Regulation of NF-B-Induced Inflammatory Signaling by Lipid Peroxidation-Derived Aldehydes

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.

Obesity, bariatric surgery and oxidative stress

“…This suggests that the patients were predisposed to develop many diseases, as well as to face accelerated aging, because the cytotoxicity caused by lipid oxidation favors uncontrolled cell growth and/or cell death. 26 However, the risk appeared to decline after bariatric surgery, since LPO in the post-surgical obese group was lower than in the pre-surgical obese group. This result may be explained by the decline in body weight presented by the patients since, according to Yesilbursa,27 weight loss is accompanied by reduced ROS production and decreased MDA levels.…”

Reactive Oxygen Species, Redox Signaling and Neuroinflammation in Alzheimer's Disease: The NF-κB Connection

“…Likewise, when cells are exposed to conditions of oxidative stress such as hypoxia or reperfusion injury, the activation of NF-κB by endogenous ROS has been clearly demonstrated [66,72,73]. The toxic intermediates of lipid peroxidation, in particular 4-hydroxynonenal, also have been shown to be involved in NF-κB activation in various experimental conditions [74][75][76] In conformity with these findings, antioxidants of various types and most notably N-acetylcysteine and pyrrolidine thiocarbamate have been shown to prevent NF-κB activation by different inducers like cytokines, viruses, dsRNA, endotoxins, phorbol ester, lipopolysaccharide etc. in a large number of cell lines [67,69,75].…”

Blood ALDH1 and GST Activity in Diabetes Type 2 and its Correlation with Glycated Hemoglobin

“…Excessive levels of LDAs are decreased by several enzyme systems that are able to oxidize them to acids like aldehyde dehydrogenase (ALDH) or catalyze their conjugation with endogenous ligands like glutathione-S-transferase (GST) [ 5 ] . There are only a few studies on erythrocyte glutathione S-transferase (GST) activity in DM, the results of which are ambiguous.…”