Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
High sea surface temperature accompanied by high levels of solar irradiance is responsible for the disruption of the symbiosis between cnidarians and their symbiotic dinoflagellates from the genus Symbiodinium. This phenomenon, known as coral bleaching, is one of the major threats affecting coral reefs around the world. Because an important molecular trigger to bleaching appears related to the production of reactive oxygen species (ROS), it is critical to understand the function of the antioxidant network of Symbiodinium species. In this study we investigated the response of two Symbiodinium species, from contrasting environments, to a chemically induced oxidative stress. ROS produced during this oxidative burst reduced photosynthesis by 30 to 50% and significantly decreased the activity of superoxide dismutase. Lipid peroxidation levels and carotenoid concentrations, especially diatoxanthin, confirm that these molecules act as antioxidants and contribute to the stabilization of membrane lipids. The comparative analysis between the two Symbiodinium species allowed us to highlight that Symbiodinium sp. clade A temperate was more tolerant to oxidative stress than the tropical S. kawagutii clade F. These differences are very likely a consequence of adaptation to their natural environment, with the temperate species experiencing conditions of temperature and irradiance much more variable and extreme.
ISSN: 0140-7791

hal-01546161
https://hal.archives-ouvertes.fr/hal-01546161
DOI : 10.1111/pce.12825

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
In this work, we have studied quenching of the fluorescence of two well-known oxygen probes, 1-pyrene butyric acid (PBA) and tris(2,2'-bipyridine)ruthenium ([Ru(bpy)(3)](2+)) by reactive oxygen species (superoxide anion, nitric oxide derivative, hydrogen peroxide) and by the O(2) molecule. Both, time-resolved and steady state fluorescence measurements were performed in solution (ethanol, dimethyl sufoxide, water) and in micelles of Sodium Dodecyl Sulfate that serve as a model for membrane-containing biological structures. We have found that only the free radicals and O(2) can actively quench for the two probes, but not the diamagnetic H(2)O(2). Our data correspond to the classical Stern-Volmer equation. H(2)O(2) has an effect only at high molar concentrations (>0.1 M). In contrast, effective concentrations of free radicals and O(2) that lead to quenching are in millimolar range. In conclusion, our methods allows for detecting global ROS that are small free radicals without interference from the reactive hydroxyl radical. Our data suggest that the method can be used for the quantification of ROS in individual living cells based on the measurement of fluorescence lifetime of those probes
ISSN: 1053-0509

hal-01326234
https://hal.archives-ouvertes.fr/hal-01326234
DOI : 10.1007/s10895-008-0425-z

