Selective activation of NF-kappaB and E2F by low concentration of arsenite in U937 human monocytic leukemia cells
Abstract
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-...Continue Reading
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis