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Hydrogen peroxide-mediated inhibition of lipopolysaccharide-stimulated inhibitory kappa b kinase activity in rat aortic smooth muscle cells

Torrie, L.J. and MacKenzie, C. and Paul, A. and Plevin, R.J. (2001) Hydrogen peroxide-mediated inhibition of lipopolysaccharide-stimulated inhibitory kappa b kinase activity in rat aortic smooth muscle cells. British Journal of Pharmacology, 134 (2). pp. 393-401. ISSN 0007-1188

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Abstract

In rat aortic smooth muscle cells (RASMC), exposure to lipopolysaccharide (LPS) resulted in NF-κB-DNA binding, degradation of IκB-α, -β and -ε and increased activity of both α and β isoforms of inhibitory kappa B kinase (IKK). Expression of dominant-negative (DN)-IKK-α, IKK-β and NF-κB-inducing kinase (NIK) abolished LPS-stimulated NF-κB reporter activity, suggesting that activation of a NIK/IKK-dependent pathway is indispensable for NF-κB activation by LPS in this cell type. The tyrosine phosphatase inhibitor, pervanadate, abolished LPS-stimulated NF-κB-DNA-binding activity. However, the effect of pervanadate was shown to be mediated by excess hydrogen peroxide (H2O2) present in the reaction mix. Preincubation of RASMC with H2O2 inhibited LPS-stimulated IKK kinase activity and downstream NF-κB-DNA binding activity. H2O2 also strongly stimulated p38 MAP kinase activity in RASMCs. Effective inhibition of this pathway using SB203580 did not reverse the effects of H2O2 on LPS-stimulated IKK/NF-κB signalling. These studies show that hydrogen peroxide-mediated inhibition of LPS-stimulated NF-κB activation in RASMC occurs upstream of IKK. The inhibitory effect of H2O2 is not due to tyrosine phosphatase inhibition, it is mediated by H2O2 through a mechanism which is independent of any cross-talk involving MAP kinase homologues.

Item type: Article
ID code: 38861
Keywords: hydrogen peroxide, rat aortic smooth muscle cells , lipopolysaccharide, inhibitory kappa B kinase , Pharmacy and materia medica, Pharmacology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 02 Apr 2012 14:03
    Last modified: 04 Sep 2014 19:00
    URI: http://strathprints.strath.ac.uk/id/eprint/38861

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