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See detailOverexpression of GRP94 in breast cancer cells resistant to oxidative stress promotes high levels of cancer cell proliferation and migration: implications for tumor recurrence.
Dejeans, Nicolas; Glorieux, Christophe; Guénin, Samuel ULg et al

in Free Radical Biology & Medicine (2012), 52(6), 993-1002

Targeting the altered redox status of cancer cells is emerging as an interesting approach to potentiate chemotherapy. However, to maximize the effectiveness of this strategy and define the correct ... [more ▼]

Targeting the altered redox status of cancer cells is emerging as an interesting approach to potentiate chemotherapy. However, to maximize the effectiveness of this strategy and define the correct chemotherapeutic associations, it is important to understand the biological consequences of chronically exposing cancer cells to reactive oxygen species (ROS). Using an H(2)O(2)-generating system, we selected a ROS-resistant MCF-7 breast cancer cell line, namely Resox cells. By exploring different survival pathways that are usually induced during oxidative stress, we identified a constitutive overexpression of the endoplasmic reticulum chaperone, GRP94, in these cells, whereas levels of its cytoplasmic homolog HSP90, or GRP78, were not modified. This overexpression was not mediated by constitutive unfolded protein response (UPR) activation. The increase in GRP94 is tightly linked to an increase in cell proliferation and migration capacities, as shown by GRP94-silencing experiments. Interestingly, we also observed that GRP94 silencing inhibits migration and proliferation of the highly aggressive MDA-MB-231 cells. By immunohistochemistry, we showed that GRP94 expression was higher in recurrent human breast cancers than in their paired primary neoplasias. Similar to the situation in the Resox cells, this increase was not associated with an increase in UPR activation in recurrent tumors. In conclusion, this study suggests that GRP94 overexpression may be a hallmark of aggressiveness and recurrence in breast cancers. [less ▲]

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See detailAntioxidant and anti-inflammatory like properties of benzoic acid analogs on the oxidant response of neutrophils: structure/redox potential relationship study.
Franck, Thierry ULg; Mouithys-Mickalad, Ange ULg; Robert, Thierry ULg et al

in Free Radical Biology & Medicine (2012), 53(supplement 1),

We investigated the antioxidant capacity of phenolic acid derivatives by measuring their capacity to prevent ABTS oxidation and evaluating their anti-inflammatory like-properties on the oxidant response ... [more ▼]

We investigated the antioxidant capacity of phenolic acid derivatives by measuring their capacity to prevent ABTS oxidation and evaluating their anti-inflammatory like-properties on the oxidant response of neutrophils, especially on superoxide anion production and the activity of myeloperoxidase (MPO), an oxidant enzyme present and released by the primary granules of neutrophils. The superoxide anion production by PMA-stimulated neutrophils was measured by lucigenin-enhanced chimiluminescence (CL) and the activity of MPO by SIEFED to study the potential interaction of a molecule with the enzyme without interferences due to medium. The antioxidant and anti-inflammatory activities of the phenolic compounds were correlated to their redox potentials measured by voltammetry method, and discussed in relation to their molecular structure. The ability of the phenolic molecules to decrease ABTS oxidation and CL production was inversely correlated to their redox potential increasing as follows: propyl gallate > gallic acid > caffeic acid > 3,4-dihydroxybenzoic acid > ferulic acid > syringic acid > 2,6-dihydroxybenzoic acid > salicylic acid > benzoic acid. The number of hydroxyl groups (3) and their position (catechol) were essential for the efficacy of the molecules as stoichiometric antioxidants or scavengers. On MPO activity, the inhibitory capacity of the molecules was not really correlated with their redox potential and increased as follows: gallic acid > caffeic acid > 2,6-dihydroxybenzoic acid > propyl gallate > ferulic acid = syringic acid > 3,4-dihydroxybenzoic acid = salicylic acid > benzoic acid. The number of OH groups and the elongation of the carboxyl group were essential for the inhibition of MPO activity, probably by facilitating the interaction with the MPO active site or structure. The redox potential measurement seems to be a good technique to select stoichiometric antioxidants, but not anti-catalytic ones. [less ▲]

