Hydrogen peroxide induces the death astrocytes through the down-regulation of the constitutive nuclear factor-kappaB activity

Nuclear factor-kappaB (NF-κB) has a dual role in the promotion or attenuation of cell death. Here, we demonstrated the role of NF-κB in the H₂O₂-induced death of astrocytes. H₂O₂ evoked the release of lactate dehydrogenase (LDH), a marker of cell death, and concomitantly decreased the DNA binding and transcriptional activity of NF-κ3ba;B in cultured astrocytes. H₂O₂-induced astrocyte death was markedly increased by the co-treatment with pyrrolidinedithiocarbamate, an NF-κB inhibitor. Moreover, the elevation of constitutive NF-κB activity by overexpressing p65 NF-κB subunit attenuated H₂O₂ toxicity, whereas NF-κB inhibition by overexpressing Iκba;B potentiated the toxicity. NF-κB activity and H₂O₂ cytotoxicity was further found to be dependent on cell density. Compared with astrocytes in low cell density, those in high cell density exhibited a higher constitutive NF-κB activity and a stronger resistance to H₂O₂ cytotoxicity. These results indicate that the constitutive activity of NF-κB in astrocytes is required for their survival under oxidative stress such as H₂O₂.