The Experts below are selected from a list of 129 Experts worldwide ranked by ideXlab platform

Michael Aschner - One of the best experts on this subject based on the ideXlab platform.

  • glutamate aspartate transporter glast taurine transporter and metallothionein mrna levels are differentially altered in astrocytes exposed to Manganese chloride Manganese phosphate or Manganese sulfate
    Neurotoxicology, 2002
    Co-Authors: Keith M. Erikson, Robert L. Suber, Michael Aschner
    Abstract:

    Manganese (Mn)-induced neurotoxicity can occur due to environmental exposure (air pollution, soil, water) and/or metabolic aberrations (decreased biliary excretion). High brain Manganese levels lead to oxidative stress, as well as alterations in neurotransmitter metabolism with concurrent neurobehavioral deficits. Based on the few existing studies that have examined brain regional Mn concentration, it is likely that in pathological conditions, Mn concentration can reach between 100 and 500 µM. Environmental Mn exposure as a result of Methylcyclopentadienyl Manganese Tricarbonyl (MMT) combustion is in the form of phosphate or sulfate (MnPO4, MnSO4, respectively). Pharmacokinetic studies have shown that the Mn salt will determine the rate of transport into the brain: MnCl2 > MnSO4 > MnPO4. The salt-specific neurotoxicity of these species is unknown. The primary goal of this study was to examine gene expression of glutamatelaspartate transporter (GLAST), taurine transporter (tau-T), and metallothionein-I (MT-I) in astrocytes exposed to Manganese chloride (MnCl2), Manganese sulfate (MnSO4), and Manganese phosphate (MnPO4). We hypothesized that the effects of MnPO4 and MnSO4 exposure on GLAST expression in astrocytes would be similar to those induced by MnCl2, since irrespective of salt species exposure, once internalized by astrocytes, the Mn ion would be identically complexed. At the same time, we hypothesized that the magnitude of the effect would be salt-dependent, since the chemical speciation would determine the rate of intracellular uptake of Mn. MnCl2 caused a significant overall decrease (P < 0.0001) in astrocytic GLAST mRNA levels with MnSO4 causing a moderate decrease. MnPO4 exposure did not alter GLAST mRNA in astrocytes. We also sought to examine astrocytic metallothionein and taurine transporter gene expression as markers of Manganese exposure. Our findings suggest that Manganese chloride significantly decreased (P < 0.0001) astrocytic metallothionein mRNA compared to both the sulfate and phosphate species. However, astrocytic taurine transporter mRNA was not affected by Mn exposure, irrespective of the salt species. These data are consistent with the hypothesis that astrocytic neurotoxicity due to Mn exposure is dependent upon its species, with solubility, and by inference, intracellular concentration, representing a major determinant of its neurotoxicity.

  • Glutamate/aspartate transporter (GLAST), taurine transporter and metallothionein mRNA levels are differentially altered in astrocytes exposed to Manganese chloride, Manganese phosphate or Manganese sulfate
    Neurotoxicology, 2002
    Co-Authors: Keith M. Erikson, Robert L. Suber, Michael Aschner
    Abstract:

    Manganese (Mn)-induced neurotoxicity can occur due to environmental exposure (air pollution, soil, water) and/or metabolic aberrations (decreased biliary excretion). High brain Manganese levels lead to oxidative stress, as well as alterations in neurotransmitter metabolism with concurrent neurobehavioral deficits. Based on the few existing studies that have examined brain regional Mn concentration, it is likely that in pathological conditions, Mn concentration can reach between 100 and 500 µM. Environmental Mn exposure as a result of Methylcyclopentadienyl Manganese Tricarbonyl (MMT) combustion is in the form of phosphate or sulfate (MnPO4, MnSO4, respectively). Pharmacokinetic studies have shown that the Mn salt will determine the rate of transport into the brain: MnCl2 > MnSO4 > MnPO4. The salt-specific neurotoxicity of these species is unknown. The primary goal of this study was to examine gene expression of glutamatelaspartate transporter (GLAST), taurine transporter (tau-T), and metallothionein-I (MT-I) in astrocytes exposed to Manganese chloride (MnCl2), Manganese sulfate (MnSO4), and Manganese phosphate (MnPO4). We hypothesized that the effects of MnPO4 and MnSO4 exposure on GLAST expression in astrocytes would be similar to those induced by MnCl2, since irrespective of salt species exposure, once internalized by astrocytes, the Mn ion would be identically complexed. At the same time, we hypothesized that the magnitude of the effect would be salt-dependent, since the chemical speciation would determine the rate of intracellular uptake of Mn. MnCl2 caused a significant overall decrease (P < 0.0001) in astrocytic GLAST mRNA levels with MnSO4 causing a moderate decrease. MnPO4 exposure did not alter GLAST mRNA in astrocytes. We also sought to examine astrocytic metallothionein and taurine transporter gene expression as markers of Manganese exposure. Our findings suggest that Manganese chloride significantly decreased (P < 0.0001) astrocytic metallothionein mRNA compared to both the sulfate and phosphate species. However, astrocytic taurine transporter mRNA was not affected by Mn exposure, irrespective of the salt species. These data are consistent with the hypothesis that astrocytic neurotoxicity due to Mn exposure is dependent upon its species, with solubility, and by inference, intracellular concentration, representing a major determinant of its neurotoxicity.

Keith M. Erikson - One of the best experts on this subject based on the ideXlab platform.

  • glutamate aspartate transporter glast taurine transporter and metallothionein mrna levels are differentially altered in astrocytes exposed to Manganese chloride Manganese phosphate or Manganese sulfate
    Neurotoxicology, 2002
    Co-Authors: Keith M. Erikson, Robert L. Suber, Michael Aschner
    Abstract:

    Manganese (Mn)-induced neurotoxicity can occur due to environmental exposure (air pollution, soil, water) and/or metabolic aberrations (decreased biliary excretion). High brain Manganese levels lead to oxidative stress, as well as alterations in neurotransmitter metabolism with concurrent neurobehavioral deficits. Based on the few existing studies that have examined brain regional Mn concentration, it is likely that in pathological conditions, Mn concentration can reach between 100 and 500 µM. Environmental Mn exposure as a result of Methylcyclopentadienyl Manganese Tricarbonyl (MMT) combustion is in the form of phosphate or sulfate (MnPO4, MnSO4, respectively). Pharmacokinetic studies have shown that the Mn salt will determine the rate of transport into the brain: MnCl2 > MnSO4 > MnPO4. The salt-specific neurotoxicity of these species is unknown. The primary goal of this study was to examine gene expression of glutamatelaspartate transporter (GLAST), taurine transporter (tau-T), and metallothionein-I (MT-I) in astrocytes exposed to Manganese chloride (MnCl2), Manganese sulfate (MnSO4), and Manganese phosphate (MnPO4). We hypothesized that the effects of MnPO4 and MnSO4 exposure on GLAST expression in astrocytes would be similar to those induced by MnCl2, since irrespective of salt species exposure, once internalized by astrocytes, the Mn ion would be identically complexed. At the same time, we hypothesized that the magnitude of the effect would be salt-dependent, since the chemical speciation would determine the rate of intracellular uptake of Mn. MnCl2 caused a significant overall decrease (P < 0.0001) in astrocytic GLAST mRNA levels with MnSO4 causing a moderate decrease. MnPO4 exposure did not alter GLAST mRNA in astrocytes. We also sought to examine astrocytic metallothionein and taurine transporter gene expression as markers of Manganese exposure. Our findings suggest that Manganese chloride significantly decreased (P < 0.0001) astrocytic metallothionein mRNA compared to both the sulfate and phosphate species. However, astrocytic taurine transporter mRNA was not affected by Mn exposure, irrespective of the salt species. These data are consistent with the hypothesis that astrocytic neurotoxicity due to Mn exposure is dependent upon its species, with solubility, and by inference, intracellular concentration, representing a major determinant of its neurotoxicity.