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See detailFunctional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction.
Turki, Ahmed; Hayot, Maurice; Carnac, Gilles et al

in Free Radical Biology & Medicine (2012), 53(5), 1068-79

Facioscapulohumeral muscular dystrophy (FSHD), the most frequent muscular dystrophy, is an autosomal dominant disease. In most individuals with FSHD, symptoms are restricted to muscles of the face, arms ... [more ▼]

Facioscapulohumeral muscular dystrophy (FSHD), the most frequent muscular dystrophy, is an autosomal dominant disease. In most individuals with FSHD, symptoms are restricted to muscles of the face, arms, legs, and trunk. FSHD is genetically linked to contractions of the D4Z4 repeat array causing activation of several genes. One of these maps in the repeat itself and expresses the DUX4 (the double homeobox 4) transcription factor causing a gene deregulation cascade. In addition, analyses of the RNA or protein expression profiles in muscle have indicated deregulations in the oxidative stress response. Since oxidative stress affects peripheral muscle function, we investigated mitochondrial function and oxidative stress in skeletal muscle biopsies and blood samples from patients with FSHD and age-matched healthy controls, and evaluated their association with physical performances. We show that specifically, oxidative stress (lipid peroxidation and protein carbonylation), oxidative damage (lipofuscin accumulation), and antioxidant enzymes (catalase, copper-zinc-dependent superoxide dismutase, and glutathione reductase) were higher in FSHD than in control muscles. FSHD muscles also presented abnormal mitochondrial function (decreased cytochrome c oxidase activity and reduced ATP synthesis). In addition, the ratio between reduced (GSH) and oxidized glutathione (GSSG) was strongly decreased in all FSHD blood samples as a consequence of GSSG accumulation. Patients with FSHD also had reduced systemic antioxidative response molecules, such as low levels of zinc (a SOD cofactor), selenium (a GPx cofactor involved in the elimination of lipid peroxides), and vitamin C. Half of them had a low ratio of gamma/alpha tocopherol and higher ferritin concentrations. Both systemic oxidative stress and mitochondrial dysfunction were correlated with functional muscle impairment. Mitochondrial ATP production was significantly correlated with both quadriceps endurance (T(LimQ)) and maximal voluntary contraction (MVC(Q)) values (rho=0.79, P=0.003; rho=0.62, P=0.05, respectively). The plasma concentration of oxidized glutathione was negatively correlated with the T(LimQ), MVC(Q) values, and the 2-min walk distance (MWT) values (rho=-0.60, P=0.03; rho=-0.56, P=0.04; rho=-0.93, P<0.0001, respectively). Our data characterized oxidative stress in patients with FSHD and demonstrated a correlation with their peripheral skeletal muscle dysfunction. They suggest that antioxidants that might modulate or delay oxidative insult may be useful in maintaining FSHD muscle functions. [less ▲]

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See detailRole of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis.
Chretien, Aline; Dierick, Jean-Francois; Delaive, Edouard et al

in Free Radical Biology & Medicine (2008), 44(9), 1732-51

The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta1-independent changes in protein synthesis are ... [more ▼]

The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta1-independent changes in protein synthesis are involved in this morphogenesis and to study possible mechanisms occurring earlier than TGF-beta1 overexpression. Among the multiple TGF-beta1-independent changes in protein neosynthesis, followed or not by posttranslational modifications, identified by proteomic analysis herein, those of ezrin, L-caldesmon, and HSP27 were particularly studied. Rho-GTPase cdc42 was shown to be responsible for p38(MAPK) activation, in turn triggering phosphorylation of L-caldesmon and HSP27. Cdc42 was also shown to be mainly responsible for the increase in TGF-beta1 mRNA level observed at 24 h after treatment with H(2)O(2) and onward. This study further clarified the mechanisms of senescence-like morphogenesis in addition to the previously demonstrated role of TGF-beta1 signaling pathways. [less ▲]

