Trisubstituted organotin pesticides are lethal for different cell types. In this study we investigated whether triphenyltin chloride (TPT) causes apoptosis in HL-60 promyelocytic cells and, if so, by what mechanisms. We report that 5 μM TPT increased intracellular Ca2+ in HL-60 cells within seconds; concomitantly actin depolymerization was detected 30 s and 1 min after the treatment. This was followed 15 min later by NF-κB activation, and apoptotic bodies and DNA fragmentation were evident after 3 and 6 h, respectively. At these times TPT also induced the release of tumor necrosis factor-α (TNF-α). Prior treatment of the cells with a polyclonal antibody to human TNF-α abolished TPT-induced DNA fragmentation, which suggests that the ultimate effect of TPT may be mediated by TNF-α. Prior treatment of the cells with 100 μM pyrrolidine dithiocarbamate, an antioxidant and potent inhibitor of NF-κB activation, prevented actin depolymerization, NF-κB activation, and DNA fragmentation, although it did not affect TPT-induced Ca2+ mobilization. These findings suggest that TPT increases intracellular Ca2+, alters actin polymerization and the cytoskeleton, and induces NF-κB activation, TNF-α synthesis, DNA degradation, and apoptosis. Reactive oxygen species seem to be essential to NF-κB activation, TNF-α synthesis, and the subsequent steps.

NF-κB activation by triphenyltin triggers apoptosis in HL-60 cells / M. Marinovich, B. Viviani, E. Corsini, F. Ghilardi, C.L. Galli. - In: EXPERIMENTAL CELL RESEARCH. - ISSN 0014-4827. - 226:1(1996), pp. 98-104.

NF-κB activation by triphenyltin triggers apoptosis in HL-60 cells

M. Marinovich
Primo
;
B. Viviani
Secondo
;
E. Corsini;C.L. Galli
Ultimo
1996

Abstract

Trisubstituted organotin pesticides are lethal for different cell types. In this study we investigated whether triphenyltin chloride (TPT) causes apoptosis in HL-60 promyelocytic cells and, if so, by what mechanisms. We report that 5 μM TPT increased intracellular Ca2+ in HL-60 cells within seconds; concomitantly actin depolymerization was detected 30 s and 1 min after the treatment. This was followed 15 min later by NF-κB activation, and apoptotic bodies and DNA fragmentation were evident after 3 and 6 h, respectively. At these times TPT also induced the release of tumor necrosis factor-α (TNF-α). Prior treatment of the cells with a polyclonal antibody to human TNF-α abolished TPT-induced DNA fragmentation, which suggests that the ultimate effect of TPT may be mediated by TNF-α. Prior treatment of the cells with 100 μM pyrrolidine dithiocarbamate, an antioxidant and potent inhibitor of NF-κB activation, prevented actin depolymerization, NF-κB activation, and DNA fragmentation, although it did not affect TPT-induced Ca2+ mobilization. These findings suggest that TPT increases intracellular Ca2+, alters actin polymerization and the cytoskeleton, and induces NF-κB activation, TNF-α synthesis, DNA degradation, and apoptosis. Reactive oxygen species seem to be essential to NF-κB activation, TNF-α synthesis, and the subsequent steps.
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/181520
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