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Sample records for active oxygen metabolism

  1. Changes to coral health and metabolic activity under oxygen deprivation.

    PubMed

    Murphy, James W A; Richmond, Robert H

    2016-01-01

    On Hawaiian reefs, the fast-growing, invasive algae Gracilaria salicornia overgrows coral heads, restricting water flow and light, thereby smothering corals. Field data shows hypoxic conditions (dissolved oxygen (DO2) < 2 mg/L) occurring underneath algal mats at night, and concurrent bleaching and partial tissue loss of shaded corals. To analyze the impact of nighttime oxygen-deprivation on coral health, this study evaluated changes in coral metabolism through the exposure of corals to chronic hypoxic conditions and subsequent analyses of lactate, octopine, alanopine, and strombine dehydrogenase activities, critical enzymes employed through anaerobic respiration. Following treatments, lactate and octopine dehydrogenase activities were found to have no significant response in activities with treatment and time. However, corals subjected to chronic nighttime hypoxia were found to exhibit significant increases in alanopine dehydrogenase activity after three days of exposure and strombine dehydrogenase activity starting after one overnight exposure cycle. These findings provide new insights into coral metabolic shifts in extremely low-oxygen environments and point to ADH and SDH assays as tools for quantifying the impact of hypoxia on coral health. PMID:27114888

  2. Changes to coral health and metabolic activity under oxygen deprivation

    PubMed Central

    Richmond, Robert H.

    2016-01-01

    On Hawaiian reefs, the fast-growing, invasive algae Gracilaria salicornia overgrows coral heads, restricting water flow and light, thereby smothering corals. Field data shows hypoxic conditions (dissolved oxygen (DO2) < 2 mg/L) occurring underneath algal mats at night, and concurrent bleaching and partial tissue loss of shaded corals. To analyze the impact of nighttime oxygen-deprivation on coral health, this study evaluated changes in coral metabolism through the exposure of corals to chronic hypoxic conditions and subsequent analyses of lactate, octopine, alanopine, and strombine dehydrogenase activities, critical enzymes employed through anaerobic respiration. Following treatments, lactate and octopine dehydrogenase activities were found to have no significant response in activities with treatment and time. However, corals subjected to chronic nighttime hypoxia were found to exhibit significant increases in alanopine dehydrogenase activity after three days of exposure and strombine dehydrogenase activity starting after one overnight exposure cycle. These findings provide new insights into coral metabolic shifts in extremely low-oxygen environments and point to ADH and SDH assays as tools for quantifying the impact of hypoxia on coral health. PMID:27114888

  3. Oxygen-independent induction of enzyme activities related to oxygen metabolism in yeast by copper.

    PubMed

    Galiazzo, F; Schiesser, A; Rotilio, G

    1988-04-14

    Aerobic growth of Saccharomyces cerevisiae in the presence of CuSO4 (between 0.1 and 1 mM) caused a generalized induction of major enzyme activities involved in 'housekeeping' routes of oxygen metabolism (cytochrome oxidase, glutathione peroxidases and catalase) which were comparable to or higher than that observed with Cu,Zn-superoxide dismutase. Fumarase and glutathione transferase, tested as controls for oxygen-unrelated activities, were found to decrease under the same conditions. In the absence of oxygen, copper addition to yeast resulted in significant increases of Cu,Zn-superoxide dismutase and glutathione peroxidases and a slight increase of cytochrome oxidase, with catalase remaining undetectable irrespective of whether or not copper was present. Other metal ions tested (Mn2+, Co2+) were unable to produce such effects. It is concluded that copper has a general inducing effect on enzymes related to metabolism of oxygen and oxygen derivatives, which is mediated neither by formation of O2-. and H2O2 nor by interaction with copper-specific apoproteins. These results point to a general role of copper as regulator of the expression of major enzyme activities involved in biological oxygen activation. PMID:2831994

  4. Cellular Metabolic Activity and the Oxygen and Hydrogen Stable Isotope Composition of Intracellular Water and Metabolites

    NASA Astrophysics Data System (ADS)

    Kreuzer-Martin, H. W.; Hegg, E. L.

    2008-12-01

    Intracellular water is an important pool of oxygen and hydrogen atoms for biosynthesis. Intracellular water is usually assumed to be isotopically identical to extracellular water, but an unexpected experimental result caused us to question this assumption. Heme O isolated from Escherichia coli cells grown in 95% H218O contained only a fraction of the theoretical value of labeled oxygen at a position where the O atom was known to be derived from water. In fact, fewer than half of the oxygen atoms were labeled. In an effort to explain this surprising result, we developed a method to determine the isotope ratios of intracellular water in cultured cells. The results of our experiments showed that during active growth, up to 70% of the oxygen atoms and 50% of the hydrogen atoms in the intracellular water of E. coli are generated during metabolism and can be isotopically distinct from extracellular water. The fraction of isotopically distinct atoms was substantially less in stationary phase and chilled cells, consistent with our hypothesis that less metabolically-generated water would be present in cells with lower metabolic activity. Our results were consistent with and explained the result of the heme O labeling experiment. Only about 40% of the O atoms on the heme O molecule were labeled because, presumably, only about 40% of the water inside the cells was 18O water that had diffused in from the culture medium. The rest of the intracellular water contained 16O atoms derived from either nutrients or atmospheric oxygen. To test whether we could also detect metabolically-derived hydrogen atoms in cellular constituents, we isolated fatty acids from log-phase and stationary phase E. coli and determined the H isotope ratios of individual fatty acids. The results of these experiments showed that environmental water contributed more H atoms to fatty acids isolated in stationary phase than to the same fatty acids isolated from log-phase cells. Stable isotope analyses of

  5. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model

    PubMed Central

    Tegtmeier, Dorothee; Thompson, Claire L.; Schauer, Christine

    2015-01-01

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success. PMID:26637604

  6. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model.

    PubMed

    Tegtmeier, Dorothee; Thompson, Claire L; Schauer, Christine; Brune, Andreas

    2016-02-01

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success. PMID:26637604

  7. Reactive Oxygen Species in the Paraventricular Nucleus of the Hypothalamus Alter Sympathetic Activity During Metabolic Syndrome

    PubMed Central

    Cruz, Josiane C.; Flôr, Atalia F. L.; França-Silva, Maria S.; Balarini, Camille M.; Braga, Valdir A.

    2015-01-01

    The paraventricular nucleus of the hypothalamus (PVN) contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II), which activates AT1 receptors in the circumventricular organs (OCVs), mainly in the subfornical organ (SFO). Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS), leading to increases in sympathetic nerve activity (SNA). Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS): dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin, and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS. PMID:26779026

  8. In vivo imaging of brain metabolism activity using a phosphorescent oxygen-sensitive probe

    PubMed Central

    Tsytsarev, Vassiliy; Arakawa, Hiroyuki; Borisov, Sergei; Pumbo, Elena; Erzurumlu, Reha S.; Papkovsky, Dmitri B.

    2013-01-01

    Several approaches have been adopted for real-time imaging of neural activity in vivo. We tested a new cell-penetrating phosphorescent oxygen-sensitive probe, NanO2-IR, to monitor temporal and spatial dynamics of oxygen metabolism in the neocortex following peripheral sensory stimulation. Probe solution was applied to the surface of anesthetized mouse brain; optical imaging was performed using a MiCAM-02 system. Trains of whisker stimuli were delivered and associated changes in phosphorescent signal were recorded in the contralateral somatosensory (“barrel”) cortex. Sensory stimulation led to changes in oxygenation of activated areas of the barrel cortex. The oxygen imaging results were compared to those produced by the voltage-sensitive dye RH-1691. While the signals emitted by the two probes differed in shape and amplitude, they both faithfully indicated specific whisker evoked cortical activity. Thus, NanO2-IR probe can be used as a tool in visualization and realtime analysis of sensory- evoked neural activity in vivo. PMID:23624034

  9. XPC silencing in normal human keratinocytes triggers metabolic alterations through NOX-1 activation-mediated reactive oxygen species

    PubMed Central

    Rezvani, Hamid Reza; Rossignol, Rodrigue; Ali, Nsrein; Benard, Giovanni; Tang, Xiuwei; Yang, Hee Seung; Jouary, Thomas; de Verneuil, Hubert; Taïeb, Alain; Kim, Arianna L.; Mazurier, Frédéric

    2011-01-01

    Summary Cancer cells utilize complex mechanisms to remodel their bioenergetic properties. We exploited the intrinsic genomic stability of xeroderma pigmentosum C (XPC) to understand the interrelationships between genomic instability, reactive oxygen species (ROS) generation, and metabolic alterations during neoplastic transformation. We showed that knockdown of XPC (XPCKD) in normal human keratinocytes results in metabolism remodeling through NADPH oxidase-1 (NOX-1) activation, which in turn leads to increased ROS levels. While enforcing antioxidant defenses by overexpressing catalase, CuZnSOD, or MnSOD could not block the metabolism remodeling, impaired NOX-1 activation abrogates both alteration in ROS levels and modifications of energy metabolism. As NOX-1 activation is observed in human squamous cell carcinomas (SCCs), the blockade of NOX-1 could be a target for the prevention and the treatment of skin cancers. PMID:21167810

  10. Ventilation rates and activity levels of juvenile jumbo squid under metabolic suppression in the oxygen minimum zone.

    PubMed

    Trübenbach, Katja; Pegado, Maria R; Seibel, Brad A; Rosa, Rui

    2013-02-01

    The Humboldt (jumbo) squid, Dosidicus gigas, is a part-time resident of the permanent oxygen minimum zone (OMZ) in the Eastern Tropical Pacific and, thereby, it encounters oxygen levels below its critical oxygen partial pressure. To better understand the ventilatory mechanisms that accompany the process of metabolic suppression in these top oceanic predators, we exposed juvenile D. gigas to the oxygen levels found in the OMZ (1% O(2), 1 kPa, 10 °C) and measured metabolic rate, activity cycling patterns, swimming mode, escape jet (burst) frequency, mantle contraction frequency and strength, stroke volume and oxygen extraction efficiency. In normoxia, metabolic rate varied between 14 and 29 μmol O(2) g(-1) wet mass h(-1), depending on the level of activity. The mantle contraction frequency and strength were linearly correlated and increased significantly with activity level. Additionally, an increase in stroke volume and ventilatory volume per minute was observed, followed by a mantle hyperinflation process during high activity periods. Squid metabolic rate dropped more than 75% during exposure to hypoxia. Maximum metabolic rate was not achieved under such conditions and the metabolic scope was significantly decreased. Hypoxia changed the relationship between mantle contraction strength and frequency from linear to polynomial with increasing activity, indicating that, under hypoxic conditions, the jumbo squid primarily increases the strength of mantle contraction and does not regulate its frequency. Under hypoxia, jumbo squid also showed a larger inflation period (reduced contraction frequency) and decreased relaxed mantle diameter (shortened diffusion pathway), which optimize oxygen extraction efficiency (up to 82%/34%, without/with consideration of 60% potential skin respiration). Additionally, they breathe 'deeply', with more powerful contractions and enhanced stroke volume. This deep-breathing behavior allows them to display a stable ventilatory volume per

  11. Oxygen dependence of the cytotoxicity and metabolic activation of 4-alkylamino-5-nitroquinoline bioreductive drugs.

    PubMed Central

    Siim, B. G.; Atwell, G. J.; Wilson, W. R.

    1994-01-01

    The cytotoxic potency of 4-alkylamino-5-nitroquinoline drugs in AA8 cell cultures is enhanced up to 60-fold under hypoxia, with wide variations in selectivity for hypoxic cells observed for different members of this series. This study uses three representative 5-nitroquinolines to examine whether these differences in hypoxia-selective cytotoxicity are cell line specific, and to explore quantitatively the oxygen dependence of the cytotoxicity and metabolism of these compounds. The parent compound 5NQ, its 5NQ, its 8-methyl analogue (8Me5NQ) and the 8-methylamino analogue (8NHMe-5NQ) each showed similar hypoxic selectivity (ratio of concentration x time for 90% kill for zero versus 20% oxygen of 13-18-, 30-69- and 1.2-1.4-fold respectively in the three cell lines tested (AA8 Chinese hamster ovary, EMT6/Ak mouse mammary tumour and FME human melanoma). The cytotoxicity and metabolism (covalent binding) of radiolabelled 8Me-5NQ was investigated in AA8 cultures over a range of oxygen tensions (0-95%). The oxygen tension in solution required for 50% inhibition of log cell kill or adduct formation observed under anoxia (C50) was 0.01 and 0.02% oxygen respectively, suggesting that bioreductive alkylation is the mechanism of 8Me-5NQ toxicity. The K-value (oxygen concentration for cytotoxic potency equal to the mean of the potencies at zero and infinite oxygen) was similar (0.02% oxygen). Calculations based on measured rate constants for formation of the nitroradical anion of 8Me-5NQ and rates of radical loss through disproportionation or reaction with oxygen, predict a K-value for 8Me-5NQ of 0.025% oxygen, in good agreement with the experimentally determined value. Modelling of cell killing expected by the combination of 8Me-5NQ plus radiation suggested that tumour cells at intermediate oxygen tensions (0.01-1%) will be partially resistant to this treatment, and would limit the use of these 5-nitroquinolines in combination with radiation, unless sufficient drug could be

  12. Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition.

    PubMed

    Hinson, Jack A; Reid, Angela B; McCullough, Sandra S; James, Laura P

    2004-10-01

    Large doses of the analgesic acetaminophen cause centrilobular hepatic necrosis in man and in experimental animals. It has been previously shown that acetaminophen is metabolically activated by CYP enzymes to N-acetyl-p-benzoquinone imine. This species is normally detoxified by GSH, but following a toxic dose GSH is depleted and the metabolite covalently binds to a number of different proteins. Covalent binding occurs only to the cells developing necrosis. Recently we showed that these cells also contain nitrated tyrosine residues. Nitrotyrosine is mediated by peroxynitrite, a reactive nitrogen species formed by rapid reaction between nitric oxide and superoxide and is normally detoxified by GSH. Thus, acetaminophen toxicity occurs with increased oxygen/nitrogen stress. This manuscript will review current data on acetaminophen covalent binding, increased oxygen/nitrogen stress, and mitochondrial permeability transition, a toxic mechanism that is both mediated by and leads to increased oxygen/nitrogen stress. PMID:15554248

  13. Influence of uranium (VI) on the metabolic activity of stable multispecies biofilms studied by oxygen microsensors and fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Krawczyk-Bärsch, Evelyn; Grossmann, Kay; Arnold, Thuro; Hofmann, Susann; Wobus, Axel

    2008-11-01

    The effect of uranium added in ecologically relevant concentrations (1 × 10 -5 and 1 × 10 -6 M) to stable multispecies biofilms was studied by electrochemical oxygen microsensors with tip diameters of 10 μm and by confocal laser fluorescence microscopy (CLSM). The microsensor profile measurements in the stable multispecies biofilms exposed to uranium showed that the oxygen concentration decreased faster with increasing biofilm depth compared to the uranium free biofilms. In the uranium containing biofilms, the oxygen consumption, calculated from the steady-state microprofiles, showed high consumption rates of up to 61.7 nmol cm -3 s -1 in the top layer (0-70 μm) and much lower consumption rates in the lower zone of the biofilms. Staining experiments with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and 4,6-diamidino-2-phenylindole (DAPI) confirmed the high respiratory activities of the bacteria in the upper layer. Analysis of the amplified 16S rRNA gene fragments showed that the addition of uranium in ecologically relevant concentrations did not change the bacterial diversity in the stable multispecies biofilms and is therefore not responsible for the different oxygen profiles in the biofilms. The fast decrease in the oxygen concentrations in the biofilm profiles showed that the bacteria in the top region of the biofilms, i.e., the metabolically most active biofilm zone, battle the toxic effects of aqueous uranium with an increased respiratory activity. This increased respiratory activity results in O 2 depleted zones closer to the biofilm/air interface which may trigger uranium redox processes, since suitable redox partners, e.g., extracellular polymeric substance (EPS) and other organics (e.g., metabolites), are sufficiently available in the biofilm porewaters. Such redox reactions may lead to precipitation of uranium (IV) solids and consequently to a removal of uranium from the aqueous phase.

  14. [Human oxygen metabolism at high altitudes].

    PubMed

    Dabrowski, Wojciech; Dabrowski, Roman; Wyciszczok, Tomasz; Falk, Joanna

    2006-01-01

    The rapid tourism development resulted in higher incidence of the diseases related to oxygen metabolism pathologies at high altitudes. On the other hand, the lack of ability of close monitoring of changes during oxygen breathing in these conditions still makes it a subject of high interest for clinical studies. It seems that the main problem in oxygen metabolism at high altitudes is the disorder of pulmonary oxygen diffusion. In this paper the authors present the current knowledge, based on available literature, about the high-altitude oxygen metabolism. PMID:16813271

  15. PET Quantification of Cerebral Oxygen Metabolism in Small Animals

    PubMed Central

    Temma, Takashi; Koshino, Kazuhiro; Moriguchi, Tetsuaki; Enmi, Jun-ichiro; Iida, Hidehiro

    2014-01-01

    Understanding cerebral oxygen metabolism is of great importance in both clinical diagnosis and animal experiments because oxygen is a fundamental source of brain energy and supports brain functional activities. Since small animals such as rats are widely used to study various diseases including cerebral ischemia, cerebrovascular diseases, and neurodegenerative diseases, the development of a noninvasive in vivo measurement method of cerebral oxygen metabolic parameters such as oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) as well as cerebral blood flow (CBF) and cerebral blood volume (CBV) has been a priority. Although positron emission tomography (PET) with 15O labeled gas tracers has been recognized as a powerful way to evaluate cerebral oxygen metabolism in humans, this method could not be applied to rats due to technical problems and there were no reports of PET measurement of cerebral oxygen metabolism in rats until an 15O-O2 injection method was developed a decade ago. Herein, we introduce an intravenous administration method using two types of injectable 15O-O2 and an 15O-O2 gas inhalation method through an airway placed in the trachea, which enables oxygen metabolism measurements in rats. PMID:25202714

  16. Oxygen-deficient metabolism and corneal edema

    PubMed Central

    Leung, B.K.; Bonanno, J.A.; Radke, C.J.

    2014-01-01

    Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem–Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema. PMID:21820076

  17. Oxygen-deficient metabolism and corneal edema.

    PubMed

    Leung, B K; Bonanno, J A; Radke, C J

    2011-11-01

    Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem-Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema. PMID:21820076

  18. Common catabolic enzyme patterns in a microplankton community of the Humboldt Current System off northern and central-south Chile: Malate dehydrogenase activity as an index of water-column metabolism in an oxygen minimum zone

    NASA Astrophysics Data System (ADS)

    González, R. R.; Quiñones, R. A.

    2009-07-01

    An extensive subsurface oxygen minimum zone off northern and central-south Chile, associated with the Peru-Chile undercurrent, has important effects on the metabolism of the organisms inhabiting therein. Planktonic species deal with the hypoxic and anoxic environments by relying on biochemical as well as physiological processes related to their anaerobic metabolisms. Here we characterize, for the first time, the potential enzymatic activities involved in the aerobic and anaerobic energy production pathways of microplanktonic organisms (<100 μm), their relationship, and this relationship's association with the oxygen concentration and microplanktonic biomass in the oxygen minimum zone and adjacent areas of the Humboldt Current System water column. Our results demonstrate significant potential enzymatic activity of catabolic pathways in the oxygen minimum zone. Malate dehydrogenase had the highest oxidizing activity of nicotinamide adenine dinucleotide (reduced form) in the batch of catabolic enzymatic activities assayed, including potential pyruvate oxidoreductases activity, the electron transport system, and dissimilatory nitrate reductase. Malate dehydrogenase correlated significantly with almost all the enzymes analyzed within and above the oxygen minimum zone, and also with the oxygen concentration and microplankton biomass in the water column of the Humboldt Current System, especially in the oxygen minimum zone off Iquique. These results suggest a possible specific pattern for the catabolic activity of the microplanktonic realm associated with the oxygen minimum zone spread along the Humboldt Current System off Chile. We hypothesize that malate dehydrogenase activity could be an appropriate indicator of microplankton catabolism in the oxygen minimum zone and adjacent areas.

  19. Metabolic Prosthesis for Oxygenation of Ischemic Tissue

    SciTech Connect

    Greenbaum, Elias

    2009-01-01

    This communication discloses new ideas and preliminary results on the development of a "metabolic prosthesis" for local oxygenation of ischemic tissue under physiological neutral conditions. We report for the first time the selective electrolysis of physiological saline by repetitively pulsed charge-limited electrolysis for the production of oxygen and suppression of free chlorine. For example, using 800 A amplitude current pulses and <200 sec pulse durations, we demonstrated prompt oxygen production and delayed chlorine production at the surface of a shiny 0.85 mm diameter spherical platinum electrode. The data, interpreted in terms of the ionic structure of the electric double layer, suggest a strategy for in situ production of metabolic oxygen via a new class of "smart" prosthetic implants for dealing with ischemic disease such as diabetic retinopathy. We also present data indicating that drift of the local pH of the oxygenated environment can be held constant using a feedback-controlled three electrode electrolysis system that chooses anode and cathode pair based on pH data provided by local microsensors. The work is discussed in the context of diabetic retinopathy since surgical techniques for multielectrode prosthetic implants aimed at retinal degenerative diseases have been developed.

  20. Metabolic response of Clostridium ljungdahlii to oxygen exposure.

    PubMed

    Whitham, Jason M; Tirado-Acevedo, Oscar; Chinn, Mari S; Pawlak, Joel J; Grunden, Amy M

    2015-12-01

    Clostridium ljungdahlii is an important synthesis gas-fermenting bacterium used in the biofuels industry, and a preliminary investigation showed that it has some tolerance to oxygen when cultured in rich mixotrophic medium. Batch cultures not only continue to grow and consume H2, CO, and fructose after 8% O2 exposure, but fermentation product analysis revealed an increase in ethanol concentration and decreased acetate concentration compared to non-oxygen-exposed cultures. In this study, the mechanisms for higher ethanol production and oxygen/reactive oxygen species (ROS) detoxification were identified using a combination of fermentation, transcriptome sequencing (RNA-seq) differential expression, and enzyme activity analyses. The results indicate that the higher ethanol and lower acetate concentrations were due to the carboxylic acid reductase activity of a more highly expressed predicted aldehyde oxidoreductase (CLJU_c24130) and that C. ljungdahlii's primary defense upon oxygen exposure is a predicted rubrerythrin (CLJU_c39340). The metabolic responses of higher ethanol production and oxygen/ROS detoxification were found to be linked by cofactor management and substrate and energy metabolism. This study contributes new insights into the physiology and metabolism of C. ljungdahlii and provides new genetic targets to generate C. ljungdahlii strains that produce more ethanol and are more tolerant to syngas contaminants. PMID:26431975

  1. Metabolic Response of Clostridium ljungdahlii to Oxygen Exposure

    PubMed Central

    Whitham, Jason M.; Tirado-Acevedo, Oscar; Chinn, Mari S.; Pawlak, Joel J.

    2015-01-01

    Clostridium ljungdahlii is an important synthesis gas-fermenting bacterium used in the biofuels industry, and a preliminary investigation showed that it has some tolerance to oxygen when cultured in rich mixotrophic medium. Batch cultures not only continue to grow and consume H2, CO, and fructose after 8% O2 exposure, but fermentation product analysis revealed an increase in ethanol concentration and decreased acetate concentration compared to non-oxygen-exposed cultures. In this study, the mechanisms for higher ethanol production and oxygen/reactive oxygen species (ROS) detoxification were identified using a combination of fermentation, transcriptome sequencing (RNA-seq) differential expression, and enzyme activity analyses. The results indicate that the higher ethanol and lower acetate concentrations were due to the carboxylic acid reductase activity of a more highly expressed predicted aldehyde oxidoreductase (CLJU_c24130) and that C. ljungdahlii's primary defense upon oxygen exposure is a predicted rubrerythrin (CLJU_c39340). The metabolic responses of higher ethanol production and oxygen/ROS detoxification were found to be linked by cofactor management and substrate and energy metabolism. This study contributes new insights into the physiology and metabolism of C. ljungdahlii and provides new genetic targets to generate C. ljungdahlii strains that produce more ethanol and are more tolerant to syngas contaminants. PMID:26431975

  2. Oxygen isotope ratios of PO4: An inorganic indicator of enzymatic activity and P metabolism and a new biomarker in the search for life

    PubMed Central

    Blake, Ruth E.; Alt, Jeffrey C.; Martini, Anna M.

    2001-01-01

    The distinctive relations between biological activity and isotopic effect recorded in biomarkers (e.g., carbon and sulfur isotope ratios) have allowed scientists to suggest that life originated on this planet nearly 3.8 billion years ago. The existence of life on other planets may be similarly identified by geochemical biomarkers, including the oxygen isotope ratio of phosphate (δ18Op) presented here. At low near-surface temperatures, the exchange of oxygen isotopes between phosphate and water requires enzymatic catalysis. Because enzymes are indicative of cellular activity, the demonstration of enzyme-catalyzed PO4–H2O exchange is indicative of the presence of life. Results of laboratory experiments are presented that clearly show that δ18OP values of inorganic phosphate can be used to detect enzymatic activity and microbial metabolism of phosphate. Applications of δ18Op as a biomarker are presented for two Earth environments relevant to the search for extraterrestrial life: a shallow groundwater reservoir and a marine hydrothermal vent system. With the development of in situ analytical techniques and future planned sample return strategies, δ18Op may provide an important biosignature of the presence of life in extraterrestrial systems such as that on Mars. PMID:11226207

  3. Oxygen and the evolution of metabolic pathways

    NASA Technical Reports Server (NTRS)

    Jahnke, L. L.

    1986-01-01

    While a considerable amount of evidence has been accumulated about the history of oxygen on this planet, little is known about the relative amounts to which primitive cells might have been exposed. One clue may be found in the metabolic pathways of extant microorganisms. While eucaryotes are principally aerobic organisms, a number are capable of anaerobic growth by fermentation. One such eucaryotic microorganism, Saccharomyces cerevisiae, will grow in the complete absence of oxygen when supplemented with unsaturated fatty acid and sterol. Oxygen-requiring enzymes are involved in the synthesis of both of these compounds. Studies have demonstrated that the oxidative desaturation of palmitic acid and the conversion of squalene to sterols occur in the range of 10-(3) to 10(-2) PAL. Thus, if the oxygen requirements of these enzymatic processes are an indication, eucaryotes might be more primitive than anticipated from the microfossil record. Results of studies on the oxygen requirements for sterol and unsaturated fatty acid synthesis in a more primitive procaryotic system are also discussed.

  4. Phenotypic variation in metabolism and morphology correlating with animal swimming activity in the wild: relevance for the OCLTT (oxygen- and capacity-limitation of thermal tolerance), allocation and performance models

    PubMed Central

    Baktoft, Henrik; Jacobsen, Lene; Skov, Christian; Koed, Anders; Jepsen, Niels; Berg, Søren; Boel, Mikkel; Aarestrup, Kim; Svendsen, Jon C.

    2016-01-01

    Ongoing climate change is affecting animal physiology in many parts of the world. Using metabolism, the oxygen- and capacity-limitation of thermal tolerance (OCLTT) hypothesis provides a tool to predict the responses of ectothermic animals to variation in temperature, oxygen availability and pH in the aquatic environment. The hypothesis remains controversial, however, and has been questioned in several studies. A positive relationship between aerobic metabolic scope and animal activity would be consistent with the OCLTT but has rarely been tested. Moreover, the performance model and the allocation model predict positive and negative relationships, respectively, between standard metabolic rate and activity. Finally, animal activity could be affected by individual morphology because of covariation with cost of transport. Therefore, we hypothesized that individual variation in activity is correlated with variation in metabolism and morphology. To test this prediction, we captured 23 wild European perch (Perca fluviatilis) in a lake, tagged them with telemetry transmitters, measured standard and maximal metabolic rates, aerobic metabolic scope and fineness ratio and returned the fish to the lake to quantify individual in situ activity levels. Metabolic rates were measured using intermittent flow respirometry, whereas the activity assay involved high-resolution telemetry providing positions every 30 s over 12 days. We found no correlation between individual metabolic traits and activity, whereas individual fineness ratio correlated with activity. Independent of body length, and consistent with physics theory, slender fish maintained faster mean and maximal swimming speeds, but this variation did not result in a larger area (in square metres) explored per 24 h. Testing assumptions and predictions of recent conceptual models, our study indicates that individual metabolism is not a strong determinant of animal activity, in contrast to individual morphology, which is

  5. Oxygen-sensitive flight metabolism in the dragonfly erythemis simplicicollis

    PubMed

    Harrison; Lighton

    1998-06-01

    Insect flight metabolism is completely aerobic, and insect resting metabolism is quite insensitive to atmospheric oxygen level, suggesting a large safety margin in the capacity of the tracheal system to deliver oxygen during flight. We tested the sensitivity of flight initiation and metabolism to atmospheric oxygen level in the libellulid dragonfly Erythemis (Mesothemis) simplicicollis using flow-through respirometric measurements of the rate of CO2 emission (CO2). Flight initiations were unimpaired in atmospheric oxygen levels as low as 10 %. However, flight metabolic rate was affected by ambient oxygen level. Flight CO2 decreased in hypoxic mixtures (5 kPa or 10 kPa oxygen) and increased in hyperoxic atmospheres (30 kPa or 50 kPa oxygen), suggesting that ambient oxygen level influences flight muscle oxygen partial pressure (PO2) and the vigour of flight. These are the first data to show oxygen-limitation of flight metabolism in a free-flying insect. A low safety margin for oxygen delivery during dragonfly flight is consistent with a previous hypothesis that atmospheric hyperoxia facilitated gigantism in Paleozoic protodonates. However, allometric studies of tracheal morphology, and mechanisms and capacity of gas exchange in extant insects are necessary in order to test the hypothesis that the oxygen-sensitivity of aerobic metabolism increases with body size in insects. PMID:9576884

  6. Influence of temperature, oxygen and salinity on the metabolism of the European sea bass

    NASA Astrophysics Data System (ADS)

    Claireaux, G.; Lagardère, J.-P.

    1999-09-01

    Standard (SMR) and routine (RMR) metabolic rates of groups (4 to 5 individuals) of European sea bass ( Dicentrarchus labrax) were measured at combinations of the following factors: temperature (10, 15, 20 and 25°C), oxygenation level (air saturation to 1.5 mg dm -3) and salinity (30, 20, 10 and 5‰). The influence of these environmental conditions on fish metabolic demand was then analysed through ANOVA. At 10, 15, 20 and 25°C, standard metabolic rates were 36, 65, 89, and 91 mg O 2 kg -1 h -1, respectively, while routine oxygen consumptions covered most of the metabolic range accessible. Osmoregulatory costs are linked to metabolic activity through ventilation. This relationship was highlighted by the observed interaction between environmental salinity and temperature. We were, however, unable to detect interactions between salinity and routine metabolic rate, or between salinity and oxygenation level. In order to delineate more precisely the restrictions imposed by water oxygenation on fish metabolic performance we determined the limiting oxygen concentration curves at each experimental temperature. We followed up by modelling the bass active metabolic rate (AMR) and metabolic scope (MS) as functions of both ambient temperature and oxygenation. These mathematical models allowed the characterisation of the controlling and limiting effects of water temperature and oxygen content on the metabolic capacity of the species. Thus, AMR at 10, 15 and 20°C were estimated at 65, 160 and 360 mg O 2 kg -1 h -1, respectively. However, at higher temperature (25°C) AMR dropped slightly (to 340 mg O 2 kg -1 h -1). Bass MS increased by a factor of 9 between 10 and 20°C, but diminished at higher temperatures. The present study contributes to our current understanding of the influences of environmental factors on the metabolism of sea bass and provides a bioenergetic basis for a study of how environmental constraints govern the spatial and temporal distribution pattern of this

  7. Inner retinal metabolic rate of oxygen by oxygen tension and blood flow imaging in rat

    PubMed Central

    Wanek, Justin; Teng, Pang-yu; Albers, John; Blair, Norman P.; Shahidi, Mahnaz

    2011-01-01

    Abstract The metabolic function of inner retinal cells relies on the availability of nutrients and oxygen that are supplied by the retinal circulation. Assessment of retinal tissue vitality and function requires knowledge of both the rate of oxygen delivery and consumption. The purpose of the current study is to report a novel technique for assessment of the inner retinal metabolic rate of oxygen (MO2) by combined measurements of retinal blood flow and vascular oxygen tension (PO2) in rat. The application of this technology has the potential to broaden knowledge of retinal oxygen dynamics and advance understanding of disease pathophysiology. PMID:21991548

  8. Oxidative metabolism, ROS and NO under oxygen deprivation.

    PubMed

    Blokhina, Olga; Fagerstedt, Kurt V

    2010-05-01

    Oxygen deprivation, in line with other stress conditions, is accompanied by reactive oxygen (ROS) and nitrogen species (RNS) formation and is characterised by a set of metabolic changes collectively named as the 'oxidative stress response'. The controversial induction of oxidative metabolism under the lack of oxygen is necessitated by ROS and RNS signaling in the induction of adaptive responses, and inevitably results in oxidative damage. To prevent detrimental effects of oxidative stress, the levels of ROS and NO are tightly controlled on transcriptional, translational and metabolic levels. Hypoxia triggers the induction of genes responsible for ROS and NO handling and utilization (respiratory burst oxidase, non-symbiotic hemoglobins, several cytochromes P450, mitochondrial dehydrogenases, and antioxidant-related transcripts). The level of oxygen in the tissue is also under metabolic control via multiple mechanisms: Regulation of glycolytic and fermentation pathways to manage pyruvate availability for respiration, and adjustment of mitochondrial electron flow through NO and ROS balance. Both adaptive strategies are controlled by energy status and aim to decrease the respiratory capacity and to postpone complete anoxia. Besides local oxygen concentration, ROS and RNS formation is controlled by an array of antioxidants. Hypoxic treatment leads to the upregulation of multiple transcripts associated with ascorbate, glutathione and thioredoxin metabolism. The production of ROS and NO is an integral part of the response to oxygen deprivation which encompasses several levels of metabolic regulation to sustain redox signaling and to prevent oxidative damage. PMID:20303775

  9. Label-free oxygen-metabolic photoacoustic microscopy in vivo

    PubMed Central

    Yao, Junjie; Maslov, Konstantin I.; Zhang, Yu; Xia, Younan; Wang, Lihong V.