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See detailUncoupling protein 1 affects the yeast mitoproteome and oxygen free radical production
Douette, Pierre ULg; Gerkens, Pascal; Navet, Rachel ULg et al

in Free Radical Biology & Medicine (2006), 40(2), 303-315

Uncoupling protein I (UCP1) is a mitochondrial inner membrane protein that dissipates the proton electrochemical gradient built up by the respiratory chain. its activity is stimulated by free fatty acids ... [more ▼]

Uncoupling protein I (UCP1) is a mitochondrial inner membrane protein that dissipates the proton electrochemical gradient built up by the respiratory chain. its activity is stimulated by free fatty acids and inhibited by purine nucleotides. Here we investigated how active and regulated recombinant UCP1 expressed in yeast at similar to 1 and similar to 10 mu g/mg of total mitochondrial proteins induced changes in the mitochondrial proteome and in oxygen free radical production. Using two-dimensional differential in-gel electrophoresis (2D-DIGE), we found that most of the proteins involved in the response to ectopically expressed UCP1 are related to energy metabolism. We also quantified the cellular H2O2 release in the absence or in the presence of UCP1. Our results suggest that UCP1 has a dual influence on free radical generation. On one side, FFA-activated UCP1 was able to decrease the superoxide anion production, demonstrating that a decrease in the generation of reactive oxygen species is an obligatory outcome of UCP1 activity even in a heterologous context. On the other side, an increase in UCP1 content was concomitant with an increase in the basal release of superoxide anion by mitochondria as a side consequence of the overall increase in oxidative metabolism. (c) 2005 Elsevier Inc. All rights reserved. [less ▲]

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See detailMitochondrial uncoupling proteins: new insights from functional and proteomic studies.
Douette, P.; Sluse, Francis ULg

in Free Radical Biology & Medicine (2006), 40

Mitochondria are the major sites of ATP synthesis through oxidative phosphorylation, a process that is weakened by proton leak. Uncoupling proteins are mitochondrial membrane proteins specialized in ... [more ▼]

Mitochondria are the major sites of ATP synthesis through oxidative phosphorylation, a process that is weakened by proton leak. Uncoupling proteins are mitochondrial membrane proteins specialized in inducible proton conductance. They dissipate the proton electrochemical gradient established by the respiratory chain at the expense of reducing substrates. Several physiological roles have been suggested for uncoupling proteins, including roles in the control of the cellular energy balance and in preventive action against oxidative stress. This review focuses on new leads emerging from comparative proteomics about the involvement of uncoupling protein in the mitochondrial physiology. A brief overview on uncoupling proteins and on proteomics applied to mitochondria is also presented herein. [less ▲]

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See detailTransient modifications of respiratory capacity in thymic cells during murine radioleukemogenesis
Verlaet, Myriam ULg; Duyckaerts, Claire ULg; Rahmouni, Souad ULg et al

in Free Radical Biology & Medicine (2002), 33(1), 76-82

The evolution of mitochondrial oxidative phosphorylation was studied during cancer induction in a model of thymic radiolymphomagenesis in C57BL/Ka mice. During the preneoplastic period, thymuses displayed ... [more ▼]

The evolution of mitochondrial oxidative phosphorylation was studied during cancer induction in a model of thymic radiolymphomagenesis in C57BL/Ka mice. During the preneoplastic period, thymuses displayed an increase of the cytochrome c oxidase activity and oxygen consumption together with oxidative DNA damage assessed by the presence of the 8-hydroxydeoxyguanine DNA base modification. These transient changes in mitochondrial functional activity were not observed in thymuses of mice rescued from lymphoma development by a bone marrow graft, suggesting an important role of mitochondria for neoplastic transformation in this model. which might therefore be of interest to test the utilization of antioxidants for the prevention of radiation-induced malignancies. (C) 2002 Elsevier Science Inc. [less ▲]

