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Christian Bronner - One of the best experts on this subject based on the ideXlab platform.
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aronia melanocarpa juice induces a redox sensitive p73 related caspase 3 dependent apoptosis in human leukemia Cells
PLOS ONE, 2012Co-Authors: Tanveer Sharif, Mahmoud Alhosin, Cyril Auger, Carole Minker, Jonghun Kim, Nelly Etienneselloum, Pierre Bories, Hinrich Gronemeyer, Annelise Lobstein, Christian BronnerAbstract:Polyphenols are natural compounds widely present in fruits and vegetables, which have antimutagenic and anticancer properties. The aim of the present study was to determine the anticancer effect of a polyphenol-rich Aronia melanocarpa juice (AMJ) containing 7.15 g/L of polyphenols in the acute lymphoblastic leukemia Jurkat Cell Line, and, if so, to clarify the underlying mechanism and to identify the active polyphenols involved. AMJ inhibited Cell proliferation, which was associated with Cell cycle arrest in G(2)/M phase, and caused the induction of apoptosis. These effects were associated with an upregulation of the expression of tumor suppressor p73 and active caspase 3, and a downregulation of the expression of cyclin B1 and the epigenetic integrator UHRF1. AMJ significantly increased the formation of reactive oxygen species (ROS), decreased the mitochondrial membrane potential and caused the release of cytochrome c into the cytoplasm. Treatment with intraCellular ROS scavengers prevented the AMJ-induced apoptosis and upregulation of the expression of p73 and active caspase 3. The fractionation of the AMJ and the use of identified isolated compounds indicated that the anticancer activity was associated predominantly with chlorogenic acids, some cyanidin glycosides, and derivatives of quercetin. AMJ treatment also induced apoptosis of different human lymphoblastic leukemia Cells (HSB-2, Molt-4 and CCRF-CEM). In addition, AMJ exerted a strong pro-apoptotic effect in human primary lymphoblastic leukemia Cells but not in human normal primary T-lymphocytes. Thus, the present findings indicate that AMJ exhibits strong anticancer activity through a redox-sensitive mechanism in the p53-deficient Jurkat Cells and that this effect involves several types of polyphenols. They further suggest that AMJ has chemotherapeutic properties against acute lymphoblastic leukemia by selectively targeting lymphoblast-derived tumor Cells.
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Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia Cell apoptosis.
Cellular signalling, 2010Co-Authors: Abdurazzag Abusnina, Christian Bronner, Mahmoud Alhosin, Guy Fuhrmann, Thérèse Keravis, Christian D. Muller, Claire LugnierAbstract:Thymoquinone (TQ), the active principle of Nigella sativa black seeds, has anti-proliferative properties on numerous cancer Cell types. Others and we have previously reported that TQ acts as agent that triggers Cell cycle arrest and apoptosis through either a p53- or p73-dependent pathway. However, the immediate targets recruited upon TQ-induced cytotoxicity have not yet been clearly identified. We therefore asked whether cyclic nucleotide phosphodiesterases (PDEs) could be involved in TQ-triggered pro-apoptotic reactivity; PDEs are regulators of intraCellular levels of cyclic nucleotides and therefore can modulate cAMP and cGMP-dependent Cell death pathways. Our results showed that TQ specifically repressed PDE1A expression in the acute lymphoblastic leukemia Jurkat Cell Line. This effect is concomitant with the previously described sequential deregulation of the expression of the tumor suppressor protein p73 and the epigenetic integrator UHRF1 (Ubiquitin-like, PHD Ring Finger 1). Interestingly, RNA-interference knock-down of PDE1A expression as well as decreased PDE1A expression induced growth inhibition of Jurkat Cells, Cell cycle arrest and apoptosis through an activation of p73 and a repression of UHRF1. Conversely, PDE1A re-expression counteracted the Cellular pro-apoptotic effects of TQ in association with a p73 repression and UHRF1 re-expression. Altogether, our results show that TQ induced an initial down-regulation of PDE1A with a subsequent down-regulation of UHRF1 via a p73-dependent mechanism. This study further proposes that PDE1A might be involved in the epigenetic code inheritance by regulating, via p73, the epigenetic integrator UHRF1. Our findings also suggest that a forced inhibition of PDE1A expression might be a new therapeutic strategy for the management of acute lymphoblastic leukemia.