Éditeur(s) : Université Bordeaux 1
Résumé : The mercury cycle was explored in the Petit-Saut reservoir / Sinnamary Estuary continuum in French Guiana. Main processes involve (i) photo-induced reduction, (ii) adsorption and desorption at the particle surfaces, (iii) methylating bacterial activity, (iv) precipitation and dissolution of iron oxyhydroxides and sulfides. Sources of mercury to the Petit-Saut reservoir consist of the partly impacted river-tributaries, the atmospheric deposition and the flooded soils or vegetation. Once into the reservoir, divalent mercury undergoes a large spectrum of transformations including speciation and phase changes. We, here, probe these processes and demonstrate that the Petit-Saut reservoir behaves as a privileged site for atmospheric recycling and in situ methylation. At the air / water interface, the mercury evasion exceeds by 50 % the direct atmospheric deposition. The in situ monomethylmercury (MMHg) production mostly occurs at the water-column chemocline and near the benthic interface. It reaches, for the whole reservoir, 8.1 moles yr-1 which corresponds to a 0.06 % d-1 methylation rate. We calculated that the 2003/04 period MMHg outputs from the reservoir to the Sinnamary Estuary averaged 13.5 moles yr-1 while the inputs were 5.4 moles yr-1. The dynamic Sinnamary Estuary is the genuine geochemical reactor of the continuum. There, the divalent mercury undergoes rapid yet profound partitioning among phases, recycling to the atmosphere and methylation processes. Those mostly originate from the long-scale oxygen paucity of the dam discharged waters. The expression of marked redox gradients and the intense organic matter turnover enhance the production of methylable inorganic mercurial species and tend to favor the sulfate reducing bacteria (methylating agents) activity. As a result, the dynamic Sinnamary Estuary exports 60 % more MMHg than it does import: 27 versus 17 moles yr-1. Further at large, in the saline estuary, we determined: (i) a non conservative behavior of dissolved (< 0.2 µm) mercury, (ii) a lowering of the mercury level of particles during mixing with the Amazon plume and (iii) a gradual dilution of the estuarine mercury concentrations by oceanic waters.
La retenue de Petit-Saut et, à l'aval, l'estuaire du Sinnamary sont deux centres d'altération du cycle naturel du mercure. Les processus sont, entre autres, (i) la photoréduction, (ii) la sorption / désorption en surface des particules, (iii) l'activité méthylante des bactéries, (iv) la dissolution / précipitation des oxyhydroxydes et des sulfures de fer. Les sources de mercure vers la retenue sont variées. Elles regroupent, en premier lieu, les affluents (partiellement orpaillés), l'atmosphère, les sols et la végétation ennoyés. Dans la colonne d'eau, les formes divalentes du mercure subissent un train complet de transformations couplant changements de phase et de spéciation. Nos résultats illustrent ces processus et démontrent que la retenue constitue un site privilégié de recyclage vers l'atmosphère et de méthylation. A l'interface air / eau, les exports en mercure de la retenue excèdent de 50 % le dépôt atmosphérique. La production endogène de monométhylmercure (MMHg) a lieu dans des sites particuliers : la chemocline et l'interface benthique. Elle atteint pour l'ensemble de la retenue 8,1 moles a-1 soit un taux de méthylation de 0,06 % j-1. On estime que la retenue exporte vers l'estuaire du Sinnamary 13,5 moles a-1 de MMHg alors qu'elle n'importe que 5,4 moles a-1. L'estuaire dynamique du Sinnamary constitue le véritable réacteur chimique du système fonctionnant en liaison avec celui de la retenue. Le mercure y décrit un cycle rapide aux processus de partition, de recyclage et de méthylation marqués. Ces processus résultent de l'oxygénation incomplète et durable des masses d'eau anoxiques exportées par la retenue de Petit-Saut. L'expression de gradients rédox prononcés conjuguée à un intense recyclage de la matière organique y favorise la production de formes méthylables de mercure ainsi que l'activité des bactéries sulfatoréductrices (agents de la méthylation). C'est pourquoi, l'estuaire dynamique du Sinnamary exporte 60 % plus de MMHg qu'il n'importe : 27 contre 17 moles a-1. Plus en aval, dans l'estuaire salin, nous avons mis en évidence : (i) un comportement non conservatif du mercure dissous, (ii) un appauvrissement du mercure des particules suite au mélange avec le panache de l'Amazone et (iii) une dilution des concentrations par les masses d'eau océaniques.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2006/these-1508.pdf
http://archimer.ifremer.fr/doc/00000/1508/

Éditeur(s) : HAL CCSD Federation of American Society of Experimental Biology
Résumé : International audience
Testes of most male mammals present the particularity of being externalized from the body and are consequently slightly cooler than core body temperature (4-8 degrees C below). Although, hypothermia of the testis is known to increase germ cells apoptosis, little is known about the underlying molecular mechanisms, including cold sensors, transduction pathways, and apoptosis triggers. In this study, using a functional knockout mouse model of the cold and menthol receptors, dubbed transient receptor potential melastatine 8 (TRPM8) channels, we found that TRPM8 initiated the cold-shock response by differentially modulating cold- and heat-shock proteins. Besides, apoptosis of germ cells increased in proportion to the cooling level in control mice but was independent of temperature in knockout mice. We also observed that the rate of germ cell death correlated positively with the reactive oxygen species level and negatively with the expression of the detoxifying enzymes. This result suggests that the TRPM8 sensor is a key determinant of germ cell fate under hypothermic stimulation.Borowiec, A.-S., Sion, B., Chalmel, F., Rolland, A. D., Lemonnier, L., De Clerck, T., Bokhobza, A., Derouiche, S., Dewailly, E., Slomianny, C., Mauduit, C., Benahmed, M., Roudbaraki, M., Jegou, B., Prevarskaya, N., Bidaux, G. Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation.
ISSN: 0892-6638

hal-01390973
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390973
DOI : 10.1096/fj.201600257R
PUBMED : 27317670

