The Experts below are selected from a list of 140721 Experts worldwide ranked by ideXlab platform
Prasada Rao S Kodavanti - One of the best experts on this subject based on the ideXlab platform.
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aroclor 1254 a developmental neurotoxicant alters energy metabolism and Intracellular Signaling associated protein networks in rat cerebellum and hippocampus
Toxicology and Applied Pharmacology, 2011Co-Authors: Prasada Rao S Kodavanti, Joyce E Royland, Cristina Osorio, Ram Ramabhadran, Oscar AlzateAbstract:The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca{sup 2+}-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit {beta}more » (ATP5B), creatine kinase, and malate dehydrogenase), calcium Signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and Intracellular Signaling, which might result in developmental neurotoxicity. -- Highlights: Black-Right-Pointing-Pointer We performed brain proteomic analysis of rats exposed to the neurotoxicant, Aroclor 1254. Black-Right-Pointing-Pointer Cerebellum and hippocampus were analyzed by 2D DIGE and Mass spectrometry. Black-Right-Pointing-Pointer Proteins affected participate in Energy metabolism, calcium Signaling and nervous system growth.« less
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aroclor 1254 a developmental neurotoxicant alters energy metabolism and Intracellular Signaling associated protein networks in rat cerebellum and hippocampus
Toxicology and Applied Pharmacology, 2011Co-Authors: Prasada Rao S Kodavanti, Joyce E Royland, Cristina Osorio, Ram Ramabhadran, Oscar AlzateAbstract:The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca(2+)-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit β (ATP5B), creatine kinase, and malate dehydrogenase), calcium Signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and Intracellular Signaling, which might result in developmental neurotoxicity.
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differential effects of commercial polybrominated diphenyl ether and polychlorinated biphenyl mixtures on Intracellular Signaling in rat brain in vitro
Toxicological Sciences, 2005Co-Authors: Prasada Rao S Kodavanti, Thomas R WardAbstract:Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and have been detected in human blood, adipose tissue, and breast milk. Developmental and long-term exposures to these contaminants may pose a human health risk, especially to children. Previously, we demonstrated that polychlorinated biphenyls (PCBs), which are neurotoxic and structurally similar to PBDEs, perturbed Intracellular Signaling events, including calcium homeostasis and subsequent events such as protein kinase C (PKC), which are critical for the normal function and development of the nervous system. The objective of the present study was to test whether commercial PBDE mixtures (DE-71, a pentabrominated dipheyl ether mixture, and DE-79, a mostly octabromodiphenyl ether mixture) affected Intracellular Signaling mechanisms in a similar way to that of PCBs and other organohalogens, as an attempt to understand the common mode of action for these persistent chemicals. PKC translocation was studied by determining 3 H-phorbol ester ( 3 H-PDBu) binding in rat cerebellar granule cells, and calcium buffering was determined by measuring 45 Ca 2+ uptake by microsomes and mitochondria isolated from adult male rat brain (frontal cortex, cerebellum, and hippocampus). As seen with PCBs, DE-71 increased PKC translocation and
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differential effects of commercial polybrominated diphenyl ether and polychlorinated biphenyl mixtures on Intracellular Signaling in rat brain in vitro
Toxicological Sciences, 2005Co-Authors: Prasada Rao S Kodavanti, Thomas R WardAbstract:Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and have been detected in human blood, adipose tissue, and breast milk. Developmental and long-term exposures to these contaminants may pose a human health risk, especially to children. Previously, we demonstrated that polychlorinated biphenyls (PCBs), which are neurotoxic and structurally similar to PBDEs, perturbed Intracellular Signaling events, including calcium homeostasis and subsequent events such as protein kinase C (PKC), which are critical for the normal function and development of the nervous system. The objective of the present study was to test whether commercial PBDE mixtures (DE-71, a pentabrominated dipheyl ether mixture, and DE-79, a mostly octabromodiphenyl ether mixture) affected Intracellular Signaling mechanisms in a similar way to that of PCBs and other organohalogens, as an attempt to understand the common