CD36 Mediated Reactive Oxygen Species Formation Contributes to Thrombosis.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1901-1901
Author(s):  
Wei Li ◽  
Maria Febbraio ◽  
Roy L. Silverstein
Keyword(s):  
Reactive Oxygen Species ◽  
Carotid Artery ◽  
Vessel Wall ◽  
Carotid Arteries ◽  
Reactive Oxygen ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Carotid Artery Injury ◽  
Artery Injury ◽  
Ros Formation

Abstract We previously showed that mice in which the CD36 gene was deleted had significantly prolonged time to form an occlusive thrombus in response to FeCl3-induced vascular injury than wild type (WT) mice. In other studies we and others have shown that CD36 promotes reactive oxygen species (ROS) formation in murine models of cerebral and cardiac ischemia. In this study, we examined the formation and roles of ROS in FeCl3-induced carotid artery injury and thrombosis using CD36 null and WT mice. Hydroethidine, a fluorescent superoxide indicator, was injected via the jugular vein and then carotid artery injury was induced in the contralateral artery by direct topical application of FeCl3 at concentrations of 7.5% or 12.5%. Fluorescence images were monitored with intravital microscopy. FeCl3 dose dependently induced significant accumulation of ROS in the vessel wall; however, the degree was significantly less in CD36 null mice than in WT mice exposed to the lower dose of FeCl3. Direct injection of Edavarone (1 mg/Kg body weight), a free radical scavenger, significantly elongated the time to thrombosis in WT mice. Thrombosis time was also increased in the CD36 null mice, but not to the same extent as WT. We also found fewer endothelial cell-derived microparticles (CD105 positive) in plasma of CD36 null mice 3 minutes after injury with the low dose of FeCl3. Immunoblots of lysates prepared from carotid arteries with thrombi or from untreated normal carotid arteries showed that levels of peroxiredoxin 2 (Prx 2), an antioxidant enzyme known to detoxify ROS, were lower in the thrombi formed from CD36 null mice, but higher in the normal vessel wall, suggesting that an anti-oxidative system may exist in the vessel wall of CD36 null mice. We conclude that CD36 plays a role in ROS formation during thrombosis and may also sensitize the vessel to injury induced by FeCl3. High Prx 2 expression in the vessel wall in CD36 null mice may contribute to the anti-oxidative effect observed in these mice.

scholarly journals Intradialytic granulocyte reactive oxygen species production: a prospective, crossover trial.

1993 ◽  
Vol 4 (2) ◽  
pp. 178-186 ◽  
Author(s):  
J Himmelfarb ◽  
K A Ault ◽  
D Holbrook ◽  
D A Leeber ◽  
R M Hakim
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Fold Increase ◽  
Ros Production ◽  
Oxygen Species ◽  
Susceptibility To Infection ◽  
Flow Cytometric ◽  
Ros Formation ◽  
Dialysis Membranes ◽  
Species Production

By the use of flow cytometric techniques, this prospective, randomized crossover study was designed to analyze intradialytic granulocyte reactive oxygen species (ROS) formation in whole blood with complement-activating and noncomplement-activating hollow fiber membranes. Dialysis with a complement-activating membrane resulted in a 6.5-fold increase in granulocyte hydrogen peroxide production 15 min after dialysis initiation and remained significantly elevated (P < 0.01) through the first 30 min with this membrane in comparison to both predialysis values and simultaneous values with a noncomplement-activating membrane. Further studies demonstrated that blood obtained at 15 min with a complement-activating membrane generated significantly less granulocyte ROS production in response to Staphylococcus aureus incubation than blood obtained either predialysis or at the same time in dialysis with a noncomplement-activating membrane. Both complement-activating and noncomplement-activating dialysis membranes caused slightly decreased granulocyte responsiveness to phorbol myristate acetate. It was concluded that hemodialysis with complement-activating membranes results in increased granulocyte ROS production and decreased responsiveness to S. aureus challenge during the dialysis procedure. These results document the potential role of ROS in hemodialysis-associated pathology and susceptibility to infection.

Effects of reactive oxygen species on prostacyclin production in perinatal rat lung cells

1989 ◽  
Vol 66 (3) ◽  
pp. 1321-1327 ◽  
Author(s):  
D. S. Lee ◽  
E. A. McCallum ◽  
D. M. Olson
Keyword(s):  
Reactive Oxygen Species ◽  
Glucose Oxidase ◽  
Reactive Oxygen ◽  
Radical Scavenger ◽  
Lung Cells ◽  
Oxygen Species ◽  
Rat Lung ◽  
Lactate Dehydrogenase Release ◽  
Culture Model