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Cnidarians living in symbiosis with photosynthetic dinoflagellates (commonly named zooxanthellae) are exposed to high concentrations of reactive oxygen species (ROS) upon illumination. To quench ROS production, both the cnidarian host and zooxanthellae express a full suite of antioxidant enzymes. Studying antioxidative balance is therefore crucial to understanding how symbiotic cnidarians cope with ROS production. We characterized glutathione peroxidases (GPx) in the symbiotic cnidarian Anemonia viridis by analysis of their isoform diversity, their activity distribution in the three cellular compartments (ectoderm, endoderm and zooxanthellae) and their involvement in the response to thermal stress. We identified a GPx repertoire through a phylogenetic analysis showing 7 GPx transcripts belonging to the A. viridis host and 4 GPx transcripts strongly related to Symbiodinium sp. The biochemical approach, used for the first time with a cnidarian species, allowed the identification of GPx activity in the three cellular compartments and in the animal mitochondrial fraction, and revealed a high GPx electrophoretic diversity. The symbiotic lifestyle of zooxanthellae requires more GPx activity and diversity than that of free-living species. Heat stress induced no modification of GPx activities. We highlight a high GPx diversity in A. viridis tissues by genomic and biochemical approaches. GPx activities represent an overall constitutive enzymatic pattern inherent to symbiotic lifestyle adaptation. This work allows the characterization of the GPx family in a symbiotic cnidarian and establishes a foundation for future studies of GPx in symbiotic cnidarians.
ISSN: 0300-9084

hal-01404424
http://hal.upmc.fr/hal-01404424
http://hal.upmc.fr/hal-01404424/document
http://hal.upmc.fr/hal-01404424/file/Pey_Characterization_of.pdf
DOI : 10.1016/j.biochi.2016.10.016

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Several epidemiologic studies have shown an interactive effect of heavy smoking and heavy alcohol drinking on the development of hepatocellular carcinoma. It has also been recently described that chronic hepatocyte death can trigger excessive compensatory proliferation resulting later in the formation of tumors in mouse liver. As we previously demonstrated that both benzo[a]pyrene (B[a]P), an environmental agent found in cigarette smoke, and ethanol possess similar targets, especially oxidative stress, to trigger death of liver cells, we decided to study here the cellular and molecular mechanisms of the effects of B[a]P/ethanol coexposure on cell death. After an 18-h incubation with 100nM B[a]P, primary rat hepatocytes were supplemented with 50mM ethanol for 5 or 8h. B[a]P/ethanol coexposure led to a greater apoptotic cell death that could be linked to an increase in lipid peroxidation. Plasma membrane remodeling, as depicted by membrane fluidity elevation and physicochemical alterations in lipid rafts, appeared to play a key role, because both toxicants acted with specific complementary effects. Membrane remodeling was shown to induce an accumulation of lysosomes leading to an important increase in low-molecular-weight iron cellular content. Finally, ethanol metabolism, but not that of B[a]P, by providing reactive oxygen species, induced the ultimate toxic process. Indeed, in lysosomes, ethanol promoted the Fenton reaction, lipid peroxidation, and membrane permeabilization, thereby triggering cell death. To conclude, B[a]P exposure, by depleting hepatocyte membrane cholesterol content, would constitute a favorable ground for a later toxic insult such as ethanol intoxication. Membrane stabilization of both plasma membrane and lysosomes might be a potential target for further investigation considering cytoprotective strategies.
ISSN: 0891-5849

hal-01018147
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01018147
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01018147/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01018147/file/Cooperative-interaction_final.pdf
PUBMED : 24681337

