5 ng/g fresh weight) using liquid chromatography - tandem mass spectrometry. Only rats exposed to cyanobacterial biomass had clearly higher hepatic and splenic somatic indexes while markers of oxidative stress (glutathione-S-transferase, glutathione reductase, lipid peroxidatio) were significantly increased in the group exposed to the high dose of MCs. Most of ...
The present study was aimed at evaluation of the response of Japanese quails to cyanobacterial bi... more The present study was aimed at evaluation of the response of Japanese quails to cyanobacterial biomass administered in feed using biochemical profiles and parameters of reproduction. Effects of cyanobacterial biomass were studied according to the OECD 206 Guideline on Avian Reproduction Toxicity. A total of 16 control and 16 experimental pairs (32 males and 32 females) were analyzed. The chronic exposure of parent birds lasted eight weeks with the daily sum of 61.62 microg MCs including 26.54 microg MC-RR, 7.62 microg MC-YR and 27.39 microg MC-LR. There was no mortality both in control and cyanobacterial-biomass-exposed adults during the present study. Nor did the birds show any clinical signs of intoxication. Lactate dehydrogenase activity was increased about three-fold in exposed birds. No other biochemical parameters were showing significant differences. A total of 824 and 821 eggs were laid by control and exposed birds, respectively, during the eight-week study period. Eggs laid...
The aim of the present study was to evaluate differences between juvenile and adult Japanese quai... more The aim of the present study was to evaluate differences between juvenile and adult Japanese quails in responses to the exposure to cyanobacterial biomass in the diet. The OECD 205 Guideline on Avian Dietary Toxicity Test (1984) was employed in the experiment. A total of 75 freshly hatched chicks and 30 adults were exposed to cyanobacterial biomass for 15 days and blood sampled daily and on days 5, 10 and 15, respectively. Japanese quail chicks and adults received the same daily dose of approximately 224.4 ng microcystins per gram of body weight. Biochemical responses were compared against controls. No Japanese quail chicks and adults died during the acute 15-day-cyanobacterial-biomass exposure. Biochemical responses to the biomass in diet were first observed from day 5 post exposure to cyanobacterial biomass both in chicks and adults and there were age-related differences in the parameters changed. The responses of adult birds included an increase in lactate dehydrogenase, a drop i...
Concentrations of polyaromatic hydrocarbons (PAHs), chlorinated pesticides, polychlorinated biphe... more Concentrations of polyaromatic hydrocarbons (PAHs), chlorinated pesticides, polychlorinated biphenyls, dibenzo-p-dioxins and dibenzo-p-furans (PCDDs/Fs) in ambient air in Košetice, a background locality in the South Bohemia, have been estimated in the period from July to December 1994. The 24-hours samples have been taken by the means of a high-volume sampler. Sample analysis involved Soxhlet extraction of polyurethane foam, extract preconcentration and
7. Expression of MHC II Genes G. Drozina12, J. Kohoutek12, N. Jabrane-Ferrat13 and B. M. Peterlin... more 7. Expression of MHC II Genes G. Drozina12, J. Kohoutek12, N. Jabrane-Ferrat13 and B. M. Peterlin12 (12) Departments of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California, San Francisco, CA 94143, USA (13) Structural Immuno-Pharmacology, Institute of Pharmacology and Structural Biology, CNRS VMR 5089, 31400 Toulouse, France Abstract Innate and adaptive immunity are connected via antigen processing and presentation (APP), which results in the
Page 1. Sources and Distributions of Polycyclic Aromatic Hydrocarbons and Toxicity of Polluted At... more Page 1. Sources and Distributions of Polycyclic Aromatic Hydrocarbons and Toxicity of Polluted Atmosphere Aerosols Gerhard Lammel, Jirí Novák, Linda Landlová, Alice Dvorská, Jana Klánová, Pavel Cˇ upr, Jirí Kohoutek, Eberhard Reimer and Lenka krdlíková 1 Introduction ...
