Hydrogen peroxide induces the death of astrocytes through the down-regulation of the constitutive nuclear factor-kappaB activity.
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).
Choi
Jung-Jin
JJ
Division of NanoSciences, Ewha Women's University, Seoul, Republic of Korea.
Choi
Jiwoong
J
Kang
Chi-Dug
CD
Chen
Xia
X
Wu
Chun-Fu
CF
Ko
Kwang Ho
KH
Kim
Won-Ki
WK
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016328:NF-kappa B; D016877:Oxidants; D006861:Hydrogen Peroxide