  • Glutamate/aspartate transporter (GLAST), taurine transporter and metallothionein mRNA levels are differentially altered in astrocytes exposed to Manganese chloride, Manganese phosphate or Manganese sulfate
    Neurotoxicology, 2002
    Co-Authors: Keith M. Erikson, Robert L. Suber, Michael Aschner
    Abstract:

    Manganese (Mn)-induced neurotoxicity can occur due to environmental exposure (air pollution, soil, water) and/or metabolic aberrations (decreased biliary excretion). High brain Manganese levels lead to oxidative stress, as well as alterations in neurotransmitter metabolism with concurrent neurobehavioral deficits. Based on the few existing studies that have examined brain regional Mn concentration, it is likely that in pathological conditions, Mn concentration can reach between 100 and 500 µM. Environmental Mn exposure as a result of Methylcyclopentadienyl Manganese Tricarbonyl (MMT) combustion is in the form of phosphate or sulfate (MnPO4, MnSO4, respectively). Pharmacokinetic studies have shown that the Mn salt will determine the rate of transport into the brain: MnCl2 > MnSO4 > MnPO4. The salt-specific neurotoxicity of these species is unknown. The primary goal of this study was to examine gene expression of glutamatelaspartate transporter (GLAST), taurine transporter (tau-T), and metallothionein-I (MT-I) in astrocytes exposed to Manganese chloride (MnCl2), Manganese sulfate (MnSO4), and Manganese phosphate (MnPO4). We hypothesized that the effects of MnPO4 and MnSO4 exposure on GLAST expression in astrocytes would be similar to those induced by MnCl2, since irrespective of salt species exposure, once internalized by astrocytes, the Mn ion would be identically complexed. At the same time, we hypothesized that the magnitude of the effect would be salt-dependent, since the chemical speciation would determine the rate of intracellular uptake of Mn. MnCl2 caused a significant overall decrease (P < 0.0001) in astrocytic GLAST mRNA levels with MnSO4 causing a moderate decrease. MnPO4 exposure did not alter GLAST mRNA in astrocytes. We also sought to examine astrocytic metallothionein and taurine transporter gene expression as markers of Manganese exposure. Our findings suggest that Manganese chloride significantly decreased (P < 0.0001) astrocytic metallothionein mRNA compared to both the sulfate and phosphate species. However, astrocytic taurine transporter mRNA was not affected by Mn exposure, irrespective of the salt species. These data are consistent with the hypothesis that astrocytic neurotoxicity due to Mn exposure is dependent upon its species, with solubility, and by inference, intracellular concentration, representing a major determinant of its neurotoxicity.

Robert L. Suber - One of the best experts on this subject based on the ideXlab platform.

  • glutamate aspartate transporter glast taurine transporter and metallothionein mrna levels are differentially altered in astrocytes exposed to Manganese chloride Manganese phosphate or Manganese sulfate
    Neurotoxicology, 2002
    Co-Authors: Keith M. Erikson, Robert L. Suber, Michael Aschner
    Abstract:

    Manganese (Mn)-induced neurotoxicity can occur due to environmental exposure (air pollution, soil, water) and/or metabolic aberrations (decreased biliary excretion). High brain Manganese levels lead to oxidative stress, as well as alterations in neurotransmitter metabolism with concurrent neurobehavioral deficits. Based on the few existing studies that have examined brain regional Mn concentration, it is likely that in pathological conditions, Mn concentration can reach between 100 and 500 µM. Environmental Mn exposure as a result of Methylcyclopentadienyl Manganese Tricarbonyl (MMT) combustion is in the form of phosphate or sulfate (MnPO4, MnSO4, respectively). Pharmacokinetic studies have shown that the Mn salt will determine the rate of transport into the brain: MnCl2 > MnSO4 > MnPO4. The salt-specific neurotoxicity of these species is unknown. The primary goal of this study was to examine gene expression of glutamatelaspartate transporter (GLAST), taurine transporter (tau-T), and metallothionein-I (MT-I) in astrocytes exposed to Manganese chloride (MnCl2), Manganese sulfate (MnSO4), and Manganese phosphate (MnPO4). We hypothesized that the effects of MnPO4 and MnSO4 exposure on GLAST expression in astrocytes would be similar to those induced by MnCl2, since irrespective of salt species exposure, once internalized by astrocytes, the Mn ion would be identically complexed. At the same time, we hypothesized that the magnitude of the effect would be salt-dependent, since the chemical speciation would determine the rate of intracellular uptake of Mn. MnCl2 caused a significant overall decrease (P < 0.0001) in astrocytic GLAST mRNA levels with MnSO4 causing a moderate decrease. MnPO4 exposure did not alter GLAST mRNA in astrocytes. We also sought to examine astrocytic metallothionein and taurine transporter gene expression as markers of Manganese exposure. Our findings suggest that Manganese chloride significantly decreased (P < 0.0001) astrocytic metallothionein mRNA compared to both the sulfate and phosphate species. However, astrocytic taurine transporter mRNA was not affected by Mn exposure, irrespective of the salt species. These data are consistent with the hypothesis that astrocytic neurotoxicity due to Mn exposure is dependent upon its species, with solubility, and by inference, intracellular concentration, representing a major determinant of its neurotoxicity.

