Hydrogen peroxide induces the death of astrocytes through the down-regulation of the constitutive nuclear factor-kappaB activity
Hydrogen peroxide induces the death of astrocytes through the down-regulation of the constitutive nuclear factor-kappaB activity
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DOI：
10.1080/10715760601173010
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Kim, Won-Ki
中科院分区：
文献类型：
--
作者：
Choi, Jung-Jin;Choi, Jiwoong;Kim, Won-Ki
核因子-κ B（NF-κ B）在促进或减弱细胞死亡中具有双重作用。在这里，我们证明了NF-κ B B在H2 O2诱导的星形胶质细胞死亡中的作用。H2 O2诱发乳酸脱氢酶（LDH）的释放，细胞死亡的标志物，并伴随着降低DNA结合和NF-κ B B的转录活性在培养的星形胶质细胞。与NF-κ B抑制剂吡咯烷二硫代氨基甲酸酯共同处理可显著增加H2 O2诱导的星形胶质细胞死亡。此外，通过过表达p65 NF-κ B亚基来提高组成性NF-κ B活性可减弱H2 O2毒性，而通过过表达I κ B来抑制NF-κ B活性可增强毒性。进一步发现NF-κ B活性和H2 O2细胞毒性依赖于细胞密度。与低细胞密度组相比，高细胞密度组的NF-κ B B活性更高，对H2 O2细胞毒性的抵抗力更强。这些结果表明星形胶质细胞中NF-κ B的组成性活性是其在氧化应激如H2 O2下存活所必需的。
Nuclear factor-kappaB (NF-kappa B) has a dual role in the promotion or attenuation of cell death. Here, we demonstrated the role of NF-kappa B 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-kappa B in cultured astrocytes. H2O2-induced astrocyte death was markedly increased by the co-treatment with pyrrolidinedithiocarbamate, an NF-kappa B inhibitor. Moreover, the elevation of constitutive NF-kappa B activity by overexpressing p65 NF-kappa B subunit attenuated H2O2 toxicity, whereas NF-kappa B inhibition by overexpressing I kappa B potentiated the toxicity. NF-kappa B 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-kappa B activity and a stronger resistance to H2O2 cytotoxicity. These results indicate that the constitutive activity of NF-kappa B in astrocytes is required for their survival under oxidative stress such as H2O2.