scholarly journals Do antioxidants impair signaling by reactive oxygen species and lipid oxidation products?

FEBS Letters ◽  
2012 ◽  
Vol 586 (21) ◽  
pp. 3767-3770 ◽  
Author(s):  
Etsuo Niki
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Oxidation ◽  
Reactive Oxygen ◽  
Oxidation Products ◽  
Oxygen Species ◽  
Lipid Oxidation Products

Cell signalling by oxidized lipids and the role of reactive oxygen species in the endothelium

2005 ◽  
Vol 33 (6) ◽  
pp. 1385-1389 ◽  
Author(s):  
J.W. Zmijewski ◽  
A. Landar ◽  
N. Watanabe ◽  
D.A. Dickinson ◽  
N. Noguchi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Oxidation ◽  
Protein Function ◽  
Cell Signalling ◽  
Reactive Oxygen ◽  
Oxidation Products ◽  
Oxidized Lipids ◽  
Oxygen Species ◽  
Post Translational Modification ◽  
Lipid Oxidation Products

The controlled formation of ROS (reactive oxygen species) and RNS (reactive nitrogen species) is now known to be critical in cellular redox signalling. As with the more familiar phosphorylation-dependent signal transduction pathways, control of protein function is mediated by the post-translational modification at specific amino acid residues, notably thiols. Two important classes of oxidant-derived signalling molecules are the lipid oxidation products, including those with electrophilic reactive centres, and decomposition products such as lysoPC (lysophosphatidylcholine). The mechanisms can be direct in the case of electrophiles, as they can modify signalling proteins by post-translational modification of thiols. In the case of lysoPC, it appears that secondary generation of ROS/RNS, dependent on intracellular calcium fluxes, can cause the secondary induction of H2O2 in the cell. In either case, the intracellular source of ROS/RNS has not been defined. In this respect, the mitochondrion is particularly interesting since it is now becoming apparent that the formation of superoxide from the respiratory chain can play an important role in cell signalling, and oxidized lipids can stimulate ROS formation from an undefined source. In this short overview, we describe recent experiments that suggest that the cell signalling mediated by lipid oxidation products involves their interaction with mitochondria. The implications of these results for our understanding of adaptation and the response to stress in cardiovascular disease are discussed.

Interaction of electrophilic lipid oxidation products with mitochondria in endothelial cells and formation of reactive oxygen species

2006 ◽  
Vol 290 (5) ◽  
pp. H1777-H1787 ◽  
Author(s):  
Aimee Landar ◽  
Jaroslaw W. Zmijewski ◽  
Dale A. Dickinson ◽  
Claire Le Goffe ◽  
Michelle S. Johnson ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Reactive Oxygen ◽  
Direct Interaction ◽  
Oxidation Products ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Oxygen Species ◽  
Lipid Oxidation Products ◽  
Ros Formation

Electrophilic lipids, such as 4-hydroxynonenal (HNE), and the cyclopentenones 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and 15-J2-isoprostane induce both reactive oxygen species (ROS) formation and cellular antioxidant defenses, such as heme oxygenase-1 (HO-1) and glutathione (GSH). When we compared the ability of these distinct electrophiles to stimulate GSH and HO-1 production, the cyclopentenone electrophiles were somewhat more potent than HNE. Over the concentration range required to observe equivalent induction of GSH, dichlorofluorescein fluorescence was used to determine both the location and amounts of electrophilic lipid-dependent ROS formation in endothelial cells. The origin of the ROS on exposure to these compounds was largely mitochondrial. To investigate the possibility that the increased ROS formation was due to mitochondrial localization of the lipids, we prepared a novel fluorescently labeled form of the electrophilic lipid 15d-PGJ2. The lipid demonstrated strong colocalization with the mitochondria, an effect which was not observed by using a fluorescently labeled nonelectrophilic lipid. The role of mitochondria was confirmed by using cells deficient in functional mitochondria. On the basis of these data, we propose that ROS formation in endothelial cells is due to the direct interaction of these lipids with the organelle.

