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Biochem Pharmacol. 2000 Oct 15;60(8):1075-83.

Oxidative stress interference with the nuclear factor-kappa B activation pathways.

Author information

1
Laboratory of Virology & Immunology, Institute of Pathology B23, University of Liege, B-4000 Liege, Belgium.

Abstract

While intracellular redox balance is tightly controlled in many cell types, its modification leads to important cellular changes derived, in part, from a modification of the pattern of gene expression. This modification relies on many transcription factors whose activities are either increased or reduced by a disbalance of the redox environment. Among these transcription factors, nuclear factor-kappa B (NF-kappa B) plays a pivotal role in inducing genes involved in the control of the immune system as well as in the response to injury and infection. Because NF-kappa B can be induced in many cells by a diverse set of stimulating agents, it has been proposed that agents activating it do so by increasing oxidative stress within the cell. However, this model was not found to be universal, since the dependence between NF-kappa B activation and intracellular reactive oxygen species (ROS) generation was only detected in certain cell lines. The origin of this dependency is still unknown, but could very well be situated in a particular kinase or in adaptator molecules of the signaling cascade, leading to inhibitor kappa B alpha (I kappa B alpha phosphorylation. On the other hand, NF-kappa B can be activated by oxidants in many cell types, but this activation is well characterized only in lymphocytes. This activation is distinct from that of classical activators such as proinflammatory cytokines and phorbol esters, because the activation mechanisms appear to converge on a particular tyrosine residue of I kappa B-alpha instead of the two classical N-terminal serines. The nature of the protein kinases or protein phosphatases involved in this process is still undetermined. It will be a challenge in the future to identify the kinases/phosphatases activated by oxidants and to discover why ROS are required in some cells to turn on the transduction pathway leading to NF-kappa B activation by physiological stimuli.

PMID:
11007944
DOI:
10.1016/s0006-2952(00)00371-3
[Indexed for MEDLINE]

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