    2011-01-01

    Almost all diseases, especially cancer and diabetes, manifest abnormal oxygen metabolism. Accurately measuring the metabolic rate of oxygen (MRO2) can be helpful for fundamental pathophysiological studies, and even early diagnosis and treatment of disease. Current techniques either lack high resolution or rely on exogenous contrast. Here, we propose label-free metabolic photoacoustic microscopy (mPAM) with small vessel resolution to noninvasively quantify MRO2in vivo in absolute units. mPAM is the unique modality for simultaneously imaging all five anatomical, chemical, and fluid-dynamic parameters required for such quantification: tissue volume, vessel cross-section, concentration of hemoglobin, oxygen saturation of hemoglobin, and blood flow speed. Hyperthermia, cryotherapy, melanoma, and glioblastoma were longitudinally imaged in vivo. Counterintuitively, increased MRO2 does not necessarily cause hypoxia or increase oxygen extraction. In fact, early-stage cancer was found to be hyperoxic despite hypermetabolism. PMID:21806264

  10. Label-free oxygen-metabolic photoacoustic microscopy in vivo

    NASA Astrophysics Data System (ADS)

    Yao, Junjie; Maslov, Konstantin I.; Zhang, Yu; Xia, Younan; Wang, Lihong V.

    2011-07-01

    Almost all diseases, especially cancer and diabetes, manifest abnormal oxygen metabolism. Accurately measuring the metabolic rate of oxygen (MRO2) can be helpful for fundamental pathophysiological studies, and even early diagnosis and treatment of disease. Current techniques either lack high resolution or rely on exogenous contrast. Here, we propose label-free metabolic photoacoustic microscopy (mPAM) with small vessel resolution to noninvasively quantify MRO2 in vivo in absolute units. mPAM is the unique modality for simultaneously imaging all five anatomical, chemical, and fluid-dynamic parameters required for such quantification: tissue volume, vessel cross-section, concentration of hemoglobin, oxygen saturation of hemoglobin, and blood flow speed. Hyperthermia, cryotherapy, melanoma, and glioblastoma were longitudinally imaged in vivo. Counterintuitively, increased MRO2 does not necessarily cause hypoxia or increase oxygen extraction. In fact, early-stage cancer was found to be hyperoxic despite hypermetabolism.

  11. Critical oxygen levels and metabolic suppression in oceanic oxygen minimum zones.

    PubMed

    Seibel, Brad A

    2011-01-15

    The survival of oceanic organisms in oxygen minimum zones (OMZs) depends on their total oxygen demand and the capacities for oxygen extraction and transport, anaerobic ATP production and metabolic suppression. Anaerobic metabolism and metabolic suppression are required for daytime forays into the most extreme OMZs. Critical oxygen partial pressures are, within a range, evolved to match the minimum oxygen level to which a species is exposed. This fact demands that low oxygen habitats be defined by the biological response to low oxygen rather than by some arbitrary oxygen concentration. A broad comparative analysis of oxygen tolerance facilitates the identification of two oxygen thresholds that may prove useful for policy makers as OMZs expand due to climate change. Between these thresholds, specific physiological adaptations to low oxygen are required of virtually all species. The lower threshold represents a limit to evolved oxygen extraction capacity. Climate change that pushes oxygen concentrations below the lower threshold (~0.8 kPa) will certainly result in a transition from an ecosystem dominated by a diverse midwater fauna to one dominated by diel migrant biota that must return to surface waters at night. Animal physiology and, in particular, the response of animals to expanding hypoxia, is a critical, but understudied, component of biogeochemical cycles and oceanic ecology. Here, I discuss the definition of hypoxia and critical oxygen levels, review adaptations of animals to OMZs and discuss the capacity for, and prevalence of, metabolic suppression as a response to temporary residence in OMZs and the possible consequences of climate change on OMZ ecology. PMID:21177952

  12. Apollo experience report: Assessment of metabolic expenditures. [extravehicular activity

    NASA Technical Reports Server (NTRS)

    Waligora, J. M.; Hawkins, W. R.; Humbert, G. F.; Nelson, L. J.; Vogel, S. J.; Kuznetz, L. H.

    1975-01-01

    A significant effort was made to assess the metabolic expenditure for extravehicular activity on the lunar surface. After evaluation of the real-time data available to the flight controller during extravehicular activity, three independent methods of metabolic assessment were chosen based on the relationship between heart rate and metabolic production, between oxygen consumption and metabolic production, and between the thermodynamics of the liquid-cooled garment and metabolic production. The metabolic assessment procedure is analyzed and discussed. Real-time use of this information by the Apollo flight surgeon is discussed. Results and analyses of the Apollo missions and comments concerning future applications are included.

  13. Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation

    PubMed Central

    Yi, Ji; Liu, Wenzhong; Chen, Siyu; Backman, Vadim; Sheibani, Nader; Sorenson, Christine M.; Fawzi, Amani A.; Linsenmeier, Robert A.; Zhang, Hao F.

    2015-01-01

    The lack of capability to quantify oxygen metabolism noninvasively impedes both fundamental investigation and clinical diagnosis of a wide spectrum of diseases including all the major blinding diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Using visible light optical coherence tomography (vis-OCT), we demonstrated accurate and robust measurement of retinal oxygen metabolic rate (rMRO2) noninvasively in rat eyes. We continuously monitored the regulatory response of oxygen consumption to a progressive hypoxic challenge. We found that both oxygen delivery, and rMRO2 increased from the highly regulated retinal circulation (RC) under hypoxia, by 0.28 ± 0.08 μL min−1 (p < 0.001), and 0.20 ± 0.04 μL min−1 (p < 0.001) per 100 mmHg systemic pO2 reduction, respectively. The increased oxygen extraction compensated for the deficient oxygen supply from the poorly regulated choroidal circulation. Results from an oxygen diffusion model based on previous oxygen electrode measurements corroborated our in vivo observations. We believe that vis-OCT has the potential to reveal the fundamental role of oxygen metabolism in various retinal diseases. PMID:26658555

  14. A quantitative study of oxygen as a metabolic regulator

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krishnan; LaManna, Joseph C.; Cabrera, Marco E.

    2003-01-01

    An acute reduction in oxygen delivery to a tissue is associated with metabolic changes aimed at maintaining ATP homeostasis. However, given the complexity of the human bioenergetic system, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). In particular, we are interested in determining mechanisms relating cellular oxygen concentration to observed metabolic responses at the cellular, tissue, organ, and whole body levels and in quantifying how changes in tissue oxygen availability affect the pathways of ATP synthesis and the metabolites that control these pathways. In this study, we extend a previously developed mathematical model of human bioenergetics, to provide a physicochemical framework that permits quantitative understanding of oxygen as a metabolic regulator. Specifically, the enhancement--sensitivity analysis--permits studying the effects of variations in tissue oxygenation and parameters controlling cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The analysis can distinguish between parameters that must be determined accurately and those that require less precision, based on their effects on model predictions. This capability may prove to be important in optimizing experimental design, thus reducing use of animals.

  15. A Quantitative Study of Oxygen as a Metabolic Regulator

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krishnan; LaManna, Joseph C.; Cabera, Marco E.

    2000-01-01

    An acute reduction in oxygen delivery to a tissue is associated with metabolic changes aimed at maintaining ATP homeostasis. However, given the complexity of the human bio-energetic system, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). In particular, we are interested in determining mechanisms relating cellular oxygen concentration to observed metabolic responses at the cellular, tissue, organ, and whole body levels and in quantifying how changes in tissue oxygen availability affect the pathways of ATP synthesis and the metabolites that control these pathways. In this study; we extend a previously developed mathematical model of human bioenergetics, to provide a physicochemical framework that permits quantitative understanding of oxygen as a metabolic regulator. Specifically, the enhancement - sensitivity analysis - permits studying the effects of variations in tissue oxygenation and parameters controlling cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The analysis can distinguish between parameters that must be determined accurately and those that require less precision, based on their effects on model predictions. This capability may prove to be important in optimizing experimental design, thus reducing use of animals.

  16. Glutamate metabolism of astrocytes during hyperbaric oxygen exposure and its effects on central nervous system oxygen toxicity.

    PubMed

    Chen, Yu-Liang; Li, Dan; Wang, Zhong-Zhuang; Xu, Wei-Gang; Li, Run-Ping; Zhang, Jun-Dong

    2016-01-20

    Hyperbaric oxygen (HBO) has been used widely in many underwater missions and clinical work. However, exposure to extremely high oxygen pressure may cause central nervous system oxygen toxicity (CNS-OT). The regulation of astrocyte glutamate metabolism is closely related to epilepsy. This study aimed to observe the effects of HBO exposure on glutamate metabolism in astrocytes and confirm the role of glutamate metabolism in CNS-OT. Anesthetized rats were exposed to 5 atmosphere absolute HBO for 80 min and microdialysis samples of brain interstitial fluid were continuously collected. Extracellular glutamate and glutamine concentrations were also detected. Freely moving rats were exposed to HBO of the same pressure for 20 min and glutamine synthetase (GS) activity in brain tissues was measured. Finally, we observed the effects of different doses of drugs related to glutamate metabolism on the latency of CNS-OT. Results showed that HBO exposure significantly increased glutamate content, whereas glutamine content was significantly reduced. Moreover, HBO exposure significantly reduced GS activity. Glutamate transporter-1 (GLT-1) selective antagonist ceftriaxone prolonged CNS-OT latency, whereas GLT-1 selective inhibitor dihydrokainate shortened CNS-OT latency. In summary, HBO exposure improved glutamate concentration and reduced glutamine concentration by inhibition of GS activity. GLT-1 activation also participated in the prevention of HBO-induced CNS-OT. Our research will provide a potential new target to terminate or attenuate CNS-OT. PMID:26619231

  17. Free radicals and activated oxygen.

    PubMed

    Famaey, J P

    1982-01-01

    Superoxide anion (0(-2)), hydrogen peroxide (H2O2) and hydroxyl radical (OH.) are products of the biological reduction of 0(2). They are very reactive and poorly tolerated within living systems and enzymes that catalytically scavenge these products have been evolved as defense mechanisms. These include superoxide dismutases (SOD), catalase and peroxidases. Large amounts of O-2 are produced by different enzymatic and non enzymatic biological processes. Large amounts of activated oxygens are produced by phagocytosing cells such as macrophages and polymorphonuclear cells. This production is associated with the bactericidal actions of these cells but it also largely contributes to exacerbate and sustain the inflammation where these cells congregate. The arachidonic acid pathway triggered by the inflammatory stimuli is also a source for these oxidizing radicals. The production of activated oxygens has been associated with the normal aging process but also with various toxic reactions (e.g. the toxicity of the herbicide paraquat, of the ionizing radiations, of certain antibiotics such as streptonigrin, etc. . . .). O-2 induces the depolymerization of hyaluronic acid which lends viscosity and lubricating properties to synovial fluids. SOD possess antiinflammatory properties and a bovine SOD, orgotein, has now been largely investigated by intramuscular and intraarticular injections in the treatment of rheumatic diseases. Various antiinflammatory compounds (e.g. the salicylates) are able either to inhibit the production of these oxygen radicals or to scavenge them which seems of importance for their antiinflammatory properties. Singlet oxygen, another activated oxygen, might also play a role in the inflammatory process. PMID:6295769

  18. Metabolic assessments during extra-vehicular activity

    NASA Astrophysics Data System (ADS)

    Osipov, Yu. Yu.; Spichkov, A. N.; Filipenkov, S. N.

    Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha'(ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO 2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

  19. Effect of hyperbaric oxygenation on carbohydrate metabolism protein synthesis in the myocardium during sustained hypodynamia

    NASA Technical Reports Server (NTRS)

    Makarov, G. A.

    1980-01-01

    Glycolysis and the intensity of protein synthesis were studied in 140 white male rats in subcellular fractions of the myocardium during 45 day hypodynamia and hyperbaric oxygenation. Hypodynamia increased: (1) the amount of lactic acids; (2) the amount of pyruvic acid; (3) the lactate/pyruvate coefficient; and (4) the activities of aldolase and lactate dehydrogenase. Hyperbaric oxygenation was found to have a favorable metabolic effect on the animals with hypodynamia.

  20. Imaging Oxygen Metabolism In Acute Stroke Using MRI

    PubMed Central

    An, Hongyu; Ford, Andria L.; Vo, Katie D.; Liu, Qingwei; Chen, Yasheng; Lee, Jin-Moo; Lin, Weili

    2014-01-01

    The ability to image the ischemic penumbra during hyper-acute stroke promises to identify patients who may benefit from treatment intervention beyond population-defined therapeutic time windows. MR blood oxygenation level dependent (BOLD) contrast imaging has been explored in ischemic stroke. This review provides an overview of several BOLD-based methods, including susceptibility weighted imaging (SWI), R2, R2*, R2′, R2* under oxygen challenge, MR_OEF and MROMI approaches to assess cerebral oxygen metabolism in ischemic stroke. We will review the underlying pathophysiological basis of the imaging approaches, followed by a brief introduction of BOLD contrast. Finally, we will discuss the applications of the BOLD approaches in patients with ischemic stroke. BOLD-based methods hold promise for imaging tissue oxygenation during acute ischemia. Further technical refinement and validation studies in stroke patients against positron emission tomography (PET) measurements are needed. PMID:24707451

  1. Inner retinal oxygen metabolism in the 50/10 oxygen-induced retinopathy model

    PubMed Central

    Soetikno, Brian T.; Yi, Ji; Shah, Ronil; Liu, Wenzhong; Purta, Patryk; Zhang, Hao F.; Fawzi, Amani A.

    2015-01-01

    Retinopathy of prematurity (ROP) represents a major cause of childhood vision loss worldwide. The 50/10 oxygen-induced retinopathy (OIR) model mimics the findings of ROP, including peripheral vascular attenuation and neovascularization. The oxygen metabolism of the inner retina has not been previously explored in this model. Using visible-light optical coherence tomography (vis-OCT), we measured the oxygen saturation of hemoglobin and blood flow within inner retinal vessels, enabling us to compute the inner retinal oxygen delivery (irDO2) and metabolic rate of oxygen (irMRO2). We compared these measurements between age-matched room-air controls and rats with 50/10 OIR on postnatal day 18. To account for a 61% decrease in the irDO2 in the OIR group, we found an overall statistically significant decrease in retinal vascular density affecting the superficial and deep retinal vascular capillary networks in rats with OIR compared to controls. Furthermore, matching the reduced irDO2, we found a 59% decrease in irMRO2, which we correlated with a statistically significant reduction in retinal thickness in the OIR group, suggesting that the decreased irMRO2 was due to decreased neuronal oxygen utilization. By exploring these biological and metabolic changes in great detail, our study provides an improved understanding of the pathophysiology of OIR model. PMID:26576731

  2. Metabolism of 11-oxygenated steroids. Metabolism in vitro by preparations of liver

    PubMed Central

    Bush, I. E.; Hunter, Sheila A.; Meigs, R. A.

    1968-01-01

    1. The isolation and partial purification of 11β-hydroxy steroid dehydrogenase from rat and guinea-pig liver microsomes has been achieved by conventional methods. 2. The efficiency of different 11-oxygenated steroids as substrates has been examined. The relative efficiencies confirm in the main the stereochemical theory of the enzyme–coenzyme–substrate complex that was proposed earlier on the basis of studies in vivo. Δ4-3-Ketones and 5α-hydrogen steroids are readily metabolized by the enzyme. 5β-Hydrogen steroids and Δ4-3-ketones with certain large α-substituents are metabolized to a limited extent or not at all. Halogen substitution in the 9α-position enhances the rate of reduction of 11-ketones but blocks the oxidation of the related 11β-ols. 3. 9α-Fluorocortisol is a competitive inhibitor of the oxidation of cortisol, but 9α-fluorocortisone is reduced at five to ten times the initial velocity of cortisone. 4. 11β-Hydroxy steroid dehydrogenase activity has been found in liver microsomes of rat, guinea pig, rabbit and calf. 5. Relative substrate efficiencies and Km values are similar in whole (debris-free) homogenates, washed microsomes and acetone-dried powders of washed microsomes. 6. A variety of conditions have been examined for the observation of 11β-hydroxy steroid dehydrogenase activity. NADP(H) is an efficient and NAD(H) a very poor coenzyme for the reaction. PMID:4384445

  3. Inner Retinal Oxygen Delivery and Metabolism in Streptozotocin Diabetic Rats

    PubMed Central

    Wanek, Justin; Teng, Pang-yu; Blair, Norman P.; Shahidi, Mahnaz

    2014-01-01

    Purpose. The purpose of the study is to report global measurements of inner retinal oxygen delivery (DO2_IR) and oxygen metabolism (MO2_IR) in streptozotocin (STZ) diabetic rats. Methods. Phosphorescence lifetime and blood flow imaging were performed in rats 4 (STZ/4wk; n = 10) and 6 (STZ/6wk; n = 10) weeks following injection of STZ to measure retinal arterial (O2A) and venous (O2V) oxygen contents and total retinal blood flow (F). DO2_IR and MO2_IR were calculated from measurements of F and O2A and of F and the arteriovenous oxygen content difference, respectively. Data in STZ rats were compared to those in healthy control rats (n = 10). Results. Measurements of O2A and O2V were not significantly different among STZ/4wk, STZ/6wk, and control rats (P ≥ 0.28). Likewise, F was similar among all groups of rats (P = 0.81). DO2_IR measurements were 941 ± 231, 956 ± 232, and 973 ± 243 nL O2/min in control, STZ/4wk, and STZ/6wk rats, respectively (P = 0.95). MO2_IR measurements were 516 ± 175, 444 ± 103, and 496 ± 84 nL O2/min in control, STZ/4wk, and STZ/6wk rats, respectively (P = 0.37). Conclusions. Global inner retinal oxygen delivery and metabolism were not significantly impaired in STZ rats in early diabetes. PMID:24550355

  4. Visible light optical coherence tomography measure retinal oxygen metabolic response to systemic oxygenation (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yi, Ji; Liu, Wenzhong; Chen, Siyu; Backman, Vadim; Sheibani, Nader; Sorenson, Christine M.; Fawzi, Amani A.; Linsenmeier, Robert A.; Zhang, Hao F.

    2016-03-01

    The lack of capability to quantify oxygen metabolism noninvasively impedes both fundamental investigation and clinical diagnosis of a wide spectrum of diseases including all the major blinding diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Using visible light optical coherence tomography (vis-OCT), we demonstrated accurate and robust measurement of retinal oxygen metabolic rate (rMRO2) noninvasively in rat eyes. The rMRO2 was calculated by concurrent measurement of blood flow and blood oxygen saturation (sO2). Blood flow was calculated by the principle of Doppler optical coherence tomography, where the phase shift between two closely spaced A-lines measures the axial velocity. The distinct optical absorption spectra of oxy- and deoxy-hemoglobin provided the contrast for sO2 measurement, combined with the spectroscopic analysis of vis-OCT signal within the blood vessels. We continuously monitored the regulatory response of oxygen consumption to a progressive hypoxic challenge. We found that both oxygen delivery, and rMRO2 increased from the highly regulated retinal circulation (RC) under hypoxia, by 0.28+/-0.08 μL/min (p<0.001), and 0.20+/-0.04 μL/min (p<0.001) per 100 mmHg systemic pO2 reduction, respectively. The increased oxygen extraction compensated for the deficient oxygen supply from the poorly regulated choroidal circulation (CC).

  5. Active oxygen doctors the evidence

    NASA Astrophysics Data System (ADS)

    Castelló, Ana; Francès, Francesc; Corella, Dolores; Verdú, Fernando

    2009-02-01

    Investigation at the scene of a crime begins with the search for clues. In the case of bloodstains, the most frequently used reagents are luminol and reduced phenolphthalein (or phenolphthalin that is also known as the Kastle-Meyer colour test). The limitations of these reagents have been studied and are well known. Household cleaning products have evolved with the times, and new products with active oxygen are currently widely used, as they are considered to be highly efficient at removing all kinds of stains on a wide range of surfaces. In this study, we investigated the possible effects of these new cleaning products on latent bloodstains that may be left at a scene of a crime. To do so, various fabrics were stained with blood and then washed using cleaning agents containing active oxygen. The results of reduced phenolphthalein, luminol and human haemoglobin tests on the washed fabrics were negative. The conclusion is that these new products alter blood to such an extent that it can no longer be detected by currently accepted methods employed in criminal investigations. This inability to locate bloodstains means that highly important evidence (e.g. a DNA profile) may be lost. Consequently, it is important that investigators are aware of this problem so as to compensate for it.

  6. Linking Pulmonary Oxygen Uptake, Muscle Oxygen Utilization and Cellular Metabolism during Exercise

    PubMed Central

    Lai, Nicola; Camesasca, Marco; Saidel, Gerald M.; Dash, Ranjan K.; Cabrera, Marco E.

    2014-01-01

    The energy demand imposed by physical exercise on the components of the oxygen transport and utilization system requires a close link between cellular and external respiration in order to maintain ATP homeostasis. Invasive and non-invasive experimental approaches have been used to elucidate mechanisms regulating the balance between oxygen supply and consumption during exercise. Such approaches suggest that the mechanism controlling the various subsystems coupling internal to external respiration are part of a highly redundant and hierarchical multi-scale system. In this work, we present a “systems biology” framework that integrates experimental and theoretical approaches able to provide simultaneously reliable information on the oxygen transport and utilization processes occurring at the various steps in the pathway of oxygen from air to mitochondria, particularly at the onset of exercise. This multi-disciplinary framework provides insights into the relationship between cellular oxygen consumption derived from measurements of muscle oxygenation during exercise and pulmonary oxygen uptake by indirect calorimetry. With a validated model, muscle oxygen dynamic responses is simulated and quantitatively related to cellular metabolism under a variety of conditions. PMID:17380394

  7. Spatial control of the energy metabolism of yeast cells through electrolytic generation of oxygen

    NASA Astrophysics Data System (ADS)

    Warnke, Christian; Mair, Thomas; Witte, Hartmut; Reiher, Antje; Hauser, Marcus J. B.; Krost, Alois

    2009-12-01

    The metabolic dynamics of yeast cells is controlled by electric pulses delivered through a spatially extended yeast cell/Au electrode interface. Concomitant with voltage pulses, oxygen is generated electrolytically at the electrode surface and delivered to the cells. The generation of oxygen was investigated in dependence of the applied voltage, width of the voltage pulses and temperature of the electrolytic solution. The local oxygen pulses at the electrodes lead to a transient activation of the aerobic energy metabolism of the yeast cells causing a perturbation in their energy balance. The effect of these local perturbations on the temporal dynamics of glycolysis in yeast cells is quantified in dependence of the energy state of cells.

  8. Taking their breath away: metabolic responses to low-oxygen levels in anchialine shrimps (Crustacea: Atyidae and Alpheidae).

    PubMed

    Havird, Justin C; Vaught, Rebecca C; Weeks, Jeffrey R; Fujita, Yoshihisa; Hidaka, Michio; Santos, Scott R; Henry, Raymond P

    2014-12-01

    Crustaceans generally act as oxy-regulators, maintaining constant oxygen uptake as oxygen partial pressures decrease, but when a critical low level is reached, ventilation and aerobic metabolism shut down. Cave-adapted animals, including crustaceans, often show a reduced metabolic rate possibly owing in part to the hypoxic nature of such environments. However, metabolic rates have not been thoroughly explored in crustaceans from anchialine habitats (coastal ponds and caves), which can experience variable oxygenic regimes. Here, an atypical oxy-conforming pattern of oxygen uptake is reported in the Hawaiian anchialine atyid Halocaridina rubra, along with other unusual metabolic characteristics. Ventilatory rates are near-maximal in normoxia and did not increase appreciably as PO₂ declined, resulting in a decline in VO₂ during progressive hypoxia. Halocaridina rubra maintained in anoxic waters survived for seven days (the duration of the experiment) with no measureable oxygen uptake, suggesting a reliance on anaerobic metabolism. Supporting this, lactate dehydrogenase activity was high, even in normoxia, and oxygen debts were quickly repaid by an unusually extreme increase in oxygen uptake upon exposure to normoxia. In contrast, four related anchialine shrimp species from the Ryukyu Islands, Japan, exhibited physiological properties consistent with previously studied crustaceans. The unusual respiratory patterns found in H. rubra are discussed in the context of a trade-off in gill morphology for osmoregulatory ion transport vs. diffusion of respiratory gasses. Future focus on anchialine species may offer novel insight into the diversity of metabolic responses to hypoxia and other physiological challenges experienced by crustaceans. PMID:25193179

  9. Continuous Dissolved Oxygen Measurements and Modelling Metabolism in Peatland Streams

    PubMed Central

    Dick, Jonathan J.; Soulsby, Chris; Birkel, Christian; Malcolm, Iain; Tetzlaff, Doerthe

    2016-01-01

    Stream water dissolved oxygen was monitored in a 3.2km2 moorland headwater catchment in the Scottish Highlands. The stream consists of three 1st order headwaters and a 2nd order main stem. The stream network is fringed by peat soils with no riparian trees, though dwarf shrubs provide shading in the lower catchment. Dissolved oxygen (DO) is regulated by the balance between atmospheric re-aeration and the metabolic processes of photosynthesis and respiration. DO was continuously measured for >1 year and the data used to calibrate a mass balance model, to estimate primary production, respiration and re-aeration for a 1st order site and in the 2nd order main stem. Results showed that the stream was always heterotrophic at both sites. Sites were most heterotrophic in the summer reflecting higher levels of stream metabolism. The 1st order stream appeared more heterotrophic which was consistent with the evident greater biomass of macrophytes in the 2nd order stream, with resulting higher primary productivity. Comparison between respiration, primary production, re-aeration and potential physical controls revealed only weak relationships. However, the most basic model parameters (e.g. the parameter linking light and photosynthesis) controlling ecosystem processes resulted in significant differences between the sites which seem related to the stream channel geometry. PMID:27556278

  10. Continuous Dissolved Oxygen Measurements and Modelling Metabolism in Peatland Streams.

    PubMed

    Dick, Jonathan J; Soulsby, Chris; Birkel, Christian; Malcolm, Iain; Tetzlaff, Doerthe

    2016-01-01

    Stream water dissolved oxygen was monitored in a 3.2km2 moorland headwater catchment in the Scottish Highlands. The stream consists of three 1st order headwaters and a 2nd order main stem. The stream network is fringed by peat soils with no riparian trees, though dwarf shrubs provide shading in the lower catchment. Dissolved oxygen (DO) is regulated by the balance between atmospheric re-aeration and the metabolic processes of photosynthesis and respiration. DO was continuously measured for >1 year and the data used to calibrate a mass balance model, to estimate primary production, respiration and re-aeration for a 1st order site and in the 2nd order main stem. Results showed that the stream was always heterotrophic at both sites. Sites were most heterotrophic in the summer reflecting higher levels of stream metabolism. The 1st order stream appeared more heterotrophic which was consistent with the evident greater biomass of macrophytes in the 2nd order stream, with resulting higher primary productivity. Comparison between respiration, primary production, re-aeration and potential physical controls revealed only weak relationships. However, the most basic model parameters (e.g. the parameter linking light and photosynthesis) controlling ecosystem processes resulted in significant differences between the sites which seem related to the stream channel geometry. PMID:27556278

  11. A Quantitative Study of Oxygen as a Metabolic Regulator

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krishnan; LaManna, Joseph C.; Cabrera, Marco E.

    1999-01-01

    An acute reduction in oxygen (O2) delivery to a tissue is generally associated with a decrease in phosphocreatine, increases in ADP, NADH/NAD, and inorganic phosphate, increased rates of glycolysis and lactate production, and reduced rates of pyruvate and fatty acid oxidation. However, given the complexity of the human bioenergetic system and its components, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in tissue O2 availability affect the pathways of ATP synthesis and the metabolites that control these pathways. In this study, we extend a previously developed mathematical model of human bioenergetics to provide a physicochemical framework that permits quantitative understanding of O2 as a metabolic regulator. Specifically, the enhancement permits studying the effects of variations in tissue oxygenation and in parameters controlling the rate of cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The whole body is described as a bioenergetic system consisting of metabolically distinct tissue/organ subsystems that exchange materials with the blood. In order to study the dynamic response of each subsystem to stimuli, we solve the ordinary differential equations describing the temporal evolution of metabolite levels, given the initial concentrations. The solver used in the present study is the packaged code LSODE, as implemented in the NASA Lewis kinetics and sensitivity analysis code, LSENS. A major advantage of LSENS is the efficient procedures supporting systematic sensitivity analysis, which provides the basic methods for studying parameter sensitivities (i.e., changes in model behavior due to parameter variation

  12. Effect of ectomycorrhizal colonization and drought on reactive oxygen species metabolism of Nothofagus dombeyi roots.

    PubMed

    Alvarez, Maricel; Huygens, Dries; Fernandez, Carlos; Gacitúa, Yessy; Olivares, Erick; Saavedra, Isabel; Alberdi, Miren; Valenzuela, Eduardo

    2009-08-01

    Infection with ectomycorrhizal fungi can increase the ability of plants to resist drought stress through morphophysiological and biochemical mechanisms. However, the metabolism of antioxidative enzyme activities in the ectomycorrhizal symbiosis remains poorly understood. This study investigated biomass production, reactive oxygen metabolism (hydrogen peroxide and malondialdehyde concentration) and antioxidant enzyme activity (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) in pure cultures of the ectomycorrhizal fungi Descolea antartica Sing. and Pisolithus tinctorius (Pers.) Coker & Couch, and non-mycorrhizal and mycorrhizal roots of Nothofagus dombeyi (Mirb.) roots under well-watered conditions and drought conditions (DC). The studied ectomycorrhizal fungi regulated their antioxidative enzyme metabolism differentially in response to drought, resulting in cellular damage in D. antartica but not in P. tinctorius. Ectomycorrhizal inoculation and water treatment had a significant effect on all parameters studied, including relative water content of the plant. As such, N. dombeyi plants in symbiosis experienced a lower oxidative stress effect than non-mycorrhizal plants under DC. Additionally, ectomycorrhizal N. dombeyi roots showed a greater antioxidant enzyme activity relative to non-mycorrhizal roots, an effect which was further expressed under DC. The association between the non-specific P. tinctorius and N. dombeyi had a more effective reactive oxygen species (ROS) metabolism than the specific D. antartica-N. dombeyi symbiosis. We conclude that the combination of effective ROS prevention and ROS detoxification by ectomycorrhizal plants resulted in reduced cellular damage and increased plant growth relative to non-mycorrhizal plants under drought. PMID:19483186

  13. Response of C2C12 Myoblasts to Hypoxia: The Relative Roles of Glucose and Oxygen in Adaptive Cellular Metabolism

    PubMed Central

    Li, Wei; Hu, Zhen-Fu; Chen, Bin; Ni, Guo-Xin

    2013-01-01

    Background. Oxygen and glucose are two important nutrients for mammalian cell function. In this study, the effect of glucose and oxygen concentrations on C2C12 cellular metabolism was characterized with an emphasis on detecting whether cells show oxygen conformance (OC) in response to hypoxia. Methods. After C2C12 cells being cultured in the levels of glucose at 0.6 mM (LG), 5.6 mM (MG), or 23.3 mM(HG) under normoxic or hypoxic (1% oxygen) condition, cellular oxygen consumption, glucose consumption, lactate production, and metabolic status were determined. Short-term oxygen consumption was measured with a novel oxygen biosensor technique. Longer-term measurements were performed with standard glucose, lactate, and cell metabolism assays. Results. It was found that oxygen depletion in normoxia is dependent on the glucose concentration in the medium. Cellular glucose uptake and lactate production increased significantly in hypoxia than those in normoxia. In hypoxia the cellular response to the level of glucose was different to that in normoxia. The metabolic activities decreased while glucose concentration increased in normoxia, while in hypoxia, metabolic activity was reduced in LG and MG, but unchanged in HG condition. The OC phenomenon was not observed in the present study. Conclusions. Our findings suggested that a combination of low oxygen and low glucose damages the viability of C2C12 cells more seriously than low oxygen alone. In addition, when there is sufficient glucose, C2C12 cells will respond to hypoxia by upregulating anaerobic respiration, as shown by lactate production. PMID:24294605

  14. Effects of adenosine metabolism in astrocytes on central nervous system oxygen toxicity.

    PubMed

    Chen, Yu-liang; Zhang, Ya-nan; Wang, Zhong-zhuang; Xu, Wei-gang; Li, Run-ping; Zhang, Jun-dong

    2016-03-15

    Hyperbaric oxygen (HBO) is widely used in military operations, especially underwater missions. However, prolonged and continuous inhalation of HBO can cause central nervous system oxygen toxicity (CNS-OT), which greatly limits HBO's application. The regulation of astrocytes to the metabolism of adenosine is involved in epilepsy. In our study, we aimed to observe the effects of HBO exposure on the metabolism of adenosine in the brain. Furthermore, we aimed to confirm the possible mechanism underlying adenosine's mediation of the CNS-OT. Firstly, anesthetized rats exposed to 5 atm absolute HBO for 80 min. The concentrations of extracellular adenosine, ATP, ADP, and AMP were detected. Secondly, free-moving rats were exposed to HBO at the same pressure for 20 min, and the activities of 5'-nucleotidase and ADK in brain tissues were measured. For the mechanism studies, we observed the effects of a series of different doses of drugs related to adenosine metabolism on the latency of CNS-OT. Results showed HBO exposure could increase adenosine content by inhibiting ADK activity and improving 5'-nucleotidase activity. And adenosine metabolism during HBO exposure may be a protective response against HBO-induced CNS-OT. Moreover, the improvement of adenosine concentration, activation of adenosine A1R, or suppression of ADK and adenosine A2AR, which are involved in the prevention of HBO-induced CNS-OT. This is the first study to demonstrate HBO exposure regulated adenosine metabolism in the brain. Adenosine metabolism and adenosine receptors are related to HBO-induced CNS-OT development. These results will provide new potential targets for the termination or the attenuation of CNS-OT. PMID:26806404

  15. Microfluidic Platform Generates Oxygen Landscapes for Localized Hypoxic Activation

    PubMed Central

    Rexius, Megan L.; Mauleon, Gerardo; Malik, Asrar B.; Rehman, Jalees; Eddington, David T.