Scavenging Reactive Lipids to Prevent Oxidative Injury

2021 ◽  
Vol 61 (1) ◽  
pp. 291-308 ◽  
Author(s):  
Linda S. May-Zhang ◽  
Annet Kirabo ◽  
Jiansheng Huang ◽  
MacRae F. Linton ◽  
Sean S. Davies ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Host Defense ◽  
Reactive Oxygen ◽  
Oxidative Injury ◽  
Oxidation Products ◽  
Oxygen Species ◽  
The Past ◽  
Lipid Oxidation Products ◽  
Induce Lipid Peroxidation

Oxidative injury due to elevated levels of reactive oxygen species is implicated in cardiovascular diseases, Alzheimer's disease, lung and liver diseases, and many cancers. Antioxidant therapies have generally been ineffective at treating these diseases, potentially due to ineffective doses but also due to interference with critical host defense and signaling processes. Therefore, alternative strategies to prevent oxidative injury are needed. Elevated levels of reactive oxygen species induce lipid peroxidation, generating reactive lipid dicarbonyls. These lipid oxidation products may be the most salient mediators of oxidative injury, as they cause cellular and organ dysfunction by adducting to proteins, lipids, and DNA. Small-molecule compounds have been developed in the past decade to selectively and effectively scavenge these reactive lipid dicarbonyls. This review outlines evidence supporting the role of lipid dicarbonyls in disease pathogenesis, as well as preclinical data supporting the efficacy of novel dicarbonyl scavengers in treating or preventing disease.

scholarly journals Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization

2017 ◽  
Vol 313 (5) ◽  
pp. C541-C555 ◽  
Author(s):  
Pinaki Chaudhuri ◽  
Michael A. Rosenbaum ◽  
Lutz Birnbaumer ◽  
Linda M. Graham
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Transient Receptor Potential ◽  
Reactive Oxygen ◽  
Oxidation Products ◽  
Oxygen Species ◽  
Subsequent Increase ◽  
Erk Activation ◽  
Lipid Oxidation Products ◽  
Nadph Oxidase Activation

Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels, and the subsequent increase in intracellular Ca2+ leads to TRPC5 activation. The goal of this study is to elucidate the steps in the pathway between TRPC6 activation and TRPC5 externalization. Following TRPC6 activation by lysoPC, extracellular regulated kinase (ERK) is phosphorylated. This leads to phosphorylation of p47phox and subsequent NADPH oxidase activation with increased production of reactive oxygen species. ERK activation requires TRPC6 opening and influx of Ca2+ as evidenced by the failure of lysoPC to induce ERK phosphorylation in TRPC6−/− endothelial cells. ERK siRNA blocks the lysoPC-induced activation of NADPH oxidase, demonstrating that ERK activation is upstream of NADPH oxidase. The reactive oxygen species produced by NADPH oxidase promote myosin light chain kinase (MLCK) activation with phosphorylation of MLC and TRPC5 externalization. Downregulation of ERK, NADPH oxidase, or MLCK with the relevant siRNA prevents TRPC5 externalization. Blocking MLCK activation prevents the prolonged rise in intracellular calcium levels and preserves endothelial migration in the presence of lysoPC.

scholarly journals Phospholipid oxidation products in ferroptotic myocardial cell death

2019 ◽  
Vol 317 (1) ◽  
pp. H156-H163 ◽  
Author(s):  
Aleksandra Stamenkovic ◽  
Grant N. Pierce ◽  
Amir Ravandi
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Myocardial Cell ◽  
Oxidation Products ◽  
Oxygen Species ◽  
New Therapeutic Approaches

Cell death is an important component of the pathophysiology of any disease. Myocardial disease is no exception. Understanding how and why cells die, particularly in the heart where cardiomyocyte regeneration is limited at best, becomes a critical area of study. Ferroptosis is a recently described form of nonapoptotic cell death. It is an iron-mediated form of cell death that occurs because of accumulation of lipid peroxidation products. Reactive oxygen species and iron-mediated phospholipid peroxidation is a hallmark of ferroptosis. To date, ferroptosis has been shown to be involved in cell death associated with Alzheimer’s disease, Huntington’s disease, cancer, Parkinson’s disease, and kidney degradation. Myocardial reperfusion injury is characterized by iron deposition as well as reactive oxygen species production. These conditions, therefore, favor the induction of ferroptosis. Currently there is no available treatment for reperfusion injury, which accounts for up to 50% of the final infarct size. This review will summarize the evidence that ferroptosis can induce cardiomyocyte death following reperfusion injury and the potential for this knowledge to open new therapeutic approaches for myocardial ischemia-reperfusion injury.

