Regulation of NF-B-Induced Inflammatory Signaling by Lipid Peroxidation-Derived Aldehydes
Open Access
- 17 April 2013
- journal article
- review article
- Published by Hindawi Limited in Oxidative Medicine and Cellular Longevity
- Vol. 2013, 1-11
- https://doi.org/10.1155/2013/690545
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-B 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-B signaling pathways that may help to develop therapeutic strategies for the prevention of a number of inflammatory diseases.Keywords
This publication has 110 references indexed in Scilit:
- Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signalingCellular Signalling, 2012
- Clinical trials of antioxidants as cancer prevention agents: Past, present, and futureFree Radical Biology & Medicine, 2011
- Aldose reductase inhibition suppresses oxidative stress-induced inflammatory disordersChemico-Biological Interactions, 2011
- Role of 4-hydroxynonenal in epidermal growth factor receptor-mediated signaling in retinal pigment epithelial cellsExperimental Eye Research, 2011
- Involvements of the lipid peroxidation product, HNE, in the pathogenesis and progression of Alzheimer's diseaseBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2010
- Reactive oxygen species, cellular redox systems, and apoptosisFree Radical Biology & Medicine, 2010
- Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disordersExperimental Gerontology, 2009
- The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenalArchives of Biochemistry and Biophysics, 2008
- Free radicals and antioxidants in normal physiological functions and human diseaseThe International Journal of Biochemistry & Cell Biology, 2007
- The Pecking Order of Free Radicals and Antioxidants: Lipid Peroxidation, α-Tocopherol, and AscorbateArchives of Biochemistry and Biophysics, 1993