ABSTRACT The ambient air and soil monitoring network was established in 22 countries of Central a... more ABSTRACT The ambient air and soil monitoring network was established in 22 countries of Central and Eastern Europe (CEE) in support of the Global Monitoring Plan under the Stockholm Convention on Persistent Organic Pollutants. Polyurethane foam based passive air samplers were used as a tool for monitoring of POPs in ambient air at remote, rural, suburban, and urban sites with the aim of filling the information gaps identified in this UN region. High atmospheric levels of PCBs, HCHs, DDTs or HCB were observed at the rural as well as urban sites indicating that organochlorines still pose a significant problem in CEE. Pesticide storage, industrial complexes, military zones, and landfills were responsible for the elevated levels of POPs in this survey. The background levels of these compounds, however, were often elevated, too. (C) Author(s) 2012. This work is distributed under the Creative Commons Attribution 3.0 License.
Retinoic acids and their derivatives have been recently identified by chemical analyses in cyanob... more Retinoic acids and their derivatives have been recently identified by chemical analyses in cyanobacteria and algae. Given the essential role of retinoids for vertebrate development this has raised concerns about a potential risk for vertebrates exposed to retinoids during cyanobacterial blooms. Our study focuses on extracellular compounds produced by phytoplankton cells (exudates). In order to address the capacity for the production of retinoids or compounds with retinoid-like activity we compared the exudates of ten cyanobacteria and algae using in vitro reporter gene assay. Exudates of three cyanobacterial species showed retinoid-like activity in the range of 269-2,265 ng retinoid equivalents (REQ)/L, while there was no detectable activity in exudates of the investigated algal species. The exudates of one green alga (Desmodesmus quadricaudus) and the two cyanobacterial species with greatest REQ levels, Microcystis aeruginosa and Cylindrospermopsis raciborskii, were selected for testing of the potential relation of retinoid-like activity to developmental toxicity in zebrafish embryos. The exudates of both cyanobacteria were indeed provoking diverse teratogenic effects (e.g. tail, spine and mouth deformation) and interference with growth in zebrafish embryos, while such effects were not observed for the alga. Fish embryos were also exposed to all-trans retinoic acid (ATRA) in a range equivalent to the REQ concentrations detected in exudates by in vitro bioassays. Both the phenotypes and effective concentrations of exudates corresponded to ATRA equivalents, supporting the hypothesis that the teratogenic effects of cyanobacterial exudates are likely to be associated with retinoid-like activity. The study documents that some cyanobacteria are able to produce and release retinoid-like compounds into the environment at concentrations equivalent to those causing teratogenicity in zebrafish. Hence, the characterization of retinoid-like and teratogenic potency should be included in the assessment of the potential adverse effects caused by the release of toxic and bioactive compounds during cyanobacterial blooms.
Plakoglobin is an important component of intercellular junctions, including both desmosomes and a... more Plakoglobin is an important component of intercellular junctions, including both desmosomes and adherens junctions, which is known as a tumor suppressor. Although mutations in the plakoglobin gene (Jup) and/or changes in its protein levels have been observed in various disease states, including cancer progression or cardiovascular defects, the information about endogenous or exogenous stimuli orchestrating Jup expression is limited. Here we show that the aryl hydrocarbon receptor (AhR) may regulate Jup expression in a cell-specific manner. We observed a significant suppressive effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a model toxic exogenous activator of the AhR signaling, on Jup expression in a variety of experimental models derived from rodent tissues, including contact-inhibited rat liver progenitor cells (where TCDD induces cell proliferation), rat and mouse hepatoma cell models (where TCDD inhibits cell cycle progression), cardiac cells derived from the mouse embryonic stem cells, or cardiomyocytes isolated from neonatal rat hearts. The small interfering RNA (siRNA)-mediated knockdown of AhR confirmed its role in both basal and TCDD-deregulated Jup expression. The analysis of genomic DNA located ~2.5kb upstream of rat Jup gene revealed a presence of evolutionarily conserved AhR binding motifs, which were confirmed upon their cloning into luciferase reporter construct. The siRNA-mediated knockdown of Jup expression affected both proliferation and attachment of liver progenitor cells. The present data indicate that the AhR may contribute to negative regulation of Jup gene expression in rodent cellular models, which may affect cell adherence and proliferation.
