Biphasic role of nuclear factor-kappa B on cell survival and COX-2 expression in SOD1 Tg astrocytes after oxygen glucose deprivation

Abstract

In cytoplasm, nuclear factor-kappa B (NF-kappa B) is associated with the inhibitory protein, I kappa B alpha. On activation by H2O2, I kappa B alpha is phosphorylated and degraded, exposing the nuclear localization signals on the NF-kappa B heterodimer. Cyclooxygenase-2 (COX-2), which mediates prostaglandin synthesis during inflammation, is induced by oxidative stress mediated by NF-kappa B. We investigated whether the NF-kappa B signaling pathway affected cell death and COX-2 expression after hypoxia-induced oxidative stress in wild-type (WT) and copper/zinc-superoxide dismutase transgenic (SOD1 Tg) astrocytes. In WT astrocytes, phospho-I kappa B alpha was highly expressed after oxygen-glucose deprivation (OGD) and 2 h of reperfusion, concomitant with the decrease in I kappa B alpha. The NF-kappa B p50 level increased similarly in WT and SOD1 Tg astrocytes (1.2-/1.4-fold) after OGD. Electrophoretic mobility shift assay showed higher DNA-binding activity of NF-kappa B p50 in WT than in SOD1 Tg astrocytes 6 h after 4 h of OGD. The COX-2 level was induced by 2.7- and 1.3-fold after OGD in WT and SOD1 Tg astrocytes, and an antioxidant protected both groups against OGD injury. Superoxide dismutase transgenic cells were 23% more protective against OGD injury than WTs when assessed by lactate dehydrogenase release. Ho