Trends in Cell Biology
Volume 1, Issues 2–3, August–September 1991, Pages 39-42
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A role for oxygen radicals as second messengers

https://doi.org/10.1016/0962-8924(91)90072-HGet rights and content

Abstract

All cells seem to produce oxygen radicals. Recent results suggest that small nontoxic amounts of these radicals are released by various cell types in response to stimulation with tumour necrosis factor (TNF), interleukin 1 (IL-1) and phorbol esters, all of which activate a cytoplasmic form of the transcription factor NF-κB by releasing an inhibitory protein subunit. Activation is inhibited by agents that remove oxygen radicals, and mimicked by exposure to mild oxidant stress. This article proposes that oxygen radicals act as second messengers for a variety of agents, including the immunomodulatory cytokines TNF and IL-1, in at least one type of regulatory pathway activating NF-κB.

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      TNF-α and IL-1α promote the formation of reactive oxygen species (ROS), which in turn activate the transcription factor nuclear factor (NF)-κB [2] and induce the translocation of NF-κB from the cytosol to the nucleus. H2O2 rapidly and effectively activates NF-κB signaling, and prolonged activation of NF-κB leads to the development of oxidative stress [3–6]. Oxidative stress occurs via increased production of reactive oxygen species (ROS) or impairment of antioxidant defenses that neutralize ROS [7].

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