The Experts below are selected from a list of 249 Experts worldwide ranked by ideXlab platform
Lei Yixiong - One of the best experts on this subject based on the ideXlab platform.
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a detection of telomerase activity in balb c 3t3 cell transformation induced by three kinds of Nickel Compounds with trap silver staining assay
Modern Preventive Medicine, 1999Co-Authors: Lei YixiongAbstract:In orter to research the genotoxic lesions of Nickel Compounds inducing BALB/c-3T3 cell transformation,telomerase activities in these cells transformed were detected with TRAP-silver staining assay.The results showed that telomerase activities in BALB/c-3T3 cells transformed by Nickel(Ⅱ) sulfide,Nickel chloride and Nickel sulfate were all positive,indicating that the positive expression of telomerase activity in the cells transformed might be related to genotoxic lesions and the cell transforming activity of three kinds of Nickel Compounds.These results demonstrate the carcinogenesis or possible carcinogenesis of these Nickel Compounds.
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A DETECTION OF TELOMERASE ACTIVITY IN BALB/c-3T3 CELL TRANSFORMATION INDUCED BY THREE KINDS OF Nickel Compounds WITH TRAP-SILVER STAINING ASSAY.
Modern Preventive Medicine, 1999Co-Authors: Lei YixiongAbstract:In orter to research the genotoxic lesions of Nickel Compounds inducing BALB/c-3T3 cell transformation,telomerase activities in these cells transformed were detected with TRAP-silver staining assay.The results showed that telomerase activities in BALB/c-3T3 cells transformed by Nickel(Ⅱ) sulfide,Nickel chloride and Nickel sulfate were all positive,indicating that the positive expression of telomerase activity in the cells transformed might be related to genotoxic lesions and the cell transforming activity of three kinds of Nickel Compounds.These results demonstrate the carcinogenesis or possible carcinogenesis of these Nickel Compounds.
Evert Nieboer - One of the best experts on this subject based on the ideXlab platform.
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Toxicity, Uptake, and Mutagenicity of Particulate and Soluble Nickel Compounds
Environmental Health Perspectives, 1994Co-Authors: Glenn G. Fletcher, Franco E. Rossetto, John Turnbull, Evert NieboerAbstract:Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 micrograms Ni/ml for particulate Nickel Compounds and 45 to 60 micrograms Ni/ml for water-soluble salts (NiCl2, NiSO4, ...
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Toxicity, uptake, and mutagenicity of particulate and soluble Nickel Compounds.
Environmental health perspectives, 1994Co-Authors: Glenn G. Fletcher, Franco E. Rossetto, J D Turnbull, Evert NieboerAbstract:Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 micrograms Ni/ml for particulate Nickel Compounds and 45 to 60 micrograms Ni/ml for water-soluble salts (NiCl2, NiSO4, Ni(CH3COO)2). The Ni(OH)2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 to 8 micrograms Ni/ml), while three Nickel oxides were more variable and less toxic (LC50's of 18 to 130 micrograms Ni/ml). Most Compounds displayed nuclear to cytoplasmic Nickel ratios of approximately 1:1.5 to 1:5 (except approximately 1:20 for Nickel salts). At the LC50's, a 75-fold range in exposure levels occurred compared to a 10-fold range in cytoplasmic and nuclear Nickel concentrations, [Ni]. Cellular Nickel distribution indicated three groupings: inert Compounds (green NiO, lithium Nickel oxide, relatively low nuclear and cytosolic [Ni]); water-soluble salts (very low nuclear [Ni]; high cytosolic [Ni]), and slightly soluble Compounds (relatively high cytosolic and nuclear [Ni]). Nickel Compounds are considered to be only weak or equivocal mutagens. In this study, a low but significant increase in mutation rate at the gpt locus was shown. Although the results would not be sufficient to deem Nickel Compounds mutagenic by traditional criteria, characterization by PCR analysis indicated that the spontaneous and Nickel-induced mutants exhibited different and compound-specific mutational spectra (thus confirming Nickel compound involvement). The results reported illustrate some of the methodologic problems involved in testing "weak" mutagens and indicate that alternative approaches may be necessary in classifying the mutagenicity of Nickel and other Compounds.