    2014-01-01

    An open-well microfluidic platform generates an oxygen landscape using gas-perfused networks which diffuse across a membrane. The device enables real-time analysis of cellular and tissue responses to oxygen tension to define how cells adapt to heterogeneous oxygen conditions found in the physiological setting. We demonstrate that localized hypoxic activation of cells elicited specific metabolic and gene responses in human microvascular endothelial cells and bone marrow-derived mesenchymal stem cells. A robust demonstration of the compatibility of the device with standard laboratory techniques demonstrates the wide utility of the method. This platform is ideally suited to study real-time cell responses and cell-cell interactions within physiologically relevant oxygen landscapes. PMID:25315003

  16. Physiological characterization of xylose metabolism in Aspergillus niger under oxygen-limited conditions.

    PubMed

    Meijer, S; Panagiotou, G; Olsson, L; Nielsen, J

    2007-10-01

    The physiology of Aspergillus niger was studied under different aeration conditions. Five different aeration rates were investigated in batch cultivations of A. niger grown on xylose. Biomass, intra- and extra-cellular metabolites profiles were determined and ten different enzyme activities in the central carbon metabolism were assessed. The focus was on organic acid production with a special interest in succinate production. The fermentations revealed that oxygen limitation significantly changes the physiology of the micro-organism. Changes in extra cellular metabolite profiles were observed, that is, there was a drastic increase in polyol production (erythritol, xylitol, glycerol, arabitol, and mannitol) and to a lesser extent in the production of reduced acids (malate and succinate). The intracellular metabolite profiles indicated changes in fluxes, since several primary metabolites, like the intermediates of the TCA cycle accumulated during oxygen limitation (on average three fold increase). Also the enzyme activities showed changes between the exponential growth phase and the oxygen limitation phase. In general, the oxygen availability has a significant impact on the physiology of this fungus causing dramatic alterations in the central carbon metabolism that should be taken into account in the design of A. niger as a succinate cell factory. PMID:17335061

  17. Defining the Ischemic Penumbra using Magnetic Resonance Oxygen Metabolic Index

    PubMed Central

    An, Hongyu; Ford, Andria L.; Chen, Yasheng; Zhu, Hongtu; Ponisio, Rosana; Kumar, Gyanendra; Shanechi, Amirali Modir; Khoury, Naim; Vo, Katie D.; Williams, Jennifer; Derdeyn, Colin P.; Diringer, Michael N.; Panagos, Peter; Powers, William J.; Lee, Jin-Moo; Lin, Weili

    2015-01-01

    Background and Purpose Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel MRI approach which measures oxygen metabolic index (OMI), a parameter closely related to PET-derived cerebral metabolic rate of oxygen utilization, to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold which differentiates ischemic core from penumbra and (2) a reversible-injury threshold which differentiates penumbra from tissue not-at-risk for infarction. Methods Forty acute ischemic stroke patients underwent MRI at three time-points after stroke onset: < 4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured CBF, and an asymmetric spin echo sequence measured OEF, to derive OMI (OMI=CBF*OEF). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in three tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict: infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method. Results The optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for non-reperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue. Conclusions OMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample. PMID:25721017

  18. Adaptation of chondrocytes to low oxygen tension: relationship between hypoxia and cellular metabolism.

    PubMed

    Rajpurohit, R; Koch, C J; Tao, Z; Teixeira, C M; Shapiro, I M

    1996-08-01

    In endochondral bone, the growth cartilage is the site of rapid growth. Since the vascular supply to the cartilage is limited, it is widely assumed that cells of the cartilage are hypoxic and that limitations in the oxygen supply regulate the energetic state of the maturing cells. In this report, we evaluate the effects of oxygen tension on chondrocyte energy metabolism, thiol status, and expression of transcription elements, HIF and AP-1. Imposition of an hypoxic environment on cultured chondrocytes caused a proportional increase in glucose utilization and elevated levels of lactate synthesis. Although we observed a statistical increase in the activities of phosphofructokinase, pyruvate kinase, lactate dehydrogenase, and creatine kinase after exposure to lowered oxygen concentrations, the effect was small. The cultured cells exhibited a decreased utilization of glutamine, possibly due to down regulation of mitochondrial function and inhibition of oxidative deamination. With respect to total energy generation, we noted that these cells are quite capable of maintaining the energy charge of the cell at low oxygen tensions. Indeed, no changes in the absolute quantity of adenine nucleotides or the energy charge ratio was observed. Hypoxia caused a decrease in the glutathione content of cultured chondrocytes and a concomitant rise in cell and medium cysteine levels. It is likely that the fall in cell glutathione level is due to decreased synthesis of the tripeptide under reduced oxygen stress and the limited supply of glutamate. The observed rise in cellular and medium cysteine levels probably reflects an increase in the rate of degradation of glutathione and a decrease in synthesis of the peptide. To explore how cells transduce these metabolic effects, gel retardation assays were used to study chondrocyte HIF and AP-1 binding activities. Chondrocyte nuclear preparations bound an HIF-oligonucleotide; however, at low oxygen tensions, no increase in HIF binding was

  19. Eucalanoid copepod metabolic rates in the oxygen minimum zone of the eastern tropical north Pacific: Effects of oxygen and temperature

    NASA Astrophysics Data System (ADS)

    Cass, Christine J.; Daly, Kendra L.

    2014-12-01

    The eastern tropical north Pacific Ocean (ETNP) contains one of the world's most severe oxygen minimum zones (OMZs), where oxygen concentrations are less than 2 μmol kg-1. OMZs cause habitat compression, whereby species intolerant of low oxygen are restricted to near-surface oxygenated waters. Copepods belonging to the family Eucalanidae are dominant zooplankters in this region and inhabit a variety of vertical habitats within the OMZ. The purpose of this study was to compare the metabolic responses of three species of eucalanoid copepods, Eucalanus inermis, Rhincalanus rostrifrons, and Subeucalanus subtenuis, to changes in temperature and environmental oxygen concentrations. Oxygen consumption and urea, ammonium, and phosphate excretion rates were measured via end-point experiments at three temperatures (10, 17, and 23 °C) and two oxygen concentrations (100% and 15% air saturation). S. subtenuis, which occurred primarily in the upper 50 m of the water column at our study site, inhabiting well-oxygenated to upper oxycline conditions, had the highest metabolic rates per unit weight, while E. inermis, which was found throughout the water column to about 600 m depth in low oxygen waters, typically had the lowest metabolic rates. Rates for R. rostrifrons (found primarily between 200 and 300 m depth) were intermediate between the other two species and more variable. Metabolic ratios suggested that R. rostrifrons relied more heavily on lipids to fuel metabolism than the other two species. S. subtenuis was the only species that demonstrated a decrease in oxygen consumption rates (at intermediate 17 °C temperature treatment) when environmental oxygen concentrations were lowered. The percentage of total measured nitrogen excreted as urea (% urea-N), as well as overall urea excretion rates, responded in a complex manner to changes in temperature and oxygen concentration. R. rostrifrons and E. inermis excreted a significantly higher % of urea-N in low oxygen treatments at

  20. Isolation-hypoxia and re-oxygenation of the pallial cavity of female Crepipatella dilatata during estuarine salinity changes requires increased glyoxylase activity and antioxidant metabolism to avoid oxidative damage to female tissues and developing embryos.

    PubMed

    Cubillos, Víctor; Chaparro, Oscar; Segura, Cristian; Montory, Jaime; Cruces, Edgardo; Burritt, David

    2016-08-01

    The estuarine slipper limpet Crepipatella dilatata is a gastropod that can survive prolonged periods of low salinities (< 24 PSU) caused by tidal changes and/or prolonged periods of rain. During low salinity events, C. dilatata can isolate its body from the outside environment, by sealing its shell against the substrate on which it grows. Prolonged isolation periods from the surrounding environment can greatly lower available oxygen levels inside of the pallial cavity, impacting on the physiology of both females and their incubated encapsulated embryos. When salinity levels return to normal, isolation is terminated and the inflow of seawater results in re-oxygenation. In this study we show that when re-oxygenation of the pallial cavity takes place, oxidative damage, in the form of increased levels of lipid peroxides and protein carbonyls, occurs in both maternal tissues and in incubated embryos. To avoid terminal oxidative damage both females and their embryos increase their levels of the glyoxalase pathway enzymes (GLX-I and GLX-II) and general antioxidant metabolism (SOD, CAT, GR, GPOX and GST). As a result the levels of oxidative damage decline to basal levels within 24 h of reoxygenation. Thus the combination of isolation, a behavioural strategy, combined with encapsulation of embryos and a capacity to up regulate relatively rapidly the glyoxylase pathway and general antioxidant metabolism, play major roles in facilitating the survival of C. dilatata in the small estuaries of Southern Chile. PMID:27232979

  1. Effect of Oxygen on Glucose Metabolism: Utilization of Lactate in Staphylococcus Aureus as Revealed by In Vivo NMR Studies

    PubMed Central

    Gaspar, Paula; Pinho, Mariana G.; Neves, Ana Rute

    2013-01-01

    The ability to successfully adapt to changing host conditions is crucial for full virulence of bacterial pathogens. Staphylococcus aureus has to cope with fluctuating oxygen concentrations during the course of infection. Hence, we studied the effect of oxygen on glucose metabolism in non-growing S. aureus COL-S cells by in vivo 13C-NMR. Glucose catabolism was probed at different oxygen concentrations in suspensions of cells grown aerobically (direct effects on metabolism) or anaerobically (transcriptional adjustment to oxygen deprivation). In aerobically-grown cells, the rate of glucose consumption diminished progressively with decreasing oxygen concentrations. Additionally, oxygen deprivation resulted in biphasic glucose consumption, with the second phase presenting a higher rate. The fructose-1,6-bisphosphate pool peaked while glucose was still abundant, but the transient maximum varied with the oxygen concentration. As oxygen became limiting mannitol/mannitol-1-phosphate were detected as products of glucose catabolism. Under anoxic conditions, accumulation of mannitol-1-phosphate ceased with the switch to higher glucose consumption rates, which implies the activation of a more efficient means by which NAD+ can be regenerated. The distribution of end-products deriving from glucose catabolism was dramatically affected by oxygen: acetate increased and lactate decreased with the oxygen concentration; ethanol was formed only anaerobically. Moreover, oxygen promoted the energetically favourable conversion of lactate into acetate, which was particularly noticeable under fully oxygenated conditions. Interestingly, under aerobiosis growing S. aureus cells also converted lactate to acetate, used simultaneously glucose and lactate as substrates for growth, and grew considerably well on lactate-medium. We propose that the efficient lactate catabolism may endow S. aureus with a metabolic advantage in its ecological niche. PMID:23472168

  2. Inhibition of Cancer Cell Proliferation by PPARγ is Mediated by a Metabolic Switch that Increases Reactive Oxygen Species Levels

    PubMed Central

    Srivastava, Nishi; Kollipara, Rahul K.; Singh, Dinesh K.; Sudderth, Jessica; Hu, Zeping; Nguyen, Hien; Wang, Shan; Humphries, Caroline G.; Carstens, Ryan; Huffman, Kenneth E.; DeBerardinis, Ralph J.; Kittler, Ralf

    2014-01-01

    SUMMARY The nuclear receptor peroxisome-proliferation activated receptor gamma (PPARγ), a transcriptional master regulator of glucose and lipid metabolism, inhibits the growth of several common cancers including lung cancer. In this study, we show that the mechanism by which activation of PPARγ inhibits proliferation of lung cancer cells is based on metabolic changes. We found that treatment with the PPARγ agonist pioglitazone triggers a metabolic switch that inhibits pyruvate oxidation and reduces glutathione levels. These PPARγ-induced metabolic changes result in a marked increase of reactive oxygen species (ROS) levels that lead to rapid hypophosphorylation of retinoblastoma protein (RB) and cell cycle arrest. The antiproliferative effect of PPARγ activation can be prevented by suppressing pyruvate dehydrogenase kinase 4 (PDK4) or β-oxidation of fatty acids in vitro and in vivo. Our proposed mechanism also suggests that metabolic changes can rapidly and directly inhibit cell cycle progression of cancer cells by altering ROS levels. PMID:25264247

  3. Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels.

    PubMed

    Srivastava, Nishi; Kollipara, Rahul K; Singh, Dinesh K; Sudderth, Jessica; Hu, Zeping; Nguyen, Hien; Wang, Shan; Humphries, Caroline G; Carstens, Ryan; Huffman, Kenneth E; DeBerardinis, Ralph J; Kittler, Ralf

    2014-10-01

    The nuclear receptor peroxisome-proliferation-activated receptor gamma (PPARγ), a transcriptional master regulator of glucose and lipid metabolism, inhibits the growth of several common cancers, including lung cancer. In this study, we show that the mechanism by which activation of PPARγ inhibits proliferation of lung cancer cells is based on metabolic changes. We found that treatment with the PPARγ agonist pioglitazone triggers a metabolic switch that inhibits pyruvate oxidation and reduces glutathione levels. These PPARγ-induced metabolic changes result in a marked increase of reactive oxygen species (ROS) levels that lead to rapid hypophosphorylation of retinoblastoma protein (RB) and cell-cycle arrest. The antiproliferative effect of PPARγ activation can be prevented by suppressing pyruvate dehydrogenase kinase 4 (PDK4) or β-oxidation of fatty acids in vitro and in vivo. Our proposed mechanism also suggests that metabolic changes can rapidly and directly inhibit cell-cycle progression of cancer cells by altering ROS levels. PMID:25264247

  4. Melatonin: an ancient molecule that makes oxygen metabolically tolerable.

    PubMed

    Manchester, Lucien C; Coto-Montes, Ana; Boga, Jose Antonio; Andersen, Lars Peter H; Zhou, Zhou; Galano, Annia; Vriend, Jerry; Tan, Dun-Xian; Reiter, Russel J

    2015-11-01

    Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant, circadian rhythm regulator, anti-inflammatory and immunoregulating molecule, and as an oncostatic agent. We hypothesize that the initial and primary function of melatonin in photosynthetic cyanobacteria, which appeared on Earth 3.5-3.2 billion years ago, was as an antioxidant. The evolution of melatonin as an antioxidant by this organism was necessary as photosynthesis is associated with the generation of toxic-free radicals. The other secondary functions of melatonin came about much later in evolution. We also surmise that mitochondria and chloroplasts may be primary sites of melatonin synthesis in all eukaryotic cells that possess these organelles. This prediction is made on the basis that mitochondria and chloroplasts of eukaryotes developed from purple nonsulfur bacteria (which also produce melatonin) and cyanobacteria when they were engulfed by early eukaryotes. Thus, we speculate that the melatonin-synthesizing actions of the engulfed bacteria were retained when these organelles became mitochondria and chloroplasts, respectively. That mitochondria are likely sites of melatonin formation is supported by the observation that this organelle contains high levels of melatonin that are not impacted by blood melatonin concentrations. Melatonin has a remarkable array of means by which it thwarts oxidative damage. It, as well as its metabolites, is differentially effective in scavenging a variety of reactive oxygen and reactive nitrogen species. Moreover, melatonin and its metabolites modulate a large number of antioxidative and pro-oxidative enzymes, leading to a reduction in oxidative damage. The actions of melatonin on radical metabolizing/producing enzymes may be mediated by the Keap1-Nrf2-ARE pathway. Beyond its direct free radical scavenging and indirect antioxidant effects, melatonin has a variety of physiological and metabolic advantages that may enhance its

  5. Forest clearfelling effects on dissolved oxygen and metabolism in peatland streams.

    PubMed

    O'Driscoll, Connie; O'Connor, Mark; Asam, Zaki-Ul-Zaman; de Eyto, Elvira; Brown, Lee E; Xiao, Liwen

    2016-01-15

    Peatlands cover ∼3% of the world's landmass and large expanses have been altered significantly as a consequence of land use change. Forestry activities are a key pressure on these catchments increasing suspended sediment and nutrient export to receiving waters. The aim of this study was to investigate stream dissolved oxygen (DO) and metabolic activity response following clearfelling of a 39-year-old lodgepole pine and Sitka spruce forestry in an upland peat catchment. Significant effects of clearfelling on water temperature, flows, DO and stream metabolic (photosynthesis, respiration) rates were revealed. Stream temperature and discharge significantly increased in the study stream following clearfelling. Instream ecosystem respiration increased significantly following clearfelling, indicating an increase in the net consumption of organic carbon. PMID:26513323

  6. Oxidative stress alters arginine metabolism in rat brain: effect of sub-convulsive hyperbaric oxygen exposure.

    PubMed

    Ito, T; Yufu, K; Mori, A; Packer, L

    1996-08-01

    The effect of hyperbaric oxygenation on arginine metabolism was investigated. Rats were exposed to oxygen at 3 atmospheres absolute for 2 h. Under these conditions, lipid peroxidation and activation of the anti-oxidant system were observed. Levels of thiobarbiturate reactive substances and carbon-centered radicals were increased in the cerebral cortex, while superoxide dismutase activity was also increased in the mitochondrial and cytosolic fraction of cerebrocortical homogenates. This suggested that the increase of both Mn and Cu,Zn-superoxide dismutase activities was probably an early compensatory reaction to oxidative stress. Levels of arginine as well as its metabolite, guanidinoacetic acid, were increased in the cerebral cortex. This increase seemed to be, at least in part, explained by a decrease in the arginase activity in the same region. Moreover, arginase activity in the brain showed heterogeneous distribution. Arginine: glycine amidinotransferase activity was decreased in the pons-medulla oblongata. The observed effects of hyperbaric oxygenation seem to favor nitric oxide generation. PMID:8837048

  7. Anaerobic Metabolism at Thermal Extremes: A Metabolomic Test of the Oxygen Limitation Hypothesis in an Aquatic Insect

    PubMed Central

    Verberk, W. C. E. P.; Sommer, U.; Davidson, R. L.; Viant, M. R.

    2013-01-01

    Thermal limits in ectotherms may arise through a mismatch between supply and demand of oxygen. At higher temperatures, the ability of their cardiac and ventilatory activities to supply oxygen becomes insufficient to meet their elevated oxygen demand. Consequently, higher levels of oxygen in the environment are predicted to enhance tolerance of heat, whereas reductions in oxygen are expected to reduce thermal limits. Here, we extend previous research on thermal limits and oxygen limitation in aquatic insect larvae and directly test the hypothesis of increased anaerobic metabolism and lower energy status at thermal extremes. We quantified metabolite profiles in stonefly nymphs under varying temperatures and oxygen levels. Under normoxia, the concept of oxygen limitation applies to the insects studied. Shifts in the metabolome of heat-stressed stonefly nymphs clearly indicate the onset of anaerobic metabolism (e.g., accumulation of lactate, acetate, and alanine), a perturbation of the tricarboxylic acid cycle (e.g., accumulation of succinate and malate), and a decrease in energy status (e.g., ATP), with corresponding decreases in their ability to survive heat stress. These shifts were more pronounced under hypoxic conditions, and negated by hyperoxia, which also improved heat tolerance. Perturbations of metabolic pathways in response to either heat stress or hypoxia were found to be somewhat similar but not identical. Under hypoxia, energy status was greatly compromised at thermal extremes, but energy shortage and anaerobic metabolism could not be conclusively identified as the sole cause underlying thermal limits under hyperoxia. Metabolomics proved useful for suggesting a range of possible mechanisms to explore in future investigations, such as the involvement of leaking membranes or free radicals. In doing so, metabolomics provided a more complete picture of changes in metabolism under hypoxia and heat stress. PMID:23604617

  8. Viscosity dictates metabolic activity of Vibrio ruber

    PubMed Central

    Borić, Maja; Danevčič, Tjaša; Stopar, David

    2012-01-01

    Little is known about metabolic activity of bacteria, when viscosity of their environment changes. In this work, bacterial metabolic activity in media with viscosity ranging from 0.8 to 29.4 mPas was studied. Viscosities up to 2.4 mPas did not affect metabolic activity of Vibrio ruber. On the other hand, at 29.4 mPas respiration rate and total dehydrogenase activity increased 8 and 4-fold, respectively. The activity of glucose-6-phosphate dehydrogenase (GPD) increased up to 13-fold at higher viscosities. However, intensified metabolic activity did not result in faster growth rate. Increased viscosity delayed the onset as well as the duration of biosynthesis of prodigiosin. As an adaptation to viscous environment V. ruber increased metabolic flux through the pentose phosphate pathway and reduced synthesis of a secondary metabolite. In addition, V. ruber was able to modify the viscosity of its environment. PMID:22826705

  9. Neuron Specific Metabolic Adaptations Following Multi-Day Exposures to Oxygen Glucose Deprivation

    PubMed Central

    Zeiger, Stephanie L. H.; McKenzie, Jennifer R.; Stankowski, Jeannette N.; Martin, Jacob A.; Cliffel, David E.; McLaughlin, BethAnn

    2010-01-01

    Prior exposure to sub toxic insults can induce a powerful endogenous neuroprotective program known as ischemic preconditioning. Current models typically rely on a single stress episode to induce neuroprotection whereas the clinical reality is that patients may experience multiple transient ischemic attacks (TIAs) prior to suffering a stroke. We sought to develop a neuron enriched preconditioning model using multiple oxygen glucose deprivation (OGD) episodes to assess the endogenous protective mechanisms neurons implement at the metabolic and cellular level for stress adaptations. We found that neurons exposed to a five minute period of glucose deprivation recovered oxygen utilization and lactate production using novel microphysiometry techniques. Using the non-toxic and energetically favorable five minute exposure, we developed a preconditioning paradigm where neurons are exposed to this brief OGD for three consecutive days. These cells experienced 45% greater survival following an otherwise lethal event and exhibited a longer lasting window of protection in comparison to our previous in vitro preconditioning model using a single stress. As in other models, preconditioned cells exhibited mild caspase activation, an increase in oxidized proteins and a requirement for reactive oxygen species for neuroprotection. Heat shock protein 70 was upregulated during preconditioning, yet the majority of this protein was released extracellularly. We believe coupling this neuron enriched multiday model with microphysiometry will allow us to assess neuronal specific real-time metabolic adaptations necessary for preconditioning. PMID:20656023

  10. Metabolic scaling theory in plant biology and the three oxygen paradoxa of aerobic life.

    PubMed

    Kutschera, Ulrich; Niklas, Karl J

    2013-12-01

    Alfred Russell Wallace was a field naturalist with a strong interest in general physiology. In this vein, he wrote that oxygen (O2), produced by green plants, is "the food of protoplasm, without which it cannot continue to live". Here we summarize current models relating body size to respiration rates (in the context of the metabolic scaling theory) and show that oxygen-uptake activities, measured at 21 vol.% O2, correlate closely with growth patterns at the level of specific organs within the same plant. Thus, whole plant respiration can change ontogenetically, corresponding to alterations in the volume fractions of different tissues. Then, we describe the evolution of cyanobacterial photosynthesis during the Paleoarchean, which changed the world forever. By slowly converting what was once a reducing atmosphere to an oxidizing one, microbes capable of O2-producing photosynthesis modified the chemical nature and distribution of the element iron (Fe), slowly drove some of the most ancient prokaryotes to extinction, created the ozone (O3) layer that subsequently shielded the first terrestrial plants and animals from harmful UV radiation, but also made it possible for Earth's forest to burn, sometimes with catastrophic consequences. Yet another paradox is that the most abundant protein (i.e., the enzyme Rubisco, Ribulose-1,5-biphosphate carboxylase/oxygenase) has a greater affinity for oxygen than for carbon dioxide (CO2), even though its function is to bind with the latter rather than the former. We evaluate this second "oxygen paradox" within the context of photorespiratory carbon loss and crop yield reduction in C3 vs. C4 plants (rye vs. maize). Finally, we analyze the occurrence of reactive oxygen species (ROS) as destructive by-products of cellular metabolism, and discuss the three "O2-paradoxa" with reference to A. R. Wallace's speculations on "design in nature". PMID:23982798

  11. Cerebral metabolic rate of oxygen (CMRO2) assessed by combined Doppler and spectroscopic OCT

    PubMed Central

    Chong, Shau Poh; Merkle, Conrad W.; Leahy, Conor; Srinivasan, Vivek J.

    2015-01-01

    A method of measuring cortical oxygen metabolism in the mouse brain that uses independent quantitative measurements of three key parameters: cerebral blood flow (CBF), arteriovenous oxygen extraction (OE), and hemoglobin concentration ([HbT]) is presented. Measurements were performed using a single visible light spectral/Fourier domain OCT microscope, with Doppler and spectroscopic capabilities, through a thinned-skull cranial window in the mouse brain. Baseline metabolic measurements in mice are shown to be consistent with literature values. Oxygen consumption, as measured by this method, did not change substantially during minor changes either in the fraction of inspired oxygen (FiO2) or in the fraction of inspired carbon dioxide (FiCO2), in spite of larger variations in oxygen saturations. This set of experiments supports, but does not prove, the validity of the proposed method of measuring brain oxygen metabolism. PMID:26504644

  12. Influence of host seed on metabolic activity by Enterobacter cloacae in the spermosphere

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known regarding the influences of nutrients released from plants on the metabolic activity of colonizing microbes. To gain a better understanding of these influences, we used bioluminescence- and oxygen consumption-based methods to compare bacterial metabolic activity expressed during col...

  13. Oxygen metabolism, oxygen extraction and positron emission tomography: Historical perspective and impact on basic and clinical neuroscience.

    PubMed

    Baron, Jean-Claude; Jones, Terry

    2012-06-01

    Oxygen utilization is central to the human brain's high metabolic rate. Measurement of this fundamental process, in both disease and health, has been a focus of research attention over the last 35 years. This review plots the course of the use of oxygen-15 to study regional cerebral oxygen extraction and metabolism using Positron Emission Tomography (PET) in disease and in health. The scientific discoveries and resulting conceptual changes to both basic and clinical neuroscience, as well as the new methodological approaches brought about by this area of research, are also summarized. We conclude with a brief overview of the current status of oxygen-15 PET in neuroscience, along with our visions for future developments and applications. PMID:22227130

  14. Metabolic Profiles of Anjou Pears Stored in Low Oxygen Atmospheres

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low oxygen storage atmospheres can slow ripening and prevent development of the peel disorder superficial scald on Anjou pear fruit; however, development of peel speckling can be exacerbated by low oxygen storage. To better understand how Anjou pear fruit respond to low oxygen atmospheres, a metabo...

  15. Partitioning the metabolic scope: the importance of anaerobic metabolism and implications for the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis.

    PubMed

    Ejbye-Ernst, Rasmus; Michaelsen, Thomas Y; Tirsgaard, Bjørn; Wilson, Jonathan M; Jensen, Lasse F; Steffensen, John F; Pertoldi, Cino; Aarestrup, Kim; Svendsen, Jon C

    2016-01-01

    Ongoing climate change is predicted to affect the distribution and abundance of aquatic ectotherms owing to increasing constraints on organismal physiology, in particular involving the metabolic scope (MS) available for performance and fitness. The oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis prescribes MS as an overarching benchmark for fitness-related performance and assumes that any anaerobic contribution within the MS is insignificant. The MS is typically derived from respirometry by subtracting standard metabolic rate from the maximal metabolic rate; however, the methodology rarely accounts for anaerobic metabolism within the MS. Using gilthead sea bream (Sparus aurata) and Trinidadian guppy (Poecilia reticulata), this study tested for trade-offs (i) between aerobic and anaerobic components of locomotor performance; and (ii) between the corresponding components of the MS. Data collection involved measuring oxygen consumption rate at increasing swimming speeds, using the gait transition from steady to unsteady (burst-assisted) swimming to detect the onset of anaerobic metabolism. Results provided evidence of the locomotor performance trade-off, but only in S. aurata. In contrast, both species revealed significant negative correlations between aerobic and anaerobic components of the MS, indicating a trade-off where both components of the MS cannot be optimized simultaneously. Importantly, the fraction of the MS influenced by anaerobic metabolism was on average 24.3 and 26.1% in S. aurata and P. reticulata, respectively. These data highlight the importance of taking anaerobic metabolism into account when assessing effects of environmental variation on the MS, because the fraction where anaerobic metabolism occurs is a poor indicator of sustainable aerobic performance. Our results suggest that without accounting for anaerobic metabolism within the MS, studies involving the OCLTT hypothesis could overestimate the metabolic scope available for

  16. Partitioning the metabolic scope: the importance of anaerobic metabolism and implications for the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis

    PubMed Central

    Ejbye-Ernst, Rasmus; Michaelsen, Thomas Y.; Tirsgaard, Bjørn; Wilson, Jonathan M.; Jensen, Lasse F.; Steffensen, John F.; Pertoldi, Cino; Aarestrup, Kim; Svendsen, Jon C.

    2016-01-01

    Ongoing climate change is predicted to affect the distribution and abundance of aquatic ectotherms owing to increasing constraints on organismal physiology, in particular involving the metabolic scope (MS) available for performance and fitness. The oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis prescribes MS as an overarching benchmark for fitness-related performance and assumes that any anaerobic contribution within the MS is insignificant. The MS is typically derived from respirometry by subtracting standard metabolic rate from the maximal metabolic rate; however, the methodology rarely accounts for anaerobic metabolism within the MS. Using gilthead sea bream (Sparus aurata) and Trinidadian guppy (Poecilia reticulata), this study tested for trade-offs (i) between aerobic and anaerobic components of locomotor performance; and (ii) between the corresponding components of the MS. Data collection involved measuring oxygen consumption rate at increasing swimming speeds, using the gait transition from steady to unsteady (burst-assisted) swimming to detect the onset of anaerobic metabolism. Results provided evidence of the locomotor performance trade-off, but only in S. aurata. In contrast, both species revealed significant negative correlations between aerobic and anaerobic components of the MS, indicating a trade-off where both components of the MS cannot be optimized simultaneously. Importantly, the fraction of the MS influenced by anaerobic metabolism was on average 24.3 and 26.1% in S. aurata and P. reticulata, respectively. These data highlight the importance of taking anaerobic metabolism into account when assessing effects of environmental variation on the MS, because the fraction where anaerobic metabolism occurs is a poor indicator of sustainable aerobic performance. Our results suggest that without accounting for anaerobic metabolism within the MS, studies involving the OCLTT hypothesis could overestimate the metabolic scope available for

  17. Metabolic adaptations of Azospirillum brasilense to oxygen stress by cell-to-cell clumping and flocculation.

    PubMed

    Bible, Amber N; Khalsa-Moyers, Gurusahai K; Mukherjee, Tanmoy; Green, Calvin S; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B; Alexandre, Gladys

    2015-12-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. PMID:26407887

  18. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    PubMed Central

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B.

    2015-01-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. PMID:26407887

  19. Enhanced reactive oxygen species metabolism of air space cells in hypersensitivity pneumonitis

    SciTech Connect

    Calhoun, W.J. )

    1991-06-01

    Reactive oxygen species (ROS) are produced by phagocytic cells as part of host defense mechanisms, but these same products released by air space cells have been shown to contribute to pulmonary inflammation in interstitial lung diseases and likely represent a general mechanism of lung injury. However, the possible contribution of these compounds to lung inflammation in hypersensitivity pneumonitis (HP) has yet to be reported. We performed 11 bronchoalveolar lavage (BAL) studies in six patients with HP and compared the results with results from studies in 21 healthy normal volunteers. In patients with HP, spontaneous and stimulated measures of ROS metabolism by air space cells were significantly higher than those seen in normal volunteers. When alveolar macrophages were purified by depleting neutrophils and eosinophils on density gradients of Percoll (specific gravity 1.075 gm/ml), ROS metabolism remained elevated when compared with that in cells obtained from healthy controls, confirming that alveolar macrophage ROS metabolism is enhanced in patients with HP. Further, we found significant elevations in BAL total protein, lymphocytes, eosinophils, and neutrophils in patients with HP when they were compared with normal volunteers, with an increased proportion of BAL T lymphocytes expressing CD8 and natural killer surface antigens, consistent with previous work. Lavage samples from patients with HP with clinically active disease had higher proportions of BAL eosinophils and concentrations of total protein, lower forced expiratory volume in 1 second, lower forced vital capacity, and lower arterial oxygen tensions, and higher indices of ROS metabolism than samples from patients with HP with inactive disease. HP is associated with evidence of air space inflammation, to which alveolar macrophage-derived ROS may contribute.