ABSTRACT Samples of subcutaneous abdominal adipose tissues were analysed to obtain preliminary in... more ABSTRACT Samples of subcutaneous abdominal adipose tissues were analysed to obtain preliminary information on the level of general population exposure to polychlorinated biphenyls (PCBs). Three different regions—cities and their neighbouring districts—were chosen for comparison of the levels of contamination in Slovakia: Bratislava, Trenčin and Martin. Samples were obtained by autopsy.Highest concentrations were found in patients from the relatively densely population region with heavy chemical industry (Bratislava; males 0.7–10.4 mg.kg on lipid basis, females 0.6–7.7). Lower concentrations were found in the smaller towns and zones with different type of industry (engineering): Trenčin— males 2.1–5.5, females 0.4–6.1 and Martin—males 0.4–4.7, females 0.4–4.8. The daily PCB intake in the general population of Slovakia was calculated from the obtained and published data. This intake was found to be between 0.2 and 4.0 μg.kg.day.
IVAN HOLOUBEKa,*, JAN TŘÍSKAb, PAVEL CUDLÍNb, JOSEF ČÁSLAVSKÝa, KARL-WERNER SCHRAMMc, ANTONIUS KE... more IVAN HOLOUBEKa,*, JAN TŘÍSKAb, PAVEL CUDLÍNb, JOSEF ČÁSLAVSKÝa, KARL-WERNER SCHRAMMc, ANTONIUS KETTRUPc, JIŘÍ KOHOUTEKd, PAVEL ČUPRd and EVA SCHNEIDEROVÁd aRECETOX,(Research Centre for Atmospheric and ...
Cytochrome P450 1B1 (CYP1B1) is an enzyme that has a unique tumor-specific pattern of expression ... more Cytochrome P450 1B1 (CYP1B1) is an enzyme that has a unique tumor-specific pattern of expression and is capable of bioactivating a wide range of carcinogenic compounds. We have reported previously that coordinated upregulation of CYP1B1 by inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and the aryl hydrocarbon receptor ligands, may increase bioactivation of promutagens, such as benzo[a]pyrene (BaP) in epithelial cells. Here, we extend those studies by describing a novel mechanism participating in the regulation of CYP1B1 expression, which involves activation of the p38 mitogen-activated protein kinase (p38) and mitogen- and stress-activated protein kinase 1 (MSK1). Using inhibitors of p38 and MSKs, as well as mouse embryonic cells derived from p38α-deficient and MSK1/2 double knockout mice, we show here that TNF-α potentiates CYP1B1 upregulation via the p38/MSK1 kinase cascade. Effects of this inflammatory cytokine on CYP1B1 expression further involve the positive t...
Cyanobacteria are producers of potent and environmentally abundant microcystins, representing an ... more Cyanobacteria are producers of potent and environmentally abundant microcystins, representing an emerging global health issue. In the present study, we investigated the impact of pure microcystins and cyanobacterial biomass on laboratory rats (Wistar albino rats, males, 30 days old) under different exposure scenarios. The rats were fed diets containing fish meat with microcystins in various concentrations and forms (cyanobacterial biomass and isolated microcystins) for 28 days. Although considerable amounts of microcystins (MCs) were administered to the rats, all levels of MCs in the liver were close to the detection limit (3-5 ng/g fresh weight) using liquid chromatography - tandem mass spectrometry. Only rats exposed to cyanobacterial biomass had clearly higher hepatic and splenic somatic indexes while markers of oxidative stress (glutathione-S-transferase, glutathione reductase, lipid peroxidatio) were significantly increased in the group exposed to the high dose of MCs. Most of ...
The present study was aimed at evaluation of the response of Japanese quails to cyanobacterial bi... more The present study was aimed at evaluation of the response of Japanese quails to cyanobacterial biomass administered in feed using biochemical profiles and parameters of reproduction. Effects of cyanobacterial biomass were studied according to the OECD 206 Guideline on Avian Reproduction Toxicity. A total of 16 control and 16 experimental pairs (32 males and 32 females) were analyzed. The chronic exposure of parent birds lasted eight weeks with the daily sum of 61.62 microg MCs including 26.54 microg MC-RR, 7.62 microg MC-YR and 27.39 microg MC-LR. There was no mortality both in control and cyanobacterial-biomass-exposed adults during the present study. Nor did the birds show any clinical signs of intoxication. Lactate dehydrogenase activity was increased about three-fold in exposed birds. No other biochemical parameters were showing significant differences. A total of 824 and 821 eggs were laid by control and exposed birds, respectively, during the eight-week study period. Eggs laid...