A differentiation-arrested primary cell culture model was used to examine the role of reactive oxygen species in the control of prostacyclin (PGI2) production in the perinatal rat lung. Coincubation of the lung cells with arachidonic acid (AA) and xanthine (X, 0.25 mM) plus xanthine oxidase (XO, 10 mU/ml) or with AA and glucose (25 mM) plus glucose oxidase (25 mU/ml) augmented the AA-induced PGI2 output. Superoxide dismutase (10 U/ml) did not alter the X + XO effect, whereas catalase (10 U/ml) eliminated both X + XO and glucose plus glucose oxidase effects. H2O2 (1–200 microM) showed a dose-related biphasic augmentation with peak stimulation at 20 microM. Catalase again blocked this effect, but dimethylthiourea, a hydroxyl radical scavenger, did not. A 20-min pretreatment of the cells with X + XO, glucose plus glucose oxidase, or H2O2, however, diminished the capacity of the cells to convert exogenous AA to PGI2. This pretreatment effect was also blocked by catalase. The responses were similar in lung cells obtained from day 20 rat fetuses (term = 22 days) and 1-day-old newborn rats. Lactate dehydrogenase release was not detected during treatment periods but increased significantly after exposure to reactive oxygen species.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Danina M. Muntean ◽  
Adrian Sturza ◽  
Maria D. Dănilă ◽  
Claudia Borza ◽  
Oana M. Duicu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Myocardial Injury ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Early Reperfusion ◽  
Coronary Syndromes ◽  
Ros Formation ◽  
St Elevation ◽  
Protective Strategies ◽  
Routine Therapy

Ischaemia/reperfusion (I/R) injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST-elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS). Besides their harmful role when highly generated during early reperfusion, minimal ROS formation during ischaemia and/or at reperfusion is critical for the redox signaling of cardioprotection. In the past decades, mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion. Mitochondria dysfunction associated with I/R myocardial injury is further described and ultimately analyzed with respect to its role as source of both deleterious and beneficial ROS. Furthermore, the contribution of ROS in the highly investigated field of conditioning strategies is analyzed. In the end, the vascular sources of mitochondria-derived ROS are briefly reviewed.

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.

Induction of Noxa Via Generation of Reactive Oxygen Species Plays a Key Role in Induction of CLL Cell Apoptosis by Two Novel p53-Independent Cytotoxic Agents.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2752-2752
Author(s):  
Andrew Steele ◽  
Archibald G Prentice ◽  
Anastasios Chanalaris ◽  
A. Victor Hoffbrand ◽  
Kate Cwynarski ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Apoptosis ◽  
Conflicts Of Interest ◽  
Reactive Oxygen ◽  
Cytotoxic Agents ◽  
Ros Generation ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Independent Manner ◽  
Factor C

Abstract Abstract 2752 Poster Board II-728 Approximately 15% of CLL patients present with a deletion of chromosome 17p, resulting in the loss of the p53 gene. The percentage of 17p-deleted patients can increase to between 30–50% following treatment with cytotoxic agents which induce CLL apoptosis via upregulation of p53. Therefore, identification of novel agents which kill CLL cells independently of p53 is of crucial importance. We have recently shown that two chemically unrelated agents, 2-phenylacetylenesulfonamide (PAS) and the sesquiterpene lactone LC1 kill CLL cells regardless of the functional status of p53. Furthermore, in contrast to the conventional drugs chlorambucil and fludarabine, PAS and LC1 induce apoptosis in the absence of p53 elevation. However, the mechanisms of action by which these agents induce p53-independent apoptosis are unclear. We have previously shown that both PAS and LC1 initiated CLL cell apoptosis within 6-10h with, maximal killing by 48h. Here we show that treatment of CLL cells with either agent results in the generation of reactive oxygen species (ROS), the activating phosphorylation of the pro-apoptotic MAP kinase family member JNK (Fig 1), resulting in turn in upregulation of its downstream target, the transcription factor c-JUN (Fig 2). The BH3-only pro-apoptotic protein Noxa was originally described as a pro-apoptotic target for upregulation by p53. However, both PAS (Figs1 and 2) and LC1 upregulated Noxa in a p53-independent manner. Addition of N-acetylcysteine (NAC), a free radical scavenger, decreased ROS generation by PAS or LC1 and also prevented phosphorylation of JNK and Noxa upregulation (Fig 1) and also the upregulation of c-JUN. NAC also strikingly abrogated apoptosis induction by either agent, as shown by quantitation of cleavage of the caspase 3 substrate poly (ADP ribose) polymerase (PARP; Fig 1). Taken together, the data suggest both PAS and LC1 induce p53-independent apoptosis via upregulation of ROS and the subsequent induction of Noxa. The data are also compatible with a role for JNK and c-JUN in the events leading to Noxa upregulation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Reactive Oxygen Species and Induction of Lignin Peroxidase in Phanerochaete chrysosporium

2003 ◽  
Vol 69 (11) ◽  
pp. 6500-6506 ◽  
Author(s):  
Paula A. Belinky ◽  
Nufar Flikshtein ◽  
Sergey Lechenko ◽  
Shimon Gepstein ◽  
Carlos G. Dosoretz
Keyword(s):  
Reactive Oxygen Species ◽  
Oxidative Damage ◽  
Phanerochaete Chrysosporium ◽  
Hydroxyl Radicals ◽  
Lignin Peroxidase ◽  
Manganese Superoxide Dismutase ◽  
Reactive Oxygen ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Atmospheric Air