  • Glutamate/aspartate transporter (GLAST), taurine transporter and metallothionein mRNA levels are differentially altered in astrocytes exposed to Manganese chloride, Manganese phosphate or Manganese sulfate
    Neurotoxicology, 2002
    Co-Authors: Keith M. Erikson, Robert L. Suber, Michael Aschner
    Abstract:

    Manganese (Mn)-induced neurotoxicity can occur due to environmental exposure (air pollution, soil, water) and/or metabolic aberrations (decreased biliary excretion). High brain Manganese levels lead to oxidative stress, as well as alterations in neurotransmitter metabolism with concurrent neurobehavioral deficits. Based on the few existing studies that have examined brain regional Mn concentration, it is likely that in pathological conditions, Mn concentration can reach between 100 and 500 µM. Environmental Mn exposure as a result of Methylcyclopentadienyl Manganese Tricarbonyl (MMT) combustion is in the form of phosphate or sulfate (MnPO4, MnSO4, respectively). Pharmacokinetic studies have shown that the Mn salt will determine the rate of transport into the brain: MnCl2 > MnSO4 > MnPO4. The salt-specific neurotoxicity of these species is unknown. The primary goal of this study was to examine gene expression of glutamatelaspartate transporter (GLAST), taurine transporter (tau-T), and metallothionein-I (MT-I) in astrocytes exposed to Manganese chloride (MnCl2), Manganese sulfate (MnSO4), and Manganese phosphate (MnPO4). We hypothesized that the effects of MnPO4 and MnSO4 exposure on GLAST expression in astrocytes would be similar to those induced by MnCl2, since irrespective of salt species exposure, once internalized by astrocytes, the Mn ion would be identically complexed. At the same time, we hypothesized that the magnitude of the effect would be salt-dependent, since the chemical speciation would determine the rate of intracellular uptake of Mn. MnCl2 caused a significant overall decrease (P < 0.0001) in astrocytic GLAST mRNA levels with MnSO4 causing a moderate decrease. MnPO4 exposure did not alter GLAST mRNA in astrocytes. We also sought to examine astrocytic metallothionein and taurine transporter gene expression as markers of Manganese exposure. Our findings suggest that Manganese chloride significantly decreased (P < 0.0001) astrocytic metallothionein mRNA compared to both the sulfate and phosphate species. However, astrocytic taurine transporter mRNA was not affected by Mn exposure, irrespective of the salt species. These data are consistent with the hypothesis that astrocytic neurotoxicity due to Mn exposure is dependent upon its species, with solubility, and by inference, intracellular concentration, representing a major determinant of its neurotoxicity.

Alfred Bernard - One of the best experts on this subject based on the ideXlab platform.

