Choi Jung-Jin, Choi Jiwoong, Kang Chi-Dug, Chen Xia, Wu Chun-Fu, Ko Kwang Ho, Kim Won-Ki
Division of NanoSciences, Ewha Women's University, Seoul, Republic of Korea.
Free Radic Res. 2007 May;41(5):555-62. doi: 10.1080/10715760601173010.
Nuclear factor-kappaB (NF-kappaB) has a dual role in the promotion or attenuation of cell death. Here, we demonstrated the role of NF-kappaB in the H(2)O(2)-induced death of astrocytes. H(2)O(2) evoked the release of lactate dehydrogenase (LDH), a marker of cell death, and concomitantly decreased the DNA binding and transcriptional activity of NF-kappaB in cultured astrocytes. H(2)O(2)-induced astrocyte death was markedly increased by the co-treatment with pyrrolidinedithiocarbamate, an NF-kappaB inhibitor. Moreover, the elevation of constitutive NF-kappaB activity by overexpressing p65 NF-kappaB subunit attenuated H(2)O(2) toxicity, whereas NF-kappaB inhibition by overexpressing IkappaB potentiated the toxicity. NF-kappaB activity and H(2)O(2) 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-kappaB activity and a stronger resistance to H(2)O(2) cytotoxicity. These results indicate that the constitutive activity of NF-kappaB in astrocytes is required for their survival under oxidative stress such as H(2)O(2).
核因子-κB（NF-κB）在促进或减弱细胞死亡方面具有双重作用。在此，我们证明了NF-κB在H₂O₂诱导的星形胶质细胞死亡中的作用。H₂O₂诱发了细胞死亡标志物乳酸脱氢酶（LDH）的释放，并同时降低了培养的星形胶质细胞中NF-κB的DNA结合及转录活性。与NF-κB抑制剂吡咯烷二硫代氨基甲酸盐共同处理可显著增加H₂O₂诱导的星形胶质细胞死亡。此外，通过过表达p65 NF-κB亚基提高组成型NF-κB活性可减弱H₂O₂毒性，而通过过表达IκB抑制NF-κB则会增强毒性。进一步发现，NF-κB活性和H₂O₂细胞毒性取决于细胞密度。与低细胞密度的星形胶质细胞相比，高细胞密度的星形胶质细胞表现出更高的组成型NF-κB活性以及对H₂O₂细胞毒性更强的抗性。这些结果表明，星形胶质细胞中NF-κB的组成型活性是其在诸如H₂O₂等氧化应激下存活所必需的。