scholarly journals Mapping three guanine oxidation products along DNA following exposure to three types of reactive oxygen species

2018 ◽  
Vol 121 ◽  
pp. 180-189 ◽  
Author(s):  
Brock Matter ◽  
Christopher L. Seiler ◽  
Kristopher Murphy ◽  
Xun Ming ◽  
Jianwei Zhao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxidation Products ◽  
Oxygen Species ◽  
Guanine Oxidation

scholarly journals The oxidation of dehydroascorbic acid and 2,3-diketogulonate by distinct reactive oxygen species

2018 ◽  
Vol 475 (21) ◽  
pp. 3451-3470 ◽  
Author(s):  
Rebecca A. Dewhirst ◽  
Stephen C. Fry
Keyword(s):  
Reactive Oxygen Species ◽  
Ascorbic Acid ◽  
Hydroxyl Radicals ◽  
Reactive Oxygen ◽  
Dehydroascorbic Acid ◽  
Oxidation Products ◽  
Oxygen Species ◽  
H2o2 Treatment ◽  
Fold Excess

l-Ascorbate, dehydro-l-ascorbic acid (DHA), and 2,3-diketo-l-gulonate (DKG) can all quench reactive oxygen species (ROS) in plants and animals. The vitamin C oxidation products thereby formed are investigated here. DHA and DKG were incubated aerobically at pH 4.7 with peroxide (H2O2), ‘superoxide’ (a ∼50 : 50 mixture of and ), hydroxyl radicals (•OH, formed in Fenton mixtures), and illuminated riboflavin (generating singlet oxygen, 1O2). Products were monitored electrophoretically. DHA quenched H2O2 far more effectively than superoxide, but the main products in both cases were 4-O-oxalyl-l-threonate (4-OxT) and smaller amounts of 3-OxT and OxA + threonate. H2O2, but not superoxide, also yielded cyclic-OxT. Dilute Fenton mixture almost completely oxidised a 50-fold excess of DHA, indicating that it generated oxidant(s) greatly exceeding the theoretical •OH yield; it yielded oxalate, threonate, and OxT. 1O2 had no effect on DHA. DKG was oxidatively decarboxylated by H2O2, Fenton mixture, and 1O2, forming a newly characterised product, 2-oxo-l-threo-pentonate (OTP; ‘2-keto-l-xylonate’). Superoxide yielded negligible OTP. Prolonged H2O2 treatment oxidatively decarboxylated OTP to threonate. Oxidation of DKG by H2O2, Fenton mixture, or 1O2 also gave traces of 4-OxT but no detectable 3-OxT or cyclic-OxT. In conclusion, DHA and DKG yield different oxidation products when attacked by different ROS. DHA is more readily oxidised by H2O2 and superoxide; DKG more readily by 1O2. The diverse products are potential signals, enabling organisms to respond appropriately to diverse stresses. Also, the reaction-product ‘fingerprints’ are analytically useful, indicating which ROS are acting in vivo.

Abstract 220: Detection of Cysteine Sulfenic Acid Formation: Role in Reactive Oxygen Species-dependent VEGF signaling Linked to Endothelial Migration

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Yoshimasa Nakamura ◽  
Nihal Kaplan ◽  
Leslie B Poole ◽  
Tohru Fukai ◽  
Masuko Ushio-Fukai
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Modification ◽  
Reactive Oxygen ◽  
Leading Edge ◽  
Oxidation Products ◽  
Actin Binding ◽  
Vegf Receptor ◽  
Oxygen Species ◽  
Sulfenic Acid ◽  
Vegf Signaling