mode of action for these persistent chemicals. PKC translocation was studied by determining (3)H-phorbol ester ((3)H-PDBu) binding in rat cerebellar granule cells, and calcium buffering was determined by measuring (45)Ca(2+) uptake by microsomes and mitochondria isolated from adult male rat brain (frontal cortex, cerebellum, and hippocampus). As seen with PCBs, DE-71 increased PKC translocation and inhibited (45)Ca(2+) uptake by both microsomes and mitochondria in a concentration-dependent manner. The effect of DE-71 on (45)Ca(2+) uptake seems to be similar in all three brain regions. Between the two organelles, DE-71 inhibited mitochondrial (45)Ca(2+) uptake to a greater extent than microsomal (45)Ca(2+) uptake. DE-79 had no effects on either neurochemical event even at 30 mug/ml. Aroclor 1254 altered both events to a greater extent compared to DE-71 on a weight basis. When the results were compared on a molar basis, Aroclor 1254 altered PKC translocation and microsomal (45)CaP(2+) uptake to a greater extent than DE-71, however, Aroclor 1254 and DE-71 equally affected mitochondrial (45)Ca(2+) uptake. These results indicate that PBDEs perturbed Intracellular Signaling mechanisms in rat brain as do other organohalogen compounds and the efficacy between the commercial PCB and PBDE mixtures seem to vary with different endpoints.
Robert W Jackman - One of the best experts on this subject based on the ideXlab platform.
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Intracellular Signaling during skeletal muscle atrophy
Muscle & Nerve, 2006Co-Authors: Susan C Kandarian, Robert W JackmanAbstract:A variety of conditions lead to skeletal muscle atrophy including muscle inactivity or disuse, multiple disease states (i.e., cachexia), fasting, and age-associated atrophy (sarcopenia). Given the impact on mobility in the latter conditions, inactivity could contribute in a secondary manner to muscle atrophy. Because different events initiate atrophy in these different conditions, it seems that the regulation of protein loss may be unique in each case. In fact differences exist between the regulation of the various atrophy conditions, especially sarcopenia, as evidenced in part by comparisons of transcriptional profiles as well as by the unique triggering molecules found in each case. By contrast, recent studies have shown that many of the Intracellular Signaling molecules and target genes are similar, particularly among the atrophies related to inactivity and cachexia. This review focuses on the most recent findings related to Intracellular Signaling during muscle atrophy. Key findings are discussed that relate to Signaling involving muscle ubiquitin ligases, the IGF/PI3K/Akt pathway, FOXO activity, caspase-3 activity, and NF-kappaB Signaling, and an attempt is made to construct a unifying picture of how these data can be connected to better understand atrophy. Once more detailed cellular mechanisms of the atrophy process are understood, more specific interventions can be designed for the attenuation of protein loss. Muscle Nerve, 2006
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Intracellular Signaling during skeletal muscle atrophy
Muscle & Nerve, 2006Co-Authors: Susan C Kandarian, Robert W JackmanAbstract:A variety of conditions lead to skeletal muscle atrophy including muscle inactivity or disuse, multiple disease states (i.e., cachexia), fasting, and age-associated atrophy (sarcopenia). Given the impact on mobility in the latter conditions, inactivity could contribute in a secondary manner to muscle atrophy. Because different events initiate atrophy in these different conditions, it seems that the regulation of protein loss may be unique in each case. In fact differences exist between the regulation of the various atrophy conditions, especially sarcopenia, as evidenced in part by comparisons of transcriptional profiles as well as by the unique triggering molecules found in each case. By contrast, recent studies have shown that many of the Intracellular Signaling molecules and target genes are similar, particularly among the atrophies related to inactivity and cachexia. This review focuses on the most recent findings related to Intracellular Signaling during muscle atrophy. Key findings are discussed that relate to Signaling involving muscle ubiquitin ligases, the IGF/PI3K/Akt pathway, FOXO activity, caspase-3 activity, and NF-kappaB Signaling, and an attempt is made to construct a unifying picture of how these data can be connected to better understand atrophy. Once more detailed cellular mechanisms of the atrophy process are understood, more specific interventions can be designed for the attenuation of protein loss.