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See detailRegulation of gene expression by oxygen: NF-kappaB and HIF-1, two extremes.
Michiels, Carine; Minet, Emmanuel; Mottet, Denis ULg et al

in Free Radical Biology & Medicine (2002), 33(9), 1231-42

Aerobic life is dependent on molecular oxygen for ATP regeneration, but only possible in a narrow range of oxygen concentrations. Increased oxygen tension is toxic through the generation of reactive ... [more ▼]

Aerobic life is dependent on molecular oxygen for ATP regeneration, but only possible in a narrow range of oxygen concentrations. Increased oxygen tension is toxic through the generation of reactive oxygen species (ROS), while a decrease in oxygen concentration impairs energy availability and, hence, cell viability. Cells have developed strategies to respond to changes in oxygen tension: specific systems detect excessive ROS and hypoxia, leading to the activation of specific transcription factors and expression of appropriate target genes. The aim of this review is to describe how hypoxia-inducible factor-1 (HIF-1) and nuclear factor-kappaB (NF-kappaB) are regulated and what could be the sensors to the changes in oxygen levels. Some of the physiological responses initiated by these transcription factors are also mentioned. [less ▲]

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See detailOxidative stress status in top soccer players
Pincemail, Joël ULg; Bonjean, K.; Cayeux, C. et al

in Free Radical Biology & Medicine (2002), 33(Suppl. 1), 249-249

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See detailImpaired Accumulation of Granulocytes in the Lung During Ozone Adaptation
Fievez, Laurence ULg; Kirschvink, N.; Dogne, S. et al

in Free Radical Biology & Medicine (2001), 31(5), 633-641

Respiratory alterations induced by an acute exposure to ozone (O(3)) paradoxically resolve during multiday exposure. This adaptation is characteristically accompanied by a gradual attenuation of lung ... [more ▼]

Respiratory alterations induced by an acute exposure to ozone (O(3)) paradoxically resolve during multiday exposure. This adaptation is characteristically accompanied by a gradual attenuation of lung neutrophilia. As maintenance of neutrophilia at the site of inflammation is due to cytokine-mediated delayed neutrophil apoptosis, which is associated with reduced levels of Bax, a proapoptotic protein, we sought to determine whether defects in these mechanisms could account for O(3) adaptation. Lung granulocytes obtained at different time points from calves exposed to 0.75 ppm O(3) for 12 h/d for 7 consecutive days neither showed enhancement of survival nor Bax deficiency, when compared to blood granulocytes. To further investigate the effects of an exogenous oxidative stress on neutrophil survival, human granulocytes were treated with hydrogen peroxide alone, or in combination with granulocyte/macrophage colony-stimulating factor, an antiapoptotic cytokine. Both treatments led to rapid apoptosis associated with downregulation of Bcl-x(L) and Bcl-2, two antiapoptotic proteins. This study shows that O(3) adaptation is associated with a failure in the mechanisms leading to accumulation of neutrophils at the site of inflammation, and suggests that this defect is due to direct proapoptotic effects of exogenous oxidative stress on granulocytes [less ▲]

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See detailTransduction pathways involved in Hypoxia-Inducible Factor-1 phosphorylation and activation.
Minet, E.; Michel, G.; Mottet, Denis ULg et al

in Free Radical Biology & Medicine (2001), 31(7), 847-55

Hypoxia-Inducible Factor-1 (HIF-1) is a transcription factor which is activated by hypoxia and involved in the adaptative response of the cell to oxygen deprivation. During hypoxic stress, HIF-1 triggers ... [more ▼]

Hypoxia-Inducible Factor-1 (HIF-1) is a transcription factor which is activated by hypoxia and involved in the adaptative response of the cell to oxygen deprivation. During hypoxic stress, HIF-1 triggers the overexpression of genes coding for glycolytic enzymes and angiogenic factors. To be active HIF-1 must be phosphorylated. HIF-1 is a substrate for various kinase pathways including PI-3K and the MAP kinases ERK and p38. Several transduction pathways have been proposed which act downstream of putative oxygen sensors and lead to the activation of these kinases. In this review, we summarize some of the latest advances describing the possible signaling pathways leading to HIF-1 phosphorylation and subsequent activation. The physiological relevance of these regulations is also discussed. [less ▲]

