The Experts below are selected from a list of 12183 Experts worldwide ranked by ideXlab platform
Arleen B Rifkind - One of the best experts on this subject based on the ideXlab platform.
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aryl hydrocarbon receptor activation by dioxin targets phosphoenolpyruvate carboxykinase pepck for adp ribosylation via 2 3 7 8 tetrachlorodibenzo p dioxin tcdd inducible poly adp ribose polymerase tiparp
Journal of Biological Chemistry, 2013Co-Authors: Silvia Dianimoore, Sheng Zhang, Arleen B RifkindAbstract:Abstract Effects of the Environmental Toxin and carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) include a wasting syndrome associated with decreased gluconeogenesis. TCDD is a potent activator of the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. The relationship between gene activation by the AHR and TCDD toxicities is not well understood. We recently identified a pathway by which the AHR target gene TiPARP (TCDD-inducible poly(ADP-ribose) polymerase) contributes to TCDD suppression of transcription of phosphoenolpyruvate carboxykinase (PEPCK), a key regulator of gluconeogenesis, by consuming NAD+ and decreasing Sirtuin 1 activation of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), a transcriptional activator of PEPCK. We report here that TCDD-induced TiPARP also targets PEPCK for ADP-ribosylation. Both cytosolic and mitochondrial forms of PEPCK were found to undergo ADP-ribosylation. Unexpectedly, AHR suppression also enhanced ADP-ribosylation and did so by a poly(ADP-ribose) polymerase-independent mechanism. This report 1) identifies ADP-ribosylation as a new posttranslational modification for PEPCK, 2) describes a pathway by which transcriptional induction of TiPARP by the AHR can lead to a downstream posttranslational change in a TCDD target protein (PEPCK), and 3) reveals that the AHR exerts complex, previously unidentified modulatory effects on ADP-ribosylation.
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identification of the aryl hydrocarbon receptor target gene tiparp as a mediator of suppression of hepatic gluconeogenesis by 2 3 7 8 tetrachlorodibenzo p dioxin and of nicotinamide as a corrective agent for this effect
Journal of Biological Chemistry, 2010Co-Authors: Silvia Dianimoore, Xintian Li, Dou Yeon Youn, Anthony A Sauve, Prosenjit Mondal, Arleen B RifkindAbstract:Abstract The Environmental Toxin TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, dioxin) produces diverse toxic effects including a lethal wasting syndrome whose hallmark is suppressed hepatic gluconeogenesis. All TCDD toxicities require activation of the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. While the mechanism for AHR induction of target genes is well understood, it is not known how AHR activation produces any TCDD toxicity. This report identifies for the first time an AHR target gene, TiPARP (TCDD-inducible poly(ADP-ribose) polymerase, PARP7), that can mediate a TCDD toxicity, i.e. suppression of hepatic gluconeogenesis. TCDD suppressed hepatic glucose production, expression of key gluconeogenic genes, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and NAD+ levels, and increased PARP activity and TiPARP expression. TCDD also increased acetylation and ubiquitin-dependent proteosomal degradation of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), a coactivator of PEPCK and G6Pase transcription. TiPARP overexpression reproduced TCDD effects on glucose output and NAD+ levels while TiPARP silencing diminished them. TiPARP overexpression also increased PGC1α acetylation and decreased PGC1α levels. In contrast, silencing of cytochromes P450 (CYP) 1A, main AHR induced genes, did not alter TCDD suppression of gluconeogenesis. The vitamin B3 constituent, nicotinamide (NAM), prevented TCDD suppression of glucose output, NAD+, and gluconeogenic genes and stabilized PGC1α. The corrective effects of NAM could be attributed to increased NAD+ levels and suppression of AHR target gene induction. The results reveal that TiPARP can mediate a TCDD effect, that the AHR is linked to PGC1α function and stability and that NAM has novel AHR antagonist activity.
Patrick Cadet - One of the best experts on this subject based on the ideXlab platform.
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A novel pathway by which the Environmental Toxin 4-Nonylphenol may promote an inflammatory response in inflammatory bowel disease
Medical Science Monitor Basic Research, 2014Co-Authors: Albert Kim, Byeong Ho Jung, Patrick CadetAbstract:Background 4-Nonylphenol is a ubiquitous Environmental Toxin that is formed as a byproduct in the manufacturing and/or sewage treatment of regular household items. Previous work in our lab has implicated 4-NP in the progression of autoimmune diseases such as inflammatory bowel disease in which macrophages mistakenly attack the intestinal linings, causing chronic inflammation. Several key pro-and anti-inflammatory molecules have been shown to be involved in the manifestation of this disease, including IL-23A, COX-2, IL-8, TLR-4, and IL-10.
