Protective roles of NF-κB for chromium(VI)-induced cytotoxicity is revealed by expression of IκB kinase-β mutant

Fei Chen, Jacquelyn Bower, Stephen S. Leonard, Min Ding, Yongju Lu, Yon Rojanasakul, Hsiang Fu Kung, Val Vallyathan, Vince Castranova, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


To delineate the molecular mechanisms of NF-κB-mediated regulation of chromium(VI)-induced cell death, the signaling pathway leading to the activation of NF-κB was interrupted by stable transfection of a kinase-mutated form of IκB kinase β (IKKβ-KM). Here we demonstrate a novel role for the NF-κB transcription factor in inhibiting chromium(VI)-induced cell death. Inhibition of NF-κB by IKKβ-KM or IKKβ gene deficiency resulted in a spontaneous cleavage of Bcl-xl antiapoptotic protein due to the elevated caspase-3 activity. DNA microarray assay suggested a decreased expression of genes encoding antiapoptotic proteins, cIAP1 and cIAP2, in the cells overexpressing IKKβ-KM. Chromium(VI) treatment of these NF-κB-inhibited cells induced necrotic-like cell death. Such chromium(VI)-induced cell killing could be partially inhibited by expression of exogenous cIAP1, an inhibitor of caspases, indicating that caspases along with others may be involved in chromium(VI)-induced cell death. These results suggest that NF-κB is essential for inhibiting toxic metal-induced cytotoxicity. Such inhibition may involve up-regulation of the expression of anti-death proteins including cIAP1 that prevents spontaneous caspase activation and subsequent cleavage of Bcl-xl protein.

Original languageEnglish
Pages (from-to)3342-3349
Number of pages8
JournalJournal of Biological Chemistry
Issue number5
StatePublished - Feb 1 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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