The aim of the present study was to evaluate differences between juvenile and adult Japanese quai... more The aim of the present study was to evaluate differences between juvenile and adult Japanese quails in responses to the exposure to cyanobacterial biomass in the diet. The OECD 205 Guideline on Avian Dietary Toxicity Test (1984) was employed in the experiment. A total of 75 freshly hatched chicks and 30 adults were exposed to cyanobacterial biomass for 15 days and blood sampled daily and on days 5, 10 and 15, respectively. Japanese quail chicks and adults received the same daily dose of approximately 224.4 ng microcystins per gram of body weight. Biochemical responses were compared against controls. No Japanese quail chicks and adults died during the acute 15-day-cyanobacterial-biomass exposure. Biochemical responses to the biomass in diet were first observed from day 5 post exposure to cyanobacterial biomass both in chicks and adults and there were age-related differences in the parameters changed. The responses of adult birds included an increase in lactate dehydrogenase, a drop i...
Concentrations of polyaromatic hydrocarbons (PAHs), chlorinated pesticides, polychlorinated biphe... more Concentrations of polyaromatic hydrocarbons (PAHs), chlorinated pesticides, polychlorinated biphenyls, dibenzo-p-dioxins and dibenzo-p-furans (PCDDs/Fs) in ambient air in Košetice, a background locality in the South Bohemia, have been estimated in the period from July to December 1994. The 24-hours samples have been taken by the means of a high-volume sampler. Sample analysis involved Soxhlet extraction of polyurethane foam, extract preconcentration and
7. Expression of MHC II Genes G. Drozina12, J. Kohoutek12, N. Jabrane-Ferrat13 and B. M. Peterlin... more 7. Expression of MHC II Genes G. Drozina12, J. Kohoutek12, N. Jabrane-Ferrat13 and B. M. Peterlin12 (12) Departments of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California, San Francisco, CA 94143, USA (13) Structural Immuno-Pharmacology, Institute of Pharmacology and Structural Biology, CNRS VMR 5089, 31400 Toulouse, France Abstract Innate and adaptive immunity are connected via antigen processing and presentation (APP), which results in the
Page 1. Sources and Distributions of Polycyclic Aromatic Hydrocarbons and Toxicity of Polluted At... more Page 1. Sources and Distributions of Polycyclic Aromatic Hydrocarbons and Toxicity of Polluted Atmosphere Aerosols Gerhard Lammel, Jirí Novák, Linda Landlová, Alice Dvorská, Jana Klánová, Pavel Cˇ upr, Jirí Kohoutek, Eberhard Reimer and Lenka krdlíková 1 Introduction ...
ABSTRACT The ambient air and soil monitoring network was established in 22 countries of Central a... more ABSTRACT The ambient air and soil monitoring network was established in 22 countries of Central and Eastern Europe (CEE) in support of the Global Monitoring Plan under the Stockholm Convention on Persistent Organic Pollutants. Polyurethane foam based passive air samplers were used as a tool for monitoring of POPs in ambient air at remote, rural, suburban, and urban sites with the aim of filling the information gaps identified in this UN region. High atmospheric levels of PCBs, HCHs, DDTs or HCB were observed at the rural as well as urban sites indicating that organochlorines still pose a significant problem in CEE. Pesticide storage, industrial complexes, military zones, and landfills were responsible for the elevated levels of POPs in this survey. The background levels of these compounds, however, were often elevated, too. (C) Author(s) 2012. This work is distributed under the Creative Commons Attribution 3.0 License.