  • clara cell protein as a marker of clara cell damage and bronchoalveolar blood barrier permeability
    European Respiratory Journal, 1999
    Co-Authors: Cédric Hermans, Murielle Wiedig, K Arsalane, Gerard Toubeau, Paul Falmagne, Bernard Knoops, Alfred Bernard
    Abstract:

    The 16 kDa Clara cell protein (CC16), an abundant component of airway secretions, has recently been proposed in humans as a pulmonary marker measurable not only in bronchoalveolar lavage fluid (BALF) but also in serum. The aim of the present study was to investigate the changes and determinants of CC16 concentrations in these fluids in normal rats and rats with lung injury. Female Sprague-Dawley rats were given a single i.p. injection of arachis oil (n=20) or chemicals in arachis oil (n=10) that mainly damage Clara cells (4-ipomeanol (IPO) 8 mg x kg(-1) and Methylcyclopentadienyl Manganese Tricarbonyl (MMT) 5 mg x kg(-1)) or endothelial cells (alpha-naphthylthiourea (ANTU) 5 mg x kg(-1)). CC16 concentration (mean+/-sD in microg x L(-1)), measured by a sensitive latex immunoassay, was significantly reduced in BALF of all treated groups (IPO 380+/-100; MMT 730+/-200; ANTU 1,070+/-200; controls 1,700+/-470). The same pattern of decrease was observed in the labelling of Clara cells with an anti-CC16 antiserum as well as in the CC16 messenger ribonucleic acid levels assessed by Northern enzyme-linked immunosorbent assay. In serum, by contrast, CC16 was significantly increased in all treated groups (IPO 31+/-7; MMT 22+/-12; ANTU 52+/-24; controls 15+/-6). This rise of CC16 in serum was associated with an elevation of albumin in BALF which is an index of increased bronchoalveolar/blood barrier permeability. In conclusion, lung injury induces a decrease of the 16 kDa Clara cell protein in bronchoalveolar lavage fluid owing to a reduced production by damaged Clara cells, and an increase in serum protein levels resulting from its enhanced leakage across the bronchoalveolar/blood barrier. This study provides new insights into the understanding of the changes of lung secretory proteins in bronchoalveolar lavage fluid and serum.

  • quantification of clara cell protein in rat and mouse biological fluids using a sensitive immunoassay
    European Respiratory Journal, 1998
    Co-Authors: Tadeusz Halatek, Murielle Wiedig, Gerard Toubeau, Paul Falmagne, F Broeckaert, Cédric Hermans, Ruddy Wattiez, Alfred Bernard
    Abstract:

    Clara cell protein is a 16-17 kDa protein (CC16) secreted by Clara cells in the bronchiolar lining fluid of the lung. In order to investigate the potential of this protein as a pulmonary marker in animals, CC16 was isolated from rat bronchoalveolar lavage fluid (BALF) and a sensitive latex immunoassay applicable to both rat and mouse CC16 was developed. The pattern of CC16 concentrations in rat biological fluids determined by the immunoassay was consistent with the hypothesis of a passive diffusion of the protein across the bronchoalveolar/blood barriers showing a difference of more than 5,000 fold between the concentration in the epithelial lining fluid (mean, 140 mg x L(-1)) and that in serum (20 microg x L(-1)) or urine (3 microg x L(-1)). In BALF, the CC16 concentration averaged 5,500 microg x L(-1) and was of the same magnitude as that determined on lung and trachea homogenates. CC16 was also detectable in amniotic fluid with a mean value of 800 microg x L(-1) before delivery. Damage of Clara cells produced by Methylcyclopentadienyl Manganese Tricarbonyl resulted in a significant decrease of CC16 in BALF but did not affect the serum levels of the protein. The nephrotoxicant sodium chromate by contrast had no influence on the CC16 content of BALF but markedly increased CC16 levels in both serum and urine as a result of impaired glomerular filtration and tubular reabsorption, respectively. In conclusion, mouse or rat Clara cell protein of 16-17 kDa can easily be quantified, not only in bronchoalveolar lavage fluid, but also in extrapulmonary fluids such as serum or urine. Thus, in rodents, Clara cell protein of 16-17 kDa follows the same metabolic pathway as in humans, diffusing from the respiratory tract into serum where it is eliminated by the kidneys. This serum Clara cell protein of 16-17 kDa may be useful as a peripheral marker of events taking place in the respiratory tract.

Cédric Hermans - One of the best experts on this subject based on the ideXlab platform.