Chuanshu Huang - One of the best experts on this subject based on the ideXlab platform.
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TNF-α Induction by Nickel Compounds is Specific Through ERKs/AP-1- Dependent Pathway in Human Bronchial Epithelial Cells
Current cancer drug targets, 2009Co-Authors: Jin Ding, Yi Huang, Bei-fang Ning, Wenfeng Gong, Hongyang Wang, Chang-yan Chen, Chuanshu HuangAbstract:The chronic lung inflammatory activity and carcinogenicity of Nickel Compounds have been well documented by previous studies from epidemiology both in vitro and in vivo. However, the molecular mechanism involved in Nickelinduced chronic lung inflammation is much less understood. The current study demonstrates that exposure of human bronchial epithelial cells (Beas-2B) to Nickel Compounds results in the induction of the inflammatory cytokine tumor necrosis factor-α (TNF-α) and transactivation of nuclear factor of activated T cells (NFAT), nuclear factor-κB (NF-κB), and activator protein-1 (AP-1). Further studies show that neither overexpression of IKKβ-KM, a kinase inactive mutant of IKKβ, nor the ectopic expression of a dominant negative mutant of NFAT could inhibit the TNF-α induction by Nickel exposure. Overexpression of TAM67, a dominant-negative mutant of c-Jun, dramatically reduced the TNF-α induction, suggesting that AP-1 is a mediator of TNF-α induction in Nickel responses. Our results show that ERKs are AP-1 upstream kinases responsible for TNF-α induction by Nickel exposure; although JNKs, ERKs, and p38K were all activated in the Beas-2B cells exposed to Nickel Compounds. Our results demonstrate that inflammatory TNF-α could be induced by Nickel exposure in Beas-2B cells specifically through an ERKs/AP-1-dependent pathway.
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Soluble and insoluble Nickel Compounds exert a differential inhibitory effect on cell growth through IKKα‐dependent cyclin D1 down‐regulation
Journal of cellular physiology, 2009Co-Authors: Weiming Ouyang, Max Costa, Dongyun Zhang, Udit Verma, Chuanshu HuangAbstract:It is well-known that insoluble Nickel Compounds possess much more potent carcinogenic activities as compared with soluble Nickel Compounds. Although it is assumed that the different entry and clearance rate are responsible for the difference, the mechanisms underlying the different carcinogenic activities are still not well understood yet. In the present study, we found that exposure to soluble, but not insoluble Nickel Compounds, caused a significant inhibition of cell growth and G1/G0 cell cycle arrest, which was concomitant with a marked down-regulation of cylin D1, an essential nuclear protein for controlling G1/S transition, while both soluble and insoluble Nickel Compounds showed similar effects on NFkappaB activation, HIF-1alpha protein accumulation and TNF-alpha transcription and CAP43 protein expression at same doses range. The down-regulation of cyclin D1 is due to protein degradation rather than inhibition of transcription, because the Nickel Compounds treatment did not change cyclin D1 mRNA level, while MG132, the proteasome inhibitor, can rescue the degradation of cyclin D1 caused by soluble Nickel compound. Moreover, the soluble Nickel-induced cyclin D1 degradation is dependent on its Thr286 residue and requires IKKalpha, but not HIF-1alpha, which are both reported to be involved in cyclin D1 down-regulation. Taken together, we demonstrate that soluble, but not insoluble Nickel compound, is able to cause cyclin D1 degradation and a cell growth arrest in an IKKalpha-dependent manner. Given the role of cyclin D1 and cell proliferation in carcinogenesis, we anticipate that the different effects of soluble and insoluble Nickel Compounds on cyclin D1 degradation and cell growth arrest may at least partially account for their different carcinogenic activities.