Éditeur(s) : Cushman Foundation for Foraminiferal Research
Résumé : The objectives of this study were to observe foraminiferal colonization patterns and behavior in shrimp ponds in New Caledonia during a shrimp-growing (farming) cycle. Weekly collecting at 10 stations in 8 shrimp ponds yielded a total of 170 samples accompanied by environmental data. Seawater pumped from the nearby ocean filled the ponds at the beginning of the growth cycle and its daily renewal maintained salinity at 32-39, and supplied the ponds with influxes of smaller, mostly juvenile, foraminifera. A few days after initial filling, the pioneering species Ammonia tepida and Quinqueloculina seminula appeared, with A. tepida dominant. Their high reproduction rates increased both living and dead assemblage densities during the first 10 weeks. Populations of these two species then stabilized with higher oxygen demand (drop of redox) and consumption of living foraminifera by shrimp. Only a few colonizers subsequently appeared, which was attributed to the isolation of the pond, despite the high rate of water renewal. Only one pond had notably higher species richness, but it could not be distinguished from the others by its physicochemical parameters. The species that appeared in ponds initially barren of foraminifera also survived where there was water seepage between growing cycles, suggesting that the assemblages had already reached equilibrium with the environment. Despite the number of environmental parameters measured, only oxygen and reactive organic matter correlated with the microfauna on a weekly timescale. We assume that other parameters do not significantly affect foraminifera until they reach critical threshold. Consistent with previous studies, A. tepida was the species most tolerant of organic influx, but its relative abundance dropped once the organic matter flocculated and settled, leading to disoxic conditions in the sediment. Conversely, Q. seminula was able to climb through the floc and reach the oxygenated layer, where its relative abundance increased.
Journal of Foraminiferal Research (0096-1191) (Cushman Foundation for Foraminiferal Research), 2009-10 , Vol. 39 , N. 4 , P. 249-266

Droits : 2009 Cushman Foundation for Foraminiferal Research
http://archimer.ifremer.fr/doc/2009/publication-6954.pdf
DOI:10.2113/gsjfr.39.4.249
http://archimer.ifremer.fr/doc/00000/6954/

Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
2-Amino-9H-pyrido[2,3-b]indole (AαC) is a carcinogenic heterocyclic aromatic amine formed during the combustion of tobacco. AαC undergoes bioactivation to form electrophilic N-oxidized metabolites that react with DNA to form adducts, which can lead to mutations. Many genotoxicants and toxic electrophiles react with human serum albumin (albumin); however, the chemistry of reactivity of AαC with proteins has not been studied. The genotoxic metabolites, 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AαC), 2-nitroso-9H-pyrido[2,3-b]indole (NO-AαC), N-acetyloxy-2-amino-9H-pyrido[2,3-b]indole (N-acetoxy-AαC), and their [(13)C6]AαC-labeled homologues were reacted with albumin. Sites of adduction of AαC to albumin were identified by data-dependent scanning and targeted bottom-up proteomics approaches employing ion trap and Orbitrap MS. AαC-albumin adducts were formed at Cys(34), Tyr(140), and Tyr(150) residues when albumin was reacted with HONH-AαC or NO-AαC. Sulfenamide, sulfinamide, and sulfonamide adduct formation occurred at Cys(34) (AαC-Cys(34)). N-Acetoxy-AαC also formed an adduct at Tyr(332). Albumin-AαC adducts were characterized in human plasma treated with N-oxidized metabolites of AαC and human hepatocytes exposed to AαC. High levels of N-(deoxyguanosin-8-yl)-AαC (dG-C8-AαC) DNA adducts were formed in hepatocytes. The Cys(34) was the sole amino acid of albumin to form adducts with AαC. Albumin also served as an antioxidant and scavenged reactive oxygen species generated by metabolites of AαC in hepatocytes; there was a strong decrease in reduced Cys(34), whereas the levels of Cys(34) sulfinic acid (Cys-SO2H), Cys(34)-sulfonic acid (Cys-SO3H), and Met(329) sulfoxide were greatly increased. Cys(34) adduction products and Cys-SO2H, Cys-SO3H, and Met(329) sulfoxide may be potential biomarkers to assess exposure and oxidative stress associated with AαC and other arylamine toxicants present in tobacco smoke
ISSN: 0021-9258