  20. Early oxygen-utilization and brain activity in preterm infants.

    PubMed

    Tataranno, Maria Luisa; Alderliesten, Thomas; de Vries, Linda S; Groenendaal, Floris; Toet, Mona C; Lemmers, Petra M A; Vosse van de, Renè E; van Bel, Frank; Benders, Manon J N L

    2015-01-01

    The combined monitoring of oxygen supply and delivery using Near-InfraRed spectroscopy (NIRS) and cerebral activity using amplitude-integrated EEG (aEEG) could yield new insights into brain metabolism and detect potentially vulnerable conditions soon after birth. The relationship between NIRS and quantitative aEEG/EEG parameters has not yet been investigated. Our aim was to study the association between oxygen utilization during the first 6 h after birth and simultaneously continuously monitored brain activity measured by aEEG/EEG. Forty-four hemodynamically stable babies with a GA < 28 weeks, with good quality NIRS and aEEG/EEG data available and who did not receive morphine were included in the study. aEEG and NIRS monitoring started at NICU admission. The relation between regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE), and quantitative measurements of brain activity such as number of spontaneous activity transients (SAT) per minute (SAT rate), the interval in seconds (i.e. time) between SATs (ISI) and the minimum amplitude of the EEG in μV (min aEEG) were evaluated. rScO2 was negatively associated with SAT rate (β=-3.45 [CI=-5.76- -1.15], p=0.004) and positively associated with ISI (β=1.45 [CI=0.44-2.45], p=0.006). cFTOE was positively associated with SAT rate (β=0.034 [CI=0.009-0.059], p=0.008) and negatively associated with ISI (β=-0.015 [CI=-0.026- -0.004], p=0.007). Oxygen delivery and utilization, as indicated by rScO2 and cFTOE, are directly related to functional brain activity, expressed by SAT rate and ISI during the first hours after birth, showing an increase in oxygen extraction in preterm infants with increased early electro-cerebral activity. NIRS monitored oxygenation may be a useful biomarker of brain vulnerability in high-risk infants. PMID:25965343

  1. Industry as a metabolic activity.

    PubMed

    Smart, B

    1992-02-01

    The concept of "industrial economic metabolism" can provide a bridge to better understanding between environmentalists and industry. In nature each individual or species reacts to natural stimuli, competing with others for resources, extending its domain until it loses comparative advantage and comes to equilibrium with an adjacent competitor. Those species that succeed over time flourish; those that do not, diminish or disappear. Nature's rule book has no moral or ethical ingredient beyond self-interest. Corporate metabolisms are remarkably similar to those of nature. They too react to stimuli, collect and use resources, and grow or perish based on how effectively they compete. Corporate management recognizes and responds naturally and efficiently to cost and price signals. Through them it selects resources and converts them into useful products. The efficiency with which this is done is measured by profit, the lifeblood of the corporation and its means of growth. Profit thus provides a discipline on corporate behavior, encouraging efficient performers, and, by its absence, weeding out others. Unfettered by influences other than economics, the path to corporate success is unlikely to be a compassionate one. The dilemma of the manager is that to do what is socially "right" often conflicts with what must be done to survive and prosper. Fortunately, corporations' behavior can be altered by society when their purely economic role comes into conflict with other human values. The environment and the economy are not separate systems but intertwined to form a complex natural and social setting. The human-designed economic system depends on natural resource inputs, and in turn its metabolic wastes can overload the ecological system, threatening the long-term survivability of both. Increasing concern for the environment now gives the farsighted manager new latitude. There are competitive benefits in some pollution prevention. But there are not sufficiently strong forces to

  2. Impact of hypothalamic reactive oxygen species in the regulation of energy metabolism and food intake

    PubMed Central

    Drougard, Anne; Fournel, Audren; Valet, Philippe; Knauf, Claude

    2015-01-01

    Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites) from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS) as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC) and agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,…), neurotransmitters and nutrients (glucose, lipids,…). The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes. In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders. PMID:25759638

  3. Staphylococcus epidermidis: metabolic adaptation and biofilm formation in response to different oxygen concentrations.

    PubMed

    Uribe-Alvarez, Cristina; Chiquete-Félix, Natalia; Contreras-Zentella, Martha; Guerrero-Castillo, Sergio; Peña, Antonio; Uribe-Carvajal, Salvador

    2016-02-01

    Staphylococcus epidermidis has become a major health hazard. It is necessary to study its metabolism and hopefully uncover therapeutic targets. Cultivating S. epidermidis at increasing oxygen concentration [O2] enhanced growth, while inhibiting biofilm formation. Respiratory oxidoreductases were differentially expressed, probably to prevent reactive oxygen species formation. Under aerobiosis, S. epidermidis expressed high oxidoreductase activities, including glycerol-3-phosphate dehydrogenase, pyruvate dehydrogenase, ethanol dehydrogenase and succinate dehydrogenase, as well as cytochromes bo and aa3; while little tendency to form biofilms was observed. Under microaerobiosis, pyruvate dehydrogenase and ethanol dehydrogenase decreased while glycerol-3-phosphate dehydrogenase and succinate dehydrogenase nearly disappeared; cytochrome bo was present; anaerobic nitrate reductase activity was observed; biofilm formation increased slightly. Under anaerobiosis, biofilms grew; low ethanol dehydrogenase, pyruvate dehydrogenase and cytochrome bo were still present; nitrate dehydrogenase was the main terminal electron acceptor. KCN inhibited the aerobic respiratory chain and increased biofilm formation. In contrast, methylamine inhibited both nitrate reductase and biofilm formation. The correlation between the expression and/or activity or redox enzymes and biofilm-formation activities suggests that these are possible therapeutic targets to erradicate S. epidermidis. PMID:26610708

  4. Correlative NAD(P)H-FLIM and oxygen sensing-PLIM for metabolic mapping.

    PubMed

    Kalinina, Sviatlana; Breymayer, Jasmin; Schäfer, Patrick; Calzia, Enrico; Shcheslavskiy, Vladislav; Becker, Wolfgang; Rück, Angelika

    2016-08-01

    Cellular responses to oxygen tension have been studied extensively. Oxygen tension can be determined by considering the phosphorescence lifetime of a phosphorescence sensor. The simultaneous usage of FLIM of coenzymes as NAD(P)H and FAD(+) and PLIM of oxygen sensors could provide information about correlation of metabolic pathways and oxygen tension. We investigated correlative NAD(P)H-FLIM and oxygen sensing-PLIM for simultaneously analyzing cell metabolism and oxygen tension. Cell metabolism and pO2 were observed under different hypoxic conditions in squamous carcinoma cell cultures and in complex ex vivo systems. Increased hypoxia induced an increase of the phosphorescence lifetime of Ru(BPY)3 and in most cases a decrease in the lifetime of NAD(P)H which is in agreement to the expected decrease of the protein-bound NAD(P)H during hypoxia. Oxygen was modulated directly in the mitochondrial membrane. Blocking of complex III and accumulation of oxygen could be observed by both the decrease of the phosphorescence lifetime of Ru(BPY)3 and a reduction of the lifetime of NAD(P)H which was a clear indication of acute changes in the redox state of the cells. For the first time simultaneous FLIM/PLIM has been shown to be able to visualize intracellular oxygen tension together with a change from oxidative to glycolytic phenotype. PMID:26990032

  5. Heparin, free fatty acids and an increased metabolic demand for oxygen.

    PubMed

    Jung, R T; Shetty, P S; James, W P

    1980-05-01

    Obese and lean subjects were given heparin with or without Intralipid in order to assess the effect of heparin on plasma concentration of free fatty acids (FFA) and oxidative metabolism. The FFA response depended on the triglyceride concentration and was associated with a prompt rise in oxygen consumption. Plasma catecholamines did not alter after heparin and the increase in oxygen uptake was proportional to the rise in FFA. The use of heparin, therefore, has metabolic disadvantages which may outweigh the potential benefits, for example in the management of myocardial infarction where heparin may increase the metabolic demand on the heart by increasing FFA levels. PMID:7443592

  6. Heparin, free fatty acids and an increased metabolic demand for oxygen.

    PubMed Central

    Jung, R. T.; Shetty, P. S.; James, W. P.

    1980-01-01

    Obese and lean subjects were given heparin with or without Intralipid in order to assess the effect of heparin on plasma concentration of free fatty acids (FFA) and oxidative metabolism. The FFA response depended on the triglyceride concentration and was associated with a prompt rise in oxygen consumption. Plasma catecholamines did not alter after heparin and the increase in oxygen uptake was proportional to the rise in FFA. The use of heparin, therefore, has metabolic disadvantages which may outweigh the potential benefits, for example in the management of myocardial infarction where heparin may increase the metabolic demand on the heart by increasing FFA levels. PMID:7443592

  7. Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

    PubMed Central

    Lee, Mi Jin; Lee, Seung Jun; Yun, Su Jin; Jang, Ji-Young; Kang, Hangoo; Kim, Kyongmin; Choi, In-Hong; Park, Sun

    2016-01-01

    The silver nanoparticle (AgNP) is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs’ treatment. Increased reactive oxygen species (ROS) production was detected 1 hour after 5 nm AgNPs’ treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS. PMID:26730190

  8. Metabolic suppression during protracted exposure to hypoxia in the jumbo squid, Dosidicus gigas, living in an oxygen minimum zone.

    PubMed

    Seibel, Brad A; Häfker, N Sören; Trübenbach, Katja; Zhang, Jing; Tessier, Shannon N; Pörtner, Hans-Otto; Rosa, Rui; Storey, Kenneth B

    2014-07-15

    The jumbo squid, Dosidicus gigas, can survive extended forays into the oxygen minimum zone (OMZ) of the Eastern Pacific Ocean. Previous studies have demonstrated reduced oxygen consumption and a limited anaerobic contribution to ATP production, suggesting the capacity for substantial metabolic suppression during hypoxic exposure. Here, we provide a more complete description of energy metabolism and explore the expression of proteins indicative of transcriptional and translational arrest that may contribute to metabolic suppression. We demonstrate a suppression of total ATP demand under hypoxic conditions (1% oxygen, PO2 =0.8 kPa) in both juveniles (52%) and adults (35%) of the jumbo squid. Oxygen consumption rates are reduced to 20% under hypoxia relative to air-saturated controls. Concentrations of arginine phosphate (Arg-P) and ATP declined initially, reaching a new steady state (~30% of controls) after the first hour of hypoxic exposure. Octopine began accumulating after the first hour of hypoxic exposure, once Arg-P breakdown resulted in sufficient free arginine for substrate. Octopine reached levels near 30 mmol g(-1) after 3.4 h of hypoxic exposure. Succinate did increase through hypoxia but contributed minimally to total ATP production. Glycogenolysis in mantle muscle presumably serves to maintain muscle functionality and balance energetics during hypoxia. We provide evidence that post-translational modifications on histone proteins and translation factors serve as a primary means of energy conservation and that select components of the stress response are altered in hypoxic squids. Reduced ATP consumption under hypoxia serves to maintain ATP levels, prolong fuel store use and minimize the accumulation of acidic intermediates of anaerobic ATP-generating pathways during prolonged diel forays into the OMZ. Metabolic suppression likely limits active, daytime foraging at depth in the core of the OMZ, but confers an energetic advantage over competitors that must

  9. An energetic model for oxygen-limited metabolism

    SciTech Connect

    Beronio, P.B. Jr. . Amoco Research Center); Tsao, G.T. . Lab. of Renewable Resources Engineering)

    1993-12-01

    Microbial production of 2,3-butanediol by Klebsiella oxytoca occurs under conditions of an oxygen limitation. The extent to which substrate is oxidized to 2,3-butanediol and its coproducts, (acetic acid, acetoin, and ethanol) and the relative flow rates of substrate to energetic and biosynthetic pathways are controlled by the degree of oxygen limitation. Two energetic relationships which describe the response to an oxygen limitation have been derived. The first relationship describes the coupling between growth and energy production observed under oxygen-limited conditions. This allows calculation of energetic parameters and modeling of the cell mass and substrate profiles in terms of the degree of oxygen limitation only. The second relationship describes the average degree of oxidation and the rate of the end-product flow. The model has been tested with both batch and continuous culture. During these kinetic studies, two phases of growth have been observed: energy-coupled growth, which was described above; and, energy-uncoupled growth, which arises when the degree of oxygen limitation reaches a critical value. Optimal culture performance with respect to 2,3-butanediol productivity occurs during energy-coupled growth.

  10. The impact of age on cerebral perfusion, oxygenation and metabolism during exercise in humans.

    PubMed

    Braz, Igor D; Fisher, James P

    2016-08-15

    Age is one of the most important risk factors for dementia and stroke. Examination of the cerebral circulatory responses to acute exercise in the elderly may help to pinpoint the mechanisms by which exercise training can reduce the risk of brain diseases, inform the optimization of exercise training programmes and assist with the identification of age-related alterations in cerebral vascular function. During low-to-moderate intensity dynamic exercise, enhanced neuronal activity is accompanied by cerebral perfusion increases of ∼10-30%. Beyond ∼60-70% maximal oxygen uptake, cerebral metabolism remains elevated but perfusion in the anterior portion of the circulation returns towards baseline, substantively because of a hyperventilation-mediated reduction in the partial pressure of arterial carbon dioxide (P aC O2) and cerebral vasoconstriction. Cerebral perfusion is lower in older individuals, both at rest and during incremental dynamic exercise. Nevertheless, the increase in the estimated cerebral metabolic rate for oxygen and the arterial-internal jugular venous differences for glucose and lactate are similar in young and older individuals exercising at the same relative exercise intensities. Correction for the age-related reduction in P aC O2 during exercise by the provision of supplementary CO2 is suggested to remove ∼50% of the difference in cerebral perfusion between young and older individuals. A multitude of candidates could account for the remaining difference, including cerebral atrophy, and enhanced vasoconstrictor and blunted vasodilatory pathways. In summary, age-related reductions in cerebral perfusion during exercise are partly associated with a lower P aC O2 in exercising older individuals; nevertheless the cerebral extraction of glucose, lactate and oxygen appear to be preserved. PMID:26435295

  11. Metabolic consequences of agonistic behaviour: crab fights in declining oxygen tensions.

    PubMed

    Sneddon; Taylor; Huntingford

    1999-02-01

    The energetic consequences of fighting, which may depend on environmental conditions, can be an important factor shaping contest strategy and duration. Energy expenditure may be costly to fitness because it depletes reserves that could otherwise have been allocated to reproduction, and metabolites are produced that may constrain subsequent activities. We examined the variation in the metabolic consequences of fighting in relation to hypoxia. Contests were staged between pairs of size-matched male shore crabs Carcinus maenas L., under a range of water oxygen tensions (between 10 and 100% oxygen saturation) which crabs experience in their natural habitat. Fighting under normoxic and hypoxic conditions resulted in significantly elevated concentrations of haemolymph metabolites (L-lactate and glucose) compared with crabs at rest. However, these concentrations were much lower than in crabs that had been walking on a treadmill. Glycogen concentrations differed only under hypoxic conditions: glycogen stores were reduced in crabs after fighting and this reduction was similar to that after exercise on a treadmill. Contests were shorter when they were staged below a water P o2of 6.7 kPa ( approximately 30% normoxia). As water oxygen tensions were reduced, fighting crabs had greater concentrations of L-lactate and glucose in their blood and tissues whilst glycogen stores were reduced. Fights became shorter when crabs were exposed to severe hypoxia (P o2=2 kPa) for increasing lengths of time, and blood L-lactate concentrations increased. The results suggest that as fights progressed, crabs experienced an increasing metabolic debt, in the form of accumulation of L-lactate and a reduction in energy stores, which was amplified by hypoxic conditions. Copyright 1999 The Association for the Study of Animal Behaviour. PMID:10049475

  12. Metabolic cost of extravehicular activities

    NASA Technical Reports Server (NTRS)

    Waligora, J. M.; Horrigan, D. J., Jr.

    1977-01-01

    The Skylab zero-g extravehicular activity data is of particular interest when it is considered in combination with the Apollo and Gemini data. The energy cost of extravehicular activity from Gemini through Skylab is discussed.

  13. Biochar activated by oxygen plasma for supercapacitors

    NASA Astrophysics Data System (ADS)

    Gupta, Rakesh Kumar; Dubey, Mukul; Kharel, Parashu; Gu, Zhengrong; Fan, Qi Hua

    2015-01-01

    Biochar, also known as black carbon, is a byproduct of biomass pyrolysis. As a low-cost, environmental-friendly material, biochar has the potential to replace more expensive synthesized carbon nanomaterials (e.g. carbon nanotubes) for use in future supercapacitors. To achieve high capacitance, biochar requires proper activation. A conventional approach involves mixing biochar with a strong base and baking at a high temperature. However, this process is time consuming and energy inefficient (requiring temperatures >900 °C). This work demonstrates a low-temperature (<150 °C) plasma treatment that efficiently activates a yellow pine biochar. Particularly, the effects of oxygen plasma on the biochar microstructure and supercapacitor characteristics are studied. Significant enhancement of the capacitance is achieved: 171.4 F g-1 for a 5-min oxygen plasma activation, in comparison to 99.5 F g-1 for a conventional chemical activation and 60.4 F g-1 for untreated biochar. This enhancement of the charge storage capacity is attributed to the creation of a broad distribution in pore size and a larger surface area. The plasma activation mechanisms in terms of the evolution of the biochar surface and microstructure are further discussed.

  14. Oxygen transport through soft contact lens and cornea: Lens characterization and metabolic modeling

    NASA Astrophysics Data System (ADS)

    Chhabra, Mahendra

    The human cornea requires oxygen to sustain metabolic processes critical for its normal functioning. Any restriction to corneal oxygen supply from the external environment (e.g., by wearing a low oxygen-permeability contact lens) can lead to hypoxia, which may cause corneal edema (swelling), limbal hyperemia, neovascularization, and corneal acidosis. The need for adequate oxygen to the cornea is a major driving force for research and development of hypertransmissible soft contact lenses (SCLs). Currently, there is no standard technique for measuring oxygen permeability (Dk) of hypertransmissible silicone-hydrogel SCLs. In this work, an electrochemistry-based polarographic apparatus was designed, built, and operated to measure oxygen permeability in hypertransmissible SCLs. Unlike conventional methods where a range of lens thickness is needed for determining oxygen permeabilities of SCLs, this apparatus requires only a single lens thickness. The single-lens permeameter provides a reliable, efficient, and economic tool for measuring oxygen permeabilities of commercial hypertransmissible SCLs. The single-lens permeameter measures not only the product Dk, but, following modification, it measures separately diffusivity, D, and solubility, k, of oxygen in hypertransmissible SCLs. These properties are critical for designing better lens materials that ensure sufficient oxygen supply to the cornea. Metabolism of oxygen in the cornea is influenced by contact-lens-induced hypoxia, diseases such as diabetes, surgery, and drug treatment, Thus, estimation of the in-vivo corneal oxygen consumption rate is essential for gauging adequate oxygen supply to the cornea. Therefore, we have developed an unsteady-state reactive-diffusion model for the cornea-contact-lens system to determine in-vivo human corneal oxygen-consumption rate. Finally, a metabolic model was developed to determine the relation between contact-lens oxygen transmissibility (Dk/L) and corneal oxygen deficiency. A

  15. Nitric Oxide and Reactive Oxygen Species Mediate Metabolic Changes in Barley Seed Embryo during Germination.

    PubMed

    Ma, Zhenguo; Marsolais, Frédéric; Bykova, Natalia V; Igamberdiev, Abir U

    2016-01-01

    The levels of nitric oxide (NO) and reactive oxygen species (ROS), ATP/ADP ratios, reduction levels of ascorbate and glutathione, expression of the genes encoding proteins involved in metabolism of NO and activities of the enzymes involved in fermentation and in metabolism of NO and ROS were studied in the embryos of germinating seeds of two barley (Hordeum vulgare L.) cultivars differing in dormancy level. The level of NO production continuously increased after imbibition while the level of nitrosylated SH-groups in proteins increased. This corresponded to the decrease of free SH-groups in proteins. At early stage of germination (0-48 h post imbibition) the genes encoding class 1 phytoglobin (the protein scavenging NO) and S-nitrosoglutathione reductase (scavenging S-nitrosoglutathione) were markedly expressed. More dormant cultivar exhibited lower ATP/ADP and ascorbate/dehydroascorbate ratios and lower lactate and alcohol dehydrogenase activities, while the production of NO and nitrosylation of proteins was higher as compared to the non-dormant cultivar. The obtained data indicate that at the onset of germination NO is actively generated causing nitrosylation of SH-groups and a switch from respiration to fermentation. After radicle protrusion the metabolism changes in a more reducing type as recorded by ratio of reduced and oxidized glutathione and ascorbate. The turnover of NO by the scavenging systems (phytoglobin, S-nitrosoglutathione reductase and interaction with ROS) might contribute to the maintenance of redox and energy balance of germinating seeds and lead to alleviation of dormancy. PMID:26909088

  16. Nitric Oxide and Reactive Oxygen Species Mediate Metabolic Changes in Barley Seed Embryo during Germination

    PubMed Central

    Ma, Zhenguo; Marsolais, Frédéric; Bykova, Natalia V.; Igamberdiev, Abir U.

    2016-01-01

    The levels of nitric oxide (NO) and reactive oxygen species (ROS), ATP/ADP ratios, reduction levels of ascorbate and glutathione, expression of the genes encoding proteins involved in metabolism of NO and activities of the enzymes involved in fermentation and in metabolism of NO and ROS were studied in the embryos of germinating seeds of two barley (Hordeum vulgare L.) cultivars differing in dormancy level. The level of NO production continuously increased after imbibition while the level of nitrosylated SH-groups in proteins increased. This corresponded to the decrease of free SH-groups in proteins. At early stage of germination (0–48 h post imbibition) the genes encoding class 1 phytoglobin (the protein scavenging NO) and S-nitrosoglutathione reductase (scavenging S-nitrosoglutathione) were markedly expressed. More dormant cultivar exhibited lower ATP/ADP and ascorbate/dehydroascorbate ratios and lower lactate and alcohol dehydrogenase activities, while the production of NO and nitrosylation of proteins was higher as compared to the non-dormant cultivar. The obtained data indicate that at the onset of germination NO is actively generated causing nitrosylation of SH-groups and a switch from respiration to fermentation. After radicle protrusion the metabolism changes in a more reducing type as recorded by ratio of reduced and oxidized glutathione and ascorbate. The turnover of NO by the scavenging systems (phytoglobin, S-nitrosoglutathione reductase and interaction with ROS) might contribute to the maintenance of redox and energy balance of germinating seeds and lead to alleviation of dormancy. PMID:26909088

  17. Regulation of retinal oxygen metabolism in humans during graded hypoxia.

    PubMed

    Palkovits, Stefan; Told, Reinhard; Schmidl, Doreen; Boltz, Agnes; Napora, Katarzyna J; Lasta, Michael; Kaya, Semira; Werkmeister, René M; Popa-Cherecheanu, Alina; Garhöfer, Gerhard; Schmetterer, Leopold

    2014-11-15

    Animal experiments indicate that the inner retina keeps its oxygen extraction constant despite systemic hypoxia. For the human retina no such data exist. In the present study we hypothesized that systemic hypoxia does not alter inner retinal oxygen extraction. To test this hypothesis we included 30 healthy male and female subjects aged between 18 and 35 years. All subjects were studied at baseline and during breathing 12% O₂ in 88% N₂ as well as breathing 15% O₂ in 85% N₂. Oxygen saturation in a retinal artery (SO₂art) and an adjacent retinal vein (SO₂vein) were measured using spectroscopic fundus reflectometry. Measurements of retinal venous blood velocity using bidirectional laser Doppler velocimetry and retinal venous diameters using a Retinal Vessel Analyzer (RVA) were combined to calculate retinal blood flow. Oxygen and carbon dioxide partial pressure were measured from earlobe arterialized capillary blood. Retinal blood flow was increased by 43.0 ± 23.2% (P < 0.001) and 30.0 ± 20.9% (P < 0.001) during 12% and 15% O₂ breathing, respectively. SO₂art as well as SO₂vein decreased during both 12% O₂ breathing (SO₂art: -11.2 ± 4.3%, P < 0.001; SO₂vein: -3.9 ± 8.5%, P = 0.012) and 15% O₂ breathing (SO₂art: -7.9 ± 3.6%, P < 0.001; SO₂vein: -4.0 ± 7.0%, P = 0.010). The arteriovenous oxygen difference decreased during both breathing periods (12% O2: -28.9 ± 18.7%; 15% O₂: -19.1 ± 16.7%, P < 0.001 each). Calculated oxygen extraction did, however, not change during our experiments (12% O₂: -2.8 ± 18.9%, P = 0.65; 15% O₂: 2.4 ± 15.8%, P = 0.26). Our results indicate that in healthy humans, oxygen extraction of the inner retina remains constant during systemic hypoxia. PMID:25217648

  18. Reactive oxygen species-activated nanomaterials as theranostic agents.

    PubMed

    Kim, Kye S; Lee, Dongwon; Song, Chul Gyu; Kang, Peter M

    2015-01-01

    Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use. PMID:26328770

  19. Reactive oxygen species-activated nanomaterials as theranostic agents

    PubMed Central

    Kim, Kye S; Lee, Dongwon; Song, Chul Gyu; Kang, Peter M

    2015-01-01

    Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use. PMID:26328770

  20. Leukocytic oxygen activation and microbicidal oxidative toxins.

    PubMed

    Hurst, J K; Barrette, W C

    1989-01-01

    Following a brief introduction of cellular response to stimulation comprising leukocyte activation, three major areas are discussed: (1) the neutrophil oxidase; (2) myeloperoxidase (MPO)-dependent oxidative microbicidal reactions; and (3) MPO-independent oxidative reactions. Topics included in section (A) are current views on the activation mechanism, redox composition, structural and topographic organization of the oxidase, and its respiratory products. In section (B), emphasis is placed on recent research on cidal mechanisms of HOCl, including the oxidative biochemistry of active chlorine compounds, identification of sites of lesions in bacteria, and attendant metabolic consequences. In section (C), we review the (bio)chemistry of H2O2 and .OH microbicidal reactions, with particular attention being given to addressing the controversial issue of probe methods to identify .OH radical and critical assessment of the recent proposal that MPO-independent killing arises from site-specific metal-catalyzed Fenton-type chemistry. PMID:2548810

  1. Quiescent Fibroblasts Exhibit High Metabolic Activity

    PubMed Central

    Lemons, Johanna M. S.; Feng, Xiao-Jiang; Bennett, Bryson D.; Legesse-Miller, Aster; Johnson, Elizabeth L.; Raitman, Irene; Pollina, Elizabeth A.; Rabitz, Herschel A.; Rabinowitz, Joshua D.; Coller, Hilary A.

    2010-01-01

    Many cells in mammals exist in the state of quiescence, which is characterized by reversible exit from the cell cycle. Quiescent cells are widely reported to exhibit reduced size, nucleotide synthesis, and metabolic activity. Much lower glycolytic rates have been reported in quiescent compared with proliferating lymphocytes. In contrast, we show here that primary human fibroblasts continue to exhibit high metabolic rates when induced into quiescence via contact inhibition. By monitoring isotope labeling through metabolic pathways and quantitatively identifying fluxes from the data, we show that contact-inhibited fibroblasts utilize glucose in all branches of central carbon metabolism at rates similar to those of proliferating cells, with greater overflow flux from the pentose phosphate pathway back to glycolysis. Inhibition of the pentose phosphate pathway resulted in apoptosis preferentially in quiescent fibroblasts. By feeding the cells labeled glutamine, we also detected a “backwards” flux in the tricarboxylic acid cycle from α-ketoglutarate to citrate that was enhanced in contact-inhibited fibroblasts; this flux likely contributes to shuttling of NADPH from the mitochondrion to cytosol for redox defense or fatty acid synthesis. The high metabolic activity of the fibroblasts was directed in part toward breakdown and resynthesis of protein and lipid, and in part toward excretion of extracellular matrix proteins. Thus, reduced metabolic activity is not a hallmark of the quiescent state. Quiescent fibroblasts, relieved of the biosynthetic requirements associated with generating progeny, direct their metabolic activity to preservation of self integrity and alternative functions beneficial to the organism as a whole. PMID:21049082

  2. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    SciTech Connect

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B.; Alexandre, Gladys

    2015-09-25

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacteriumAzospirillum brasilensenavigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motileA. brasilensecells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Finally, cell-to-cell clumping may thus license diazotrophy to microaerophilicA. brasilensecells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists.

  3. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    DOE PAGESBeta

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B.; Alexandre, Gladys

    2015-09-25

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacteriumAzospirillum brasilensenavigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motileA. brasilensecells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities,more » we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Finally, cell-to-cell clumping may thus license diazotrophy to microaerophilicA. brasilensecells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists.« less

  4. Biochemical studies on the metabolic activation of halogenated alkanes.

    PubMed Central

    Cheeseman, K H; Albano, E F; Tomasi, A; Slater, T F

    1985-01-01

    This paper reviews recent investigations by Slater and colleagues into the metabolic activation of halogenated alkanes in general and carbon tetrachloride in particular. It is becoming increasingly accepted that free radical intermediates are involved in the toxicity of many such compounds through mechanisms including lipid peroxidation, covalent binding, and cofactor depletion. Here we describe the experimental approaches that are used to establish that halogenated alkanes are metabolized in animal tissues to reactive free radicals. Electron spin resonance spectroscopy is used to identify free-radical products, often using spin-trapping compounds. The generation of specific free radicals by radiolytic methods is useful in the determination of the precise reactivity of radical intermediates postulated to be injurious to the cell. The enzymic mechanism of the production of such free radicals and their subsequent reactions with biological molecules is studied with specific metabolic inhibitors and free-radical scavengers. These combined techniques provide considerable insight into the process of metabolic activation of halogenated compounds. It is readily apparent, for instance, that the local oxygen concentration at the site of activation is of crucial importance to the subsequent reactions; the formation of peroxy radical derivatives from the primary free-radical product is shown to be of great significance in relation to carbon tetrachloride and may be of general importance. However, while these studies have provided much information on the biochemical mechanisms of halogenated alkane toxicity, it is clear that many problems remain to be solved. PMID:3007102

  5. Metabolic Activity - Skylab Experiment M171

    NASA Technical Reports Server (NTRS)

    1972-01-01

    This chart details Skylab's Metabolic Activity experiment (M171), a medical evaluation facility designed to measure astronauts' metabolic changes while on long-term space missions. The experiment obtained information on astronauts' physiological capabilities and limitations and provided data useful in the design of future spacecraft and work programs. Physiological responses to physical activity was deduced by analyzing inhaled and exhaled air, pulse rate, blood pressure, and other selected variables of the crew while they performed controlled amounts of physical work with a bicycle ergometer. The Marshall Space Flight Center had program responsibility for the development of Skylab hardware and experiments.

  6. Metabolic activation of 2-methylfuran by rat microsomal systems

    SciTech Connect

    Ravindranath, V.; Boyd, M.R.

    1985-05-01

    2-Methylfuran (2-MF), a constituent of cigarette smoke and coffee, causes necrosis of liver, lungs, and kidneys in rodents. 2-MF is metabolically activated by mixed-function oxidases to acetylacrolein, a reactive metabolite that binds covalently to microsomal protein. The hepatic microsomal metabolism of 2-MF to reactive metabolite required the presence of NADPH and oxygen and was dependent on incubation time and substrate concentration. The microsomal metabolism of 2-MF was inducible by pretreatment of rats with phenobarbital and was inhibited by piperonyl butoxide and N-octyl imidazole, which indicates that the metabolism of 2-MF may be mediated by cytochrome P-450. Acetylacrolein was a potent inhibitor of mixed-function oxidase and completely inhibited the microsomal metabolism of 2-MF, indicating that 2-MF is a suicide substrate for the enzyme. The sulfhydryl nucleophile cysteine was a better trapping agent of the reactive metabolite of 2-MF than N-acetylcysteine or glutathione. Lysine decreased the covalent binding of 2-MF metabolites, presumably by reacting with the aldehyde group of acetylacrolein. In addition, in the presence of NADPH, 2-MF was bioactivated by both pulmonary and renal cortical microsomes to reactive metabolites that were covalently bound to microsomal proteins.

