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

• Published in: Neuroscience letters 2000-12, Vol.295 (3), p.101-104
• Main Authors: Braun, Sigurd, Liebetrau, Wolfgang, Berning, Barbara, Behl, Christian
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Glucocorticoids; Isolated neuron and nerve. Neuroglia; Neuronal cell death; Nuclear factor-κB; Oxidative stress; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(00)01603-7

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-κB, which potentially serves neuroprotective functions. Employing electrophoretic mobility shift assays and transfection assays using a NF-κB-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-κB. GCs increased the expression of IκBα, the physiological inhibitor of NF-κB. Downregulation of NF-κB activity after overexpression of a dominant-negative mutant form of IκBα results in an increased sensitivity to oxidative stress. We conclude that the suppression of the basal NF-κB activity contributes to the enhanced vulnerability of neuronal cells to oxidative stress caused by GCs.