Retinoic acids and their derivatives have been recently identified by chemical analyses in cyanob... more Retinoic acids and their derivatives have been recently identified by chemical analyses in cyanobacteria and algae. Given the essential role of retinoids for vertebrate development this has raised concerns about a potential risk for vertebrates exposed to retinoids during cyanobacterial blooms. Our study focuses on extracellular compounds produced by phytoplankton cells (exudates). In order to address the capacity for the production of retinoids or compounds with retinoid-like activity we compared the exudates of ten cyanobacteria and algae using in vitro reporter gene assay. Exudates of three cyanobacterial species showed retinoid-like activity in the range of 269-2,265 ng retinoid equivalents (REQ)/L, while there was no detectable activity in exudates of the investigated algal species. The exudates of one green alga (Desmodesmus quadricaudus) and the two cyanobacterial species with greatest REQ levels, Microcystis aeruginosa and Cylindrospermopsis raciborskii, were selected for testing of the potential relation of retinoid-like activity to developmental toxicity in zebrafish embryos. The exudates of both cyanobacteria were indeed provoking diverse teratogenic effects (e.g. tail, spine and mouth deformation) and interference with growth in zebrafish embryos, while such effects were not observed for the alga. Fish embryos were also exposed to all-trans retinoic acid (ATRA) in a range equivalent to the REQ concentrations detected in exudates by in vitro bioassays. Both the phenotypes and effective concentrations of exudates corresponded to ATRA equivalents, supporting the hypothesis that the teratogenic effects of cyanobacterial exudates are likely to be associated with retinoid-like activity. The study documents that some cyanobacteria are able to produce and release retinoid-like compounds into the environment at concentrations equivalent to those causing teratogenicity in zebrafish. Hence, the characterization of retinoid-like and teratogenic potency should be included in the assessment of the potential adverse effects caused by the release of toxic and bioactive compounds during cyanobacterial blooms.
Plakoglobin is an important component of intercellular junctions, including both desmosomes and a... more Plakoglobin is an important component of intercellular junctions, including both desmosomes and adherens junctions, which is known as a tumor suppressor. Although mutations in the plakoglobin gene (Jup) and/or changes in its protein levels have been observed in various disease states, including cancer progression or cardiovascular defects, the information about endogenous or exogenous stimuli orchestrating Jup expression is limited. Here we show that the aryl hydrocarbon receptor (AhR) may regulate Jup expression in a cell-specific manner. We observed a significant suppressive effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a model toxic exogenous activator of the AhR signaling, on Jup expression in a variety of experimental models derived from rodent tissues, including contact-inhibited rat liver progenitor cells (where TCDD induces cell proliferation), rat and mouse hepatoma cell models (where TCDD inhibits cell cycle progression), cardiac cells derived from the mouse embryonic stem cells, or cardiomyocytes isolated from neonatal rat hearts. The small interfering RNA (siRNA)-mediated knockdown of AhR confirmed its role in both basal and TCDD-deregulated Jup expression. The analysis of genomic DNA located ~2.5kb upstream of rat Jup gene revealed a presence of evolutionarily conserved AhR binding motifs, which were confirmed upon their cloning into luciferase reporter construct. The siRNA-mediated knockdown of Jup expression affected both proliferation and attachment of liver progenitor cells. The present data indicate that the AhR may contribute to negative regulation of Jup gene expression in rodent cellular models, which may affect cell adherence and proliferation.
ABSTRACT Samples of subcutaneous abdominal adipose tissues were analysed to obtain preliminary in... more ABSTRACT Samples of subcutaneous abdominal adipose tissues were analysed to obtain preliminary information on the level of general population exposure to polychlorinated biphenyls (PCBs). Three different regions—cities and their neighbouring districts—were chosen for comparison of the levels of contamination in Slovakia: Bratislava, Trenčin and Martin. Samples were obtained by autopsy.Highest concentrations were found in patients from the relatively densely population region with heavy chemical industry (Bratislava; males 0.7–10.4 mg.kg on lipid basis, females 0.6–7.7). Lower concentrations were found in the smaller towns and zones with different type of industry (engineering): Trenčin— males 2.1–5.5, females 0.4–6.1 and Martin—males 0.4–4.7, females 0.4–4.8. The daily PCB intake in the general population of Slovakia was calculated from the obtained and published data. This intake was found to be between 0.2 and 4.0 μg.kg.day.
IVAN HOLOUBEKa,*, JAN TŘÍSKAb, PAVEL CUDLÍNb, JOSEF ČÁSLAVSKÝa, KARL-WERNER SCHRAMMc, ANTONIUS KE... more IVAN HOLOUBEKa,*, JAN TŘÍSKAb, PAVEL CUDLÍNb, JOSEF ČÁSLAVSKÝa, KARL-WERNER SCHRAMMc, ANTONIUS KETTRUPc, JIŘÍ KOHOUTEKd, PAVEL ČUPRd and EVA SCHNEIDEROVÁd aRECETOX,(Research Centre for Atmospheric and ...
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