hal-01169796
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169796
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169796/file/Manuscript_KP_JBC_REV_050515_final_TC.pdf
DOI : 10.1074/jbc.M115.646539
PUBMED : 25953894

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate. METHODOLOGY/PRINCIPAL FINDINGS: A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy. CONCLUSIONS/SIGNIFICANCE: Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.
ISSN: 1932-6203

inserm-00871491
http://www.hal.inserm.fr/inserm-00871491
http://www.hal.inserm.fr/inserm-00871491/document
http://www.hal.inserm.fr/inserm-00871491/file/Milk_Fermented_by_Propionibacterium_freudenreichii.accepted.pdf
DOI : 10.1371/journal.pone.0031892

Éditeur(s) : HAL CCSD
Résumé : International audience
Objective Oxidative stress, excess production of reactive oxygen species (ROS) and intense colonization of the respiratory tract by microorganisms are described in CF patients, leading to an influx in macrophages. This results in activation of NADPH oxidase that yields ROS, initiating the oxidative burst responsible for pathogen destruction. We showed that phagocytosis was altered in CF macrophages, yet oxidative status in this cell was not defined. The objective of this study is to draw a link between oxidative stress and plasma membrane integrity in CF macrophages, since lipid peroxidation is known to alter cell membrane. Methods Peripheral blood monocytes-derived macrophages were obtained from CF patients and healthy subjects. Plasma membrane fluidity was assessed with di4-ANEPPDHQ and oxidative status was measured with ROS indicating probes. Results In CF macrophages, membrane fluidity was increased whereas lipid peroxidation was diminished. Surprisingly, general oxidative status remained similar to the one observed in non-CF macrophages. Also, CF macrophages did not abolish chemically induced-oxidative stress. In non-CF macrophages, treatment with cholesterol slightly increased membrane fluidity whereas LPS treatment had no effect. Conclusion CF macrophages displayed an increased membrane fluidity associated with a decreased lipid peroxidation. This raises the hypothesis that membrane alteration in CF macrophages may be due to other mechanism than oxidative stress. Nevertheless, since the killing capacity of CF macrophage is defective, a deregulation of O•−2 production is very likely, suggesting alteration of NADPH oxidase or mitochondrial dysfunction
the 38th European Cystic Fibrosis Conference
Vienne, Austria

hal-01162769
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162769
DOI : 10.1016/S1569-1993(15)30217-4

Éditeur(s) : HAL CCSD
Résumé : International audience
Traffic air pollution is a major health problem and is recognized as an important risk factor for cardiovascular disease. Even so the role of particles-induced adverse health effects is well established, recent studies outlined the contribution of nitrogen dioxide (NO2) in these effects, in particular on the cardiovascular function. The main sources of this pollutant are oxidation catalysts used to reduce emissions of carbon monoxide and non-methane hydrocarbons from the exhaust of diesel engines and also to facilitate filter regeneration. However, the contribution of NO2 compared to other gaseous and particulate pollutants remains unknown. Consequently, the main objective of this study was to analyze the specific contributions of NO2 in the traffic-related air pollution-induced cardiovascular adverse effects. For this, Wistar rats were exposed for 3 weeks (3h/day, 5 days/week) to either a continuous flow of catalyzed diesel exhaust (DE), particle free or whole DE (particles concentration 2mg/m3), either to a continuous flow of NO2 used at a concentration identical to that measured in the exhaust line. The composition of the emission and the NO2 analyses were monitored on-line during the whole experiment. We evaluated cardiac function and biological effects after 16h recovery in clean air. DE or NO2 exposures induced a modest cardiac dysfunction characterized by an increase in left ventricular diameters and a decrease in fractional shortening. In the case of DE, the presence of particles did not worsen the impairment of cardiac function. In parallel to this effect, mitochondrial function was altered as illustrated by the reduction of the oxygen consumption and of the ATP production. Mitochondrial reactive oxygen species was increased only by the NO2 exposure. In conclusion, these results suggest that DE-induced cardiac dysfunction is due to, at least in part, to NO2 present in DE.
Archives of Cardiovascular Diseases Supplements
Toulouse, France