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Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat Cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1
Biochemical Pharmacology, 2010Co-Authors: Mahmoud Alhosin, Mayada Achour, Thierry Chataigneau, Tanveer Sharif, Abdurazzag Abusnina, Christian Muller, Jean Peluso, Claire Lugnier, Valérie B. Schini-kerth, Christian BronnerAbstract:The salvage anti-tumoral pathway which implicates the p53-related gene is not yet fully characterized. We therefore attempted to identify the up- and down-stream events involved in the activation of the p73-dependent pro-apoptotic pathway, by focusing on the anti-apoptotic and epigenetic integrator UHRF1 which is essential for Cell cycle progression. For this purpose, we analyzed the effects of a known anti-neoplastic drug, thymoquinone (TQ), on the p53-deficient acute lymphoblastic leukemia (ALL) Jurkat Cell Line. Our results showed that TQ inhibits the proliferation of Jurkat Cells and induces G1 Cell cycle arrest in a dose-dependent manner. Moreover, TQ treatment triggers programmed Cell death, production of reactive oxygen species (ROS) and alteration of the mitochondrial membrane potential (ΔΨm). TQ-induced apoptosis, confirmed by the presence of hypodiploid G0/G1 Cells, is associated with a rapid and sharp re-expression of p73 and dose-dependent changes of the levels of caspase-3 cleaved subunits. These modifications are accompanied by a dramatic down-regulation of UHRF1 and two of its main partners, namely DNMT1 and HDAC1, which are all involved in the epigenetic code regulation. Knockdown of p73 expression restores UHRF1 expression, reactivates Cell cycle progression and inhibits TQ-induced apoptosis. Altogether our results showed that TQ mediates its growth inhibitory effects on ALL p53-mutated Cells via the activation of a p73-dependent mitochondrial and Cell cycle checkpoint signaling pathway which subsequently targets UHRF1.
Ad A C M Peijnenburg - One of the best experts on this subject based on the ideXlab platform.
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transcriptome analysis of the human t lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells exposed to deoxynivalenol don new mechanistic insights
Toxicology and Applied Pharmacology, 2012Co-Authors: Madhumohan R Katika, Peter J M Hendriksen, Jia Shao, Henk Van Loveren, Ad A C M PeijnenburgAbstract:Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid Cells. For this, we exposed the human T-lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat Cells were exposed to 0.25 and 0.5μM DON for 3, 6 and 24h. Biological interpretation of the microarray data indicated that DON affects various processes in these Cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-κB/TNF-α pathways, T Cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T Cell activation and apoptosis. Induction of T Cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, Cells were exposed to 2 and 4μM DON for 6 and 24h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat Cell Line were also affected in the PBMCs.
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transcriptome analysis of the human t lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells exposed to deoxynivalenol don new mechanistic insights
Toxicology and Applied Pharmacology, 2012Co-Authors: Madhumohan R Katika, Peter J M Hendriksen, Henk Van Loveren, Jia Shao, Ad A C M PeijnenburgAbstract:Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid Cells. For this, we exposed the human T-lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat Cells were exposed to 0.25 and 0.5 mu M DON for 3, 6 and 24 h. Biological interpretation of the microarray data indicated that DON affects various processes in these Cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-kappa B/TNF-alpha pathways, T Cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T Cell activation and apoptosis. Induction of T Cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, Cells were exposed to 2 and 4 mu M DON for 6 and 24 h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat Cell Line were also affected in the PBMCs. (C) 2012 Elsevier Inc. All rights reserved.
Jia Shao - One of the best experts on this subject based on the ideXlab platform.
