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[Free radicals as second messengers]

M Raes1, P Renard, J Remacle

  • 1Laboratoire de Biochimie Cellulaire, Facultés Universitaires Notre-Dame-de-la-Paix, Namur, Belgique.

Comptes Rendus Des Seances De La Societe De Biologie Et De Ses Filiales
|January 1, 1995
PubMed
Summary
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Reactive oxygen intermediates are crucial for cellular responses to cytokines like IL-1 and TNF-alpha, activating the NF kappa B pathway. Further research is needed to clarify the precise molecular mechanisms and subcellular origins of these reactive oxygen species.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Context:

  • Interleukin-1 (IL-1) and Tumor Necrosis Factor-alpha (TNF-alpha) are key cytokines mediating cellular responses.
  • Activation of the transcription factor Nuclear Factor kappa B (NF kappa B) is a central event in these responses.
  • NF kappa B activation is tightly regulated by the phosphorylation of its inhibitor, I kappa B, which is influenced by intracellular reactive oxygen intermediates (ROIs).

Purpose:

  • To review the current understanding of the role of reactive oxygen intermediates in IL-1 and TNF-alpha signaling pathways.
  • To highlight unresolved questions regarding the subcellular production and specific molecular mechanisms of ROI involvement in NF kappa B activation.
  • To present recent experimental findings that shed light on the precise role of ROIs and their associated molecular players, such as peroxides and the GSSG/GSH ratio, in NF kappa B activation.

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Summary:

  • Cytokine-induced cellular responses, particularly NF kappa B activation, depend on intracellular reactive oxygen intermediates (ROIs).
  • The phosphorylation of I kappa B, an inhibitory subunit of NF kappa B, requires ROIs, with peroxides and elevated GSSG/GSH ratios implicated.
  • Key questions remain concerning the subcellular localization of ROI production and the specific kinases/phosphatases involved in peroxide-mediated signaling and the impact of high GSSG levels.

Impact:

  • Provides a comprehensive overview of the current knowledge on ROIs in cytokine signaling.
  • Identifies critical gaps in understanding the molecular intricacies of ROI-mediated NF kappa B activation.
  • Highlights recent advancements that contribute to elucidating the complex interplay between ROIs, cellular signaling, and inflammatory responses.