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See detailEvaluation of Autoantibodies against Oxidized Ldl and Antioxidant Status in Top Soccer and Basketball Players after 4 Months of Competition
Pincemail, Joël ULg; Lecomte, J.; Castiau, J. et al

in Free Radical Biology & Medicine (2000), 28(4), 559-65

Antioxidant status and titers of autoantibodies against oxidized low-density lipoproteins (ox-LDL-Ab) were investigated in top soccer (S; n = 21, age 24.6 +/- 4.3 years) and basketball (B; n 3,000 mIU/ml ... [more ▼]

Antioxidant status and titers of autoantibodies against oxidized low-density lipoproteins (ox-LDL-Ab) were investigated in top soccer (S; n = 21, age 24.6 +/- 4.3 years) and basketball (B; n 3,000 mIU/ml) in ox-LDL-Ab were found in half the players (12S and 4B) with a maximum reaching 6000 mIU/ml (normal range: 200-600 mIU/ml), showing an in vivo LDL oxidation. There was no correlation between ox-LDL-Ab titers and chlolesterol, LDL cholesterol, or antioxidant levels. Nevertheless, plasma vitamin C concentration was lower in athletes having high levels of ox-LDL-Ab when compared with those with normal levels (8.49 +/- 3.14 mirogram/ml vs. 10.39 +/- 2.55 microgram/ml), but this difference was not statistically significant. In conclusion, our data suggest that potential atherogenic and cardiovascular risks as reflected by high titers in ox-LDL-Ab may exist in some top athletes despite a nonaltered antioxidant status. [less ▲]

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See detail2-ethoxycarbonyl-2-methyl-3,4-dihydro-2H-pyrrole-1-oxide: evaluation of the spin trapping properties
Olive, Gilles ULg; Mercier, Anne; Le Moigne, François et al

in Free Radical Biology & Medicine (2000), 28(3), 403-408

The 2-ethoxycarbonyl-2-methyl-3,4-dihydro-2H-pyrrole-l-oxide (EMPO), an easily prepared pyrroline-Noxide has been tested as a free radical scavenger. Spin adducts of superoxide, hydroxyl radical, and ... [more ▼]

The 2-ethoxycarbonyl-2-methyl-3,4-dihydro-2H-pyrrole-l-oxide (EMPO), an easily prepared pyrroline-Noxide has been tested as a free radical scavenger. Spin adducts of superoxide, hydroxyl radical, and other free radicals were characterized in phosphate buffer at pH 7.0 and 5.6. At pH 7 in phosphate buffer, the EMPO/O2 2• spin adduct was estimated to be about five times more persistent than its DMPO analogue. Furthermore, its decay does not produce the EMPO/HO• adduct. [less ▲]

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See detailEGb 761 protects liver mitochondria against injury induced by in vitro anoxia/reoxygenation.
Du, G.; Willet, K.; Mouithys-Mickalad, Ange ULg et al

in Free Radical Biology & Medicine (1999), 27

The present study investigated the protective effects of Ginkgo biloba extract (EGb 761) on rat liver mitochondrial damage induced by in vitro anoxia/reoxygenation. Anoxia/reoxygenation was known to ... [more ▼]