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Environmental Toxin 4 nonylphenol and autoimmune diseases using dna microarray to examine genetic markers of cytokine expression
Archives of Medical Science, 2010Co-Authors: Celline Kim, Patrick CadetAbstract:Introduction Adverse progression of autoimmune diseases is linked to the dysregulation of cytokines. In this regard we investigated the role of 4-nonylphenol (4-NP), as a potential contributing factor in the development of immune diseases and compared it to estrogens actions since 4-NP may work via estrogen processes. Material and methods The study made cytokine level expression changes in U937 cells by microarray technology coupled to RT PCR as a validating technique. Results It was determined that 4-NP significantly up-regulated proinflammatory cytokine expression (toll-like-receptor [TLR]-6, TLR-10, interleukin [IL]-1, IL-5, IL-6, IL-17C, IL-23A, IL-8RB, IL-receptor-associated-kinase [IRAK-2], tumor-necrosis-factor-receptor [TNFR]-5, and TNFR-10). Estrogen caused insignificant increases but the changes parralelled that of 4-NP. Simultaneously, 4-NP down-regulated the expression of anti-inflammatory cytokines (IL-4 and IL-10), while estrogen up-regulated them. Conclusions 4-Nonylphenol may initiate its toxic effects and pose a risk to autoimmunity-prone individuals by eliciting effects up to 4 times more potent than estrogen. Overall, exposure to 4-NP may contribute to autoimmune susceptibility and/or exacerbate existing autoimmune conditions by dys-regulating normal expression of cytokines.
Nicholas A Kotov - One of the best experts on this subject based on the ideXlab platform.
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side by side and end to end gold nanorod assemblies for Environmental Toxin sensing
Angewandte Chemie, 2010Co-Authors: Libing Wang, Liguang Xu, Wei Chen, Hua Kuang, Ashish Agarwal, Chuanlai Xu, Nicholas A KotovAbstract:Controllable assembly of nanoscale building blocks (monomers) is a necessary part of practical realization of the unique optical, electrical, magnetic, and chemical properties of nanoscale matter in macroscale materials. Such assemblies also contain much fundamental information about collective behavior of nanocolloids, which we are just beginning to understand. The key decisive factors for the successful assembly of nanocolloids is the anisotropy of nanoscale interactions, which stems from both the shape of nanocolloids and unequal distribution of organic molecules on their surface. Gold nanorods (Au NRs) have both geometrical and chemical anisotropy components and demonstrate strong optical extinction in the range of visible and near-infrared (NIR) wavelengths convenient for both research and practical purposes. Au NRs can be assembled by interactions with organic molecules, polymers, an antibody–antigen reaction, biotin–strepavidin connectors, and DNA, leading to superstructures with different degree of organization and complexity of collective behavior. Besides the utilization of NR monomers in non-linear optics, cellular imaging, and cancer therapy, optical effects corresponding to monomer!superstructure transitions allowed preparation of excellent biosensors because of large changes in oscillation frequencies of plasmons when NR pairs are formed. These studies mostly targeted biomedical applications. Simultaneously, their unique sensing capabilities have been virtually unexplored for the needs of Environmental detection and monitoring. These challenges and impact can equal or exceed those encountered in detection of cancer. A better understanding of methods for the realization of speed/selectivity/sensitivity detection of common Environmental pollutants is thus of great importance. Therefore, we decided to explore the potential of NR assemblies taking a pervasive Environmental Toxin, namely microcystin-LR (MC-LR), as the model while also addressing the general questions about the choice of different assembly motif for different sensing tasks. MC-LR is common in both developed and developing countries, with recorded cases of mass poisoning. MC-LR originates from common bluegreen algae and causes rapid liver failure; prolonged exposure to small concentrations of MC-LR in drinking water causes liver cancer. Herein, we describe the successful use of Au NRs for detection of MC-LR, which is significantly more sensitive than the traditional techniques, such as ELISA, yielding detection limit of 5 pgmL . It is also much simpler and faster than any other methods. These two factors are critical for Environmental monitoring and have been a long-standing challenge. The pattern of the assembly strongly affects the sensitivity parameters for MC-LR detection. To realize different modes of assembly, such as side-byside and end-to-end motifs, with a degree of control sufficient for conclusive evaluation of sensing implications, two kinds of protein-carrying Au NRs were synthesized (Figure 1). One type of NR carried MC-LR antibodies (ABs) preferentially on the sides, while the other type carried antibodies located almost exclusively in the ends. These motifs were formed by using either electrostatic binding or covalent attachment of the antibodies mediated by a bifinctional linker, thioctic acid (TA).When electrostatic forces govern the placement