Dexamethasone-enhanced sensitivity of mouse hippocampal HT22 cells for oxidative stress is associated with the suppression of nuclear factor-kappaB

Glucocorticoids (GCs) exacerbate various insults to the hippocampus but the exact molecular mechanisms of this GC activity is not known. GCs can suppress the activity of the redox-sensitive nuclear factor NF-kappaB, which potentially serves neuroprotective functions. Employing electrophoretic mobility shift assays and transfection assays using a NF-kappaB-dependent reporter plasmid, we demonstrate that the increased oxidative stress sensitivity of clonal mouse hippocampal HT22 cells caused by GCs is associated with the suppression of NF-kappaB. GCs increased the expression of IkappaBalpha, the physiological inhibitor of NF-kappaB. Downregulation of NF-kappaB activity after overexpression of a dominant-negative mutant form of IkappaBalpha results in an increased sensitivity to oxidative stress. We conclude that the suppression of the basal NF-kappaB activity contributes to the enhanced vulnerability of neuronal cells to oxidative stress caused by GCs.