hal-01150495
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01150495
DOI : 10.1016/S1878-6480(15)30036-7

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Inorganic arsenic is a toxic environmental contaminant to which humans are mainly exposed through drinking water. This metalloid impairs functions of several key immune cells. Particularly, it reduces IL-2 secretion and proliferation of blood peripheral mononuclear cells stimulated by lectins that, however, do not mimic physiological T cell activation. The present study used isolated human T cells activated, in a more physiological manner, through stimulation with CD3/CD28 antibodies, to carefully analyze the impact of arsenic on T cell proliferation and cytokine expression. We demonstrate that non cytotoxic concentrations of sodium arsenite (As(III), 0.25-2μM) significantly reduce T cell proliferation by increasing the percentage of non dividing cells blocked in G1 phase and by preventing cyclin D3 and CDC25A expression. They also markedly, although not totally, reduces IL-2 expression at both mRNA and protein levels; however, metalloid-dependent inhibition of T cells could not be reversed by addition of recombinant IL-2. In addition, As(III) markedly reduces secretion of interferon-γ without impairing that of IL-4 and IL-13; it also decreases interferon-γ mRNA levels but increases those of IL-13. Finally, simultaneously to its immune effects, As(III) rapidly and potently increases expression of the redox-sensitive genes HMOX1, NQO1 and GCLM in activated T cells without altering the levels of reactive oxygen species. In conclusion, our results demonstrate that As(III) inhibits T cell proliferation, independently of IL-2, and alters the Th balance of cytokines secreted by co-stimulated T cells which thus constitute direct targets of this major environmental contaminant.
ISSN: 0300-483X

inserm-00872848
http://www.hal.inserm.fr/inserm-00872848
DOI : 10.1016/j.tox.2012.05.025
PUBMED : 22683347

Éditeur(s) : HAL CCSD
Résumé : International audience
The development of diabetic vascular complications is initiated, at least in part, by mitochondrial reactive oxygen species (ROS) production in endothelial cells. Hyperglycemia induces superoxide production in the mitochondria and initiates changes in the mitochondrial membrane potential that leads to mitochondrial dysfunction. Hydrogen sulfide (H2S) supplementation has been shown to reduce the mitochondrial oxidant production and shows efficacy against diabetic vascular damage in vivo. However, the half-life of H2S is very short and it is not specific for the mitochondria. We have therefore evaluated two novel mitochondria-targeted anethole dithiolethione and hydroxythiobenzamide H2S donors (AP39 and AP123 respectively) at preventing hyperglycemia-induced oxidative stress and metabolic changes in microvascular endothelial cells in vitro. Hyperglycemia (HG) induced significant increase in the activity of the citric acid cycle and led to elevated mitochondrial membrane potential. Mitochondrial oxidant production was increased and the mitochondrial electron transport decreased in hyperglycemic cells. AP39 and AP123 (30–300 nM) decreased HG-induced hyperpolarisation of the mitochondrial membrane and inhibited the mitochondrial oxidant production. Both H2S donors (30–300 nM) increased the electron transport at respiratory complex III and improved the cellular metabolism. Targeting H2S to mitochondria retained the cytoprotective effect of H2S against glucose-induced damage in endothelial cells suggesting that the molecular target of H2S action is within the mitochondria. Mitochondrial targeting of H2S also induced >1000-fold increase in the potency of H2S against hyperglycemia-induced injury. The high potency and long-lasting effect elicited by these H2S donors strongly suggests that these compounds could be useful against diabetic vascular complications. © 2016
Pharmacological Research

hal-01373947
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01373947
DOI : 10.1016/j.phrs.2016.08.019
PUBMED : 27565382