of ABs, they attach primarily to the sides of NRs due to the larger area of contact and thus stronger electrostatic interactions. When a TA anchor covalently binds by a S Au bond, the conjugation of the ABs occurs predominantly in the ends of the rods due to better accessibility of the gold surface to the reactive thiol end. Variation of pH also allows varying repulsion or attraction of NRs and MC-LR, modality of attachment, and geometrical characteristics of assemblies (see the Supporting Information). The number of AB molecules on the surface of one Au NR was estimated to be 31 and 10 for the side-by-side [*] L. Wang, Y. Zhu, L. Xu, Dr. W. Chen, H. Kuang, L. Liu, Prof. C. Xu School of Food Science and Technology, State Key Laboratory of Food Science and Technology Jiangnan University, Wuxi, 214122 (China) E-mail: xcl@jiangnan.edu.cn Dr. W. Chen, A. Agarwal, Prof. N. A. Kotov Department of Chemical Engineering, Department of Biomedical Engineering Department of Materials Science and Engineering University of Michigan, Ann Arbor, MI 48109 (USA) E-mail: kotov@umich.edu [] These authors contributed equally to this paper.
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simple rapid sensitive and versatile swnt paper sensor for Environmental Toxin detection competitive with elisa
Nano Letters, 2009Co-Authors: Libing Wang, Wei Che, Ong Sup Shim, Yingyue Zhu, Liqiang Liu, Chifang Peng, Nicholas A KotovAbstract:Safety of water was for a long time and still is one of the most pressing needs for many countries and different communities. Despite the fact that there are potentially many methods to evaluate water safety, finding a simple, rapid, versatile, and inexpensive method for detection of Toxins in everyday items is still a great challenge. In this study, we extend the concept of composites, impregnated porous fibrous materials, such as fabrics and papers, by single-walled carbon nanotubes (SWNTs), toward very simple but high-performance biosensors. They utilize the strong dependence of electrical conductivity through nanotubes percolation network on the width of nanotube-nanotube tunneling gap and can potentially satisfy all the requirements outlined above for the routine Toxin monitoring. An antibody to the microcystin-LR (MC-LR), one of the common culprits in mass poisonings, was dispersed together with SWNTs. This dispersion was used to dip-coat the paper rendering it conductive. The change in conductivity of the paper was used to sense the MC-LR in the water rapidly and accurately. The method has the linear detection range up to 10 nmol/L and nonlinear detection up to 40 nmol/L. The limit of detection was found to be 0.6 nmol/L (0.6 ng/mL), which satisfies the strictest World Health Organization standard for MC-LR content in drinking water (1 ng/mL) and is comparable to the detection limit of the traditional ELISA method of MC-LR detection, while drastically reducing the time of analysis by more than an order of magnitude, which is one of the major hurdles in practical applications. Similar technology of sensor preparation can also be used for a variety of other rapid Environmental sensors.
Oskar Karlsson - One of the best experts on this subject based on the ideXlab platform.
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high resolution metabolite imaging in the hippocampus following neonatal exposure to the Environmental Toxin bmaa using tof sims
ACS Chemical Neuroscience, 2014Co-Authors: Jorg Hanrieder, Eva B. Brittebo, Lorenz Gerber, Asa Persson Sandelius, Andrew G Ewing, Oskar KarlssonAbstract:The Environmental neuroToxin beta-N-methylamino-L-alanine (BMAA) is suggested to be linked with neurodegenerative disease. In a rat model, neonatal exposure to BMAA induced selective uptake in the hippocampus and caused cell loss, mineralization and astrogliosis as well as learning and memory impairments in adulthood. Moreover, neonatal exposure resulted in increased protein ubiquitination in the cornus ammonis 1 (CA1) region of the adult hippocampus indicating that BMAA may induce protein aggregation. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) based imaging is a powerful technology for spatial profiling of small molecular weight compounds in biological tissues with high chemical specificity and high spatial resolution. The aim of this study was to characterize neurochemical changes in the hippocampus of six month-old rats treated neonatally (postnatal days 9-10) with BMAA. Multivariate data analysis of whole section ToF-SIMS scans was performed to delineate anatomical regions of interest based on their chemical distribution pattern. Further analysis of spectral data obtained from the outlined anatomical regions, including CA1 and dentate gyms (DG) revealed BMAA-induced long-term changes. Increased levels of phospholipids and protein fragments in the histopathologically altered CA1 region as well as phosphate depletion in the DG were observed. Moreover, high resolution SIMS imaging revealed a specific localization of phosphatidylcholine lipids, protein signals and potassium in the histopathologically altered CA1 These findings demonstrate that ToF-SIMS based imaging is a powerful approach for probing biochemical changes in situ and might serve as promising technique for investigating neuroToxin-induced brain pathology.
