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Vanadate induction of NF-kB involves IkB kinase B and SAPK/ERK kinasa 1 in macrophages.

Authors
Chen-F; Demers-LM; Vallyathan-V; Ding-M; Lu-Y; Castranova-V; Shi-X
Source
J Biol Chem 1999 Jul; 274(29):20307-20312
NIOSHTIC No.
20000956
Abstract
The present studies investigated the signaling pathways of vanadate, a vanadium ion with +5 oxidation state, to activate NF-kappaB transcription factor, a pivotal regulator of inflammatory responses. Treatment of macrophages with vanadate results in the activation of both NF-kappaB and c-Jun N-terminal kinase (JNK). The activity of a recently identified cellular kinase, IkappaB kinase-beta (IKKbeta), was significantly elevated concomitant with the increased degradation of IkappaBalpha and enhanced NF-kappaB 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 IKKbeta or a kinase inactive form of SAPK/ERK kinase 1 (SEK1). Inactive IKKbeta was able to block vanadate-induced degradation of IkappaBalpha, 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 IkappaBalpha degradation. Both vanadate-induced degradation of IkappaBalpha 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-kappaB and JNK.
Keywords
In-vitro-studies; Carcinomas; Vandium-compounds; Metabolites; Particulates; Cardiopulmonary-system-disorders; Pulmonary-system-disorders
CODEN
JBCHA3
Publication Date
19990716
Document Type
Journal Article
Fiscal Year
1999
NTIS Accession No.
NTIS Price
Issue of Publication
29
ISSN
0021-9258
NIOSH Division
HELD
Source Name
Journal of Biological Chemistry
State
WV; PA
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