Éditeur(s) : HAL CCSD Elsevier
Résumé : Siberian cratonic mantle
International audience
The processes that control water distribution in nominally anhydrous minerals from peridotites are twofold. Melt depletion will remove water while metasomatism can potentially add water to these minerals. These processes can lead to a wide range of outcomes in water contents, which in turn could play a role in mantle rheology and long-term cratonic root stability. To examine these complexities, water concentrations in minerals from well-characterized peridotites from the Udachnaya kimberlite in the central Siberian craton were analyzed by FTIR. The peridotites span a complete top to bottom cross-section of typical cratonic lithospheric mantle (2-7 GPa and 700-1400 °C). Diffusion modeling of water content profiles across olivine grains shows that water loss during decompression is limited to the 100 μm rims of olivines; the cores preserved their mantle water contents. Water contents range from 6 to 323 ppm wt H2O in olivine, 28-301 ppm H2O in orthopyroxene (opx), 100-272 ppm H2O in clinopyroxene (cpx) and 0-23 ppm H2O in garnet. Melting modeling cannot reproduce the high water contents of cratonic mantle peridotites and any potential partial melting trend must have been erased by later events. The water contents of minerals, however, are correlated with modal abundances of clinopyroxene and garnet, bulk rock FeO, TiO2 and SiO2 as well as with light and middle rare earth elements in clinopyroxene and garnet. These relationships are best interpreted as interaction of residual, melt-depleted peridotites with silicate melt, which produced modal and cryptic metasomatism. Importantly, the water enrichment in the Siberian cratonic mantle took place prior to kimberlite magmatism and eruption. Water addition by metasomatism occurred from pressures >4 GPa all the way to the base of the cratonic root below central Siberia, but was limited to shallower levels (<5 GPa) in the Kaapvaal cratonic lithosphere. The difference in olivine water contents at the deepest levels of the Kaapvaal (<5 ppm H2O) and Siberian (6-323 ppm H2O) cratonic roots may be linked to oxygen fugacity and resulting fluid speciation or, alternatively, to reaction with different metasomatic agents. Calculated viscosities for the deepest Udachnaya samples are similar to those inferred for the asthenosphere. If these xenoliths are representative of the deep cratonic lithosphere, water is not as important a parameter as previously thought in the strength of cratonic lithosphere, otherwise the cratonic root beneath Udachnaya would have been delaminated. Alternatively, the metasomatic xenoliths may not be representative of the Siberian cratonic root and kimberlites preferentially sample cratonic mantle lithosphere material located near, and metasomatized by, melt conduits, which served as channels for upward migration of water-rich melts and fluids including kimberlites. In that case, the cratonic root overall still may have relatively low water contents, which in addition to its less metasomatized (more refractory) and thereby buoyant nature, still play a role in making it strong enough to resist delamination by the surrounding asthenosphere.
ISSN: 0016-7037

hal-01053920
https://hal.archives-ouvertes.fr/hal-01053920
DOI : 10.1016/j.gca.2014.04.011