Thomas R Ward - One of the best experts on this subject based on the ideXlab platform.
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differential effects of commercial polybrominated diphenyl ether and polychlorinated biphenyl mixtures on Intracellular Signaling in rat brain in vitro
Toxicological Sciences, 2005Co-Authors: Prasada Rao S Kodavanti, Thomas R WardAbstract:Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and have been detected in human blood, adipose tissue, and breast milk. Developmental and long-term exposures to these contaminants may pose a human health risk, especially to children. Previously, we demonstrated that polychlorinated biphenyls (PCBs), which are neurotoxic and structurally similar to PBDEs, perturbed Intracellular Signaling events, including calcium homeostasis and subsequent events such as protein kinase C (PKC), which are critical for the normal function and development of the nervous system. The objective of the present study was to test whether commercial PBDE mixtures (DE-71, a pentabrominated dipheyl ether mixture, and DE-79, a mostly octabromodiphenyl ether mixture) affected Intracellular Signaling mechanisms in a similar way to that of PCBs and other organohalogens, as an attempt to understand the common mode of action for these persistent chemicals. PKC translocation was studied by determining 3 H-phorbol ester ( 3 H-PDBu) binding in rat cerebellar granule cells, and calcium buffering was determined by measuring 45 Ca 2+ uptake by microsomes and mitochondria isolated from adult male rat brain (frontal cortex, cerebellum, and hippocampus). As seen with PCBs, DE-71 increased PKC translocation and
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differential effects of commercial polybrominated diphenyl ether and polychlorinated biphenyl mixtures on Intracellular Signaling in rat brain in vitro
Toxicological Sciences, 2005Co-Authors: Prasada Rao S Kodavanti, Thomas R WardAbstract:Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and have been detected in human blood, adipose tissue, and breast milk. Developmental and long-term exposures to these contaminants may pose a human health risk, especially to children. Previously, we demonstrated that polychlorinated biphenyls (PCBs), which are neurotoxic and structurally similar to PBDEs, perturbed Intracellular Signaling events, including calcium homeostasis and subsequent events such as protein kinase C (PKC), which are critical for the normal function and development of the nervous system. The objective of the present study was to test whether commercial PBDE mixtures (DE-71, a pentabrominated dipheyl ether mixture, and DE-79, a mostly octabromodiphenyl ether mixture) affected Intracellular Signaling mechanisms in a similar way to that of PCBs and other organohalogens, as an attempt to understand the common mode of action for these persistent chemicals. PKC translocation was studied by determining (3)H-phorbol ester ((3)H-PDBu) binding in rat cerebellar granule cells, and calcium buffering was determined by measuring (45)Ca(2+) uptake by microsomes and mitochondria isolated from adult male rat brain (frontal cortex, cerebellum, and hippocampus). As seen with PCBs, DE-71 increased PKC translocation and inhibited (45)Ca(2+) uptake by both microsomes and mitochondria in a concentration-dependent manner. The effect of DE-71 on (45)Ca(2+) uptake seems to be similar in all three brain regions. Between the two organelles, DE-71 inhibited mitochondrial (45)Ca(2+) uptake to a greater extent than microsomal (45)Ca(2+) uptake. DE-79 had no effects on either neurochemical event even at 30 mug/ml. Aroclor 1254 altered both events to a greater extent compared to DE-71 on a weight basis. When the results were compared on a molar basis, Aroclor 1254 altered PKC translocation and microsomal (45)CaP(2+) uptake to a greater extent than DE-71, however, Aroclor 1254 and DE-71 equally affected mitochondrial (45)Ca(2+) uptake. These results indicate that PBDEs perturbed Intracellular Signaling mechanisms in rat brain as do other organohalogen compounds and the efficacy between the commercial PCB and PBDE mixtures seem to vary with different endpoints.
Oscar Alzate - One of the best experts on this subject based on the ideXlab platform.