The present study investigated the protective effects of Ginkgo biloba extract (EGb 761) on rat liver mitochondrial damage induced by in vitro anoxia/reoxygenation. Anoxia/reoxygenation was known to impair respiratory activities and mitochondrial oxidative phosphorylation efficiency. ADP/O (2.57 +/- 0.11) decreased after anoxia/reoxygenation (1.75 +/- 0.09, p < .01), as well as state 3 and uncoupled respiration (-20%, p < .01), but state 4 respiration increased (p < .01). EGb 761 (50-200 microg/ml) had no effect on mitochondrial functions before anoxia, but had a specific dose-dependent protective effect after anoxia/reoxygenation. When mitochondria were incubated with 200 microg/ml EGb 761, they showed an increase in ADP/O (2.09 +/- 0.14, p < .05) and a decrease in state 4 respiration (-22%) after anoxia/reoxygenation. In EPR spin-trapping measurement, EGb 761 decreased the EPR signal of superoxide anion produced during reoxygenation. In conclusion, EGb 761 specially protects mitochondrial ATP synthesis against anoxia/reoxygenation injury by scavenging the superoxide anion generated by mitochondria [less ▲]

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See detailImpairment of the mitochondrial electron chain transport prevents NF-kappa B activation by hydrogen peroxide.
Josse, C.; Legrand-Poels, S.; Piret, B. et al

in Free Radical Biology & Medicine (1998), 25(1), 104-112

A large body of work has been devoted to mechanisms leading to the activation of the transcription factor NF-kappa B in various cell types. Several studies have indicated that NF-kappa B activation by ... [more ▼]

A large body of work has been devoted to mechanisms leading to the activation of the transcription factor NF-kappa B in various cell types. Several studies have indicated that NF-kappa B activation by numerous stimuli depends on the intracellular generation of reactive oxygen species (ROS). In this report, we first demonstrated that inhibition of the electron transport chain by either rotenone or antimycine A gave rise to dose-dependent inhibition of NF-kappa B translocation induced by 150 microM of hydrogen peroxide (H2O2). Conversely, the impairment of the mitochondrial respiratory chain did not affect T lymphocyte treatment by TNF-alpha (tumor necrosis factor alpha) or pre-B lymphocyte treatment with LPS (lipopolysaccharide). We also showed that oligomycine which inhibits ATP synthase and FCCP, which uncouples respiration also led to dose-dependent inhibition of NF-kappa B activation by H2O2. All these inhibitors were also shown to inhibit mitochondrial respiration in lymphocytes assessed by oxygen consumption. Although only a transient drop in ATP concentration was observed when lymphocytes were treated by H2O2, this effect was remarkably reinforced in the presence of oligomycine demonstrating the crucial role of ATP in the signal transduction pathway induced by H2O2. [less ▲]

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See detailGeneration of superoxide anion by mitochondria and impairment of their functions during anoxia and reoxygenation in vitro.
Du, G.; Mouithys-Mickalad, A.; Sluse, Francis ULg

in Free Radical Biology & Medicine (1998), 25

A small portion of the oxygen consumed by aerobic cells is converted to superoxide anion at the level of the mitochondrial respiratory chain. If produced in excess, this harmful radical is considered to ... [more ▼]

A small portion of the oxygen consumed by aerobic cells is converted to superoxide anion at the level of the mitochondrial respiratory chain. If produced in excess, this harmful radical is considered to impair cellular structures and functions. Damage at the level of mitochondria have been reported after ischemia and reperfusion of organs. However, the complexity of the in vivo system prevents from understanding and describing precise mechanisms and locations of mitochondrial impairment. An in vitro model of isolated-mitochondria anoxia-reoxygenation is used to investigate superoxide anion generation together with specific damage at the level of mitochondrial oxidative phosphorylation. Superoxide anion is detected by electron paramagnetic resonance spin trapping with POBN-ethanol. Mitochondrial respiratory parameters are calculated from oxygen consumption traces recorded with a Clark electrode. Respiring mitochondria produce superoxide anion in unstressed conditions, however, the production is raised during postanoxic reoxygenation. Several respiratory parameters are impaired after reoxygenation, as shown by decreases of phosphorylating and uncoupled respiration rates and of ADP/O ratio and by increase of resting respiration. Partial protection of mitochondrial function by POBN suggests that functional damage is related and secondary to superoxide anion production by the mitochondria in vitro. [less ▲]