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early hippocampal cell death and late learning and memory deficits in rats exposed to the Environmental Toxin bmaa β n methylamino l alanine during the neonatal period
Behavioural Brain Research, 2011Co-Authors: Oskar Karlsson, Anna-lena Berg, Erika Roman, Eva B. BritteboAbstract:Many cyanobacteria are reported to produce the nonprotein amino acid β-N-methylamino-L-alanine (BMAA). Cyanobacteria are extensively distributed in terrestrial and aquatic environments and recently BMAA was detected in temperate aquatic ecosystems, e.g. the Baltic Sea. Little is known about developmental effects of the mixed glutamate receptor agonist BMAA. Brain development requires an optimal level of glutamate receptor activity as the glutamatergic system modulates many vital neurodevelopmental processes. The aim of this thesis was to investigate the developmental neurotoxicity of BMAA, and its interaction with the pigment melanin. Autoradiography was utilized to determine the tissue distribution of 3H-labelled BMAA in experimental animals. Behavioral studies and histological techniques were used to study short and long-term changes in the brain following neonatal exposure to BMAA. Long-term changes in protein expression in the brain was also investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS). A notable targeting of 3H-BMAA to discrete brain regions e.g. hippocampus and striatum in mouse fetuses and neonates was determined by autoradiography. BMAA treatment of neonatal rats on postnatal days 9–10 induced acute but transient ataxia and hyperactivity. Postnatal exposure to BMAA also gave rise to reduced spatial learning and memory abilities in adulthood. Neonatal rat pups treated with BMAA at 600 mg/kg showed early neuronal cell death in the hippocampus, retrosplenial and cingulate cortices. In adulthood the CA1 region of the hippocampus displayed neuronal loss and astrogliosis. Lower doses of BMAA (50 and 200 mg/kg) caused impairments in learning and memory function without any acute or long-term morphological changes in the brain. The MALDI IMS studies, however, revealed changes in protein expression in the hippocampus and striatum suggesting more subtle effects on neurodevelopmental processes. The studies also showed that BMAA was bound and incorporated in melanin and neuromelanin, suggesting that pigmented tissues such as in the substantia nigra and eye may be sequestering BMAA. In conclusion, the findings in this thesis show that BMAA is a developmental neuroToxin in rodents. The risks posed by BMAA as a potential human neuroToxin merits further consideration, particularly if the proposed biomagnifications in the food chain are confirmed.
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LONG-TERM MORPHOLOGICAL AND PROTEIN CHANGES IN THE BRAIN OF ADULT RATS NEONATALLY TREATED WITH THE Environmental Toxin β-N-METHYLAMINO-L-ALANINE (BMAA)
2011Co-Authors: Oskar Karlsson, Anna-lena Berg, Gunnel Arnerup, Erika Roman, Anna-karin Lindström, Jonas Bergquist, Nils Gunnar Lindquist, Malin Andersson, Eva B. BritteboAbstract:LONG-TERM MORPHOLOGICAL AND PROTEIN CHANGES IN THE BRAIN OF ADULT RATS NEONATALLY TREATED WITH THE Environmental Toxin β-N-METHYLAMINO-L-ALANINE (BMAA)
Eva B. Brittebo - One of the best experts on this subject based on the ideXlab platform.