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aroclor 1254 a developmental neurotoxicant alters energy metabolism and Intracellular Signaling associated protein networks in rat cerebellum and hippocampus
Toxicology and Applied Pharmacology, 2011Co-Authors: Prasada Rao S Kodavanti, Joyce E Royland, Cristina Osorio, Ram Ramabhadran, Oscar AlzateAbstract:The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca{sup 2+}-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit {beta}more » (ATP5B), creatine kinase, and malate dehydrogenase), calcium Signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and Intracellular Signaling, which might result in developmental neurotoxicity. -- Highlights: Black-Right-Pointing-Pointer We performed brain proteomic analysis of rats exposed to the neurotoxicant, Aroclor 1254. Black-Right-Pointing-Pointer Cerebellum and hippocampus were analyzed by 2D DIGE and Mass spectrometry. Black-Right-Pointing-Pointer Proteins affected participate in Energy metabolism, calcium Signaling and nervous system growth.« less
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aroclor 1254 a developmental neurotoxicant alters energy metabolism and Intracellular Signaling associated protein networks in rat cerebellum and hippocampus
Toxicology and Applied Pharmacology, 2011Co-Authors: Prasada Rao S Kodavanti, Joyce E Royland, Cristina Osorio, Ram Ramabhadran, Oscar AlzateAbstract:The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca(2+)-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit β (ATP5B), creatine kinase, and malate dehydrogenase), calcium Signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and Intracellular Signaling, which might result in developmental neurotoxicity.
Susan C Kandarian - One of the best experts on this subject based on the ideXlab platform.
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Intracellular Signaling during skeletal muscle atrophy
Muscle & Nerve, 2006Co-Authors: Susan C Kandarian, Robert W JackmanAbstract:A variety of conditions lead to skeletal muscle atrophy including muscle inactivity or disuse, multiple disease states (i.e., cachexia), fasting, and age-associated atrophy (sarcopenia). Given the impact on mobility in the latter conditions, inactivity could contribute in a secondary manner to muscle atrophy. Because different events initiate atrophy in these different conditions, it seems that the regulation of protein loss may be unique in each case. In fact differences exist between the regulation of the various atrophy conditions, especially sarcopenia, as evidenced in part by comparisons of transcriptional profiles as well as by the unique triggering molecules found in each case. By contrast, recent studies have shown that many of the Intracellular Signaling molecules and target genes are similar, particularly among the atrophies related to inactivity and cachexia. This review focuses on the most recent findings related to Intracellular Signaling during muscle atrophy. Key findings are discussed that relate to Signaling involving muscle ubiquitin ligases, the IGF/PI3K/Akt pathway, FOXO activity, caspase-3 activity, and NF-kappaB Signaling, and an attempt is made to construct a unifying picture of how these data can be connected to better understand atrophy. Once more detailed cellular mechanisms of the atrophy process are understood, more specific interventions can be designed for the attenuation of protein loss. Muscle Nerve, 2006
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Intracellular Signaling during skeletal muscle atrophy
Muscle & Nerve, 2006Co-Authors: Susan C Kandarian, Robert W JackmanAbstract:A variety of conditions lead to skeletal muscle atrophy including muscle inactivity or disuse, multiple disease states (i.e., cachexia), fasting, and age-associated atrophy (sarcopenia). Given the impact on mobility in the latter conditions, inactivity could contribute in a secondary manner to muscle atrophy. Because different events initiate atrophy in these different conditions, it seems that the regulation of protein loss may be unique in each case. In fact differences exist between the regulation of the various atrophy conditions, especially sarcopenia, as evidenced in part by comparisons of transcriptional profiles as well as by the unique triggering molecules found in each case. By contrast, recent studies have shown that many of the Intracellular Signaling molecules and target genes are similar, particularly among the atrophies related to inactivity and cachexia. This review focuses on the most recent findings related to Intracellular Signaling during muscle atrophy. Key findings are discussed that relate to Signaling involving muscle ubiquitin ligases, the IGF/PI3K/Akt pathway, FOXO activity, caspase-3 activity, and NF-kappaB Signaling, and an attempt is made to construct a unifying picture of how these data can be connected to better understand atrophy. Once more detailed cellular mechanisms of the atrophy process are understood, more specific interventions can be designed for the attenuation of protein loss.