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See detailImpairment of mitochondrial functions abolishes NF-kappaB activation by an oxidative stress
Josse, Claire ULg; Legrand-Poels, Sylvie ULg; Piret, Bernard et al

in Free Radical Biology & Medicine (1998)

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See detailDiaspirin Crosslinked Hemoglobin (Dclhb): Absence of Increased Free Radical Generation Following Administration in a Rabbit Model of Renal Ischemia and Reperfusion
Pincemail, Joël ULg; Detry, Olivier ULg; Philippart, C. et al

in Free Radical Biology & Medicine (1995), 19(1), 1-9

In control rabbits, a renal ischemia of 60 min followed by 10 min of reperfusion resulted in an enhanced free radical production in cortical tissue, as assessed by a significant decrease of free ... [more ▼]

In control rabbits, a renal ischemia of 60 min followed by 10 min of reperfusion resulted in an enhanced free radical production in cortical tissue, as assessed by a significant decrease of free glutathione (42%), protein-bound GSH (17%), and vitamin E (49%). In contrast, catalase or glutathione peroxidase activities were not affected by these experimental conditions. Free radical production in this model was also measured directly using electron spin resonance (ESR) spectroscopy associated with a PBN (alpha-phenyl N-tert-butyl-nitrone) spin trap agent in the venous blood arising from the ischemic kidney. The signal consisted of a triplet of doublets. In contrast, no signal could be detected in control blood samples taken prior to inducing ischemia. The burst of free radical production occurred in the early phase after restoration of flow in the kidneys rendered ischemic, as evidenced by a signal of weak intensity which generally appeared within the third minute after reperfusion and progressively increased to form a well-defined asymmetric signal following 10 min of reperfusion. The precise nature of free radicals trapped by the PBN agent remains, however, to be elucidated, but analysis of the coupling constants (aN = 14.5-15 G; a beta H = 2.5-3 G) and asymmetry of the central doublets suggests that the ESR signal may arise from a nitorxy-radical adduct resulting from the spin trapping by PBN of both oxygen- or carbon-centered radicals of lipid origin. As evidenced by both direct and indirect measurements, exchange of rabbit blood immediately after inducing renal ischemia with 30 ml/kg of Diaspirin Crosslinked Hemoglobin (7.5 g/dl in lactated electrolyte) or human serum albumin (7.5 g/dl in lactated electrolyte) did not exacerbate free radical production mediated by an ischemia reperfusion phenomenon, a typical situation found in a resuscitation setting. [less ▲]

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See detailEvidence for Free Radical Formation During Human Kidney Transplantation
Pincemail, Joël ULg; Defraigne, Jean-Olivier ULg; Franssen, Christine ULg et al

in Free Radical Biology & Medicine (1993), 15(3), 343-8

Fourteen patients undergoing kidney transplantation were studied for evidence of the production of free radicals as assessed by the measurement of vitamin E (an index of lipid peroxidation) and of ... [more ▼]

Fourteen patients undergoing kidney transplantation were studied for evidence of the production of free radicals as assessed by the measurement of vitamin E (an index of lipid peroxidation) and of myeloperoxidase (a marker of neutrophil activation) in the systemic blood. Early (2 min) and late revascularization (30 min) of the kidney were respectively associated with a significant decrease of 35.5 and 40% of the initial level of plasma vitamin E. This consumption paralleled to the decrease of the vitamin E/total lipids ratio, a better indicator of vitamin E status. Heparin administration preceding renal artery clamping resulted in a twofold significant increase of baseline plasma myeloperoxidase (MPO) level (523 +/- 214 ng/ml). At kidney reperfusion, MPO concentration rose again and reached a maximum value of 1,653 +/- 882 ng/ml, indicating the presence of considerable neutrophil activation. A return to the baseline value was observed after 30 min of reperfusion. A short discussion about the possible origin of this MPO increase is given. Taken together, these data strongly suggest that free radical production, leading to lipid peroxidation phenomena, can occur within the early phase of kidney revascularization. Preliminary data using electron spin resonance with the spin-trapping technique strengthen this hypothesis. [less ▲]

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