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Nickel Compounds Render Anti-apoptotic Effect to Human Bronchial Epithelial Beas-2B Cells by Induction of Cyclooxygenase-2 through an IKKβ/p65-dependent and IKKα- and p50-independent Pathway
The Journal of biological chemistry, 2006Co-Authors: Jin Ding, Max Costa, Weiming Ouyang, Dongyun Zhang, Xinhai Zhang, Lun Song, Caifang Xue, J. Andres Melendez, Chuanshu HuangAbstract:Abstract The carcinogenicity of Nickel Compounds has been well documented both in vitro and in vivo; however, the molecular mechanisms by which Nickel Compounds cause cancers are far from understood. Because suppression of apoptosis is thought to contribute to carcinogenesis, we investigated the mechanisms implicated in Nickel-induced anti-apoptotic effect in human bronchial epithelial (Beas-2B) cells. We found that exposure of Beas-2B cells to Nickel Compounds resulted in increased cyclooxygenase-2 (COX-2) expression and that small interfering RNA (siCOX-2) knockdown of COX-2 expression resulted in increased cell sensitivity to Nickel-triggered cell apoptosis, demonstrating that COX-2 induction has an anti-apoptotic effect on Beas-2B cells. Overexpression of IKKβ-KM, a kinase inactive mutant of IKKβ, blocked NF-κB activation and COX-2 induction by Nickel Compounds, indicating that activated NF-κB may be a mediator for COX-2 induction. To further explore the contribution of the NF-κB pathway in COX-2 induction and in protection from Nickel exposure, mouse embryonic fibroblasts deficient in IKKβ, IKKα, p65, and p50 were analyzed. Loss of IKKβ impaired COX-2 induction by Nickel exposure, whereas knockout of IKKα had a marginal effect. Moreover, the NF-κB p65, and not the p50 subunit, was critical for Nickel-induced COX-2 expression. In addition, a deficiency of IKKβ or p65 rendered cells more sensitive to Nickel-induced apoptosis as compared with those in wild type cells. Finally, it was shown that reactive oxygen species H2O2 were involved in both NF-κB activation and COX-2 expression. Collectively, our results demonstrate that COX-2 induction by Nickel Compounds occurs via an IKKβ/p65 NF-κB-dependent but IKKα- and p50-independent pathway and plays a crucial role in antagonizing Nickel-induced cell apoptosis in Beas-2B cells.
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Carcinogenic effect of Nickel Compounds
Molecular and Cellular Biochemistry, 2005Co-Authors: Xianglin Shi, Max Costa, Chuanshu HuangAbstract:Nickel is a widely distributed metal that is industrially applied in many forms. Accumulated epidemiological evidence confirms that exposures to Nickel Compounds are associated with increased nasal and lung cancer incidence, both in mostly occupational exposures. Although the molecular mechanisms by which Nickel Compounds cause cancer are still under intense investigation, the carcinogenic actions of Nickel Compounds are thought to involve oxidative stress, genomic DNA damage, epigenetic effects, and the regulation of gene expression by activation of certain transcription factors related to corresponding signal transduction pathways. The present review summarizes our current knowledge on the molecular mechanisms of Nickel carcinogenesis, with special emphasis on the role of Nickel induced reactive oxygen species (ROS) and signal transduction pathways.
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Essential role of PI-3K, ERKs and calcium signal pathways in Nickel-induced VEGF expression
Molecular and Cellular Biochemistry, 2005Co-Authors: Weiming Ouyang, Max Costa, Xianglin Shi, Chuanshu HuangAbstract:Exposure to a highly Nickel-polluted environment has the potential to cause a variety of adverse health effects, such as the respiratory tract cancers. Since numerous studies have demonstrated that Nickel generally has weak mutagenic activity, research focus had turned to cell signalling activation leading to gene modulation and epigenetic changes as a plausible mechanism of carcinogenesis. Previous studies have revealed that Nickel Compounds can induce the expression of vascular endothelial growth factor (VEGF), which is a key mediator of angiogenesis both in physiological and pathologic conditions. In the present study, we investigated the potential roles of PI-3K, ERKs, p38 kinase and calcium signalling in VEGF induction by Nickel in Cl 41 cells. Exposure of Cl 41 cells to Nickel Compounds led to VEGF induction in both time- and dose-dependent manners. Pre-treatment of Cl 41 cells with PI-3K inhibitor, wortmannin or Ly294002, resulted in a striking inhibition of VEGF induction by Nickel Compounds, implicating the role of PI-3K in the induction. However, mTOR, one of downstream molecules of PI-3K, may not contribute to the induction because pre-treatment of Cl 41 cells with its inhibitor, rapamycin, did not show obvious decrease in Nickel-induced VEGF expression. Furthermore, pre-treatment of Cl 41 cells with MEK1/2-ERKs pathway inhibitor, PD98059, significantly inhibited VEGF induction by both NiCl_2 and Ni_3S_2, whereas p38 kinase inhibitor, SB202190, did not impair the induction. Pre-treatment of Cl 41 cells with intracellular calcium chelator, but not calcium channel blocker, inhibited VEGF induction by Nickel. Collectively these data demonstrate that PI-3K, ERKs and cytosolic calcium, but not p38 kinase, play essential roles in VEGF induction by Nickel Compounds.