  7. Metabolism of azo dyes: implication for detoxication and activation.

    PubMed

    Levine, W G

    1991-01-01

    Azo dyes are consumed and otherwise utilized in varying quantities in many parts of the world. Such widely used chemicals are of great concern with regard to their potential toxicity and carcinogenic properties. Their metabolism has been studied extensively and is significant for detoxication and metabolic activation. Both oxidative and reductive pathways are involved in these processes. The majority of azo dyes undergo reduction catalyzed by enzymes of the intestinal microorganisms and/or hepatic enzymes including microsomal and soluble enzymes. The selectivity of substrate and enzyme may to a large extent be determined by the oxygen sensitivity of reduction since a normal liver is mainly aerobic in all areas, whereas the microorganisms of the lower bowel exist in an anaerobic environment. However, it should be pointed out that the pO2 of centrilobular cells within the liver is only a fraction that of air, where pO2 = 150 torr. Therefore, an azo dye reduction experiment performed aerobically may not be an accurate predictor of reductive metabolism in all areas of the liver. Many of the azo dyes in common use today have highly charged substituents such as sulfonate. These resist enzymic attack and for the most part are poorly absorbed from the intestinal tract, providing poor access to the liver, the major site of the mixed-function oxidase system. Lipophilic dyes, such as DAB, which are often carcinogenic, readily access oxidative enzymes and are activated by both mixed-function oxidase and conjugating systems. Reduction of the carcinogenic dyes usually leads to loss of carcinogenic activity. By contrast, most of the highly charged water-soluble dyes become mutagenic only after reduction. Even then, most of the fully reduced amines required oxidative metabolic activation. An outstanding example is the potent human bladder carcinogen benzidine, which derives from the reduction of several azo dyes. Many problems regarding mutagenic and carcinogenic activation remain

  8. Multimodal optical imaging system for in vivo investigation of cerebral oxygen delivery and energy metabolism

    PubMed Central

    Yaseen, Mohammad A.; Srinivasan, Vivek J.; Gorczynska, Iwona; Fujimoto, James G.; Boas, David A.; Sakadžić, Sava

    2015-01-01

    Improving our understanding of brain function requires novel tools to observe multiple physiological parameters with high resolution in vivo. We have developed a multimodal imaging system for investigating multiple facets of cerebral blood flow and metabolism in small animals. The system was custom designed and features multiple optical imaging capabilities, including 2-photon and confocal lifetime microscopy, optical coherence tomography, laser speckle imaging, and optical intrinsic signal imaging. Here, we provide details of the system’s design and present in vivo observations of multiple metrics of cerebral oxygen delivery and energy metabolism, including oxygen partial pressure, microvascular blood flow, and NADH autofluorescence. PMID:26713212

  9. Multimodal optical imaging system for in vivo investigation of cerebral oxygen delivery and energy metabolism.

    PubMed

    Yaseen, Mohammad A; Srinivasan, Vivek J; Gorczynska, Iwona; Fujimoto, James G; Boas, David A; Sakadžić, Sava

    2015-12-01

    Improving our understanding of brain function requires novel tools to observe multiple physiological parameters with high resolution in vivo. We have developed a multimodal imaging system for investigating multiple facets of cerebral blood flow and metabolism in small animals. The system was custom designed and features multiple optical imaging capabilities, including 2-photon and confocal lifetime microscopy, optical coherence tomography, laser speckle imaging, and optical intrinsic signal imaging. Here, we provide details of the system's design and present in vivo observations of multiple metrics of cerebral oxygen delivery and energy metabolism, including oxygen partial pressure, microvascular blood flow, and NADH autofluorescence. PMID:26713212

  10. Cold tolerance is unaffected by oxygen availability despite changes in anaerobic metabolism.

    PubMed

    Boardman, Leigh; Sørensen, Jesper G; Koštál, Vladimír; Šimek, Petr; Terblanche, John S

    2016-01-01

    Insect cold tolerance depends on their ability to withstand or repair perturbations in cellular homeostasis caused by low temperature stress. Decreased oxygen availability (hypoxia) can interact with low temperature tolerance, often improving insect survival. One mechanism proposed for such responses is that whole-animal cold tolerance is set by a transition to anaerobic metabolism. Here, we provide a test of this hypothesis in an insect model system (Thaumatotibia leucotreta) by experimental manipulation of oxygen availability while measuring metabolic rate, critical thermal minimum (CTmin), supercooling point and changes in 43 metabolites in moth larvae at three key timepoints (before, during and after chill coma). Furthermore, we determined the critical oxygen partial pressure below which metabolic rate was suppressed (c. 4.5 kPa). Results showed that altering oxygen availability did not affect (non-lethal) CTmin nor (lethal) supercooling point. Metabolomic profiling revealed the upregulation of anaerobic metabolites and alterations in concentrations of citric acid cycle intermediates during and after chill coma exposure. Hypoxia exacerbated the anaerobic metabolite responses induced by low temperatures. These results suggest that cold tolerance of T. leucotreta larvae is not set by oxygen limitation, and that anaerobic metabolism in these larvae may contribute to their ability to survive in necrotic fruit. PMID:27619175

  11. The effects of clofibrate ingestion on alveolar macrophage peroxisome content and oxygen metabolism.

    PubMed

    Drath, D B; Davies, P; Shorrey, J M; Simpson, P

    1982-07-01

    Respiratory burst activity in alveolar macrophages in response to particulate and soluble challenges, such as zymosan particles and phorbol myristate acetate (PMA), is not nearly as dependent upon membrane stimulation as in neutrophils. Microperoxisomes are subcellular organelles containing catalase and are present in lung macrophages and cells of other organs. Evidence from liver cells indicates that peroxisomes are intimately involved with hydrogen peroxide and lipid metabolism. Clofibrate (2-(p-chlorophenoxy)-2-methylpropionic acid ethyl, Atromid-S-), a hypolipidemic drug known to cause peroxisomal proliferation in liver cells, was studied with respect to its ability to cause increases in the microperoxisome content and to alter the cellular metabolism of alveolar macrophages. Liver weight increased over a 2-week drug treatment period while lung weight remained unchanged. Plasma triglyceride levels were decreased by the treatment, indicating the effectiveness of the drug. Unlike the effect on liver cells, however, clofibrate did not cause a proliferation of microperoxisomes, as determined by morphometric analysis. Oxygen consumption and hydrogen peroxide generation by alveolar macrophages in response to either stimulant (zymosan or PMA) was no greater in clofibrate-treated rats than in controls. Superoxide release, when expressed as the change in response to PMA, appeared elevated in the drug group; statistical significance, however, was not demonstrated. The hexose monophosphate shunt (HMP), which produces reducing equivalents for lipid biosynthesis, was elevated in macrophages from clofibrate-treated rats when expressed similarly. The significance of these results in relation to the known effects of the drug on liver cells. PMID:6291347

  12. Differential contribution of key metabolic substrates and cellular oxygen in HIF signalling.

    PubMed

    Zhdanov, Alexander V; Waters, Alicia H C; Golubeva, Anna V; Papkovsky, Dmitri B

    2015-01-01

    Changes in availability and utilisation of O2 and metabolic substrates are common in ischemia and cancer. We examined effects of substrate deprivation on HIF signalling in PC12 cells exposed to different atmospheric O2. Upon 2-4h moderate hypoxia, HIF-α protein levels were dictated by the availability of glutamine and glucose, essential for deep cell deoxygenation and glycolytic ATP flux. Nuclear accumulation of HIF-1α dramatically decreased upon inhibition of glutaminolysis or glutamine deprivation. Elevation of HIF-2α levels was transcription-independent and associated with the activation of Akt and Erk1/2. Upon 2h anoxia, HIF-2α levels strongly correlated with cellular ATP, produced exclusively via glycolysis. Without glucose, HIF signalling was suppressed, giving way to other regulators of cell adaptation to energy crisis, e.g. AMPK. Consequently, viability of cells deprived of O2 and glucose decreased upon inhibition of AMPK with dorsomorphin. The capacity of cells to accumulate HIF-2α decreased after 24h glucose deprivation. This effect, associated with increased AMPKα phosphorylation, was sensitive to dorsomorphin. In chronically hypoxic cells, glutamine played no major role in HIF-2α accumulation, which became mainly glucose-dependent. Overall, the availability of O2 and metabolic substrates intricately regulates HIF signalling by affecting cell oxygenation, ATP levels and pathways involved in production of HIF-α. PMID:25447307

  13. Maternal hypoxia decreases capillary supply and increases metabolic inefficiency leading to divergence in myocardial oxygen supply and demand.

    PubMed

    Hauton, David; Al-Shammari, Abdullah; Gaffney, Eamonn A; Egginton, Stuart

    2015-01-01

    Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO2=0.12) at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. 14C-labelled glucose and 3H-palmitate were provided as substrates and metabolism quantified from recovery of 14CO2 and 3H2O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05), despite recording a 2-fold increase in glucose oxidation (P<0.01) and 2.5-fold increase (P<0.01) in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01) and suppressed palmitate oxidation (P<0.05), suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01), although pyruvate dehydrogenase sensitivity to insulin was lost (NS), while citrate synthase activity declined by 30% (P<0.001) and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001). Calculated metabolic efficiency decreased 4-fold (P<0.01) for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to preserve

  14. Maternal Hypoxia Decreases Capillary Supply and Increases Metabolic Inefficiency Leading to Divergence in Myocardial Oxygen Supply and Demand

    PubMed Central

    Hauton, David; Al-Shammari, Abdullah; Gaffney, Eamonn A.; Egginton, Stuart

    2015-01-01

    Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO2=0.12) at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. 14C-labelled glucose and 3H-palmitate were provided as substrates and metabolism quantified from recovery of 14CO2 and 3H2O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05), despite recording a 2-fold increase in glucose oxidation (P<0.01) and 2.5-fold increase (P<0.01) in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01) and suppressed palmitate oxidation (P<0.05), suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01), although pyruvate dehydrogenase sensitivity to insulin was lost (NS), while citrate synthase activity declined by 30% (P<0.001) and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001). Calculated metabolic efficiency decreased 4-fold (P<0.01) for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to preserve

  15. METABOLISM AND METABOLIC ACTIVATION OF CHEMICALS: IN-SILICO SIMULATION

    EPA Science Inventory

    The role of metabolism in prioritizing chemicals according to their potential adverse health effects is extremely important because innocuous parents can be transformed into toxic metabolites. This work presents the TIssue MEtabolism Simulator (TIMES) platform for simulating met...

  16. Coupling of cerebral blood flow and oxygen metabolism is conserved for chromatic and luminance stimuli in human visual cortex.

    PubMed

    Leontiev, Oleg; Buracas, Giedrius T; Liang, Christine; Ances, Beau M; Perthen, Joanna E; Shmuel, Amir; Buxton, Richard B

    2013-03-01

    The ratio of the changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) during brain activation is a critical determinant of the magnitude of the blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI). Cytochrome oxidase (CO), a key component of oxidative metabolism in the mitochondria, is non-uniformly distributed in visual area V1 in distinct blob and interblob regions, suggesting significant spatial variation in the capacity for oxygen metabolism. The goal of this study was to test whether CBF/CMRO(2) coupling differed when these subpopulations of neurons were preferentially stimulated, using chromatic and luminance stimuli to preferentially stimulate either the blob or interblob regions. A dual-echo spiral arterial spin labeling (ASL) technique was used to measure CBF and BOLD responses simultaneously in 7 healthy human subjects. When the stimulus contrast levels were adjusted to evoke similar CBF responses (mean 65.4% ± 19.0% and 64.6% ± 19.9%, respectively for chromatic and luminance contrast), the BOLD responses were remarkably similar (1.57% ± 0.39% and 1.59% ± 0.35%) for both types of stimuli. We conclude that CBF-CMRO(2) coupling is conserved for the chromatic and luminance stimuli used, suggesting a consistent coupling for blob and inter-blob neuronal populations despite the difference in CO concentration. PMID:23238435

  17. Diabetes-Induced Decrease in Renal Oxygen Tension: Effects of an Altered Metabolism

    NASA Astrophysics Data System (ADS)

    Palm, Fredrik; Carlsson, Per-Ola; Fasching, Angelica; Hansell, Peter; Liss, Per

    During conditions with experimental diabetes mellitus, it is evident that several alterations in renal oxygen metabolism occur, including increased mitochondrial respiration and increased lactate accumulation in the renal tissue. Consequently, these alterations will contribute to decrease the interstitial pO2, preferentially in the renal medulla of animals with sustained long-term hyperglycemia.

  18. Improving estimates of ecosystem metabolism by reducing effects of tidal advection on dissolved oxygen time series

    EPA Science Inventory

    In aquatic systems, time series of dissolved oxygen (DO) have been used to compute estimates of ecosystem metabolism. Central to this open-water method is the assumption that the DO time series is a Lagrangian specification of the flow field. However, most DO time series are coll...

  19. Usurping the mitochondrial supremacy: extramitochondrial sources of reactive oxygen intermediates and their role in beta cell metabolism and insulin secretion.

    PubMed

    Gray, Joshua P; Heart, Emma

    2010-05-01

    Insulin secretion from pancreatic beta cells is a process dependent on metabolism. While oxidative stress is a well-known inducer of beta cell toxicity and impairs insulin secretion, recent studies suggest that low levels of metabolically-derived reactive oxygen intermediates (ROI) also play a positive role in insulin secretion. Glucose metabolism is directly correlated with ROI production, particularly in beta cells in which glucose uptake is proportional to the extracellular concentration of glucose. Low levels of exogenously added ROI or quinones, which stimulate ROI production, positively affect insulin secretion, while antioxidants block insulin secretion, suggesting that ROI activate unidentified redox-sensitive signal transduction components within these cells. The mitochondria are one source of ROI: increased metabolic flux increases mitochondrial membrane potential resulting in electron leakage and adventitious ROI production. A second source of ROI are cytosolic and plasma membrane oxidoreductases which oxidize NAD(P)H and directly produce ROI through the reduction of molecular oxygen. The mechanism of ROI-mediated potentiation of insulin secretion remains an important topic for future study. PMID:20397883

  20. Effects of Antioxidant Supplements (BioPQQ™) on Cerebral Blood Flow and Oxygen Metabolism in the Prefrontal Cortex.

    PubMed

    Nakano, Masahiko; Murayama, Yuta; Hu, Lizhen; Ikemoto, Kazuto; Uetake, Tatsuo; Sakatani, Kaoru

    2016-01-01

    Pyrroloquinoline quinone (PQQ) is a quinone compound originally identified in methanol-utilizing bacteria and is a cofactor for redox enzymes. At the Meeting of the International Society on Oxygen Transport to Tissue (ISOTT) 2014, we reported that PQQ disodium salt (BioPQQ™) improved cognitive function in humans, as assessed by the Stroop test. However, the physiological mechanism of PQQ remains unclear. In the present study, we measured regional cerebral blood flow (rCBF) and oxygen metabolism in prefrontal cortex (PFC), before and after administration of PQQ, using time-resolved near-infrared spectroscopy (tNIRS). A total of 20 healthy subjects between 50 and 70 years of age were administered BioPQQ™ (20 mg) or placebo orally once daily for 12 weeks. Hemoglobin (Hb) concentration and absolute tissue oxygen saturation (SO2) in the bilateral PFC were evaluated under resting conditions using tNIRS. We found that baseline concentrations of hemoglobin and total hemoglobin in the right PFC significantly increased after administration of PQQ (p < 0.05). In addition, decreases in SO2 level in the PFC were more pronounced in the PQQ group than in the placebo group (p < 0.05). These results suggest that PQQ causes increased activity in the right PFC associated with increases in rCBF and oxygen metabolism, resulting in enhanced cognitive function. PMID:27526146

  1. Effect of Exercise Training on Enos Expression, NO Production and Oxygen Metabolism in Human Placenta

    PubMed Central

    Ramírez-Vélez, Robinson; Bustamante, Juanita; Czerniczyniec, Analia; Aguilar de Plata, Ana C.; Lores-Arnaiz, Silvia

    2013-01-01

    Objective To determine the effects of combined aerobic and resistance exercise training during the second half of pregnancy on endothelial NOS expression (eNOS), nitric oxide (NO) production and oxygen metabolism in human placenta. Methods The study included 20 nulliparous in gestational week 16–20, attending prenatal care at three tertiary hospitals in Colombia who were randomly assigned into one of two groups: The exercise group (n = 10) took part in an exercise session three times a week for 12 weeks which consisted of: aerobic exercise at an intensity of 55–75% of their maximum heart rate for 60 min and 25 mins. Resistance exercise included 5 exercise groups circuit training (50 repetitions of each) using barbells (1–3 kg/exercise) and low-to-medium resistance bands. The control group (n = 10) undertook their usual physical activity. Mitochondrial and cytosol fractions were isolated from human placental tissue by differential centrifugation. A spectrophotometric assay was used to measure NO production in cytosolic samples from placental tissue and Western Blot technique to determine eNOS expression. Mitochondrial superoxide levels and hydrogen peroxide were measured to determine oxygen metabolism. Results Combined aerobic and resistance exercise training during pregnancy leads to a 2-fold increase in eNOS expression and 4-fold increase in NO production in placental cytosol (p = 0.05). Mitochondrial superoxide levels and hydrogen peroxide production rate were decreased by 8% and 37% respectively in the placental mitochondria of exercising women (p = 0.05). Conclusion Regular exercise training during the second half of pregnancy increases eNOS expression and NO production and decreases reactive oxygen species generation in human placenta. Collectively, these data demonstrate that chronic exercise increases eNOS/NO production, presumably by increasing endothelial shear stress. This adaptation may contribute to the beneficial effects of

  2. Differential contribution of key metabolic substrates and cellular oxygen in HIF signalling

    SciTech Connect

    Zhdanov, Alexander V.; Waters, Alicia H.C.; Golubeva, Anna V.; Papkovsky, Dmitri B.

    2015-01-01

    Changes in availability and utilisation of O{sub 2} and metabolic substrates are common in ischemia and cancer. We examined effects of substrate deprivation on HIF signalling in PC12 cells exposed to different atmospheric O{sub 2}. Upon 2–4 h moderate hypoxia, HIF-α protein levels were dictated by the availability of glutamine and glucose, essential for deep cell deoxygenation and glycolytic ATP flux. Nuclear accumulation of HIF-1α dramatically decreased upon inhibition of glutaminolysis or glutamine deprivation. Elevation of HIF-2α levels was transcription-independent and associated with the activation of Akt and Erk1/2. Upon 2 h anoxia, HIF-2α levels strongly correlated with cellular ATP, produced exclusively via glycolysis. Without glucose, HIF signalling was suppressed, giving way to other regulators of cell adaptation to energy crisis, e.g. AMPK. Consequently, viability of cells deprived of O{sub 2} and glucose decreased upon inhibition of AMPK with dorsomorphin. The capacity of cells to accumulate HIF-2α decreased after 24 h glucose deprivation. This effect, associated with increased AMPKα phosphorylation, was sensitive to dorsomorphin. In chronically hypoxic cells, glutamine played no major role in HIF-2α accumulation, which became mainly glucose-dependent. Overall, the availability of O{sub 2} and metabolic substrates intricately regulates HIF signalling by affecting cell oxygenation, ATP levels and pathways involved in production of HIF-α. - Highlights: • Gln and Glc regulate HIF levels in hypoxic cells by maintaining low O{sub 2} and high ATP. • HIF-α levels under anoxia correlate with cellular ATP and critically depend on Glc. • Gln and Glc modulate activity of Akt, Erk and AMPK, regulating HIF production. • HIF signalling is differentially inhibited by prolonged Glc and Gln deprivation. • Unlike Glc, Gln plays no major role in HIF signalling in chronically hypoxic cells.

  3. SAFETY ASPECTS OF OXYGEN AERATION ACTIVATED SLUDGE SYSTEMS

    EPA Science Inventory

    This project was carried out to assess the impact of the use of oxygen and oxygen-enriched air for aeration of activated sludge systems on the safety of municipal waste-water treatment plants and their personnel. The tasks included (1) determination of oxygen combustion hazards f...

  4. Henry's Law Activity of Oxygen in Molten Iron

    NASA Astrophysics Data System (ADS)

    Matousek, J. W.

    2015-09-01

    A model is proposed for the solubility of oxygen in molten iron in dilute solutions in which the oxygen exists in two states, free and associated. Only the free oxygen has thermodynamic activity in the sense of interaction with an electrochemical cell to produce the voltage described by the Nernst equation.

  5. BIOLOGICALLY ENHANCED OXYGEN TRANSFER IN THE ACTIVATED SLUDGE PROCESS (JOURNAL)

    EPA Science Inventory

    Biologically enhanced oxgyen transfer has been a hypothesis to explain observed oxygen transfer rates in activated sludge systems that were well above that predicted from aerator clean-water testing. The enhanced oxygen transfer rates were based on tests using BOD bottle oxygen ...

  6. Tolerance and metabolic response of acetogenic bacteria toward oxygen.

    PubMed

    Karnholz, Arno; Küsel, Kirsten; Gössner, Anita; Schramm, Andreas; Drake, Harold L

    2002-02-01

    The acetogens Sporomusa silvacetica, Moorella thermoacetica, Clostridium magnum, Acetobacterium woodii, and Thermoanaerobacter kivui (i) grew in both semisolid and liquid cultivation media containing O(2) and (ii) consumed small amounts of O(2). Low concentrations of O(2) caused a lag phase in growth but did not alter the ability of these acetogens to synthesize acetate via the acetyl coenzyme A pathway. Cell extracts of S. silvacetica, M. thermoacetica, and C. magnum contained peroxidase and NADH oxidase activities; catalase and superoxide dismutase activities were not detected. PMID:11823254

  7. Metabolic activities and probiotic potential of bifidobacteria.

    PubMed

    Russell, D A; Ross, R P; Fitzgerald, G F; Stanton, C

    2011-09-01

    It has been shown that the gut microbiota regulates fat storage in the body and that disturbances in its composition can lead to the development of certain metabolic disease states. Bifidobacteria are found among the resident microbiota in the gastrointestinal tract (GIT) and their metabolic activities have been shown to beneficially influence the human host. It has been reported that they inhibit intestinal colonisation by pathogenic microorganisms and have anti-carcinogenic, immunostimulatory, and anti-diarrhoeal properties, as well as aiding in the alleviation of lactose intolerance and ability to lower serum cholesterol levels in humans. One particular health promoting property of bifidobacteria is bioactive fatty acid production, which when ingested, may confer health benefits on the host. A bioactive fatty acid produced by bifidobacteria is conjugated linoleic acid (CLA), of which cis-9, trans-11 (c9, t11) and trans-10, cis-12 (t10, c12) CLA are the main biologically active CLA isomers. The production of CLA by Bifidobacterium can also have a positive effect on the immune system of the human host leading to numerous health benefits. This is an example of the metabolic activities of an ingested bacterium being beneficial to the host, rather than the direct interaction of the bacterium with the host. PMID:21763022

  8. Functions for diverse metabolic activities in heterochromatin.

    PubMed

    Su, Xue Bessie; Pillus, Lorraine

    2016-03-15

    Growing evidence demonstrates that metabolism and chromatin dynamics are not separate processes but that they functionally intersect in many ways. For example, the lysine biosynthetic enzyme homocitrate synthase was recently shown to have unexpected functions in DNA damage repair, raising the question of whether other amino acid metabolic enzymes participate in chromatin regulation. Using an in silico screen combined with reporter assays, we discovered that a diverse range of metabolic enzymes function in heterochromatin regulation. Extended analysis of the glutamate dehydrogenase 1 (Gdh1) revealed that it regulates silent information regulator complex recruitment to telomeres and ribosomal DNA. Enhanced N-terminal histone H3 proteolysis is observed in GDH1 mutants, consistent with telomeric silencing defects. A conserved catalytic Asp residue is required for Gdh1's functions in telomeric silencing and H3 clipping. Genetic modulation of α-ketoglutarate levels demonstrates a key regulatory role for this metabolite in telomeric silencing. The metabolic activity of glutamate dehydrogenase thus has important and previously unsuspected roles in regulating chromatin-related processes. PMID:26936955

  9. Noninvasive optical characterization of muscle blood flow, oxygenation, and metabolism in women with fibromyalgia

    PubMed Central

    2012-01-01

    Introduction Women with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM. Methods Fourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily increasing from 20 to 70% maximal voluntary isometric contraction (MVIC). For the cuff occlusion protocol, forearm arterial blood flow was occluded via a tourniquet on the upper arm for 3 minutes. Leg or arm muscle hemodynamics, including relative blood flow (rBF), oxy- and deoxy-hemoglobin concentration ([HbO2] and [Hb]), total hemoglobin concentration (THC) and blood oxygen saturation (StO2), were continuously monitored throughout protocols using a custom-built hybrid diffuse optical instrument that combined a commercial near-infrared oximeter for tissue oxygenation measurements and a custom-designed diffuse correlation spectroscopy (DCS) flowmeter for tissue blood flow measurements. Relative oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO2) were calculated from the measured blood flow and oxygenation data. Post-manipulation (fatiguing exercise or cuff occlusion) recovery in muscle hemodynamics was characterized by the recovery half-time, a time interval from the end of manipulation to the time that tissue hemodynamics reached a half-maximal value. Results Subjects with FM had similar hemodynamic and metabolic response/recovery patterns as healthy controls during exercise and during arterial occlusion. However, tissue r

  10. Blood oxygen transport and metabolism of the confined lugworm Arenicola marina (L.).

    PubMed

    Toulmond, A

    1975-12-01

    Oxygen consumption (MO2), haemoglobin oxygen saturation level (SVO2) and pH (pHv) in prebranchial blood were measured in lugworms experimentally confined in sea water at 15 degrees C. Total blood flow through the gills (Vb) was estimated. For sea water oxygen partial pressure (PwO2) between 120 and 150 Torr MO2, SVO2 and Vb were high and nearly constant. For PwO2 less than 120 Torr, Vb fell quickly, MO2 progressively dropped, and metabolism remained aerobic at the expense of the prebrancial blood oxygen store. For PwO2 less than 50 Torr, Vb and SvO2 values were extremely low, and the low pHv and the modified buffer power of the surrounding sea water showed that anaerobic metabolism was occurring. Changes in respiratory gas exchanges and metabolism during the tidal cycle are deduced from the comparison of these results with data obtained in the field. PMID:2646

  11. Reduction of Reactive Oxygen Species Ameliorates Metabolism-Secretion Coupling in Islets of Diabetic GK Rats by Suppressing Lactate Overproduction

    PubMed Central

    Sasaki, Mayumi; Fujimoto, Shimpei; Sato, Yuichi; Nishi, Yuichi; Mukai, Eri; Yamano, Gen; Sato, Hiroki; Tahara, Yumiko; Ogura, Kasane; Nagashima, Kazuaki; Inagaki, Nobuya

    2013-01-01

    We previously demonstrated that impaired glucose-induced insulin secretion (IS) and ATP elevation in islets of Goto-Kakizaki (GK) rats, a nonobese model of diabetes, were significantly restored by 30–60-min suppression of endogenous reactive oxygen species (ROS) overproduction. In this study, we investigated the effect of a longer (12 h) suppression of ROS on metabolism-secretion coupling in β-cells by exposure to tempol, a superoxide (O2−) dismutase mimic, plus ebselen, a glutathione peroxidase mimic (TE treatment). In GK islets, both H2O2 and O2− were sufficiently reduced and glucose-induced IS and ATP elevation were improved by TE treatment. Glucose oxidation, an indicator of Krebs cycle velocity, also was improved by TE treatment at high glucose, whereas glucokinase activity, which determines glycolytic velocity, was not affected. Lactate production was markedly increased in GK islets, and TE treatment reduced lactate production and protein expression of lactate dehydrogenase and hypoxia-inducible factor 1α (HIF1α). These results indicate that the Warburg-like effect, which is characteristic of aerobic metabolism in cancer cells by which lactate is overproduced with reduced linking to mitochondria metabolism, plays an important role in impaired metabolism-secretion coupling in diabetic β-cells and suggest that ROS reduction can improve mitochondrial metabolism by suppressing lactate overproduction through the inhibition of HIF1α stabilization. PMID:23349483

  12. Reduction of reactive oxygen species ameliorates metabolism-secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction.

    PubMed

    Sasaki, Mayumi; Fujimoto, Shimpei; Sato, Yuichi; Nishi, Yuichi; Mukai, Eri; Yamano, Gen; Sato, Hiroki; Tahara, Yumiko; Ogura, Kasane; Nagashima, Kazuaki; Inagaki, Nobuya

    2013-06-01

    We previously demonstrated that impaired glucose-induced insulin secretion (IS) and ATP elevation in islets of Goto-Kakizaki (GK) rats, a nonobese model of diabetes, were significantly restored by 30-60-min suppression of endogenous reactive oxygen species (ROS) overproduction. In this study, we investigated the effect of a longer (12 h) suppression of ROS on metabolism-secretion coupling in β-cells by exposure to tempol, a superoxide (O2(-)) dismutase mimic, plus ebselen, a glutathione peroxidase mimic (TE treatment). In GK islets, both H2O2 and O2(-) were sufficiently reduced and glucose-induced IS and ATP elevation were improved by TE treatment. Glucose oxidation, an indicator of Krebs cycle velocity, also was improved by TE treatment at high glucose, whereas glucokinase activity, which determines glycolytic velocity, was not affected. Lactate production was markedly increased in GK islets, and TE treatment reduced lactate production and protein expression of lactate dehydrogenase and hypoxia-inducible factor 1α (HIF1α). These results indicate that the Warburg-like effect, which is characteristic of aerobic metabolism in cancer cells by which lactate is overproduced with reduced linking to mitochondria metabolism, plays an important role in impaired metabolism-secretion coupling in diabetic β-cells and suggest that ROS reduction can improve mitochondrial metabolism by suppressing lactate overproduction through the inhibition of HIF1α stabilization. PMID:23349483

  13. Metabolic activity of microorganisms in evaporites

    NASA Technical Reports Server (NTRS)

    Rothschild, L. J.; Giver, L. J.; White, M. R.; Mancinelli, R. L.

    1994-01-01

    Crystalline salt is generally considered so hostile to most forms of life that it has been used for centuries as a preservative. Here, we present evidence that prokaryotes inhabiting a natural evaporite crust of halite and gypsum are metabolically active while inside the evaporite for at least 10 months. In situ measurements demonstrated that some of these "endoevaporitic" microorganisms (probably the cyanobacterium Synechococcus Nageli) fixed carbon and nitrogen. Denitrification was not observed. Our results quantified the slow microbial activity that can occur in salt crystals. Implications of this study include the possibility that microorganisms found in ancient evaporite deposits may have been part of an evaporite community.

  14. Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia

    PubMed Central

    Dehaes, Mathieu; Aggarwal, Alpna; Lin, Pei-Yi; Rosa Fortuno, C; Fenoglio, Angela; Roche-Labarbe, Nadège; Soul, Janet S; Franceschini, Maria Angela; Grant, P Ellen

    2014-01-01

    Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO2i) and CBF indices (CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2 remained unchanged after the therapy. Thus, FDNIRS–DCS can provide information complimentary to SO2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS–DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization. PMID:24064492

  15. Oxygen Metabolic Responses of Three Species of Large Benthic Foraminifers with Algal Symbionts to Temperature Stress

    PubMed Central

    Fujita, Kazuhiko; Okai, Takaaki; Hosono, Takashi

    2014-01-01

    Water temperature affects the physiology of large benthic foraminifers (LBFs) with algal symbionts dwelling in coral reef environments. However, the detailed physiological responses of LBF holobionts to temperature ranges occurring in their habitats are not known. We report net oxygen (O2) production and respiration rates of three LBF holobionts (Baculogypsina sphaerulata and Calcarina gaudichaudii hosting diatom symbionts, and Amphisorus kudakajimensis hosting dinoflagellate symbionts) measured in the laboratory at water temperatures ranging from 5°C to 45°C in 2.5°C or 5°C intervals and with light saturation levels of ∼500 µmol m−2 s−1. In addition, the recovery of net O2 production and respiration rates after exposure to temperature stress was assessed. The net O2 production and respiration rates of the three LBF holobionts peaked at ∼30°C, indicating their optimal temperature for a short exposure period. At extreme high temperatures (≥40°C), the net O2 production rates of all three LBF holobionts declined to less than zero and the respiration rates slightly decreased, indicating that photosynthesis of algal symbionts was inactivated. At extreme low temperatures (≤10°C for two calcarinid species and ≤5°C for A. kudakajimensis), the net O2 production and respiration rates were near zero, indicating a weakening of holobiont activity. After exposure to extreme high or low temperature, the net O2 production rates did not recover until the following day, whereas the respiration rates recovered rapidly, suggesting that a longer time (days) is required for recovery from damage to the photosystem by temperature stress compared to the respiration system. These results indicate that the oxygen metabolism of LBF holobionts can generally cope well with conditions that fluctuate diurnally and seasonally in their habitats. However, temporal heat and cold stresses with high light levels may induce severe damage to algal symbionts and also damage to host

  16. CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity

    PubMed Central

    O’Brien III, William G.; Berka, Vladimir; Tsai, Ah-Lim; Zhao, Zhaoyang; Lee, Cheng Chi

    2015-01-01

    Erythrocytes are the key target in 5′-AMP induced hypometabolism. To understand how regulation of endogenous erythrocyte AMP levels modulates systemic metabolism, we generated mice deficient in both CD73 and AMPD3, the key catabolic enzymes for extracellular and intra-erythrocyte AMP, respectively. Under physiological conditions, these mice displayed enhanced capacity for physical activity accompanied by significantly higher food and oxygen consumption, compared to wild type mice. Erythrocytes from Ampd3−/− mice exhibited higher half-saturation pressure of oxygen (p50) and about 3-fold higher levels of ATP and ADP, while they maintained normal 2,3-bisphosphoglycerate (2,3-BPG), methemoglobin levels and intracellular pH. The affinity of mammalian hemoglobin for oxygen is thought to be regulated primarily by 2,3-BPG levels and pH (the Bohr effect). However, our results show that increased endogenous levels of ATP and ADP, but not AMP, directly increase the p50 value of hemoglobin. Additionally, the rise in erythrocyte p50 directly correlates with an enhanced capability of systemic metabolism. PMID:26249166

  17. Effect of exercise training on respiration and reactive oxygen species metabolism in eel red muscle.

    PubMed

    Mortelette, Hélène; Amérand, Aline; Sébert, Philippe; Belhomme, Marc; Calvès, Patrick; Moisan, Christine

    2010-07-31

    This paper deals with the effects of exercise training on oxygen consumption (MO(2)) and ROS metabolism in the red muscle of trained and untrained female silver eels. Their critical swimming speed (U(crit)) was determined before and after a 4-day training (10h of swimming at 70% of U(crit) and 14 h at 50%, every day). The U(crit) of trained eels increased significantly (by about 7%). The in vitro MO(2) and ROS production by the red fibres were higher (not significant) in trained than in untrained eels, but the ROS production/MO(2) ratio was alike in both groups. The antioxidant-enzyme activities and lipoperoxidation index in trained eels were both lower than those of the untrained ones. These biochemical changes related to the increase in U(crit) suggest that such a training session could maintained or even increased aerobic power of the red muscle without deleterious impact by ROS. These regulations could play a role in the eel's swimming performance efficiency. PMID:20566309

  18. Visible-light OCT to quantify retinal oxygen metabolism (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Zhang, Hao F.; Yi, Ji; Chen, Siyu; Liu, Wenzhong; Soetikno, Brian T.

