Inhibition of apoptosis and transcription factor binding activity by zinc pyrithione in human umbilical vein endothelial cells.

Abstract

Cell death has been characterized as occurring by one of two ways: necrosis or apoptosis. Necrotic cell death is passive, resulting from severe trauma, whereas apoptotic death requires the active participation of the cell and occurs in response to a signal that triggers a characteristic series of events. The actual mechanisms regulating the apoptotic pathway have yet to be fully elucidated. However, regulation appears to depend on the balance between apoptosis-suppressing and apoptosis-inducing factors within the cell. Accordingly, apoptosis may be initiated by the activation or suppression of transcription factors involved in the regulation of apoptotic factors. The ability of zinc to inhibit apoptosis has been well documented, but the mechanisms of this protection have yet to be elucidated. In view of the ability of zinc to alter transcriptional events, we sought to determine if zinc may prevent apoptosis by altering transcription factor binding activity. Of particular interest were the transcription factors Nuclear Factor kappa B (NF$\kappa$B), Activator Protein-1 (AP-1), and Sp1, which have previously been shown to be associated with apoptosis. (Abstract shortened by UMI.)