GPx-1 Gene Delivery Modulates NFκB Activation Following Diverse Environmental Injuries Through a Specific Subunit of the IKK Complex

Numerous environmental stimuli alter cell functions by the induction of intracellular reactive oxygen species, such as superoxide and hydrogen peroxide (H2O2). These redox alterations can change the activity of kinases and phosphatases responsible for controlling intracellular signal transduction cascades important in determining how cells react to their environment. One such well known pathway includes nuclear factor-κB (NFκB); however, the exact redox-sensitive factors important in controlling H2O2-mediated activation of NFκB remain unclear. In the present study, we have investigated how intracellular clearance of H2O2, using a recombinant adenovirus expressing glutathione peroxidase-1 (GPx-1), modulates NFκB activation following UV irradiation, tumor necrosis factor-α, or H2O2 treatment of MCF-7 cells. Findings from these studies demonstrate that GPx-1 overexpression can down-regulate NFκB DNA binding, and transcriptional activation of an NFκB-dependent luciferase reporter, to varying extents following...