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Review
. 2013:2013:690545.
doi: 10.1155/2013/690545. Epub 2013 Apr 17.

Regulation of NF-κB-induced inflammatory signaling by lipid peroxidation-derived aldehydes

Umesh C S Yadav  1 , Kota V Ramana
Affiliations
Review

Regulation of NF-κB-induced inflammatory signaling by lipid peroxidation-derived aldehydes

Umesh C S Yadav et al. Oxid Med Cell Longev. 2013.

Abstract

Oxidative stress plays a critical role in the pathophysiology of a wide range of diseases including cancer. This view has broadened significantly with the recent discoveries that reactive oxygen species initiated lipid peroxidation leads to the formation of potentially toxic lipid aldehyde species such as 4-hydroxy-trans-2-nonenal (HNE), acrolein, and malondialdehyde which activate various signaling intermediates that regulate cellular activity and dysfunction via a process called redox signaling. The lipid aldehyde species formed during synchronized enzymatic pathways result in the posttranslational modification of proteins and DNA leading to cytotoxicity and genotoxicty. Among the lipid aldehyde species, HNE has been widely accepted as a most toxic and abundant lipid aldehyde generated during lipid peroxidation. HNE and its glutathione conjugates have been shown to regulate redox-sensitive transcription factors such as NF-κB and AP-1 via signaling through various protein kinase cascades. Activation of redox-sensitive transcription factors and their nuclear localization leads to transcriptional induction of several genes responsible for cell survival, differentiation, and death. In this review, we describe the mechanisms by which the lipid aldehydes transduce activation of NF-κB signaling pathways that may help to develop therapeutic strategies for the prevention of a number of inflammatory diseases.

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Figures

Figure 1
Figure 1
Three reaction steps in free radical initiated lipid (LH)—peroxidation leading to the formation of reactive lipid molecules (LOO·) that form lipid-derived aldehydes such as HNE, acrolein, MDA, and HHE.
Figure 2
Figure 2
Contribution of lipid peroxidation-derived aldehydes in various disease complications.
Figure 3
Figure 3
Regulation of lipid aldehyde-induced inflammatory signaling by aldose reductase.
See this image and copyright information in PMC

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