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The implication of oxidative stress as primary mechanism inducing doxorubicin (DOX) cardiotoxicity is still questionable as many in vitro studies implied supra-clinical drug doses or unreliable methodologies for reactive oxygen species (ROS) detection. The aim of this study was to clarify whether oxidative stress is involved in compliance with the conditions of clinical use of DOX, and using reliable tools for ROS detection. We examined the cytotoxic mechanisms of 2 μM DOX 1 day after the beginning of the treatment in differentiated H9c2 rat embryonic cardiac cells. Cells were exposed for 2 or 24 h with DOX to mimic a single chronic dosage or to favor accumulation, respectively. We found that apoptosis was prevalent in cells exposed for a short period with DOX: cells showed typical hallmarks as loss of anchorage ability, mitochondrial hyperpolarization followed by the collapse of mitochondrial activity, and nuclear condensation. Increasing the exposure period favored a shift to necrosis as the cells preferentially exhibited early DNA impairment and nuclear swelling. In either case, measuring the fluorescence lifetime of 1-pyrenebutyric acid or the intensities of dihydroethidium or amplex red showed a consistent pattern in ROS production which was a slight increased level far from representative of an oxidative stress. Moreover, pre-treatment with dexrazoxane provided a cytoprotective effect although it failed to detoxify ROS. Our data support that oxidative stress is unlikely to be the primary mechanism of DOX cardiac toxicity in vitro.
ISSN: 0300-8177

hal-01285736
https://hal-univ-perp.archives-ouvertes.fr/hal-01285736
DOI : 10.1007/s11010-016-2653-x

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
: Previously, we demonstrated that eicosapentaenoic acid enhanced ethanol-induced oxidative stress and cell death in primary rat hepatocytes via an increase in membrane fluidity and lipid raft clustering. In this context, another n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), was tested with a special emphasis on physical and chemical alteration of lipid rafts. Pretreatment of hepatocytes with DHA reduced significantly ethanol-induced oxidative stress and cell death. DHA protection could be related to an alteration of lipid rafts. Indeed, rafts exhibited a marked increase in membrane fluidity and packing defects leading to the exclusion of a raft protein marker, flotillin. Furthermore, DHA strongly inhibited disulfide bridge formation, even in control cells, thus suggesting a disruption of protein-protein interactions inside lipid rafts. This particular spatial organization of lipid rafts due to DHA subsequently prevented the ethanol-induced lipid raft clustering. Such a prevention was then responsible for the inhibition of phospholipase C-γ translocation into rafts, and consequently of both lysosome accumulation and elevation in cellular low-molecular-weight iron content, a prooxidant factor. In total, the present study suggests that DHA supplementation could represent a new preventive approach for patients with alcoholic liver disease based upon modulation of the membrane structures.
ISSN: 0278-6915

hal-00860153
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00860153
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00860153/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00860153/file/Sergent-et-al-incl-figures-accepted.pdf
DOI : 10.1016/j.fct.2013.07.061

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The early apoptotic events induced by environmental pollutants with carcinogenic properties are poorly understood. Here, we focus on the early cytotoxic effects of benzo[a]pyrene (B[a]P). In F258 rat hepatic epithelial cells, B[a]P induces intrinsic apoptosis via a mitochondrial dysfunction characterized by the release of hexokinase II (HKII) from the mitochondria. Cancer cells often have an anomalous cell energy metabolism; since HKII dysfunction regulates B[a]P-induced apoptosis in F258 cells, but may also alter cell energy metabolism, HKII release from the mitochondria may represent an important B[a]P-related carcinogenic issue. Thus in the present study, we aimed at deciphering the mechanisms underlying HKII dysfunction upon B[a]P exposure. We show that while glycogen synthase kinase 3 beta (GSK3β) regulated the expression of HKII at the transcriptional level, glycogen synthase kinase 3 alpha (GSK3α) was involved in B[a]P-induced apoptosis via a decrease in c-Myc expression. The reduced level of c-Myc caused the relocation of HKII from the mitochondria to the cytosol, thereby being involved in the formation of reactive oxygen species and apoptosis. In conclusion, we show that the couple GSK3α/c-Myc plays a key role in B[a]P-induced early apoptotic cell signaling via HKII dysfunction.
ISSN: 0887-2333

hal-00682104
https://hal.archives-ouvertes.fr/hal-00682104
https://hal.archives-ouvertes.fr/hal-00682104/document
https://hal.archives-ouvertes.fr/hal-00682104/file/1-s2.0-S0887233311003018-main%20Dendel%C3%A9_%7B75929874-2DF9-47C3-92F6-92AF398668E5%7D.pdf
DOI : 10.1016/j.tiv.2011.11.001