    2016-03-01

    We explored, both numerically and experimentally, whether OCT can be a good candidate to accurately measure retinal oxygen metabolism. We first used statistical methods to numerically simulate photon transport in the retina to mimic OCT working under different spectral ranges. Then we analyze accuracy of OCT oximetry subject to parameter variations such as vessel size, pigmentation, and oxygenation. We further developed an experimental OCT system based on the spectral range identified by our simulation work. We applied the newly developed OCT to measure both retinal hemoglobin oxygen saturation (sO2) and retinal retinal flow. After obtaining the retinal sO2 and blood velocity, we further measured retinal vessel diameter and calculated the retinal oxygen metabolism rate (MRO2). To test the capability of our OCT, we imaged wild-type Long-Evans rats ventilated with both normal air and air mixtures with various oxygen concentrations. Our simulation suggested that OCT working within visible spectral range is able to provide accurate measurement of retinal MRO2 using inverse Fourier transform spectral reconstruction. We called this newly developed technology vis-OCT, and showed that vis-OCT was able to measure the sO2 value in every single major retinal vessel around the optical disk as well as in micro retinal vessels. When breathing normal air, the averaged sO2 in arterial and venous blood in Long-Evans rats was measured to be 95% and 72%, respectively. When we challenge the rats using air mixtures with different oxygen concentrations, vis-OCT measurement followed analytical models of retinal oxygen diffusion and pulse oximeter well.

  19. Flexible Sheet-Type Sensor for Noninvasive Measurement of Cellular Oxygen Metabolism on a Culture Dish.

    PubMed

    Kojima, Mari; Takehara, Hiroaki; Akagi, Takanori; Shiono, Hirofumi; Ichiki, Takanori

    2015-01-01

    A novel flexible sensor was developed for the noninvasive oxygen metabolism measurement of cultivated cells and tissues. This device is composed of a transparent double-layered polymer sheet of ethylene-vinyl alcohol (EVOH) and poly(dimethylsiloxane) (PDMS) having an array of microhole structures of 90 μm diameter and 50 μm depth on its surface. All the microhole structures were equipped with a 1-μm-thick optical chemical sensing layer of platinum porphyrin-fluoropolymer on their bottom. The three-dimensional microstructures of the sensor were fabricated by a newly developed simple and low-cost production method named self-aligned hot embossing. The device was designed to be attached slightly above the cells cultivated on a dish to form a temporarily closed microspace over the target cells during measurement. Since the change in oxygen concentration is relatively fast in the microcompartmentalized culture medium, a rapid evaluation of the oxygen consumption rate is possible by measuring the phosphorescence lifetime of the platinum porphyrin-fluoropolymer. The combined use of the device and an automated optical measurement system enabled the high-throughput sensing of cellular oxygen consumption (100 points/min). We monitored the oxygen metabolism of the human breast cancer cell line MCF7 on a Petri dish and evaluated the oxygen consumption rate to be 0.72 ± 0.12 fmol/min/cell. Furthermore, to demonstrate the utility of the developed sensing system, we demonstrated the mapping of the oxygen consumption rate of rat brain slices and succeeded in visualizing a clear difference among the layer structures of the hippocampus, i.e., the cornu ammonis (CA1 and CA3) and dentate gyrus (DG). PMID:26624889

  20. Flexible Sheet-Type Sensor for Noninvasive Measurement of Cellular Oxygen Metabolism on a Culture Dish

    PubMed Central

    Akagi, Takanori; Shiono, Hirofumi; Ichiki, Takanori

    2015-01-01

    A novel flexible sensor was developed for the noninvasive oxygen metabolism measurement of cultivated cells and tissues. This device is composed of a transparent double-layered polymer sheet of ethylene-vinyl alcohol (EVOH) and poly(dimethylsiloxane) (PDMS) having an array of microhole structures of 90 μm diameter and 50 μm depth on its surface. All the microhole structures were equipped with a 1-μm-thick optical chemical sensing layer of platinum porphyrin-fluoropolymer on their bottom. The three-dimensional microstructures of the sensor were fabricated by a newly developed simple and low-cost production method named self-aligned hot embossing. The device was designed to be attached slightly above the cells cultivated on a dish to form a temporarily closed microspace over the target cells during measurement. Since the change in oxygen concentration is relatively fast in the microcompartmentalized culture medium, a rapid evaluation of the oxygen consumption rate is possible by measuring the phosphorescence lifetime of the platinum porphyrin-fluoropolymer. The combined use of the device and an automated optical measurement system enabled the high-throughput sensing of cellular oxygen consumption (100 points/min). We monitored the oxygen metabolism of the human breast cancer cell line MCF7 on a Petri dish and evaluated the oxygen consumption rate to be 0.72 ± 0.12 fmol/min/cell. Furthermore, to demonstrate the utility of the developed sensing system, we demonstrated the mapping of the oxygen consumption rate of rat brain slices and succeeded in visualizing a clear difference among the layer structures of the hippocampus, i.e., the cornu ammonis (CA1 and CA3) and dentate gyrus (DG). PMID:26624889

  1. PARALLEL EVALUATION OF AIR- AND OXYGEN-ACTIVATED SLUDGE

    EPA Science Inventory

    To provide data on the relative merits of air and oxygen in the activated sludge process, two 1900-cu m/day (0.5-mgd) activated sludge pilot plant, one air and one oxygen system, were operated side-by-side at the Joint Water Pollution Control Plant, Carson, California. Both of th...

  2. Changes in fetal ovine metabolism and oxygen delivery with fetal bypass.

    PubMed

    Lam, Christopher T; Baker, R Scott; Clark, Kenneth E; Eghtesady, Pirooz

    2011-07-01

    Since the 1980s, attempts at experimental fetal cardiac bypass for the purpose of correcting severe congenital heart defects in the womb have been hampered by deterioration of placental function. This placental pathophysiology in turn affects transplacental transport of nutrients and gas exchange. To date, the effects of bypass on fetal metabolism and oxygen delivery have not been studied. Nine Suffolk sheep fetuses from 109-121 days gestation were instrumented and placed on fetal bypass for 30 min and followed postbypass for 2 h. Blood gases, glucose, and lactate were serially measured in the fetal arterial and umbilical venous circulations throughout the procedure. Insulin and glucagon levels were serially measured by immunoassay in fetal plasma. Fetal-placental hemodynamics were measured continuously. The expression of glycogen content was examined in fetal liver. Oxygen delivery to the fetus and fetal oxygen consumption were significantly deranged after the conduct of bypass (in-group ANOVA (P = 0.001) and overall contrast (P = 0.072) with planned contrast (P < 0.05) for delivery and consumption, respectively). There were significant alterations in fetal glucose metabolism in the postbypass period; however, insulin and glucagon levels did not change. Fetal liver glycogen content appeared lower after bypass. This is the first report documenting fetal metabolic dysregulation that occurs in response to the conduct of fetal bypass. The significant alterations in fetal oxygen and glucose delivery coupled with hepatic glycogen depletion complicate and impede fetal recovery. These initial findings warrant further investigation of interventions to restore metabolic and hemodynamic homeostasis after fetal bypass. PMID:21508289

  3. Metabolic profiles of d’Anjou pears stored in low oxygen atmospheres

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low oxygen storage atmospheres slow ripening and prevent superficial scald development on d’Anjou pear fruit. A metabolic profiling approach was employed to characterize peel metabolites in d’Anjou pears stored at 1C in air, 1.5kPa O2/0.5kPa CO2 (CA), or 0.5kPa O2/0.5kPa CO2 (UA) for up to 6 months...

  4. Cerebral oxygen metabolism and blood flow in human cerebral ischemic infarction

    SciTech Connect

    Lenzi, G.L.; Frackowiak, R.S.; Jones, T.

    1982-09-01

    Fifteen patients with acute cerebral hemispheric infarcts have been studied with positron emission tomography and the /sup 15/O steady-state inhalation technique. Thirteen follow-up studies were also performed. The values of cerebral oxygen metabolism (CMRO/sub 2/), cerebral blood flow (CBF), and oxygen extraction ration (OER) have been calculated for the infarcted regions, their borders, the symmetrical regions in contralateral cerebral hemispheres, and the cerebellar hemispheres. This study demonstrates that in the completed stroke there are thresholds for regional CMRO/sub 2/ and regional CBF below which the general clinical outcome of the patients is usually poor. The ischaemic lesions invariably produce an uncoupling between the greatly decreased metabolic demand and the less affected blood supply, with very frequent instances of relative hyperperfusion. Remote effects of the hemispheric infarcts have been demonstrated, such as crossed cerebellar diaschisis and contralateral transhemispheric depression. The level of consciousness correlates with oxygen uptake and blood flow both in the posterior fossa and in the contralateral cerebral hemispheres. The follow-up studies of individual patients underline the high variability of metabolism-to-flow balance during the acute phase of the illness, and stress the need for more studies focused on repeated assessments of homogeneous patient populations.

  5. Mild training program in metabolic syndrome improves the efficiency of the oxygen pathway.

    PubMed

    Passoni, Elisabetta; Lania, Antonino; Adamo, Saverio; Grasso, Gabriele Simone; Noè, Donatella; Miserocchi, Giuseppe; Beretta, Egidio

    2015-03-01

    In sedentary patients suffering of metabolic syndrome, we evaluated the effects of mild exercise program (EP) on the efficiency of the oxygen delivery system. The prescription of exercise (40 min/session, 3 times/week) was tailored at workload corresponding to ∼90% individual anaerobic threshold (AT). EP improved significantly by ∼10% peak values of oxygen consumption (VO2) and heart rate (HR). Furthermore, in response to steady state workload at 90% AT, EP shortened the time constant of VO2, HR and the ratio VO2/HR (reflecting arterio-venous O2 concentration difference) by ∼6s. EP also decreased the elastic respiratory work due to a change in breathing pattern implying a larger contribution of respiratory rate, at the expense of tidal volume during exercise hyperventilation. In all subjects the perceived fatigue (Borg) decreased after training. This study supports a positive effect of a mild EP for the adaptive response of the oxygen chain to face metabolic needs compatible with daily life in patients affected by metabolic syndrome. PMID:25554064

  6. Integration of Carbon, Nitrogen, and Oxygen Metabolism in Escherichia coli--Final Report

    SciTech Connect

    Rabinowitz, Joshua D; Wingreen, Ned s; Rabitz, Herschel A; Xu, Yifan

    2012-10-22

    A key challenge for living systems is balancing utilization of multiple elemental nutrients, such as carbon, nitrogen, and oxygen, whose availability is subject to environmental fluctuations. As growth can be limited by the scarcity of any one nutrient, the rate at which each nutrient is assimilated must be sensitive not only to its own availability, but also to that of other nutrients. Remarkably, across diverse nutrient conditions, E. coli grows nearly optimally, balancing effectively the conversion of carbon into energy versus biomass. To investigate the link between the metabolism of different nutrients, we quantified metabolic responses to nutrient perturbations using LC-MS based metabolomics and built differential equation models that bridge multiple nutrient systems. We discovered that the carbonaceous substrate of nitrogen assimilation, -ketoglutarate, directly inhibits glucose uptake and that the upstream glycolytic metabolite, fructose-1,6-bisphosphate, ultrasensitively regulates anaplerosis to allow rapid adaptation to changing carbon availability. We also showed that NADH controls the metabolic response to changing oxygen levels. Our findings support a general mechanism for nutrient integration: limitation for a nutrient other than carbon leads to build-up of the most closely related product of carbon metabolism, which in turn feedback inhibits further carbon uptake.

  7. Perioperative cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle physiology

    PubMed Central

    Dehaes, Mathieu; Cheng, Henry H.; Buckley, Erin M.; Lin, Pei-Yi; Ferradal, Silvina; Williams, Kathryn; Vyas, Rutvi; Hagan, Katherine; Wigmore, Daniel; McDavitt, Erica; Soul, Janet S.; Franceschini, Maria Angela; Newburger, Jane W.; Ellen Grant, P.

    2015-01-01

    Congenital heart disease (CHD) patients are at risk for neurodevelopmental delay. The etiology of these delays is unclear, but abnormal prenatal cerebral maturation and postoperative hemodynamic instability likely play a role. A better understanding of these factors is needed to improve neurodevelopmental outcome. In this study, we used bedside frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) to assess cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle (SV) CHD undergoing surgery and compared them to controls. Our goals were 1) to compare cerebral hemodynamics between unanesthetized SV and healthy neonates, and 2) to determine if FDNIRS-DCS could detect alterations in cerebral hemodynamics beyond cerebral hemoglobin oxygen saturation (SO2). Eleven SV neonates were recruited and compared to 13 controls. Preoperatively, SV patients showed decreased cerebral blood flow (CBFi), cerebral oxygen metabolism (CMRO2i) and SO2; and increased oxygen extraction fraction (OEF) compared to controls. Compared to preoperative values, unstable postoperative SV patients had decreased CMRO2i and CBFi, which returned to baseline when stable. However, SO2 showed no difference between unstable and stable states. Preoperative SV neonates are flow-limited and show signs of impaired cerebral development compared to controls. FDNIRS-DCS shows potential to improve assessment of cerebral development and postoperative hemodynamics compared to SO2 alone. PMID:26713191

  8. Myocardial oxidative metabolism and protein synthesis during mechanical circulatory support by extracorporeal membrane oxygenation

    PubMed Central

    Priddy, Colleen M. O′Kelly; Kajimoto, Masaki; Ledee, Dolena R.; Bouchard, Bertrand; Isern, Nancy; Olson, Aaron K.; Rosiers, Christine Des

    2013-01-01

    Extracorporeal membrane oxygenation (ECMO) provides essential mechanical circulatory support necessary for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur, which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative metabolism and protein synthesis. We focused on the amino acid leucine and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart 1) the fractional contribution of leucine (FcLeucine) and pyruvate to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and 2) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 h of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (∼40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining 1) metabolic flexibility indicated by ability to respond to pyruvate and 2) a normal or increased capacity for global protein synthesis. PMID:23203964

  9. Contributions to elevated metabolism during recovery: dissecting the excess postexercise oxygen consumption (EPOC) in the desert iguana (Dipsosaurus dorsalis).

    PubMed

    Hancock, Thomas V; Gleeson, Todd T

    2008-01-01

    The excess postexercise oxygen consumption (EPOC), a measure of recovery costs, is known to be large in ectothermic vertebrates such as the desert iguana (Dipsosaurus dorsalis), especially after vigorous activity. To analyze the cause of these large recovery costs in a terrestrial ectotherm, Dipsosaurus were run for 15 s at maximal-intensity (distance 35.0+/-1.9 m; 2.33+/-0.13 m s(-1)) while O(2) uptake was monitored via open-flow respirometry. Muscle metabolites (adenylates, phosphocreatine, and lactate) were measured at rest and after 0, 3, 10, and 60 min of recovery. Cardiac and ventilatory activity during rest and recovery were measured, as were whole-body lactate and blood lactate, which were used to estimate total muscle activity. This vigorous activity was supported primarily by glycolysis (65%) and phosphocreatine hydrolysis (29%), with only a small contribution from aerobic metabolism (2.5%). Aerobic recovery lasted 43.8+/-4.6 min, and EPOC measured 0.166+/-0.025 mL O(2) g(-1). This was a large proportion (98%) of the total suprabasal metabolic cost of the activity to the animal. The various contributions to EPOC after this short but vigorous activity were quantified, and a majority of EPOC was accounted for. The two primary causes of EPOC were phosphocreatine repletion (32%-50%) and lactate glycogenesis (30%-47%). Four other components played smaller roles: ATP repletion (8%-13%), elevated ventilatory activity (2%), elevated cardiac activity (2%), and oxygen store resaturation (1%). PMID:18040968

  10. Structural adaptation of microvessel diameters in response to metabolic stimuli: where are the oxygen sensors?

    PubMed

    Reglin, Bettina; Secomb, Timothy W; Pries, Axel R

    2009-12-01

    Maintenance of functional vascular networks requires structural adaptation of vessel diameters in response to hemodynamic and metabolic conditions. The mechanisms by which diameters respond to the metabolic state are not known, but may involve the release of vasoactive substances in response to low oxygen by tissue ("tissue signaling", e.g., CO2, adenosine), by vessel walls ("wall signaling", e.g., prostaglandins, adenosine), and/or by red blood cells (RBCs) ("RBC signaling", e.g., ATP and nitric oxide). Here, the goal was to test the potential of each of these locations of oxygen-dependent signaling to control steady-state vascular diameters and tissue oxygenation. A previously developed theoretical model of structural diameter adaptation based on experimental data on microvascular network morphology and hemodynamics was used. Resulting network characteristics were analyzed with regard to tissue oxygenation (Oxdef; percentage of tissue volume with PO2<1 Torr) and the difference between estimated blood flow velocities and corresponding experimental data [velocity error (Verr); root mean square deviation of estimated vs. measured velocity]. Wall signaling led to Oxdef<1% and to the closest hemodynamic similarity (Verr: 0.60). Tissue signaling also resulted in a low oxygen deficit, but a higher Verr (0.73) and systematic diameter deviations. RBC signaling led to widespread hypoxia (Oxdef: 4.7%), unrealistic velocity distributions (Verr: 0.81), and shrinkage of small vessels. The results suggest that wall signaling plays a central role in structural control of vessel diameters in microvascular networks of given angioarchitecture. Tissue-derived and RBC-derived signaling of oxygen levels may be more relevant for the regulation of angiogenesis and/or smooth muscle tone. PMID:19783778

  11. Structural adaptation of microvessel diameters in response to metabolic stimuli: where are the oxygen sensors?

    PubMed Central

    Reglin, Bettina; Secomb, Timothy W.

    2009-01-01

    Maintenance of functional vascular networks requires structural adaptation of vessel diameters in response to hemodynamic and metabolic conditions. The mechanisms by which diameters respond to the metabolic state are not known, but may involve the release of vasoactive substances in response to low oxygen by tissue (“tissue signaling”, e.g., CO2, adenosine), by vessel walls (“wall signaling”, e.g., prostaglandins, adenosine), and/or by red blood cells (RBCs) (“RBC signaling”, e.g., ATP and nitric oxide). Here, the goal was to test the potential of each of these locations of oxygen-dependent signaling to control steady-state vascular diameters and tissue oxygenation. A previously developed theoretical model of structural diameter adaptation based on experimental data on microvascular network morphology and hemodynamics was used. Resulting network characteristics were analyzed with regard to tissue oxygenation (Oxdef; percentage of tissue volume with Po2 < 1 Torr) and the difference between estimated blood flow velocities and corresponding experimental data [velocity error (Verr); root mean square deviation of estimated vs. measured velocity]. Wall signaling led to Oxdef < 1% and to the closest hemodynamic similarity (Verr: 0.60). Tissue signaling also resulted in a low oxygen deficit, but a higher Verr (0.73) and systematic diameter deviations. RBC signaling led to widespread hypoxia (Oxdef: 4.7%), unrealistic velocity distributions (Verr: 0.81), and shrinkage of small vessels. The results suggest that wall signaling plays a central role in structural control of vessel diameters in microvascular networks of given angioarchitecture. Tissue-derived and RBC-derived signaling of oxygen levels may be more relevant for the regulation of angiogenesis and/or smooth muscle tone. PMID:19783778

  12. Phloem metabolism and function have to cope with low internal oxygen.

    PubMed

    van Dongen, Joost T; Schurr, Ulrich; Pfister, Michelle; Geigenberger, Peter

    2003-04-01

    We have investigated the consequences of endogenous limitations in oxygen delivery for phloem transport in Ricinus communis. In situ oxygen profiles were measured directly across stems of plants growing in air (21% [v/v] oxygen), using a microsensor with a tip diameter of approximately 30 microm. Oxygen levels decreased from 21% (v/v) at the surface to 7% (v/v) in the vascular region and increased again to 15% (v/v) toward the hollow center of the stem. Phloem sap exuding from small incisions in the bark of the stem was hypoxic, and the ATP to ADP ratio (4.1) and energy charge (0.78) were also low. When 5-cm stem segments of intact plants were exposed to zero external oxygen for 90 min, oxygen levels within the phloem decreased to approximately 2% (v/v), and ATP to ADP ratio and adenylate energy charge dropped further to 1.92 and 0.68, respectively. This was accompanied by a marked decrease in the phloem sucrose (Suc) concentration and Suc transport rate, which is likely to be explained by the inhibition of retrieval processes in the phloem. Germinating seedlings were used to analyze the effect of a stepwise decrease in oxygen tension on phloem transport and energy metabolism in more detail. Within the endosperm embedding the cotyledons-next to the phloem loading sites-oxygen decreased from approximately 14% (v/v) in 6-d-old seedlings down to approximately 6% (v/v) in 10-d-old seedlings. This was paralleled by a similar decrease of oxygen inside the hypocotyl. When the endosperm was removed and cotyledons incubated in a 100 mM Suc solution with 21%, 6%, 3%, or 0.5% (v/v) oxygen for 3 h before phloem sap was analyzed, decreasing oxygen tensions led to a progressive decrease in phloem energy state, indicating a partial inhibition of respiration. The estimated ratio of NADH to NAD(+) in the phloem exudate remained low (approximately 0.0014) when oxygen was decreased to 6% and 3% (v/v) but increased markedly (to approximately 0.008) at 0.5% (v/v) oxygen, paralleled by

  13. Active site densities, oxygen activation and adsorbed reactive oxygen in alcohol activation on npAu catalysts.

    PubMed

    Wang, Lu-Cun; Friend, C M; Fushimi, Rebecca; Madix, Robert J

    2016-07-01

    The activation of molecular O2 as well as the reactivity of adsorbed oxygen species is of central importance in aerobic selective oxidation chemistry on Au-based catalysts. Herein, we address the issue of O2 activation on unsupported nanoporous gold (npAu) catalysts by applying a transient pressure technique, a temporal analysis of products (TAP) reactor, to measure the saturation coverage of atomic oxygen, its collisional dissociation probability, the activation barrier for O2 dissociation, and the facility with which adsorbed O species activate methanol, the initial step in the catalytic cycle of esterification. The results from these experiments indicate that molecular O2 dissociation is associated with surface silver, that the density of reactive sites is quite low, that adsorbed oxygen atoms do not spill over from the sites of activation onto the surrounding surface, and that methanol reacts quite facilely with the adsorbed oxygen atoms. In addition, the O species from O2 dissociation exhibits reactivity for the selective oxidation of methanol but not for CO. The TAP experiments also revealed that the surface of the npAu catalyst is saturated with adsorbed O under steady state reaction conditions, at least for the pulse reaction. PMID:27376884

  14. Metabolically active Crenarchaeota in Altamira Cave.

    PubMed

    Gonzalez, Juan M; Portillo, M Carmen; Saiz-Jimenez, Cesareo

    2006-01-01

    Altamira Cave contains valuable paleolithic paintings dating back to 15,000 years. The conservation of these unique paintings is attracting increasing interest, and so, understanding microbial proliferation in Altamira Cave represents a prioritary objective. Here, we show for the first time that members of the Crenarchaeota were metabolically active components of developing microbial communities. RNA was extracted directly from the studied environment, and a number of 16S rRNA gene sequences belonging to the low-temperature Crenarchaeota were detected. Although low-temperature Crenarchaeota detected in a variety of ecosystems by using molecular techniques remain uncultured, this RNA-based study confirms an active participation of the Crenarchaeota in cave biogeochemical cycles. PMID:16292522

  15. Gene Regulatory and Metabolic Adaptation Processes of Dinoroseobacter shibae DFL12T during Oxygen Depletion*

    PubMed Central

    Laass, Sebastian; Kleist, Sarah; Bill, Nelli; Drüppel, Katharina; Kossmehl, Sebastian; Wöhlbrand, Lars; Rabus, Ralf; Klein, Johannes; Rohde, Manfred; Bartsch, Annekathrin; Wittmann, Christoph; Schmidt-Hohagen, Kerstin; Tielen, Petra; Jahn, Dieter; Schomburg, Dietmar

    2014-01-01

    Metabolic flexibility is the key to the ecological success of the marine Roseobacter clade bacteria. We investigated the metabolic adaptation and the underlying changes in gene expression of Dinoroseobacter shibae DFL12T to anoxic life by a combination of metabolome, proteome, and transcriptome analyses. Time-resolved studies during continuous oxygen depletion were performed in a chemostat using nitrate as the terminal electron acceptor. Formation of the denitrification machinery was found enhanced on the transcriptional and proteome level, indicating that D. shibae DFL12T established nitrate respiration to compensate for the depletion of the electron acceptor oxygen. In parallel, arginine fermentation was induced. During the transition state, growth and ATP concentration were found to be reduced, as reflected by a decrease of A578 values and viable cell counts. In parallel, the central metabolism, including gluconeogenesis, protein biosynthesis, and purine/pyrimidine synthesis was found transiently reduced in agreement with the decreased demand for cellular building blocks. Surprisingly, an accumulation of poly-3-hydroxybutanoate was observed during prolonged incubation under anoxic conditions. One possible explanation is the storage of accumulated metabolites and the regeneration of NADP+ from NADPH during poly-3-hydroxybutanoate synthesis (NADPH sink). Although D. shibae DFL12T was cultivated in the dark, biosynthesis of bacteriochlorophyll was increased, possibly to prepare for additional energy generation via aerobic anoxygenic photophosphorylation. Overall, oxygen depletion led to a metabolic crisis with partly blocked pathways and the accumulation of metabolites. In response, major energy-consuming processes were reduced until the alternative respiratory denitrification machinery was operative. PMID:24648520

  16. Gene regulatory and metabolic adaptation processes of Dinoroseobacter shibae DFL12T during oxygen depletion.

    PubMed

    Laass, Sebastian; Kleist, Sarah; Bill, Nelli; Drüppel, Katharina; Kossmehl, Sebastian; Wöhlbrand, Lars; Rabus, Ralf; Klein, Johannes; Rohde, Manfred; Bartsch, Annekathrin; Wittmann, Christoph; Schmidt-Hohagen, Kerstin; Tielen, Petra; Jahn, Dieter; Schomburg, Dietmar

    2014-05-01

    Metabolic flexibility is the key to the ecological success of the marine Roseobacter clade bacteria. We investigated the metabolic adaptation and the underlying changes in gene expression of Dinoroseobacter shibae DFL12(T) to anoxic life by a combination of metabolome, proteome, and transcriptome analyses. Time-resolved studies during continuous oxygen depletion were performed in a chemostat using nitrate as the terminal electron acceptor. Formation of the denitrification machinery was found enhanced on the transcriptional and proteome level, indicating that D. shibae DFL12(T) established nitrate respiration to compensate for the depletion of the electron acceptor oxygen. In parallel, arginine fermentation was induced. During the transition state, growth and ATP concentration were found to be reduced, as reflected by a decrease of A578 values and viable cell counts. In parallel, the central metabolism, including gluconeogenesis, protein biosynthesis, and purine/pyrimidine synthesis was found transiently reduced in agreement with the decreased demand for cellular building blocks. Surprisingly, an accumulation of poly-3-hydroxybutanoate was observed during prolonged incubation under anoxic conditions. One possible explanation is the storage of accumulated metabolites and the regeneration of NADP(+) from NADPH during poly-3-hydroxybutanoate synthesis (NADPH sink). Although D. shibae DFL12(T) was cultivated in the dark, biosynthesis of bacteriochlorophyll was increased, possibly to prepare for additional energy generation via aerobic anoxygenic photophosphorylation. Overall, oxygen depletion led to a metabolic crisis with partly blocked pathways and the accumulation of metabolites. In response, major energy-consuming processes were reduced until the alternative respiratory denitrification machinery was operative. PMID:24648520

  17. A New Functional MRI Approach for Investigating Modulations of Brain Oxygen Metabolism.

    PubMed

    Griffeth, Valerie E M; Blockley, Nicholas P; Simon, Aaron B; Buxton, Richard B

    2013-01-01

    Functional MRI (fMRI) using the blood oxygenation level dependent (BOLD) signal is a common technique in the study of brain function. The BOLD signal is sensitive to the complex interaction of physiological changes including cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral oxygen metabolism (CMRO2). A primary goal of quantitative fMRI methods is to combine BOLD imaging with other measurements (such as CBF measured with arterial spin labeling) to derive information about CMRO2. This requires an accurate mathematical model to relate the BOLD signal to the physiological and hemodynamic changes; the most commonly used of these is the Davis model. Here, we propose a new nonlinear model that is straightforward and shows heuristic value in clearly relating the BOLD signal to blood flow, blood volume and the blood flow-oxygen metabolism coupling ratio. The model was tested for accuracy against a more detailed model adapted for magnetic fields of 1.5, 3 and 7T. The mathematical form of the heuristic model suggests a new ratio method for comparing combined BOLD and CBF data from two different stimulus responses to determine whether CBF and CMRO2 coupling differs. The method does not require a calibration experiment or knowledge of parameter values as long as the exponential parameter describing the CBF-CBV relationship remains constant between stimuli. The method was found to work well for 1.5 and 3T but is prone to systematic error at 7T. If more specific information regarding changes in CMRO2 is required, then with accuracy similar to that of the Davis model, the heuristic model can be applied to calibrated BOLD data at 1.5T, 3T and 7T. Both models work well over a reasonable range of blood flow and oxygen metabolism changes but are less accurate when applied to a simulated caffeine experiment in which CBF decreases and CMRO2 increases. PMID:23826367

  18. Reconstructing ecosystem functions of the active microbial community of the Baltic Sea oxygen depleted sediments.

    PubMed

    Thureborn, Petter; Franzetti, Andrea; Lundin, Daniel; Sjöling, Sara

    2016-01-01

    Baltic Sea deep water and sediments hold one of the largest anthropogenically induced hypoxic areas in the world. High nutrient input and low water exchange result in eutrophication and oxygen depletion below the halocline. As a consequence at Landsort Deep, the deepest point of the Baltic Sea, anoxia in the sediments has been a persistent condition over the past decades. Given that microbial communities are drivers of essential ecosystem functions we investigated the microbial community metabolisms and functions of oxygen depleted Landsort Deep sediments by metatranscriptomics. Results show substantial expression of genes involved in protein metabolism demonstrating that the Landsort Deep sediment microbial community is active. Identified expressed gene suites of metabolic pathways with importance for carbon transformation including fermentation, dissimilatory sulphate reduction and methanogenesis were identified. The presence of transcripts for these metabolic processes suggests a potential for heterotrophic-autotrophic community synergism and indicates active mineralisation of the organic matter deposited at the sediment as a consequence of the eutrophication process. Furthermore, cyanobacteria, probably deposited from the water column, are transcriptionally active in the anoxic sediment at this depth. Results also reveal high abundance of transcripts encoding integron integrases. These results provide insight into the activity of the microbial community of the anoxic sediment at the deepest point of the Baltic Sea and its possible role in ecosystem functioning. PMID:26823996

  19. Reconstructing ecosystem functions of the active microbial community of the Baltic Sea oxygen depleted sediments

    PubMed Central

    Franzetti, Andrea; Lundin, Daniel; Sjöling, Sara

    2016-01-01

    Baltic Sea deep water and sediments hold one of the largest anthropogenically induced hypoxic areas in the world. High nutrient input and low water exchange result in eutrophication and oxygen depletion below the halocline. As a consequence at Landsort Deep, the deepest point of the Baltic Sea, anoxia in the sediments has been a persistent condition over the past decades. Given that microbial communities are drivers of essential ecosystem functions we investigated the microbial community metabolisms and functions of oxygen depleted Landsort Deep sediments by metatranscriptomics. Results show substantial expression of genes involved in protein metabolism demonstrating that the Landsort Deep sediment microbial community is active. Identified expressed gene suites of metabolic pathways with importance for carbon transformation including fermentation, dissimilatory sulphate reduction and methanogenesis were identified. The presence of transcripts for these metabolic processes suggests a potential for heterotrophic-autotrophic community synergism and indicates active mineralisation of the organic matter deposited at the sediment as a consequence of the eutrophication process. Furthermore, cyanobacteria, probably deposited from the water column, are transcriptionally active in the anoxic sediment at this depth. Results also reveal high abundance of transcripts encoding integron integrases. These results provide insight into the activity of the microbial community of the anoxic sediment at the deepest point of the Baltic Sea and its possible role in ecosystem functioning. PMID:26823996

  20. Myocardial Oxidative Metabolism and Protein Synthesis during Mechanical Circulatory Support by Extracorporeal Membrane Oxygenation

    SciTech Connect

    Priddy, MD, Colleen M.; Kajimoto, Masaki; Ledee, Dolena; Bouchard, Bertrand; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-02-01

    Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support essential for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative. We focused on the amino acid leucine, and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart (i) the fractional contribution of leucine (FcLeucine) and pyruvate (FCpyruvate) to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and (ii) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 hours of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (~ 40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. Conclusion: The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining (i) metabolic flexibility indicated by ability to respond to pyruvate, and (ii) a normal or increased capacity for global protein synthesis, suggesting an improved protein balance.