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high resolution metabolite imaging in the hippocampus following neonatal exposure to the Environmental Toxin bmaa using tof sims
ACS Chemical Neuroscience, 2014Co-Authors: Jorg Hanrieder, Eva B. Brittebo, Lorenz Gerber, Asa Persson Sandelius, Andrew G Ewing, Oskar KarlssonAbstract:The Environmental neuroToxin beta-N-methylamino-L-alanine (BMAA) is suggested to be linked with neurodegenerative disease. In a rat model, neonatal exposure to BMAA induced selective uptake in the hippocampus and caused cell loss, mineralization and astrogliosis as well as learning and memory impairments in adulthood. Moreover, neonatal exposure resulted in increased protein ubiquitination in the cornus ammonis 1 (CA1) region of the adult hippocampus indicating that BMAA may induce protein aggregation. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) based imaging is a powerful technology for spatial profiling of small molecular weight compounds in biological tissues with high chemical specificity and high spatial resolution. The aim of this study was to characterize neurochemical changes in the hippocampus of six month-old rats treated neonatally (postnatal days 9-10) with BMAA. Multivariate data analysis of whole section ToF-SIMS scans was performed to delineate anatomical regions of interest based on their chemical distribution pattern. Further analysis of spectral data obtained from the outlined anatomical regions, including CA1 and dentate gyms (DG) revealed BMAA-induced long-term changes. Increased levels of phospholipids and protein fragments in the histopathologically altered CA1 region as well as phosphate depletion in the DG were observed. Moreover, high resolution SIMS imaging revealed a specific localization of phosphatidylcholine lipids, protein signals and potassium in the histopathologically altered CA1 These findings demonstrate that ToF-SIMS based imaging is a powerful approach for probing biochemical changes in situ and might serve as promising technique for investigating neuroToxin-induced brain pathology.
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early hippocampal cell death and late learning and memory deficits in rats exposed to the Environmental Toxin bmaa β n methylamino l alanine during the neonatal period
Behavioural Brain Research, 2011Co-Authors: Oskar Karlsson, Anna-lena Berg, Erika Roman, Eva B. BritteboAbstract:Many cyanobacteria are reported to produce the nonprotein amino acid β-N-methylamino-L-alanine (BMAA). Cyanobacteria are extensively distributed in terrestrial and aquatic environments and recently BMAA was detected in temperate aquatic ecosystems, e.g. the Baltic Sea. Little is known about developmental effects of the mixed glutamate receptor agonist BMAA. Brain development requires an optimal level of glutamate receptor activity as the glutamatergic system modulates many vital neurodevelopmental processes. The aim of this thesis was to investigate the developmental neurotoxicity of BMAA, and its interaction with the pigment melanin. Autoradiography was utilized to determine the tissue distribution of 3H-labelled BMAA in experimental animals. Behavioral studies and histological techniques were used to study short and long-term changes in the brain following neonatal exposure to BMAA. Long-term changes in protein expression in the brain was also investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS). A notable targeting of 3H-BMAA to discrete brain regions e.g. hippocampus and striatum in mouse fetuses and neonates was determined by autoradiography. BMAA treatment of neonatal rats on postnatal days 9–10 induced acute but transient ataxia and hyperactivity. Postnatal exposure to BMAA also gave rise to reduced spatial learning and memory abilities in adulthood. Neonatal rat pups treated with BMAA at 600 mg/kg showed early neuronal cell death in the hippocampus, retrosplenial and cingulate cortices. In adulthood the CA1 region of the hippocampus displayed neuronal loss and astrogliosis. Lower doses of BMAA (50 and 200 mg/kg) caused impairments in learning and memory function without any acute or long-term morphological changes in the brain. The MALDI IMS studies, however, revealed changes in protein expression in the hippocampus and striatum suggesting more subtle effects on neurodevelopmental processes. The studies also showed that BMAA was bound and incorporated in melanin and neuromelanin, suggesting that pigmented tissues such as in the substantia nigra and eye may be sequestering BMAA. In conclusion, the findings in this thesis show that BMAA is a developmental neuroToxin in rodents. The risks posed by BMAA as a potential human neuroToxin merits further consideration, particularly if the proposed biomagnifications in the food chain are confirmed.
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LONG-TERM MORPHOLOGICAL AND PROTEIN CHANGES IN THE BRAIN OF ADULT RATS NEONATALLY TREATED WITH THE Environmental Toxin β-N-METHYLAMINO-L-ALANINE (BMAA)
2011Co-Authors: Oskar Karlsson, Anna-lena Berg, Gunnel Arnerup, Erika Roman, Anna-karin Lindström, Jonas Bergquist, Nils Gunnar Lindquist, Malin Andersson, Eva B. BritteboAbstract:LONG-TERM MORPHOLOGICAL AND PROTEIN CHANGES IN THE BRAIN OF ADULT RATS NEONATALLY TREATED WITH THE Environmental Toxin β-N-METHYLAMINO-L-ALANINE (BMAA)