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transcriptome analysis of the human t lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells exposed to deoxynivalenol don new mechanistic insights
Toxicology and Applied Pharmacology, 2012Co-Authors: Madhumohan R Katika, Peter J M Hendriksen, Jia Shao, Henk Van Loveren, Ad A C M PeijnenburgAbstract:Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid Cells. For this, we exposed the human T-lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat Cells were exposed to 0.25 and 0.5μM DON for 3, 6 and 24h. Biological interpretation of the microarray data indicated that DON affects various processes in these Cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-κB/TNF-α pathways, T Cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T Cell activation and apoptosis. Induction of T Cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, Cells were exposed to 2 and 4μM DON for 6 and 24h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat Cell Line were also affected in the PBMCs.
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transcriptome analysis of the human t lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells exposed to deoxynivalenol don new mechanistic insights
Toxicology and Applied Pharmacology, 2012Co-Authors: Madhumohan R Katika, Peter J M Hendriksen, Henk Van Loveren, Jia Shao, Ad A C M PeijnenburgAbstract:Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid Cells. For this, we exposed the human T-lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat Cells were exposed to 0.25 and 0.5 mu M DON for 3, 6 and 24 h. Biological interpretation of the microarray data indicated that DON affects various processes in these Cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-kappa B/TNF-alpha pathways, T Cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T Cell activation and apoptosis. Induction of T Cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, Cells were exposed to 2 and 4 mu M DON for 6 and 24 h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat Cell Line were also affected in the PBMCs. (C) 2012 Elsevier Inc. All rights reserved.
Yewmin Tzeng - One of the best experts on this subject based on the ideXlab platform.
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cytotoxic constituents from andrographis paniculata induce Cell cycle arrest in Jurkat Cells
Phytotherapy Research, 2008Co-Authors: Madamanchi Geethangili, Yerra Koteswara Rao, Shihhua Fang, Yewmin TzengAbstract:Herbal medicines are now attracting attention as potential sources of anticancer agents. Andrographis paniculata is a traditionally used anticancer herb in Indian and Chinese herbal medicine. Phytochemical investigation of the ethanol extract of the aerial parts of this herb resulted in the isolation of 14 compounds including flavonoids and labdane diterpenoids. This is the first isolation of compound 6 from a natural source, and the aerial parts of A. paniculata are a rich source for the molecule andrographolide (9, 1.375%, w/w). The structures of the isolated compounds were established by means of spectral data. The cytotoxic activities of these isolates were evaluated against Jurkat, PC-3, HepG2 and Colon 205 tumor Cells, and normal Cells PBMCs. The bioactivity assays showed that metabolites 1–4 and 6–8 exhibited moderate cytotoxic activity against Jurkat, PC-3 and Colon 205 Cell Lines, where compound 6 had IC50 values of 0.05, 0.07 and 0.05 mm, respectively. Further, among these effective compounds, 3 and 6 selectively blocked the Cell cycle progression at G0/G1, while 1, 2, 4, 7 and 8 blocked the same at G2/M phase of the Jurkat Cell Line. This is the first Cell cycle analysis for the above mentioned isolates on the Jurkat Cells. Therefore, these plant-derived compounds may play a role in the prevention and/or management of cancer. Copyright © 2008 John Wiley & Sons, Ltd.
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cytotoxic constituents from andrographis paniculata induce Cell cycle arrest in Jurkat Cells
Phytotherapy Research, 2008Co-Authors: Madamanchi Geethangili, Yerra Koteswara Rao, Shihhua Fang, Yewmin TzengAbstract:Herbal medicines are now attracting attention as potential sources of anticancer agents. Andrographis paniculata is a traditionally used anticancer herb in Indian and Chinese herbal medicine. Phytochemical investigation of the ethanol extract of the aerial parts of this herb resulted in the isolation of 14 compounds including flavonoids and labdane diterpenoids. This is the first isolation of compound 6 from a natural source, and the aerial parts of A. paniculata are a rich source for the molecule andrographolide (9, 1.375%, w/w). The structures of the isolated compounds were established by means of spectral data. The cytotoxic activities of these isolates were evaluated against Jurkat, PC-3, HepG2 and Colon 205 tumor Cells, and normal Cells PBMCs. The bioactivity assays showed that metabolites 1-4 and 6-8 exhibited moderate cytotoxic activity against Jurkat, PC-3 and Colon 205 Cell Lines, where compound 6 had IC(50) values of 0.05, 0.07 and 0.05 mm, respectively. Further, among these effective compounds, 3 and 6 selectively blocked the Cell cycle progression at G0/G1, while 1, 2, 4, 7 and 8 blocked the same at G2/M phase of the Jurkat Cell Line. This is the first Cell cycle analysis for the above mentioned isolates on the Jurkat Cells. Therefore, these plant-derived compounds may play a role in the prevention and/or management of cancer.