Pierre Giusti - One of the best experts on this subject based on the ideXlab platform.
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Study of the Size Distribution of Sulfur, Vanadium, and Nickel Compounds in Four Crude Oils and Their Distillation Cuts by Gel Permeation Chromatography Inductively Coupled Plasma High-Resolution Mass Spectrometry
Energy and Fuels, 2014Co-Authors: Alain Desprez, Brice Bouyssiere, Carine Arnaudguilhem, Gabriel Krier, Alex Vernex-loset, Pierre GiustiAbstract:The size distribution of sulfur, vanadium, and Nickel was determined for four crude oils and their distillation cuts using gel permeation chromatography (GPC) coupled to inductively coupled plasma high-resolution mass spectrometry (ICP HR MS). The results show a trimodal distribution of vanadium and Nickel Compounds in the crude oils, the atmospheric residues, and the vacuum residues and, for sulfur Compounds, either a mono- or bimodal distribution depending upon the distillation cut considered. A correlation exists between the sulfur fraction retention times and the temperature cuts of the distillation for a temperature below 560 degrees C and also between the viscosity of the crude oils and the proportion of trapped sulfur Compounds in a higher boiling temperature fraction. The thermic treatment applied for the distillation increases the aggregation of low- and medium-molecular-weight Compounds of vanadium and Nickel into higher molecular weight aggregates between the crude oil on the one hand and the atmospheric residue and vacuum residue on the other hand, especially when the crude oil has a high total sulfur content.
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study of the size distribution of sulfur vanadium and Nickel Compounds in four crude oils and their distillation cuts by gel permeation chromatography inductively coupled plasma high resolution mass spectrometry
Energy & Fuels, 2014Co-Authors: Alain Desprez, Brice Bouyssiere, Carine Arnaudguilhem, Gabriel Krier, Lionel Vernexloset, Pierre GiustiAbstract:The size distribution of sulfur, vanadium, and Nickel was determined for four crude oils and their distillation cuts using gel permeation chromatography (GPC) coupled to inductively coupled plasma high-resolution mass spectrometry (ICP HR MS). The results show a trimodal distribution of vanadium and Nickel Compounds in the crude oils, the atmospheric residues, and the vacuum residues and, for sulfur Compounds, either a mono- or bimodal distribution depending upon the distillation cut considered. A correlation exists between the sulfur fraction retention times and the temperature cuts of the distillation for a temperature below 560 °C and also between the viscosity of the crude oils and the proportion of trapped sulfur Compounds in a higher boiling temperature fraction. The thermic treatment applied for the distillation increases the aggregation of low- and medium-molecular-weight Compounds of vanadium and Nickel into higher molecular weight aggregates between the crude oil on the one hand and the atmosphe...
Max Costa - One of the best experts on this subject based on the ideXlab platform.
