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首页> 外文期刊>Journal of biochemical and molecular toxicology >Selective activation of NF-kappaB and E2F by low concentration of arsenite in U937 human monocytic leukemia cells.
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Selective activation of NF-kappaB and E2F by low concentration of arsenite in U937 human monocytic leukemia cells.

机译：U937人单核细胞白血病细胞中低浓度的亚砷对NF-κB和E2F的选择性激活。

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Arsenite has been reported to exert dose-dependent dual effects: triggering apoptosis at relatively high concentrations, whereas inducing partial differentiation at low concentrations in leukemia cells. However, the relevant molecular mechanisms of its action at low and nonapoptotic concentrations remain to be elucidated. We examined the effect of arsenite on activation of key transcription factors in cultured U937 human monocytes/macrophages. Electrophoretic mobility shift assay (EMSA), protein/DNA array and luciferase reporter assay were used to analyze the effect of arsenite on the functional activities of transcription factors. Protein/DNA array analysis showed that activation of E2F was seen after 6-h exposure to 1 and 10 microM arsenite. In contrast, activation of NF-kappaB took place only at 1 microM arsenite, whereas 10 microM arsenite showed no recognizable effect on this nuclear transcription factor in the protein/DNA array analysis. EMSA using a NF-kappaB consensus probe indicates the functional activation of RelB/p50 in the presence of 1 microM arsenite, confirming the above results. Luciferase reporter assay for NF-kappaB showed activation of NF-kappaB in the presence of 1 microM arsenite. Interleukin (IL)-8 and B-cell-activating factor of the tumor necrosis factor family (BAFF) mRNA expression, which have been shown to be regulated through NF-kappaB, were activated in the presence of 1 microM arsenite. These results support the hypothesis that the primary action of nonapoptotic concentrations of arsenite in this cell line is activation of NF-kappaB, signaling as a decision maker for end results such as inflammation disease or cancer. This finding offers the possibility of providing a logical explanation for the observations made by many scientists that chronic exposure of human populations to low doses of arsenic is significantly correlated to clinical signs of inflammation in many tissues.
机译：据报道，亚砷酸盐具有剂量依赖性的双重作用：在相对较高的浓度下触发凋亡，而在低浓度的白血病细胞中诱导部分分化。然而，在低和非凋亡浓度下其作用的相关分子机理仍有待阐明。我们检查了砷对培养的U937人单核细胞/巨噬细胞中关键转录因子激活的影响。电泳迁移率迁移分析（EMSA），蛋白质/ DNA阵列和荧光素酶报告基因分析用于分析砷对转录因子功能活性的影响。蛋白质/ DNA阵列分析表明，暴露于1和10 microM亚砷酸6小时后E2F激活。相反，在蛋白质/ DNA阵列分析中，NF-κB的活化仅在1 microM的亚砷酸盐中发生，而10 microM的亚砷酸盐对此核转录因子未显示可识别的作用。使用NF-kappaB共有探针的EMSA表明在1 microM亚砷酸盐存在下RelB / p50的功能激活，证实了上述结果。 NF-κB的萤光素酶报告基因检测显示，在1 microM亚砷酸盐存在下，NF-κB的活化。肿瘤坏死因子家族（BAFF）mRNA表达的白介素（IL）-8和B细胞激活因子已被证明通过NF-κB调节，在1 microM亚砷酸盐存在下被激活。这些结果支持以下假设：该细胞系中非凋亡浓度的亚砷酸盐的主要作用是激活NF-κB，这是最终结果如炎症，疾病或癌症的决策者。这一发现为许多科学家的观察提供了逻辑上的解释，即人类长期暴露于低剂量的砷与许多组织炎症的临床体征显着相关。

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