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differential effects of synthesized 2 oxygenated chalcone derivatives modulation of human Cell cycle phase distribution
Bioorganic & Medicinal Chemistry, 2004Co-Authors: Yerra Koteswara Rao, Shihhua Fang, Yewmin TzengAbstract:Ten structurally related 2'-oxygenated chalcone derivatives, bearing either hydroxy and/or methoxy substituents on the A and B rings, were synthesized through Claisen-Schmidt condensation. The synthesis procedure was relatively easy and had an acceptable yield. The in vitro cytotoxicities of these compounds against the human tumor Cells such as Jurkat, U937 Cells, and normal Cells PHA stimulated PBMCs were investigated. Among those, compounds 1 (IC50 = 2.5 microM), 2 (1.7 microM), and 8 (3.2 microM) showed potent inhibitory activity toward Jurkat Cell Line. In parallel, compounds 1 (6.7 microM), 2 (1.5 microM), and 10 (5.3 microM) showed the highest activity against U937 Cell Line. However, the chalcones also inhibit the PHA stimulated PBMCs Cells, but the IC50 values were relatively high when compared to the tumor Cell Line values. Studies were also on the effect of synthesized chalcones on the Cell cycle phase distribution. In Jurkat Cell Line, compounds 7 and 9 showed the highest activity and the most striking effect in reduction of the percentage of Cells in the S phase, which was associated with an increase of Cells in G2/M phase. In U937 Cell Line, compound 3 increased the proportion of Cells in the G0/G1 phase and reduced the proportion in S phase. In contrast, compounds 1, 9, and 10 showed a decrease effect on the percentage of Cells in S phase and an increase effect on the percentage of Cells in the G2/M phase of the Cell cycle. Whereas in the case of PHA stimulated PBMCs, compounds 1, 4, 8, and 10 increased the percentage of Cells in G2/M phase, which was associated with a decrease effect in the S phase of the Cell cycle.
Madhumohan R Katika - One of the best experts on this subject based on the ideXlab platform.
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transcriptome analysis of the human t lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells exposed to deoxynivalenol don new mechanistic insights
Toxicology and Applied Pharmacology, 2012Co-Authors: Madhumohan R Katika, Peter J M Hendriksen, Jia Shao, Henk Van Loveren, Ad A C M PeijnenburgAbstract:Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid Cells. For this, we exposed the human T-lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat Cells were exposed to 0.25 and 0.5μM DON for 3, 6 and 24h. Biological interpretation of the microarray data indicated that DON affects various processes in these Cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-κB/TNF-α pathways, T Cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T Cell activation and apoptosis. Induction of T Cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, Cells were exposed to 2 and 4μM DON for 6 and 24h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat Cell Line were also affected in the PBMCs.
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transcriptome analysis of the human t lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells exposed to deoxynivalenol don new mechanistic insights
Toxicology and Applied Pharmacology, 2012Co-Authors: Madhumohan R Katika, Peter J M Hendriksen, Henk Van Loveren, Jia Shao, Ad A C M PeijnenburgAbstract:Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid Cells. For this, we exposed the human T-lymphocyte Cell Line Jurkat and human peripheral blood mononuclear Cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat Cells were exposed to 0.25 and 0.5 mu M DON for 3, 6 and 24 h. Biological interpretation of the microarray data indicated that DON affects various processes in these Cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-kappa B/TNF-alpha pathways, T Cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T Cell activation and apoptosis. Induction of T Cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, Cells were exposed to 2 and 4 mu M DON for 6 and 24 h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat Cell Line were also affected in the PBMCs. (C) 2012 Elsevier Inc. All rights reserved.