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Soluble and insoluble Nickel Compounds exert a differential inhibitory effect on cell growth through IKKα‐dependent cyclin D1 down‐regulation
Journal of cellular physiology, 2009Co-Authors: Weiming Ouyang, Max Costa, Dongyun Zhang, Udit Verma, Chuanshu HuangAbstract:It is well-known that insoluble Nickel Compounds possess much more potent carcinogenic activities as compared with soluble Nickel Compounds. Although it is assumed that the different entry and clearance rate are responsible for the difference, the mechanisms underlying the different carcinogenic activities are still not well understood yet. In the present study, we found that exposure to soluble, but not insoluble Nickel Compounds, caused a significant inhibition of cell growth and G1/G0 cell cycle arrest, which was concomitant with a marked down-regulation of cylin D1, an essential nuclear protein for controlling G1/S transition, while both soluble and insoluble Nickel Compounds showed similar effects on NFkappaB activation, HIF-1alpha protein accumulation and TNF-alpha transcription and CAP43 protein expression at same doses range. The down-regulation of cyclin D1 is due to protein degradation rather than inhibition of transcription, because the Nickel Compounds treatment did not change cyclin D1 mRNA level, while MG132, the proteasome inhibitor, can rescue the degradation of cyclin D1 caused by soluble Nickel compound. Moreover, the soluble Nickel-induced cyclin D1 degradation is dependent on its Thr286 residue and requires IKKalpha, but not HIF-1alpha, which are both reported to be involved in cyclin D1 down-regulation. Taken together, we demonstrate that soluble, but not insoluble Nickel compound, is able to cause cyclin D1 degradation and a cell growth arrest in an IKKalpha-dependent manner. Given the role of cyclin D1 and cell proliferation in carcinogenesis, we anticipate that the different effects of soluble and insoluble Nickel Compounds on cyclin D1 degradation and cell growth arrest may at least partially account for their different carcinogenic activities.
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Nickel Compounds Render Anti-apoptotic Effect to Human Bronchial Epithelial Beas-2B Cells by Induction of Cyclooxygenase-2 through an IKKβ/p65-dependent and IKKα- and p50-independent Pathway
The Journal of biological chemistry, 2006Co-Authors: Jin Ding, Max Costa, Weiming Ouyang, Dongyun Zhang, Xinhai Zhang, Lun Song, Caifang Xue, J. Andres Melendez, Chuanshu HuangAbstract:Abstract The carcinogenicity of Nickel Compounds has been well documented both in vitro and in vivo; however, the molecular mechanisms by which Nickel Compounds cause cancers are far from understood. Because suppression of apoptosis is thought to contribute to carcinogenesis, we investigated the mechanisms implicated in Nickel-induced anti-apoptotic effect in human bronchial epithelial (Beas-2B) cells. We found that exposure of Beas-2B cells to Nickel Compounds resulted in increased cyclooxygenase-2 (COX-2) expression and that small interfering RNA (siCOX-2) knockdown of COX-2 expression resulted in increased cell sensitivity to Nickel-triggered cell apoptosis, demonstrating that COX-2 induction has an anti-apoptotic effect on Beas-2B cells. Overexpression of IKKβ-KM, a kinase inactive mutant of IKKβ, blocked NF-κB activation and COX-2 induction by Nickel Compounds, indicating that activated NF-κB may be a mediator for COX-2 induction. To further explore the contribution of the NF-κB pathway in COX-2 induction and in protection from Nickel exposure, mouse embryonic fibroblasts deficient in IKKβ, IKKα, p65, and p50 were analyzed. Loss of IKKβ impaired COX-2 induction by Nickel exposure, whereas knockout of IKKα had a marginal effect. Moreover, the NF-κB p65, and not the p50 subunit, was critical for Nickel-induced COX-2 expression. In addition, a deficiency of IKKβ or p65 rendered cells more sensitive to Nickel-induced apoptosis as compared with those in wild type cells. Finally, it was shown that reactive oxygen species H2O2 were involved in both NF-κB activation and COX-2 expression. Collectively, our results demonstrate that COX-2 induction by Nickel Compounds occurs via an IKKβ/p65 NF-κB-dependent but IKKα- and p50-independent pathway and plays a crucial role in antagonizing Nickel-induced cell apoptosis in Beas-2B cells.