  • clara cell protein as a marker of clara cell damage and bronchoalveolar blood barrier permeability
    European Respiratory Journal, 1999
    Co-Authors: Cédric Hermans, Murielle Wiedig, K Arsalane, Gerard Toubeau, Paul Falmagne, Bernard Knoops, Alfred Bernard
    Abstract:

    The 16 kDa Clara cell protein (CC16), an abundant component of airway secretions, has recently been proposed in humans as a pulmonary marker measurable not only in bronchoalveolar lavage fluid (BALF) but also in serum. The aim of the present study was to investigate the changes and determinants of CC16 concentrations in these fluids in normal rats and rats with lung injury. Female Sprague-Dawley rats were given a single i.p. injection of arachis oil (n=20) or chemicals in arachis oil (n=10) that mainly damage Clara cells (4-ipomeanol (IPO) 8 mg x kg(-1) and Methylcyclopentadienyl Manganese Tricarbonyl (MMT) 5 mg x kg(-1)) or endothelial cells (alpha-naphthylthiourea (ANTU) 5 mg x kg(-1)). CC16 concentration (mean+/-sD in microg x L(-1)), measured by a sensitive latex immunoassay, was significantly reduced in BALF of all treated groups (IPO 380+/-100; MMT 730+/-200; ANTU 1,070+/-200; controls 1,700+/-470). The same pattern of decrease was observed in the labelling of Clara cells with an anti-CC16 antiserum as well as in the CC16 messenger ribonucleic acid levels assessed by Northern enzyme-linked immunosorbent assay. In serum, by contrast, CC16 was significantly increased in all treated groups (IPO 31+/-7; MMT 22+/-12; ANTU 52+/-24; controls 15+/-6). This rise of CC16 in serum was associated with an elevation of albumin in BALF which is an index of increased bronchoalveolar/blood barrier permeability. In conclusion, lung injury induces a decrease of the 16 kDa Clara cell protein in bronchoalveolar lavage fluid owing to a reduced production by damaged Clara cells, and an increase in serum protein levels resulting from its enhanced leakage across the bronchoalveolar/blood barrier. This study provides new insights into the understanding of the changes of lung secretory proteins in bronchoalveolar lavage fluid and serum.

  • quantification of clara cell protein in rat and mouse biological fluids using a sensitive immunoassay
    European Respiratory Journal, 1998
    Co-Authors: Tadeusz Halatek, Murielle Wiedig, Gerard Toubeau, Paul Falmagne, F Broeckaert, Cédric Hermans, Ruddy Wattiez, Alfred Bernard
    Abstract:

    Clara cell protein is a 16-17 kDa protein (CC16) secreted by Clara cells in the bronchiolar lining fluid of the lung. In order to investigate the potential of this protein as a pulmonary marker in animals, CC16 was isolated from rat bronchoalveolar lavage fluid (BALF) and a sensitive latex immunoassay applicable to both rat and mouse CC16 was developed. The pattern of CC16 concentrations in rat biological fluids determined by the immunoassay was consistent with the hypothesis of a passive diffusion of the protein across the bronchoalveolar/blood barriers showing a difference of more than 5,000 fold between the concentration in the epithelial lining fluid (mean, 140 mg x L(-1)) and that in serum (20 microg x L(-1)) or urine (3 microg x L(-1)). In BALF, the CC16 concentration averaged 5,500 microg x L(-1) and was of the same magnitude as that determined on lung and trachea homogenates. CC16 was also detectable in amniotic fluid with a mean value of 800 microg x L(-1) before delivery. Damage of Clara cells produced by Methylcyclopentadienyl Manganese Tricarbonyl resulted in a significant decrease of CC16 in BALF but did not affect the serum levels of the protein. The nephrotoxicant sodium chromate by contrast had no influence on the CC16 content of BALF but markedly increased CC16 levels in both serum and urine as a result of impaired glomerular filtration and tubular reabsorption, respectively. In conclusion, mouse or rat Clara cell protein of 16-17 kDa can easily be quantified, not only in bronchoalveolar lavage fluid, but also in extrapulmonary fluids such as serum or urine. Thus, in rodents, Clara cell protein of 16-17 kDa follows the same metabolic pathway as in humans, diffusing from the respiratory tract into serum where it is eliminated by the kidneys. This serum Clara cell protein of 16-17 kDa may be useful as a peripheral marker of events taking place in the respiratory tract.