  1. Myocardial Reloading After Extracorporeal Membrane Oxygenation Alters Substrate Metabolism While Promoting Protein Synthesis

    PubMed Central

    Kajimoto, Masaki; O'Kelly Priddy, Colleen M.; Ledee, Dolena R.; Xu, Chun; Isern, Nancy; Olson, Aaron K.; Rosiers, Christine Des; Portman, Michael A.

    2013-01-01

    Background Extracorporeal membrane oxygenation (ECMO) unloads the heart, providing a bridge to recovery in children after myocardial stunning. ECMO also induces stress which can adversely affect the ability to reload or wean the heart from the circuit. Metabolic impairments induced by altered loading and/or stress conditions may impact weaning. However, cardiac substrate and amino acid requirements upon weaning are unknown. We assessed the hypothesis that ventricular reloading with ECMO modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis. Methods and Results Sixteen immature piglets (7.8 to 15.6 kg) were separated into 2 groups based on ventricular loading status: 8‐hour ECMO (UNLOAD) and postwean from ECMO (RELOAD). We infused into the coronary artery [2‐13C]‐pyruvate as an oxidative substrate and [13C6]‐L‐leucine as an indicator for amino acid oxidation and protein synthesis. Upon RELOAD, each functional parameter, which were decreased substantially by ECMO, recovered to near‐baseline level with the exclusion of minimum dP/dt. Accordingly, myocardial oxygen consumption was also increased, indicating that overall mitochondrial metabolism was reestablished. At the metabolic level, when compared to UNLOAD, RELOAD altered the contribution of various substrates/pathways to tissue pyruvate formation, favoring exogenous pyruvate versus glycolysis, and acetyl‐CoA formation, shifting away from pyruvate decarboxylation to endogenous substrate, presumably fatty acids. Furthermore, there was also a significant increase of tissue concentrations for all CAC intermediates (≈80%), suggesting enhanced anaplerosis, and of fractional protein synthesis rates (>70%). Conclusions RELOAD alters both cytosolic and mitochondrial energy substrate metabolism, while favoring leucine incorporation into protein synthesis rather than oxidation in the CAC. Improved understanding of factors governing these metabolic perturbations may

  2. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women

    PubMed Central

    Melzer, Katarina; Heydenreich, Juliane; Schutz, Yves; Renaud, Anne; Kayser, Bengt; Mäder, Urs

    2016-01-01

    Metabolic Equivalent” (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O2/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35–41, n = 46), women 24–53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard. PMID:27447667

  3. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women.

    PubMed

    Melzer, Katarina; Heydenreich, Juliane; Schutz, Yves; Renaud, Anne; Kayser, Bengt; Mäder, Urs

    2016-01-01

    "Metabolic Equivalent" (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O₂/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35-41, n = 46), women 24-53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard. PMID:27447667

  4. Protection effect of nicotinamide on cardiomyoblast hypoxia/re-oxygenation injury: study of cellular mitochondrial metabolism.

    PubMed

    Wang, He; Liang, Xiaoping; Luo, Guoan; Ding, Mingyu; Liang, Qionglin

    2016-06-21

    Hypoxia/re-oxygenation (H/R) injury is an important cause of heart failure and results in a critical metabolism dysfunction. In this paper, the cytoprotective effect of the nicotinamide adenine dinucleotide (NAD) precursor nicotinamide was evaluated using an in vitro model of cardiac H/R injury. Nicotinamide (0-20 mM) was applied to the myoblast cell line H9c2 which was subjected to hypoxia (12, 24, 36 h) followed by a re-oxygenation process (0, 4, 8, 12 h). Cell viability was measured, and mitochondrial metabolites were extracted and then measured by HPLC/MS/MS. The present study showed that nicotinamide could down-regulate the NADH/NAD ratio and then maintain the NAD-dependent metabolism processes. Furthermore, an aberrant decrease of fumarate levels and an increase of succinate levels were observed in the nicotinamide group, which was demonstrated to be caused by nicotinamide-induced succinate dehydrogenase (SDH) inhibition. These results suggest that nicotinamide exerts a protective effect on cardiomyoblasts against H/R-induced injury through both NADH/NAD regulation and reduction of reactive oxygen species generation via SDH inhibition. PMID:27156848

  5. Can the cerebral metabolic rate of oxygen be estimated with near-infrared spectroscopy?

    NASA Astrophysics Data System (ADS)

    Boas, D. A.; Strangman, G.; Culver, J. P.; Hoge, R. D.; Jasdzewski, G.; Poldrack, R. A.; Rosen, B. R.; Mandeville, J. B.

    2003-08-01

    We have measured the changes in oxy-haemoglobin and deoxy-haemoglobin in the adult human brain during a brief finger tapping exercise using near-infrared spectroscopy (NIRS). The cerebral metabolic rate of oxygen (CMRO2) can be estimated from these NIRS data provided certain model assumptions. The change in CMRO2 is related to changes in the total haemoglobin concentration, deoxy-haemoglobin concentration and blood flow. As NIRS does not provide a measure of dynamic changes in blood flow during brain activation, we relied on a Windkessel model that relates dynamic blood volume and flow changes, which has been used previously for estimating CMRO2 from functional magnetic resonance imaging (fMRI) data. Because of the partial volume effect we are unable to quantify the absolute changes in the local brain haemoglobin concentrations with NIRS and thus are unable to obtain an estimate of the absolute CMRO2 change. An absolute estimate is also confounded by uncertainty in the flow-volume relationship. However, the ratio of the flow change to the CMRO2 change is relatively insensitive to these uncertainties. For the finger tapping task, we estimate a most probable flow-consumption ratio ranging from 1.5 to 3 in agreement with previous findings presented in the literature, although we cannot exclude the possibility that there is no CMRO2 change. The large range in the ratio arises from the large number of model parameters that must be estimated from the data. A more precise estimate of the flow-consumption ratio will require better estimates of the model parameters or flow information, as can be provided by combining NIRS with fMRI.

  6. [Need for rheologically active, vasoactive and metabolically active substances in the initial treatment of acute acoustic trauma].

    PubMed

    Pilgramm, M; Schumann, K

    1986-10-01

    Two rheologically active and 8 vasoactive and metabolically active substances were compared in eight independent studies, some of which were randomised and double blind, on 400 patients who had suffered acute acoustic trauma. The control group was given saline. Spontaneous recovery was excluded as far as possible. The following substances were tested: Dextran 40, hydroxyethyl starch 40/0.5, naftidrofurylhydrogenoxalate, Vinpocetin, betahistine, pentoxifylline, flunaricine, Regeneresen AU 4 and 0.9% saline. All groups showed superior results to the control group in both long-term and short-term tests with respect to hearing gain and tinnitis improvement. The rheologically effective substances showed no statistically significant variations. None of the vasoactive or metabolically active substances used as adjunctive therapy improved the results achieved with rheologically effective substances alone. These results demonstrate that acute acoustic trauma can be most effectively treated by rheologically active substances; vasoactive and metabolically active substances are unnecessary. Hyperbaric oxygenation is advantageous as an adjunctive therapy. PMID:2432041

  7. Probing Oxygen Activation Sites in Two Flavoprotein Oxidases Using Chloride as an Oxygen Surrogate

    SciTech Connect

    Kommoju, Phaneeswara-Rao; Chen, Zhi-wei; Bruckner, Robert C.; Mathews, F. Scott; Jorns, Marilyn Schuman

    2011-08-16

    A single basic residue above the si-face of the flavin ring is the site of oxygen activation in glucose oxidase (GOX) (His516) and monomeric sarcosine oxidase (MSOX) (Lys265). Crystal structures of both flavoenzymes exhibit a small pocket at the oxygen activation site that might provide a preorganized binding site for superoxide anion, an obligatory intermediate in the two-electron reduction of oxygen. Chloride binds at these polar oxygen activation sites, as judged by solution and structural studies. First, chloride forms spectrally detectable complexes with GOX and MSOX. The protonated form of His516 is required for tight binding of chloride to oxidized GOX and for rapid reaction of reduced GOX with oxygen. Formation of a binary MSOX-chloride complex requires Lys265 and is not observed with Lys265Met. Binding of chloride to MSOX does not affect the binding of a sarcosine analogue (MTA, methylthioactetate) above the re-face of the flavin ring. Definitive evidence is provided by crystal structures determined for a binary MSOX-chloride complex and a ternary MSOX-chloride-MTA complex. Chloride binds in the small pocket at a position otherwise occupied by a water molecule and forms hydrogen bonds to four ligands that are arranged in approximate tetrahedral geometry: Lys265:NZ, Arg49:NH1, and two water molecules, one of which is hydrogen bonded to FAD:N5. The results show that chloride (i) acts as an oxygen surrogate, (ii) is an effective probe of polar oxygen activation sites, and (iii) provides a valuable complementary tool to the xenon gas method that is used to map nonpolar oxygen-binding cavities.

  8. Nonlinear Dielectric Spectroscopy as an Indirect Probe of Metabolic Activity in Thylakoid Membrane

    PubMed Central

    Fang, Jie; Palanisami, Akilan; Rajapakshe, Kimal; Widger, William R.; Miller, John H.

    2011-01-01

    Nonlinear dielectric spectroscopy (NDS) is a non-invasive probe of cellular metabolic activity with potential application in the development of whole-cell biosensors. However, the mechanism of NDS interaction with metabolic membrane proteins is poorly understood, partly due to the inherent complexity of single cell organisms. Here we use the light-activated electron transport chain of spinach thylakoid membrane as a model system to study how NDS interacts with metabolic activity. We find protein modification, as opposed to membrane pump activity, to be the dominant source of NDS signal change in this system. Potential mechanisms for such protein modifications include reactive oxygen species generation and light-activated phosphorylation. PMID:25586698

  9. Ionizing radiations and collagen metabolism: from oxygen free radicals to radio-induced late fibrosis

    NASA Astrophysics Data System (ADS)

    Nguyen, Tan Dat; Maquart, François-Xavier; Monboisse, Jean-Claude

    2005-02-01

    Skin fibrosis is one of the most common late adverse effects observed after radiation therapy for cancer. As a dose-limiting factor and hence a major hindrance to increase the amount of radiation delivered to the tumor, this problem can be addressed according to the very early steps of the fibrotic process: the oxygen free radical production. Reactive oxygen species (ROS) generated during radiotherapy result from both inflammatory response and water radiolysis. Many studies have demonstrated that the extracellular matrix molecules are potential targets for ROS, and that collagen metabolism and properties are deeply and permanently modified after irradiation, both in vitro and in vivo. It is therefore possible to design different therapeutic approaches such as the clinical use of liposomal superoxide dismutase able to reverse the imbalance between collagen matrix synthesis and degradation. Finally, the so-called oxidative stress induced by radiation represents a significant parameter leading to fibrosis and will undoubtedly serve to design further experimental and clinical studies.

  10. Combined photoacoustic microscopy and optical coherence tomography can measure metabolic rate of oxygen

    PubMed Central

    Liu, Tan; Wei, Qing; Wang, Jing; Jiao, Shuliang; Zhang, Hao F.

    2011-01-01

    We proposed to measure the metabolic rate of oxygen (MRO2) in small animals in vivo using a multimodal imaging system that combines laser-scanning optical-resolution photoacoustic microscopy (LSOR-PAM) and spectral-domain optical coherence tomography (SD-OCT). We first tested the capability of the multimodal system to measure flow rate in a phantom made of two capillary tubes of different diameters. We then demonstrated the capability of measuring MRO2 by imaging two parallel vessels selected from the ear of a Swiss Webster mouse. The hemoglobin oxygen saturation (sO2) and the vessel diameter were measured by the LSOR-PAM and the blood flow velocity was measured by the SD-OCT, from which blood flow rate and MRO2 were further calculated. The measured blood flow rates in the two vessels agreed with each other. PMID:21559147

  11. Glucose and oxygen metabolism after penetrating ballistic-like brain injury

    PubMed Central

    Gajavelli, Shyam; Kentaro, Shimoda; Diaz, Julio; Yokobori, Shoji; Spurlock, Markus; Diaz, Daniel; Jackson, Clayton; Wick, Alexandra; Zhao, Weizhao; Leung, Lai Y; Shear, Deborah; Tortella, Frank; Bullock, M Ross

    2015-01-01

    Traumatic brain injury (TBI) is a major cause of death and disability in all age groups. Among TBI, penetrating traumatic brain injuries (PTBI) have the worst prognosis and represent the leading cause of TBI-related morbidity and death. However, there are no specific drugs/interventions due to unclear pathophysiology. To gain insights we looked at cerebral metabolism in a PTBI rat model: penetrating ballistic-like brain injury (PBBI). Early after injury, regional cerebral oxygen tension and consumption significantly decreased in the ipsilateral cortex in the PBBI group compared with the control group. At the same time point, glucose uptake was significantly reduced globally in the PBBI group compared with the control group. Examination of Fluorojade B-stained brain sections at 24 hours after PBBI revealed an incomplete overlap of metabolic impairment and neurodegeneration. As expected, the injury core had the most severe metabolic impairment and highest neurodegeneration. However, in the peri-lesional area, despite similar metabolic impairment, there was lesser neurodegeneration. Given our findings, the data suggest the presence of two distinct zones of primary injury, of which only one recovers. We anticipate the peri-lesional area encompassing the PBBI ischemic penumbra, could be salvaged by acute therapies. PMID:25669903

  12. Polyol synthesis in Aspergillus niger: influence of oxygen availability, carbon and nitrogen sources on the metabolism.

    PubMed

    Diano, A; Bekker-Jensen, S; Dynesen, J; Nielsen, J

    2006-08-01

    Polyol production has been studied in Aspergillus niger under different conditions. Fermentations have been run using high concentration of glucose or xylose as carbon source and ammonium or nitrate as nitrogen source. The growth of biomass, as freely dispersed hyphae, led to an increase of medium viscosity and hereby a decrease in mass transfer, especially oxygen transfer. The consequence was a decrease in DOT and the occurrence of a switch between fully aerobic conditions and oxygen-limited conditions. Metabolite quantification showed that polyols were the main metabolic products formed and represented up to 22% of the carbon consumed in oxygen-limited conditions. The polyol concentration and the polyol pattern depended strongly on the environmental conditions. This is due to a complex regulation of polyol production and to the fact that each polyol can fulfill different functions. In this study, erythritol, xylitol, and arabitol were produced as carbon storage compounds when the flux through the PP pathway exceeded the need in ribulose-5-phosphate for the biomass synthesis. Glycerol, erythritol, and xylitol seem to be involved in osmoregulation. Mannitol was produced when the catabolic reduction of charge was high. Its production involves the enzyme NAD-dependent mannitol-1-phosphate dehydrogenase and seems to be the main cytosolic route for the NADH reoxidation during oxygen limitation. PMID:16718677

  13. Activity-induced tissue oxygenation changes in rat cerebellar cortex: interplay of postsynaptic activation and blood flow

    PubMed Central

    Offenhauser, Nikolas; Thomsen, Kirsten; Caesar, Kirsten; Lauritzen, Martin

    2005-01-01

    Functional neuroimaging relies on the robust coupling between neuronal activity, metabolism and cerebral blood flow (CBF), but the physiological basis of the neuroimaging signals is still poorly understood. We examined the mechanisms of activity-dependent changes in tissue oxygenation in relation to variations in CBF responses and postsynaptic activity in rat cerebellar cortex. To increase synaptic activity we stimulated the monosynaptic, glutamatergic climbing fibres that excite Purkinje cells via AMPA receptors. We used local field potentials to indicate synaptic activity, and recorded tissue oxygen partial pressure (Ptiss,O2) by polarographic microelectrodes, and CBF using laser-Doppler flowmetry. The disappearance rate of oxygen in the tissue increased linearly with synaptic activity. This indicated that, without a threshold, oxygen consumption increased as a linear function of synaptic activity. The reduction in Ptiss,O2 preceded the rise in CBF. The time integral (area) of the negative Ptiss,O2 response increased non-linearly showing saturation at high levels of synaptic activity, concomitant with a steep rise in CBF. This was accompanied by a positive change in Ptiss,O2. Neuronal nitric oxide synthase inhibition enhanced the initial negative Ptiss,O2 response (‘dip’), while attenuating the evoked CBF increase and positive Ptiss,O2 response equally. This indicates that increases in CBF counteract activity-induced reductions in Ptiss,O2, and suggests the presence of a tissue oxygen reserve. The changes in Ptiss,O2 and CBF were strongly attenuated by AMPA receptor blockade. Our findings suggest an inverse relationship between negative Ptiss,O2 and CBF responses, and provide direct in vivo evidence for a tight coupling between activity in postsynaptic AMPA receptors and cerebellar oxygen consumption. PMID:15774524

  14. Metabolic Activity of Bacteria at High Pressure

    NASA Astrophysics Data System (ADS)

    Picard, A.; Daniel, I.; Oger, P.

    2008-12-01

    a depth of marine sediment of 500 m, or even beneath a water column of 6 km in surface sediments. This suggests that the metabolic activity of surface microorganisms that receive nutrients through sea water percolation into the deeper parts of the sediment, or that sink with the sediment, may represent a significant fraction of the total activity observed in subsurface environments. The present results indicate also that cells in stationary phase at HHP, which preclude growth, can still have a short-term metabolic activity independent of the growth-related activity. Consequently, surface microorganisms have the ability to impact significantly and rapidly on biogeochemical cycles in deep environments.

  15. Metabolism of reactive oxygen species and reactive nitrogen species in pepper (Capsicum annuum L.) plants under low temperature stress.

    PubMed

    Airaki, Morad; Leterrier, Marina; Mateos, Rosa M; Valderrama, Raquel; Chaki, Mounira; Barroso, Juan B; Del Río, Luis A; Palma, José M; Corpas, Francisco J

    2012-02-01

    Low temperature is an environmental stress that affects crop production and quality and regulates the expression of many genes, and the level of a number of proteins and metabolites. Using leaves from pepper (Capsicum annum L.) plants exposed to low temperature (8 °C) for different time periods (1 to 3 d), several key components of the metabolism of reactive nitrogen and oxygen species (RNS and ROS, respectively) were analysed. After 24 h of exposure at 8 °C, pepper plants exhibited visible symptoms characterized by flaccidity of stems and leaves. This was accompanied by significant changes in the metabolism of RNS and ROS with an increase of both protein tyrosine nitration (NO(2) -Tyr) and lipid peroxidation, indicating that low temperature induces nitrosative and oxidative stress. During the second and third days at low temperature, pepper plants underwent cold acclimation by adjusting their antioxidant metabolism and reverting the observed nitrosative and oxidative stress. In this process, the levels of the soluble non-enzymatic antioxidants ascorbate and glutathione, and the activity of the main NADPH-generating dehydrogenases were significantly induced. This suggests that ascorbate, glutathione and the NADPH-generating dehydrogenases have a role in the process of cold acclimation through their effect on the redox state of the cell. PMID:21414013

  16. Metabolic activity of subsurface life in deep-sea sediments.

    PubMed

    D'Hondt, Steven; Rutherford, Scott; Spivack, Arthur J

    2002-03-15

    Global maps of sulfate and methane in marine sediments reveal two provinces of subsurface metabolic activity: a sulfate-rich open-ocean province, and an ocean-margin province where sulfate is limited to shallow sediments. Methane is produced in both regions but is abundant only in sulfate-depleted sediments. Metabolic activity is greatest in narrow zones of sulfate-reducing methane oxidation along ocean margins. The metabolic rates of subseafloor life are orders of magnitude lower than those of life on Earth's surface. Most microorganisms in subseafloor sediments are either inactive or adapted for extraordinarily low metabolic activity. PMID:11896277

  17. The effect of electromagnetic radiation emitted by display screens on cell oxygen metabolism – in vitro studies

    PubMed Central

    Henrykowska, Gabriela A.; Pacholski, Krzysztof; Śmigielski, Janusz; Rutkowski, Maciej; Dziedziczak-Buczyńska, Maria; Buczyński, Andrzej

    2015-01-01

    Introduction Research studies carried out for decades have not solved the problem of the effect of electromagnetic radiation of various frequency and strength on the human organism. Due to this fact, we decided to investigate the changes taking place in human blood platelets under the effect of electromagnetic radiation (EMR) emitted by LCD monitors. Material and methods The changes of selected parameters of oxygen metabolism were measured, i.e. reactive oxygen species concentration, enzymatic activity of antioxidant defence proteins – superoxide dismutase (SOD-1) and catalase (CAT) – and malondialdehyde concentration (MDA). A suspension of human blood platelets was exposed to electromagnetic radiation of 1 kHz frequency and 150 V/m and 220 V/m intensity for 30 and 60 min. The level of changes of the selected parameters of oxidative stress was determined after the exposure and compared to the control samples (not exposed). Results The measurements revealed an increase of the concentration of reactive oxygen species. The largest increase of ROS concentration vs. the control sample was observed after exposure to EMF of 220 V/m intensity for 60 min (from x = 54.64 to x = 72.92). The measurement of MDA concentration demonstrated a statistically significant increase after 30-min exposure to an EMF of 220 V/m intensity in relation to the initial values (from x = 3.18 to x = 4.41). The enzymatic activity of SOD-1 decreased after exposure (the most prominent change was observed after 60-min and 220 V/m intensity from x = 3556.41 to x = 1084.83). The most significant change in activity of catalase was observed after 60 min and 220 v/m exposure (from x = 6.28 to x = 4.15). Conclusions The findings indicate that exposure to electromagnetic radiation of 1 kHz frequency and 150 V/m and 220 V/m intensity may cause adverse effects within blood platelets’ oxygen metabolism and thus may lead to physiological dysfunction of the organism. PMID:26788099

  18. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    SciTech Connect

    Souza, Sandra C.; Chau, Mary D.L.; Yang, Qing; Gauthier, Marie-Soleil; Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper; Dole, William P.

    2011-07-08

    Highlights: {yields} Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). {yields} ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. {yields} ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. {yields} Exposure of human adipocytes to fatty acids and (TNF{alpha}) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and

  19. Myocardial Reloading after Extracorporeal Membrane Oxygenation Alters Substrate Metabolism While Promoting Protein Synthesis

    SciTech Connect

    Kajimoto, Masaki; Priddy, Colleen M.; Ledee, Dolena; Xu, Chun; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-08-19

    Extracorporeal membrane oxygenation (ECMO) unloads the heart providing a bridge to recovery in children after myocardial stunning. Mortality after ECMO remains high.Cardiac substrate and amino acid requirements upon weaning are unknown and may impact recovery. We assessed the hypothesis that ventricular reloading modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis. Fourteen immature piglets (7.8-15.6 kg) were separated into 2 groups based on ventricular loading status: 8 hour-ECMO (UNLOAD) and post-wean from ECMO (RELOAD). We infused [2-13C]-pyruvate as an oxidative substrate and [13C6]-L-leucine, as a tracer of amino acid oxidation and protein synthesis into the coronary artery. RELOAD showed marked elevations in myocardial oxygen consumption above baseline and UNLOAD. Pyruvate uptake was markedly increased though RELOAD decreased pyruvate contribution to oxidative CAC metabolism.RELOAD also increased absolute concentrations of all CAC intermediates, while maintaining or increasing 13C-molar percent enrichment. RELOAD also significantly increased cardiac fractional protein synthesis rates by >70% over UNLOAD. Conclusions: RELOAD produced high energy metabolic requirement and rebound protein synthesis. Relative pyruvate decarboxylation decreased with RELOAD while promoting anaplerotic pyruvate carboxylation and amino acid incorporation into protein rather than to the CAC for oxidation. These perturbations may serve as therapeutic targets to improve contractile function after ECMO.

  20. Metaproteomics reveals differential modes of metabolic coupling among ubiquitous oxygen minimum zone microbes

    SciTech Connect

    Hawley, Alyse K.; Brewer, Heather M.; Norbeck, Angela D.; Pasa-Tolic, Ljiljana; Hallam, Steven J.

    2014-08-05

    Oxygen minimum zones (OMZs) are intrinsic water column features arising from respiratory oxygen demand during organic matter degradation in stratified marine waters. Currently OMZs are expanding due to global climate change. This expansion alters marine ecosystem function and the productivity of fisheries due to habitat compression and changes in biogeochemical cycling leading to fixed nitrogen loss and greenhouse gas production. Here we use metaproteomics to chart spatial and temporal patterns of gene expression along defined redox gradients in a seasonally anoxic fjord, Saanich Inlet to better understand microbial community responses to OMZ expansion. The expression of metabolic pathway components for nitrification, anaerobic ammonium oxidation (anammox), denitrification and inorganic carbon fixation predominantly co-varied with abundance and distribution patterns of Thaumarchaeota, Nitrospira, Planctomycetes and SUP05/ARCTIC96BD-19 Gammaproteobacteria. Within these groups, pathways mediating inorganic carbon fixation and nitrogen and sulfur transformations were differentially expressed across the redoxcline. Nitrification and inorganic carbon fixation pathways affiliated with Thaumarchaeota dominated dysoxic waters and denitrification, sulfur-oxidation and inorganic carbon fixation pathways affiliated with SUP05 dominated suboxic and anoxic waters. Nitrite-oxidation and anammox pathways affiliated with Nitrospina and Planctomycetes respectively, also exhibited redox partitioning between dysoxic and suboxic waters. The differential expression of these pathways under changing water column redox conditions has quantitative implications for coupled biogeochemical cycling linking different modes of inorganic carbon fixation with distributed nitrogen and sulfur-based energy metabolism extensible to coastal and open ocean OMZs.

  1. A NOVEL METABOLIC ACTIVATION PATHWAY FOR POLYCYCLIC AROMATIC HYDROCARBONS: REACTIVE OXYGEN SPECIES-MEDIATED DNA DAMAGE AND MORPHOLOGICAL CELL TRANSFORMATION IN MOUSE EMBRYO CELLS BY K-REGION DIOL METABOLITES

    EPA Science Inventory

    Benzo[ a ]pyrene (BP) is a well-studied polycyclic aromatic hydrocarbon (P AH) .Many
    mechanisms have been suggested to explain its carcinogenic activity, yet many questions still
    remain. K-region dihydrodiols (diols) ofPAHs are common metabolites and some are genotoxic. W...

  2. Modulation of bryostatin 1 muscle toxicity by nifedipine: effects on muscle metabolism and oxygen supply.

    PubMed Central

    Thompson, C. H.; Macaulay, V. M.; O'Byrne, K. J.; Kemp, G. J.; Wilner, S. M.; Talbot, D. C.; Harris, A. L.; Radda, G. K.

    1996-01-01

    Bryostatin 1, an anti-neoplastic agent and protein kinase C activator, has dose-limiting toxicity manifesting as myalgia. Studies in vivo have suggested that this myalgia may be caused by impairment of oxidative metabolism as mitochondrial capacity, muscle reoxygenation and proton washout from muscle are reduced by bryostatin, possibly as a result of vasoconstriction. To investigate these mechanisms further, and to enable use of bryostatin for prolonged periods, the effect of a vasodilator on the established effects of bryostatin on calf metabolism was studied using 31P magnetic resonance spectroscopy and near infrared spectroscopy. Six patients with disseminated melanoma were examined on four occasions: before and 1 week after initiation of long-term nifedipine (10 mg twice daily) treatment and then 4 and 48 h after bryostatin infusion (25 micrograms m(-2)). Nifedipine impaired muscle oxidative metabolism but had no effect on proton efflux or muscle reoxygenation rate. In the presence of nifedipine, two of the effects of bryostatin, impaired reoxygenation rate and reduced proton efflux, were abolished, but the impaired mitochondrial activity remained. These results show that nifedipine counteracted the vasoconstrictive effect of bryostatin 1. However, because nifedipine itself had an unexpected effect on mitochondrial metabolism, it was not possible to assess whether nifedipine modified bryostatin's effect on this variable. There was no additive detrimental effect of bryostatin on mitochondrial metabolism and nifedipine did not reduce the clinical toxicity of bryostatin 1, which cannot therefore be due to vasoconstriction. PMID:8630272

  3. Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo

    PubMed Central

    Salin, Karine; Auer, Sonya K.; Rudolf, Agata M.; Anderson, Graeme J.; Cairns, Andrew G.; Mullen, William; Hartley, Richard C.; Selman, Colin; Metcalfe, Neil B.

    2015-01-01

    There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2 in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. PMID:26382073

  4. Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo.

    PubMed

    Salin, Karine; Auer, Sonya K; Rudolf, Agata M; Anderson, Graeme J; Cairns, Andrew G; Mullen, William; Hartley, Richard C; Selman, Colin; Metcalfe, Neil B

    2015-09-01

    There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2 in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. PMID:26382073

  5. Brain metabolism and oxygenation in healthy pigs receiving hypoventilation and hyperoxia.

    PubMed

    Rostami, Elham; Rocksén, David; Ekberg, Neda R; Goiny, Michel; Ungerstedt, Urban

    2013-12-01

    Modulation in ventilatory settings is one of the approaches and interventions used to treat and prevent secondary brain damage after traumatic brain injury (TBI). Here we investigate the effect of hyperoxia in combination with hypoventilation on brain oxygenation, metabolism and intracranial pressure. Twelve pigs were divided into three groups; group1-100% hyperoxia (n=4), group 2-100% hyperoxia and 20% decrease in minute volume (MV) (n=4) and group 3-100% hyperoxia and 50% decrease in MV (n=4). Neither of the ventilator settings affected the lactate/pyruvate ratio significantly. However, there was a significant decrease of brain lactate (2.6±1.7 to 1.8±1.6mM) and a rapid and marked increase in brain oxygenation (7.9±0.7 to 61.3±17.6mmHg) in group 3. Intracranial pressure (ICP) was not significantly affected in this group, however, the ICP increased significantly in group 2 with 100% hyperoxia plus 20% reduction in minute volume. We conclude that hyperoxia in combination with 50% decrease in MV showed pronounced increase in partial brain oxygen tension (pbrO2) and decrease in brain lactate. The ventilatory modification, used in this study should be considered for further investigation as a possible therapeutic intervention for TBI patients. PMID:24013004

  6. Spermine metabolism and radiation-derived reactive oxygen species for future therapeutic implications in cancer: an additive or adaptive response.

    PubMed

    Amendola, Roberto; Cervelli, Manuela; Tempera, Giampiero; Fratini, Emiliano; Varesio, Luigi; Mariottini, Paolo; Agostinelli, Enzo

    2014-03-01

    Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalyzed reactions. Thus, combination therapy targeting polyamine metabolism could represent a promising strategy to fight hyper-proliferative disease. The aim of this work is to discuss and evaluate whether the presence of a DNA damage provoked by enzymatic ROS overproduction may act as an additive or adaptive response upon radiation and combination of hyperthermia with lysosomotropic compounds may improve the cytocidal effect of polyamines oxidation metabolites. Low level of X-irradiations delivers challenging dose of damage and an additive or adaptive response with the chronic damage induced by spermine oxidase overexpression depending on the deficiency of the DNA repair mechanisms. Since reactive oxygen species lead to membrane destabilization and cell death, we discuss the effects of BSAO and spermine association in multidrug resistant cells that resulted more sensitive to spermine metabolites than their wild-type counterparts, due to an increased mitochondrial activity. Since mammal spermine oxidase is differentially activated in a tissue specific manner, and cancer cells can differ in term of DNA repair capability, it could be of interest to open a scientific debate to use combinatory treatments to alter spermine metabolism and deliver differential response. PMID:23999645

  7. OXYGEN UTILIZATION IN ACTIVATED SLUDGE PLANTS: SIMULATION AND MODEL CALIBRATION

    EPA Science Inventory

    The objective of the research described in the report is to apply recent advances in activated sludge process modeling to the simulation of oxygen utilization rates in full scale activated sludge treatment plants. This is accomplished by calibrating the International Association ...

  8. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis.