NADPH oxidase Nox2-derived reactive oxygen species (ROS) have been implicated in VEGF receptor type2 (VEGFR2)-mediated signaling linked to endothelial cell (EC) migration. ROS-mediated protein modification involves oxidation of reactive cysteine residues to form a cysteine sulfenic acid (Cys-SOH) and subsequent oxidation products. However, the role of Cys-SOH formation in VEGF signaling and EC migration remains unknown. Using a newly-developed Cys-SOH trapping reagent, here we show that VEGF stimulation significantly increases the total Cys-SOH formation of proteins in HUVECs. VEGFR2 immunoprecipitates show significant increase in Cys-SOH within 5 min (90.3%), which remained elevated at least for 30 min (30.1%). This VEGF-induced Cys-SOH formation of VEGFR2 is prevented by pretreatment with a thiol donor antioxidant, N-acetylcysteine, which is associated with inhibition of VEGFR2 autophosphorylation (80.2%). The trapping of endogenous Cys-SOH by dimedone blocks VEGFR2 autophosphorylation (50.3%), its downstream phosphorylation of PLCgamma (70.4%) and ERK1/2 (90.1%) as well as EC migration (80.3%) without affecting p38MAPK phosphorylation. Wound scratch assay and immunofluorescence analysis reveal that Cys-SOH modified proteins are accumulated at the leading edge where they colocalize with Nox2, phospho-VEGFR2, F-actin and IQGAP1, a novel VEGFR2- and actin-binding scaffold protein, in actively migrating ECs. A significant increase in Cys-SOH is also seen in IQGAP1 coprecipitates (~250 kDa) following VEGF stimulation with peak at 2 min (50.1% increase). Knockdown of IQGAP1 using siRNA, or trapping of Cys-SOH block wound-induced Cys-SOH formation at the leading edge as well as EC migration toward the injured site. In summary, these results suggest that VEGFR2 and IQGAP1-associated proteins are targets for Cys-SOH formation at the leading edge in actively migrating ECs. The present study provides a novel mechanism of redox regulation in VEGF signaling linked to EC migration, and a rationale for the importance of identification of novel proteins that form Cys-SOH during repair process after injury and angiogenesis in vivo. This research has received full or partial funding support from the American Heart Association, AHA National Center.

scholarly journals Multiphase composition changes and reactive oxygen species formation during limonene oxidation in the new Cambridge Atmospheric Simulation Chamber (CASC)

2017 ◽  
Vol 17 (16) ◽  
pp. 9853-9868 ◽  
Author(s):  
Peter J. Gallimore ◽  
Brendan M. Mahon ◽  
Francis P. H. Wragg ◽  
Stephen J. Fuller ◽  
Chiara Giorio ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Gas Phase ◽  
Organic Aerosols ◽  
Reactive Oxygen ◽  
Oxidation Products ◽  
Oxygen Species ◽  
Particle Phase ◽  
Aerosol Formation ◽  
Organic Species ◽  
Simulation Chamber

Abstract. The chemical composition of organic aerosols influences their impacts on human health and the climate system. Aerosol formation from gas-to-particle conversion and in-particle reaction was studied for the oxidation of limonene in a new facility, the Cambridge Atmospheric Simulation Chamber (CASC). Health-relevant oxidising organic species produced during secondary organic aerosol (SOA) formation were quantified in real time using an Online Particle-bound Reactive Oxygen Species Instrument (OPROSI). Two categories of reactive oxygen species (ROS) were identified based on time series analysis: a short-lived component produced during precursor ozonolysis with a lifetime of the order of minutes, and a stable component that was long-lived on the experiment timescale (∼ 4 h). Individual organic species were monitored continuously over this time using Extractive Electrospray Ionisation (EESI) Mass Spectrometry (MS) for the particle phase and Proton Transfer Reaction (PTR) MS for the gas phase. Many first-generation oxidation products are unsaturated, and we observed multiphase aging via further ozonolysis reactions. Volatile products such as C9H14O (limonaketone) and C10H16O2 (limonaldehyde) were observed in the gas phase early in the experiment, before reacting again with ozone. Loss of C10H16O4 (7-hydroxy limononic acid) from the particle phase was surprisingly slow. A combination of reduced C = C reactivity and viscous particle formation (relative to other SOA systems) may explain this, and both scenarios were tested in the Pretty Good Aerosol Model (PG-AM). A range of characterisation measurements were also carried out to benchmark the chamber against existing facilities. This work demonstrates the utility of CASC, particularly for understanding the reactivity and health-relevant properties of organic aerosols using novel, highly time-resolved techniques.

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