Vanadate induction of NF-κB involves IκB kinase β and SAPK/ERK kinase 1 in macrophages

Fei Chen, Laurence M. Demers, Val Vallyathan, Min Ding, Yongju Lu, Vince Castranova, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

The present studies investigated the signaling pathways of vanadate, a vanadium ion with +5 oxidation state, to activate NF-κB transcription factor, a pivotal regulator of inflammatory responses. Treatment of macrophages with vanadate results in the activation of both NF-κB and c-Jun N-terminal kinase (JNK). The activity of a recently identified cellular kinase, IκB kinase-β (IKKβ), was significantly elevated concomitant with the increased degradation of IκBα and enhanced NF-κB activity in cells exposed to vanadate. To determine whether the IKK pathway and JNK pathway are interconnected or bifurcate upon vanadate stimulation, cells were transfected with either a kinase inactive form of IKKβ or a kinase inactive form of SAPK/ERK kinase 1 (SEK1). Inactive IKKβ was able to block vanadate-induced degradation of IκBα, yet it was unable to influence the activation of JNK by vanadate. Conversely, blockage of JNK activation by transfection of a kinase-inactive form of SEK1 resulted in partially inhibition of vanadate- induced IκBα degradation. Both vanadate-induced degradation of IκBα and activation of JNK were potently inhibited by pretreatment of cells with N- acetylcysteine or dimercaprol. These results demonstrate that early activation of stress kinases or change of cellular redox states plays a key role in vanadate-induced activation of NF-κB and JNK.

Original languageEnglish (US)
Pages (from-to)20307-20312
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number29
DOIs
StatePublished - Jul 16 1999

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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