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alterations of histone modifications and transgene silencing by Nickel chloride
Carcinogenesis, 2006Co-Authors: Todd Davidson, Thomas Kluz, Haobin Chen, Max CostaAbstract:Although it has been well established that insoluble Nickel Compounds are potent carcinogens and soluble Nickel Compounds are less potent, the mechanisms remain unclear. Nickel Compounds are weakly mutagenic, but cause epigenetic effects in cells. Previous studies have shown that insoluble Nickel Compounds enter cells by phagocytosis and silence gene expression, but the entry of soluble Nickel Compounds and their effects on gene silencing have not been well studied. Here, we have demonstrated, using a dye that fluoresces when Nickel ions bind, that soluble Nickel Compounds were taken up by cells. Nickel ions localized initially in the cytoplasm, but later entered the nucleus and eventually silenced a transgene. In addition, we described three major changes in histone modification of cells exposed to soluble Nickel Compounds: (i) loss of acetylation of H2A, H2B, H3 and H4; (ii) increases of H3K9 dimethylation; and (iii) substantial increases of the ubiquitination of H2A and H2B. These effects were observed at Nickel exposure conditions that had minimum effects on cell cytotoxicity. Moreover, we demonstrated that Nickel-induced transgene silencing was associated with similar changes of histone modifications in their nuclesomes. This study is the first to show that Nickel Compounds increase histone ubiquitination in cells. These new findings will further our understanding of the epigenetic mechanisms of Nickel-mediated carcinogenesis.
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Carcinogenic effect of Nickel Compounds
Molecular and Cellular Biochemistry, 2005Co-Authors: Xianglin Shi, Max Costa, Chuanshu HuangAbstract:Nickel is a widely distributed metal that is industrially applied in many forms. Accumulated epidemiological evidence confirms that exposures to Nickel Compounds are associated with increased nasal and lung cancer incidence, both in mostly occupational exposures. Although the molecular mechanisms by which Nickel Compounds cause cancer are still under intense investigation, the carcinogenic actions of Nickel Compounds are thought to involve oxidative stress, genomic DNA damage, epigenetic effects, and the regulation of gene expression by activation of certain transcription factors related to corresponding signal transduction pathways. The present review summarizes our current knowledge on the molecular mechanisms of Nickel carcinogenesis, with special emphasis on the role of Nickel induced reactive oxygen species (ROS) and signal transduction pathways.
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Essential role of PI-3K, ERKs and calcium signal pathways in Nickel-induced VEGF expression
Molecular and Cellular Biochemistry, 2005Co-Authors: Weiming Ouyang, Max Costa, Xianglin Shi, Chuanshu HuangAbstract:Exposure to a highly Nickel-polluted environment has the potential to cause a variety of adverse health effects, such as the respiratory tract cancers. Since numerous studies have demonstrated that Nickel generally has weak mutagenic activity, research focus had turned to cell signalling activation leading to gene modulation and epigenetic changes as a plausible mechanism of carcinogenesis. Previous studies have revealed that Nickel Compounds can induce the expression of vascular endothelial growth factor (VEGF), which is a key mediator of angiogenesis both in physiological and pathologic conditions. In the present study, we investigated the potential roles of PI-3K, ERKs, p38 kinase and calcium signalling in VEGF induction by Nickel in Cl 41 cells. Exposure of Cl 41 cells to Nickel Compounds led to VEGF induction in both time- and dose-dependent manners. Pre-treatment of Cl 41 cells with PI-3K inhibitor, wortmannin or Ly294002, resulted in a striking inhibition of VEGF induction by Nickel Compounds, implicating the role of PI-3K in the induction. However, mTOR, one of downstream molecules of PI-3K, may not contribute to the induction because pre-treatment of Cl 41 cells with its inhibitor, rapamycin, did not show obvious decrease in Nickel-induced VEGF expression. Furthermore, pre-treatment of Cl 41 cells with MEK1/2-ERKs pathway inhibitor, PD98059, significantly inhibited VEGF induction by both NiCl_2 and Ni_3S_2, whereas p38 kinase inhibitor, SB202190, did not impair the induction. Pre-treatment of Cl 41 cells with intracellular calcium chelator, but not calcium channel blocker, inhibited VEGF induction by Nickel. Collectively these data demonstrate that PI-3K, ERKs and cytosolic calcium, but not p38 kinase, play essential roles in VEGF induction by Nickel Compounds.