ABSTRACT We studied oxidative stress in lignin peroxidase (LIP)-producing cultures (cultures flushed with pure O2) of Phanerochaete chrysosporium by comparing levels of reactive oxygen species (ROS), cumulative oxidative damage, and antioxidant enzymes with those found in non-LIP-producing cultures (cultures grown with free exchange of atmospheric air [control cultures]). A significant increase in the intracellular peroxide concentration and the degree of oxidative damage to macromolecules, e.g., DNA, lipids, and proteins, was observed when the fungus was exposed to pure O2 gas. The specific activities of manganese superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase and the consumption of glutathione were all higher in cultures exposed to pure O2 (oxygenated cultures) than in cultures grown with atmospheric air. Significantly higher gene expression of the LIP-H2 isozyme occurred in the oxygenated cultures. A hydroxyl radical scavenger, dimethyl sulfoxide (50 mM), added to the culture every 12 h, completely abolished LIP expression at the mRNA and protein levels. This effect was confirmed by in situ generation of hydroxyl radicals via the Fenton reaction, which significantly enhanced LIP expression. The level of intracellular cyclic AMP (cAMP) was correlated with the starvation conditions regardless of the oxygenation regimen applied, and similar cAMP levels were obtained at high O2 concentrations and in cultures grown with atmospheric air. These results suggest that even though cAMP is a prerequisite for LIP expression, high levels of ROS, preferentially hydroxyl radicals, are required to trigger LIP synthesis. Thus, the induction of LIP expression by O2 is at least partially mediated by the intracellular ROS.

Intracellular generation of reactive oxygen species in endothelial cells exposed to anoxia-reoxygenation

1997 ◽  
Vol 272 (5) ◽  
pp. L897-L902 ◽  
Author(s):  
J. J. Zulueta ◽  
R. Sawhney ◽  
F. S. Yu ◽  
C. C. Cote ◽  
P. M. Hassoun
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Intracellular Ros ◽  
Ros Formation ◽  
Oxide Synthase

Reactive oxygen species (ROS) play an important role in the pathogenesis of ischemia-reperfusion injury. Extracellular H2O2 generation from bovine pulmonary artery endothelial cells (EC) is known to increase in response to anoxia-reoxygenation (A-R). To determine potential sources of intracellular ROS formation in EC in response to A-R, a fluorometric assay based on the oxidation of 2',7'-dichlorofluorescin was used. Intracellular ROS production declined 40% during 6 h of anoxia (P < 0.05). After A-R, the rates of intracellular ROS formation increased to 148 +/- 9% (P < 0.001) that of normoxic EC (100 +/- 3%). In EC exposed to A-R, allopurinol and NG-methyl-L-arginine (L-NMMA), inhibitors of xanthine oxidase (XO) and nitric oxide synthase (NOS), respectively, reduced intracellular ROS formation by 25 +/- 1% (P < 0.001) and 36 +/- 4% (P < 0.01). Furthermore, at low doses (i.e., 20 microM), deferoxamine and diethylenetriaminepentaacetic acid (DTPA) significantly inhibited intracellular ROS formation. However, at 100 microM, only deferoxamine caused further reduction in DCF fluorescence. In summary, EC respond to A-R by generating increased amounts of XO- and NOS-derived intracellular ROS. The inhibition, to a similar extent, caused by allopurinol and L-NMMA, as well as the effect of deferoxamine and DTPA suggest that the ROS detected is peroxynitrite. Based on these findings and previous work, we conclude that EC generate ROS in response to A-R from at least two different sources: a plasma membrane-bound NADPH oxidase-like enzyme that releases H2O2 extracellularly and XO, which generates intracellular O2-, which in turn may react with nitric oxide to form peroxynitrite.

scholarly journals Role of Reactive Oxygen Species in Pathogenesis of Radiocontrast-Induced Nephropathy

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Antonio Pisani ◽  
Eleonora Riccio ◽  
Michele Andreucci ◽  
Teresa Faga ◽  
Michael Ashour ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Contrast Media ◽  
Reactive Oxygen ◽  
In Vivo Studies ◽  
Ros Generation ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Iodinated Contrast ◽  
Ros Formation

In vitro and in vivo studies have demonstrated enhanced hypoxia and formation of reactive oxygen species (ROS) in the kidney following the administration of iodinated contrast media, which play a relevant role in the development of contrast media-induced nephropathy. Many studies indeed support this possibility, suggesting a protective effect of ROS scavenging or reduced ROS formation with the administration of N-acetylcysteine and bicarbonate infusion, respectively. Furthermore, most risk factors, predisposing to contrast-induced nephropathy, are prone to enhanced renal parenchymal hypoxia and ROS formation. In this review, the association of renal hypoxia and ROS-mediated injury is outlined. Generated during contrast-induced renal parenchymal hypoxia, ROS may exert direct tubular and vascular endothelial injury and might further intensify renal parenchymal hypoxia by virtue of endothelial dysfunction and dysregulation of tubular transport. Preventive strategies conceivably should include inhibition of ROS generation or ROS scavenging.

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