NF-κB in Oxidative Stress - PubMed (original) (raw)

NF-κB in Oxidative Stress

Krithika Lingappan. Curr Opin Toxicol. 2018 Feb.

Abstract

The transcription factor nuclear factor-κB (NF-κB) modulates gene expression in diverse cellular processes such as innate immune response, embryogenesis and organ development, cell proliferation and apoptosis, and stress responses to a variety of noxious stimuli. When cellular production of reactive oxygen species (ROS) overwhelms its antioxidant capacity, it leads to a state of oxidative stress, which in turn contributes to the pathogenesis of several human diseases. Different models of oxidative stress have been studied to elucidate the effects of oxidant stress on NF-κB related activities. ROS can both activate and repress NF-κB signaling in a phase and context dependent manner. The NF-κB pathway can have both anti- and pro-oxidant roles in the setting of oxidative stress. In this review, we focus on role of oxidative stress on different mediators of the NF-κB pathway, and the role of NF-κB activation in the modulation of oxidative stress. A greater understanding of the complex interplay between the NF-κB signaling and oxidative stress may lead to the development of therapeutic strategies for the treatment of a myriad of human diseases for which oxidative stress has an etiologic role.

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Figures

Figure 1

Figure 1. Effect of increased oxidative stress on NF-κB pathway

Oxidative stress can both activate and inhibit the NF-κB pathway by targeting the upstream kinases (IKK, NIK and Akt), facilitating or inhibiting the degradation of I-κB or modulation the nuclear translocation and DNA binding of the transcription factor by modifying the NF-κB heterodimers. (RHD: Rel homology domain)

Figure 2

Figure 2. Anti- and pro-oxidant role of NF-κB pathway in oxidative stress

The NF-κB pathway may play a protective role in the setting of oxidative stress by various mechanisms as shown. Activation of the pathway may also cause induction of pro-oxidant genes such as NADPH oxidase NOX2 subunit gp91phox.

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