    PubMed

    Kasischke, Karl A; Vishwasrao, Harshad D; Fisher, Patricia J; Zipfel, Warren R; Webb, Watt W

    2004-07-01

    We have found that two-photon fluorescence imaging of nicotinamide adenine dinucleotide (NADH) provides the sensitivity and spatial three-dimensional resolution to resolve metabolic signatures in processes of astrocytes and neurons deep in highly scattering brain tissue slices. This functional imaging reveals spatiotemporal partitioning of glycolytic and oxidative metabolism between astrocytes and neurons during focal neural activity that establishes a unifying hypothesis for neurometabolic coupling in which early oxidative metabolism in neurons is eventually sustained by late activation of the astrocyte-neuron lactate shuttle. Our model integrates existing views of brain energy metabolism and is in accord with known macroscopic physiological changes in vivo. PMID:15232110

  9. Event-related changes of the prefrontal cortex oxygen delivery and metabolism during driving measured by hyperspectral fNIRS

    PubMed Central

    Nosrati, Reyhaneh; Vesely, Kristin; Schweizer, Tom A.; Toronov, Vladislav

    2016-01-01

    Recent technological advancements in optical spectroscopy allow for the construction of hyperspectral (broadband) portable tissue oximeters. In a series of our recent papers we have shown that hyperspectral NIRS (hNIRS) has similar or better capabilities in the absolute tissue oximetry as frequency-domain NIRS, and that hNIRS is also very efficient in measuring temporal changes in tissue hemoglobin concentration and oxygenation. In this paper, we extend the application of hNIRS to the measurement of event-related hemodynamic and metabolic functional cerebral responses during simulated driving. In order to check if hNIRS can detect event-related changes in the brain, we measured the concentration changes of oxygenated (HbO2) and deoxygenated (HHb) hemoglobin and of the oxidized state of cytochrome c oxidase, on the right and left prefrontal cortices (PFC) simultaneously during simulated driving on sixteen healthy right-handed participants (aged between 22–32). We used our in-house hNIRS system based on a portable spectrometer with cooled CCD detector and a driving simulator with a fully functional steering wheel and foot pedals. Each participant performed different driving tasks and participants were distracted during some driving conditions by asking general knowledge true/false questions. Our findings suggest that more complex driving tasks (non-distracted) deactivate PFC while distractions during driving significantly activate PFC, which is in agreement with previous fMRI results. Also, we found the changes in the redox state of the cytochrome C oxidase to be very consistent with those in the concentrations of HbO2 and HHb. Overall our findings suggest that in addition to the suitability of absolute tissue oximetry, hyperspectral NIRS may also offer advantages in functional brain imaging. In particular, it can be used to measure the metabolic functional brain activity during actual driving. PMID:27446658

  10. Event-related changes of the prefrontal cortex oxygen delivery and metabolism during driving measured by hyperspectral fNIRS.

    PubMed

    Nosrati, Reyhaneh; Vesely, Kristin; Schweizer, Tom A; Toronov, Vladislav

    2016-04-01

    Recent technological advancements in optical spectroscopy allow for the construction of hyperspectral (broadband) portable tissue oximeters. In a series of our recent papers we have shown that hyperspectral NIRS (hNIRS) has similar or better capabilities in the absolute tissue oximetry as frequency-domain NIRS, and that hNIRS is also very efficient in measuring temporal changes in tissue hemoglobin concentration and oxygenation. In this paper, we extend the application of hNIRS to the measurement of event-related hemodynamic and metabolic functional cerebral responses during simulated driving. In order to check if hNIRS can detect event-related changes in the brain, we measured the concentration changes of oxygenated (HbO2) and deoxygenated (HHb) hemoglobin and of the oxidized state of cytochrome c oxidase, on the right and left prefrontal cortices (PFC) simultaneously during simulated driving on sixteen healthy right-handed participants (aged between 22-32). We used our in-house hNIRS system based on a portable spectrometer with cooled CCD detector and a driving simulator with a fully functional steering wheel and foot pedals. Each participant performed different driving tasks and participants were distracted during some driving conditions by asking general knowledge true/false questions. Our findings suggest that more complex driving tasks (non-distracted) deactivate PFC while distractions during driving significantly activate PFC, which is in agreement with previous fMRI results. Also, we found the changes in the redox state of the cytochrome C oxidase to be very consistent with those in the concentrations of HbO2 and HHb. Overall our findings suggest that in addition to the suitability of absolute tissue oximetry, hyperspectral NIRS may also offer advantages in functional brain imaging. In particular, it can be used to measure the metabolic functional brain activity during actual driving. PMID:27446658

  11. Oxygen tension limits nitric oxide synthesis by activated macrophages.

    PubMed Central

    McCormick, C C; Li, W P; Calero, M

    2000-01-01

    Previous studies have established that constitutive calcium-dependent ('low-output') nitric oxide synthase (NOS) is regulated by oxygen tension. We have investigated the role of oxygen tension in the synthesis of NO by the 'high-output' calcium-independent NOS in activated macrophages. Hypoxia increased macrophage NOS gene expression in the presence of one additional activator, such as lipopolysaccharide or interferon-gamma, but not in the presence of both. Hypoxia markedly reduced the synthesis of NO by activated macrophages (as measured by accumulation of nitrite and citrulline), such that, at 1% oxygen tension, NO accumulation was reduced by 80-90%. The apparent K(m) for oxygen calculated from cells exposed to a range of oxygen tensions was found to be 10.8%, or 137 microM, O(2) This value is considerably higher than the oxygen tension in tissues, and is virtually identical to that reported recently for purified recombinant macrophage NOS. The decrease in NO synthesis did not appear to be due to diminished arginine or cofactor availability, since arginine transport and NO synthesis during recovery in normoxia were normal. Analysis of NO synthesis during hypoxia as a function of extracellular arginine indicated that an altered V(max), but not K(m)(Arg), accounted for the observed decrease in NO synthesis. We conclude that oxygen tension regulates the synthesis of NO in macrophages by a mechanism similar to that described previously for the calcium-dependent low-output NOS. Our data suggest that oxygen tension may be an important physiological regulator of macrophage NO synthesis in vivo. PMID:10970783

  12. Evidence for metabolic activity of airborne bacteria

    NASA Technical Reports Server (NTRS)

    Chatigny, M. A.; Wolochow, H.

    1974-01-01

    Aerosols of the bacterium Serratia marcescens, and of uniformly labeled C-14 glucose were produced simultaneously and mixed in tubing leading to an aerosol chamber. During a subsequent period of about 5 hrs, carbon dioxide was produced metabolically within the chamber, and labeled material incorporated within the suspended particles first increased then decreased. This constitutes the first direct evidence of microbial metabolism of bacteria suspended in the air.

  13. Evidence of Circadian Rhythm, Oxygen Regulation Capacity, Metabolic Repeatability and Positive Correlations between Forced and Spontaneous Maximal Metabolic Rates in Lake Sturgeon Acipenser fulvescens

    PubMed Central

    Svendsen, Jon C.; Genz, Janet; Anderson, W. Gary; Stol, Jennifer A.; Watkinson, Douglas A.; Enders, Eva C.

    2014-01-01

    Animal metabolic rate is variable and may be affected by endogenous and exogenous factors, but such relationships remain poorly understood in many primitive fishes, including members of the family Acipenseridae (sturgeons). Using juvenile lake sturgeon (Acipenser fulvescens), the objective of this study was to test four hypotheses: 1) A. fulvescens exhibits a circadian rhythm influencing metabolic rate and behaviour; 2) A. fulvescens has the capacity to regulate metabolic rate when exposed to environmental hypoxia; 3) measurements of forced maximum metabolic rate (MMRF) are repeatable in individual fish; and 4) MMRF correlates positively with spontaneous maximum metabolic rate (MMRS). Metabolic rates were measured using intermittent flow respirometry, and a standard chase protocol was employed to elicit MMRF. Trials lasting 24 h were used to measure standard metabolic rate (SMR) and MMRS. Repeatability and correlations between MMRF and MMRS were analyzed using residual body mass corrected values. Results revealed that A. fulvescens exhibit a circadian rhythm in metabolic rate, with metabolism peaking at dawn. SMR was unaffected by hypoxia (30% air saturation (O2sat)), demonstrating oxygen regulation. In contrast, MMRF was affected by hypoxia and decreased across the range from 100% O2sat to 70% O2sat. MMRF was repeatable in individual fish, and MMRF correlated positively with MMRS, but the relationships between MMRF and MMRS were only revealed in fish exposed to hypoxia or 24 h constant light (i.e. environmental stressor). Our study provides evidence that the physiology of A. fulvescens is influenced by a circadian rhythm and suggests that A. fulvescens is an oxygen regulator, like most teleost fish. Finally, metabolic repeatability and positive correlations between MMRF and MMRS support the conjecture that MMRF represents a measure of organism performance that could be a target of natural selection. PMID:24718688

  14. Reactive Oxygen Species Mediated Activation of a Dormant Singlet Oxygen Photosensitizer: From Autocatalytic Singlet Oxygen Amplification to Chemicontrolled Photodynamic Therapy.

    PubMed

    Durantini, Andrés M; Greene, Lana E; Lincoln, Richard; Martínez, Sol R; Cosa, Gonzalo

    2016-02-01

    Here we show the design, preparation, and characterization of a dormant singlet oxygen ((1)O2) photosensitizer that is activated upon its reaction with reactive oxygen species (ROS), including (1)O2 itself, in what constitutes an autocatalytic process. The compound is based on a two segment photosensitizer-trap molecule where the photosensitizer segment consists of a Br-substituted boron-dipyrromethene (BODIPY) dye. The trap segment consists of the chromanol ring of α-tocopherol, the most potent naturally occurring lipid soluble antioxidant. Time-resolved absorption, fluorescence, and (1)O2 phosphorescence studies together with fluorescence and (1)O2 phosphorescence emission quantum yields collected on Br2B-PMHC and related bromo and iodo-substituted BODIPY dyes show that the trap segment provides a total of three layers of intramolecular suppression of (1)O2 production. Oxidation of the trap segment with ROS restores the sensitizing properties of the photosensitizer segment resulting in ∼40-fold enhancement in (1)O2 production. The juxtaposed antioxidant (chromanol) and prooxidant (Br-BODIPY) antagonistic chemical activities of the two-segment compound enable the autocatalytic, and in general ROS-mediated, activation of (1)O2 sensitization providing a chemical cue for the spatiotemporal control of (1)O2.The usefulness of this approach to selectively photoactivate the production of singlet oxygen in ROS stressed vs regular cells was successfully tested via the photodynamic inactivation of a ROS stressed Gram negative Escherichia coli strain. PMID:26789198

  15. A non-invasive fluorescence-based oxygen sensor and platform for studying cell responses to metabolic agents in real-time

    NASA Astrophysics Data System (ADS)

    Buchapudi, Koutilya Reddy

    A fluorescence-based sensor in a transverse flow/stop measurement platform has been developed to determine real-time changes in oxygen consumption rates for cell metabolic studies. The oxygen sensitive fluorophore platinum octaethylporphyrin was embedded in a cellulose acetate matrix and affixed to a fiber optic bundle, which provided for transmission of the excitation and emission wavelengths of the film. The fiber optic bundle was sealed in a sensor head that can be used in standard 24-well plates common to research labs. The utility of the sensor and sensing platform were determined by measuring the changes in oxygen consumption rates of Candida albicans during 90/30 s flow/stop cycles. Exposure of these cells to metabolic antagonists and an enhancer showed the expected decrease and increase in oxygen consumption rates in real time. The applicability of the platform to biological studies is illustrated by determination of synergistic activities between antifungal drugs and fluoride exposure in Candida albicans. The robustness of the fluorophore film is demonstrated by perfusion with different media and analyte conditions in the absence of cells. For stop cycle time intervals less than 1 minute the sensor exhibited a rapid and fairly linear change in fluorescence intensity to changing oxygen concentrations in the measurement chamber. Flow cycle fluorescence intensities were used as a baseline correction for treating the stop cycle fluorescence peaks.

  16. Estimation of dynamic metabolic activity in micro-tissue cultures from sensor recordings with an FEM model.

    PubMed

    Pfister, Cornelia; Forstmeier, Christian; Biedermann, Johannes; Schermuly, Julia; Demmel, Franz; Wolf, Peter; Kaspers, Bernd; Brischwein, Martin

    2016-05-01

    We estimated the dynamic cell metabolic activity and the distribution of the pH value and oxygen concentration in tissue samples cultured in vitro by using real-time sensor records and a numerical simulation of the underlying reaction-diffusion processes. As an experimental tissue model, we used chicken spleen slices. A finite element method model representing the biochemical processes and including the relevant sensor data was set up. By fitting the calculated results to the measured data, we derived the spatiotemporal values of the pH value, the oxygen concentration and the absolute metabolic activity (extracellular acidification and oxygen uptake rate) of the samples. Notably, the location of the samples in relation to the sensors has a great influence on the detectable metabolic rates. The long-term vitality of the tissue samples strongly depends on their size. We further discuss the benefits and limitations of the model. PMID:26296800

  17. The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation.

    PubMed

    Cerniglia, George J; Dey, Souvik; Gallagher-Colombo, Shannon M; Daurio, Natalie A; Tuttle, Stephen; Busch, Theresa M; Lin, Alexander; Sun, Ramon; Esipova, Tatiana V; Vinogradov, Sergei A; Denko, Nicholas; Koumenis, Constantinos; Maity, Amit

    2015-08-01

    Inhibition of the PI3K/Akt pathway decreases hypoxia within SQ20B human head and neck cancer xenografts. We set out to understand the molecular mechanism underlying this observation. We measured oxygen consumption using both a Clark electrode and an extracellular flux analyzer. We made these measurements after various pharmacologic and genetic manipulations. Pharmacologic inhibition of the PI3K/mTOR pathway or genetic inhibition of Akt/PI3K decreased the oxygen consumption rate (OCR) in vitro in SQ20B and other cell lines by 30% to 40%. Pharmacologic inhibition of this pathway increased phosphorylation of the E1α subunit of the pyruvate dehydrogenase (PDH) complex on Ser293, which inhibits activity of this critical gatekeeper of mitochondrial respiration. Expressing wild-type PTEN in a doxycycline-inducible manner in a cell line with mutant PTEN led to an increase in PDH-E1α phosphorylation and a decrease in OCR. Pretreatment of SQ20B cells with dichloroacetate (DCA), which inhibits PDH-E1α phosphorylation by inhibiting dehydrogenase kinases (PDK), reversed the decrease in OCR in response to PI3K/Akt/mTOR inhibition. Likewise, introduction of exogenous PDH-E1α that contains serine to alanine mutations, which can no longer be regulated by phosphorylation, also blunted the decrease in OCR seen with PI3K/mTOR inhibition. Our findings highlight an association between the PI3K/mTOR pathway and tumor cell oxygen consumption that is regulated in part by PDH phosphorylation. These results have important implications for understanding the effects of PI3K pathway activation in tumor metabolism and also in designing cancer therapy trials that use inhibitors of this pathway. PMID:25995437

  18. Oxygen Sensing via the Ethylene Response Transcription Factor RAP2.12 Affects Plant Metabolism and Performance under Both Normoxia and Hypoxia.

    PubMed

    Paul, Melanie Verena; Iyer, Srignanakshi; Amerhauser, Carmen; Lehmann, Martin; van Dongen, Joost T; Geigenberger, Peter

    2016-09-01

    Subgroup-VII-ethylene-response-factor (ERF-VII) transcription factors are involved in the regulation of hypoxic gene expression and regulated by proteasome-mediated proteolysis via the oxygen-dependent branch of the N-end-rule pathway. While research into ERF-VII mainly focused on their role to regulate anoxic gene expression, little is known on the impact of this oxygen-sensing system in regulating plant metabolism and growth. By comparing Arabidopsis (Arabidopsis thaliana) plants overexpressing N-end-rule-sensitive and insensitive forms of the ERF-VII-factor RAP2.12, we provide evidence that oxygen-dependent RAP2.12 stability regulates central metabolic processes to sustain growth, development, and anoxic resistance of plants. (1) Under normoxia, overexpression of N-end-rule-insensitive Δ13RAP2.12 led to increased activities of fermentative enzymes and increased accumulation of fermentation products, which were accompanied by decreased adenylate energy states and starch levels, and impaired plant growth and development, indicating a role of oxygen-regulated RAP2.12 degradation to prevent aerobic fermentation. (2) In Δ13RAP2.12-overexpressing plants, decreased carbohydrate reserves also led to a decrease in anoxic resistance, which was prevented by external Suc supply. (3) Overexpression of Δ13RAP2.12 led to decreased respiration rates, changes in the levels of tricarboxylic acid cycle intermediates, and accumulation of a large number of amino acids, including Ala and γ-amino butyric acid, indicating a role of oxygen-regulated RAP2.12 abundance in controlling the flux-modus of the tricarboxylic acid cycle. (4) The increase in amino acids was accompanied by increased levels of immune-regulatory metabolites. These results show that oxygen-sensing, mediating RAP2.12 degradation is indispensable to optimize metabolic performance, plant growth, and development under both normoxic and hypoxic conditions. PMID:27372243

  19. Bioirrigation impacts on sediment respiration and microbial metabolic activity

    NASA Astrophysics Data System (ADS)

    Baranov, V. A.; Lewandowski, J.; Romeijn, P.; Krause, S.

    2015-12-01

    Some bioturbators build tubes in the sediment and pump water through their burrows (ventilation). Oxygen is transferred through the burrow walls in the adjacent sediment (bioirrigation). Bioirrigation is playing a pivotal role in the mediation of biogeochemical processes in lake sediments and has the potential to enhance nutrient cycling. The present study investigates the impact of bioirrigation on lake sediment metabolism, respiration rates and in particular, the biogeochemical impacts of bioirrigation intensity as a function of organism density. We therefore apply the bioreactive Resazurin/Resorufin smart tracer system for quantifying the impact of different densities of Chironomidae (Diptera) larvae (0-2112 larvae/m2) on lake sediment respiration in a microcosm experiment. Tracer decay has been found to be proportional to the amount of the aerobic respiration at the sediment-water interface. Tracer transformation was in good agreement with Chironomidae density (correlation, r=0.9). Tracer transformation rates (and sediment respiration) were found to be correlated to Chironomidae density, with highest transformation rates observed in the microcosms with highest density of 2112 larvae/m2. This relationship was not linear though, with sediment respiration rates at the highest larvae densities declining from the linear trend predicted from lower and intermediate larvae density-respiration relationships. We interpret this effect as a density dependent suppression of the Chironomid's metabolic activity. The observations of this study have implications for eutrophied lakes with high densities of bioirrigators. Despite high density of bioirrigirrigating benthos, mineralization of the organic matter in such habitats would likely be lower than in lakes with intermediate densities of the bioturbators.

  20. Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism.

    PubMed

    Dienel, Gerald A; Cruz, Nancy F

    2016-07-01

    Aerobic glycolysis occurs during brain activation and is characterized by preferential up-regulation of glucose utilization compared with oxygen consumption even though oxygen level and delivery are adequate. Aerobic glycolysis is a widespread phenomenon that underlies energetics of diverse brain activities, such as alerting, sensory processing, cognition, memory, and pathophysiological conditions, but specific cellular functions fulfilled by aerobic glycolysis are poorly understood. Evaluation of evidence derived from different disciplines reveals that aerobic glycolysis is a complex, regulated phenomenon that is prevented by propranolol, a non-specific β-adrenoceptor antagonist. The metabolic pathways that contribute to excess utilization of glucose compared with oxygen include glycolysis, the pentose phosphate shunt pathway, the malate-aspartate shuttle, and astrocytic glycogen turnover. Increased lactate production by unidentified cells, and lactate dispersal from activated cells and lactate release from the brain, both facilitated by astrocytes, are major factors underlying aerobic glycolysis in subjects with low blood lactate levels. Astrocyte-neuron lactate shuttling with local oxidation is minor. Blockade of aerobic glycolysis by propranolol implicates adrenergic regulatory processes including adrenal release of epinephrine, signaling to brain via the vagus nerve, and increased norepinephrine release from the locus coeruleus. Norepinephrine has a powerful influence on astrocytic metabolism and glycogen turnover that can stimulate carbohydrate utilization more than oxygen consumption, whereas β-receptor blockade 're-balances' the stoichiometry of oxygen-glucose or -carbohydrate metabolism by suppressing glucose and glycogen utilization more than oxygen consumption. This conceptual framework may be helpful for design of future studies to elucidate functional roles of preferential non-oxidative glucose utilization and glycogen turnover during brain

  1. Prolyl Hydroxylase PHD3 Activates Oxygen-dependent Protein Aggregation

    PubMed Central

    Rantanen, Krista; Pursiheimo, Juha; Högel, Heidi; Himanen, Virpi; Metzen, Eric

    2008-01-01

    The HIF prolyl hydroxylases (PHDs/EGLNs) are central regulators of the molecular responses to oxygen availability. One isoform, PHD3, is expressed in response to hypoxia and causes apoptosis in oxygenated conditions in neural cells. Here we show that PHD3 forms subcellular aggregates in an oxygen-dependent manner. The aggregation of PHD3 was seen under normoxia and was strongly reduced under hypoxia or by the inactivation of the PHD3 hydroxylase activity. The PHD3 aggregates were dependent on microtubular integrity and contained components of the 26S proteasome, chaperones, and ubiquitin, thus demonstrating features that are characteristic for aggresome-like structures. Forced expression of the active PHD3 induced the aggregation of proteasomal components and activated apoptosis under normoxia in HeLa cells. The apoptosis was seen in cells prone to PHD3 aggregation and the PHD3 aggregation preceded apoptosis. The data demonstrates the cellular oxygen sensor PHD3 as a regulator of protein aggregation in response to varying oxygen availability. PMID:18337469

  2. Excited states in the active media of oxygen - iodine lasers

    SciTech Connect

    Azyazov, V N

    2009-11-30

    A review of investigations of kinetic processes in active media oxygen - iodine lasers (OILs) performed in the last decade is presented. The mechanisms of pumping and quenching of electronically and vibrationally excited O{sub 2} and I{sub 2} molecules are considered, and dissociation mechanisms of I{sub 2} in the active medium of the OIL are analysed. The values of kinetic constants of processes proceeding in the active media of OILs are recommended. (review)

  3. Optical measurement of cerebral hemodynamics and oxygen metabolism in neonates with congenital heart defects

    NASA Astrophysics Data System (ADS)

    Durduran, Turgut; Zhou, Chao; Buckley, Erin M.; Kim, Meeri N.; Yu, Guoqiang; Choe, Regine; Gaynor, J. William; Spray, Thomas L.; Durning, Suzanne M.; Mason, Stefanie E.; Montenegro, Lisa M.; Nicolson, Susan C.; Zimmerman, Robert A.; Putt, Mary E.; Wang, Jiongjiong; Greenberg, Joel H.; Detre, John A.; Yodh, Arjun G.; Licht, Daniel J.

    2010-05-01

    We employ a hybrid diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS) monitor for neonates with congenital heart disease (n=33). The NIRS-DCS device measured changes during hypercapnia of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations; cerebral blood flow (rCBFDCS); and oxygen metabolism (rCMRO2). Concurrent measurements with arterial spin-labeled magnetic resonance imaging (rCBFASL-MRI, n=12) cross-validate rCBFDCS against rCBFASL-MRI, showing good agreement (R=0.7, p=0.01). The study demonstrates use of NIRS-DCS on a critically ill neonatal population, and the results indicate that the optical technology is a promising clinical method for monitoring this population.

  4. Extracorporeal delivery of rAAV with metabolic exchange and oxygenation.

    PubMed

    Bieber, Scott; Halldorson, Jeffrey B; Finn, Eric; Ahmad, Suhail; Chamberlain, Jeffrey S; Odom, Guy L

    2013-01-01

    Over the past decade much progress has been made towards the treatment of disease with recombinant adeno-associated viral vectors, ranging from cancer to muscular dystrophies, and autoimmune diseases to cystic fibrosis. Given inherent challenges of vector delivery we developed a system incorporating commercially available dialysis equipment. This concept was evaluated in vitro utilizing rAAV expressing the reporter gene human placental alkaline phosphatase. A number of pre-circulating conditions were assessed. Vector recovery was evaluated by quantitative vector genome analysis and cellular transduction assays. A dialysis circulation time course was established, and results were recorded across varied conditions ranging from approximately 2 to 90% retention of viable vector. This approach is unique in that it focuses on efficient localized, isolated and continual delivery of vector to target tissues, provides for the preservation of tissue integrity with dialysis for metabolic exchange and allows for the transfer of oxygen through a secondary membrane post-dialysis. PMID:23528884

  5. AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators

    PubMed Central

    Moreno-Arriola, Elizabeth; EL Hafidi, Mohammed; Ortega-Cuéllar, Daniel; Carvajal, Karla

    2016-01-01

    Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co-activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases. PMID:26824904

  6. Effect of Nitric Oxide on the Oxygen Metabolism and Growth of E. faecalis

    PubMed Central

    Nishikawa, Tomoko; F. Sato, Eisuke; Choudhury, Tina; Nagata, Kumiko; Kasahara, Emiko; Matsui, Hiroshi; Watanabe, Kunihiko; Inoue, Masayasu

    2009-01-01

    Gastro-intestinal mucosal cells have a potent mechanism to eliminate a variety of pathogens using enzymes that generate reactive oxygen species and/or nitric oxide (NO). However, a large number of bacteria survive in the intestine of human subjects. Enterococcus faecalis (E. faecalis) is a Gram-positive bacterium that survives not only in the intestinal lumen but also within macrophages generating NO. It has been reported that E. faecalis generated the superoxide radical (O2−). To elucidate the role of O2− and NO in the mechanism for the pathogen surviving in the intestine and macrophages, we studied the role and metabolism of O2− and NO in and around E. faecalis. Kinetic analysis revealed that E. faecalis generated 0.5 µmol O2−/min/108 cells in a glucose-dependent manner as determined using the cytochrome c reduction method. The presence of NOC12, an NO donor, strongly inhibited the growth of E. faecalis without affecting in the oxygen consumption. However, the growth rate of NOC12-pretreated E. faecalis in NO-free medium was similar to that of untreated cells. Western blotting analysis revealed that the NOC12-treated E. faecalis revealed a large amount of nitrotyrosine-posititive proteins; the amounts of the modified proteins were higher in cytosol than in membranes. These observations suggested that O2− generated by E. faecalis reacted with NO to form peroxinitrite (ONOO−) that preferentially nitrated tyrosyl residues in cytosolic proteins, thereby reversibly inhibited cellular growth. Since E. faecalis survives even within macrophages expressing NO synthase, similar metabolism of O2− and NO may occur in and around phagocytized macrophages. PMID:19308272

  7. A unique cytosolic activity related but distinct from NQO1 catalyses metabolic activation of mitomycin C

    PubMed Central

    Joseph, P; Jaiswal, A K

    2000-01-01

    Mitomycin C (MMC) is a prototype bioreductive drug employed to treat a variety of cancers including head and neck cancer. Among the various enzymes, dicoumarol inhibitable cytosolic NAD(P)H:quinone oxidoreductase1 (NQO1) was shown to catalyse bioreductive activation of MMC leading to cross-linking of the DNA and cytotoxicity. However, the role of NQO1 in metabolic activation of MMC has been disputed. In this report, we present cellular and animal models to demonstrate that NQO1 may play only a minor role in metabolic activation of MMC. We further demonstrate that bioreductive activation of MMC is catalysed by a unique cytosolic activity which is related but distinct from NQO1. Chinese hamster ovary (CHO) cells were developed that permanently express higher levels of cDNA-derived NQO1. These cells showed significantly increased protection against menadione toxicity. However, they failed to demonstrate higher cytotoxicity due to exposure to MMC under oxygen (normal air) or hypoxia, as compared to the wild-type control CHO cells. Disruption of the NQO1 gene by homologous recombination generated NQO1–/– mice that do not express the NQO1 gene resulting in the loss of NQO1 protein and activity. The cytosolic fractions from liver and colon tissues of NQO1–/– mice showed similar amounts of DNA cross-linking upon exposure to MMC, as observed in NQO1+/+ mice. The unique cytosolic activity that activated MMC in cytosolic fractions of liver and colon tissues of NQO1–/– mice was designated as cytosolic MMC reductase. This activity, like NQO1, was inhibited by dicoumarol and immunologically related to NQO1. © 2000 Cancer Research Campaign PMID:10755406

  8. MRI-based methods for quantification of the cerebral metabolic rate of oxygen.

    PubMed

    Rodgers, Zachary B; Detre, John A; Wehrli, Felix W

    2016-07-01

    The brain depends almost entirely on oxidative metabolism to meet its significant energy requirements. As such, the cerebral metabolic rate of oxygen (CMRO2) represents a key measure of brain function. Quantification of CMRO2 has helped elucidate brain functional physiology and holds potential as a clinical tool for evaluating neurological disorders including stroke, brain tumors, Alzheimer's disease, and obstructive sleep apnea. In recent years, a variety of magnetic resonance imaging (MRI)-based CMRO2 quantification methods have emerged. Unlike positron emission tomography - the current "gold standard" for measurement and mapping of CMRO2 - MRI is non-invasive, relatively inexpensive, and ubiquitously available in modern medical centers. All MRI-based CMRO2 methods are based on modeling the effect of paramagnetic deoxyhemoglobin on the magnetic resonance signal. The various methods can be classified in terms of the MRI contrast mechanism used to quantify CMRO2: T2*, T2', T2, or magnetic susceptibility. This review article provides an overview of MRI-based CMRO2 quantification techniques. After a brief historical discussion motivating the need for improved CMRO2 methodology, current state-of-the-art MRI-based methods are critically appraised in terms of their respective tradeoffs between spatial resolution, temporal resolution, and robustness, all of critical importance given the spatially heterogeneous and temporally dynamic nature of brain energy requirements. PMID:27089912

  9. Increased oxygen radical-dependent inactivation of metabolic enzymes by liver microsomes after chronic ethanol consumption

    SciTech Connect

    Dicker, E.; Cederbaum, A.I. )

    1988-10-01

    Enzymatic and nonenzymatic mixed-function oxidase systems have been shown to generate an oxidant that catalyzes the inactivation of glutamine synthetase and other metabolic enzymes. Recent studies have shown that microsomes isolated from rats chronically fed ethanol generate reactive oxygen intermediates at elevated rates compared with controls. Microsomes from rats fed ethanol were found to be more effective than control microsomes in catalyzing the inactivation of enzymes added to the incubation system. The enzymes studied were alcohol dehydrogenase, lactic dehydrogenase, and pyruvate kinase. The inactivation process by both types of microsomal preparations was sensitive to catalase and glutathione plus glutathione peroxidase, but was not affected by superoxide dismutase or hydroxyl radical scavengers. Iron was required for the inactivation of added enzymes; microsomes from the rats fed ethanol remained more effective than control microsomes in catalyzing the inactivation of enzymes in the absence or presence of several ferric complexes. The inactivation of enzymes was enhanced by the addition of menadione or paraquat to the microsomes, and rates of inactivation were higher with the microsomes from the ethanol-fed rats. The enhanced generation of reactive oxygen intermediates and increased inactivation of enzymes by microsomes may contribute toward the hepatotoxic effects associated with ethanol consumption.

  10. Effect of ginkgolide B on brain metabolism and tissue oxygenation in severe haemorrhagic stroke

    PubMed Central

    Chi, Chun-Ling; Shen, Dong-Fang; Wang, Peng-Jun; Li, Hu-Lun; Zhang, Li

    2015-01-01

    Ginkgolide B, a diterpene, is an herbal constituent isolated from the leaves of Ginkgo biloba tree. The present study demonstrates the effect of ginkgolide B in osmotherapy on brain metabolism and tissue oxygenation. Multimodality monitoring including intracranial pressure (ICP), cerebral perfusion pressure (CPP), partial pressure of brain tissue oxygen (PbtO2), lactate/pyruvate ratio (LPR) and microdialysis were employed to study the effect of ginkgolide B osmotherapy. The results demonstrated that administration of 15% solution of ginkgolide B to the comatose patients with raised ICP (> 20 mm Hg) and resistant to standard therapy led to a significant decrease in ICP. The cerebral microdialysis was used to compare mean arterial blood pressure (MAP), ICP, CPP, PbtO2, brain lactate, pyruvate and glucose level after hourly intervals starting 3 h before and up to 4 h after hyperosmolar therapy. There was a decrease in ICP in 45 min from 23 ± 14 mm Hg (P < 0.001) to 18 ± 24 mm Hg and increase in CPP after 1 h of gingkolide B infusion from 74 ± 18 to 85 ± 22 mm Hg (P < 0.002). However there was no significant effect on MAP but PbtO2 was maintained in the range of 22-26. The peak lactate/pyruvate ratio was recorded at the time of initiation of osmotherapy (44 ± 20) with an 18% decrease over 2 h following gingkolide B therapy. Also the brain glucose remained unaffected. PMID:26064244

  11. Metaproteomics reveals differential modes of metabolic coupling among ubiquitous oxygen minimum zone microbes

    PubMed Central

    Hawley, Alyse K.; Brewer, Heather M.; Norbeck, Angela D.; Paša-Tolić, Ljiljana; Hallam, Steven J.

    2014-01-01

    Marine oxygen minimum zones (OMZs) are intrinsic water column features arising from respiratory oxygen demand during organic matter degradation in stratified waters. Currently OMZs are expanding due to global climate change with resulting feedback on marine ecosystem function. Here we use metaproteomics to chart spatial and temporal patterns of gene expression along defined redox gradients in a seasonally stratified fjord to better understand microbial community responses to OMZ expansion. The expression of metabolic pathway components for nitrification, anaerobic ammonium oxidation (anammox), denitrification, and inorganic carbon fixation were differentially expressed across the redoxcline and covaried with distribution patterns of ubiquitous OMZ microbes including Thaumarchaeota, Nitrospina, Nitrospira, Planctomycetes, and SUP05/ARCTIC96BD-19 Gammaproteobacteria. Nitrification and inorganic carbon fixation pathways affiliated with Thaumarchaeota dominated dysoxic waters, and denitrification, sulfur oxidation, and inorganic carbon fixation pathways affiliated with the SUP05 group of nitrate-reducing sulfur oxidizers dominated suboxic and anoxic waters. Nitrifier nitrite oxidation and anammox pathways affiliated with Nirospina, Nitrospira, and Planctomycetes, respectively, also exhibited redox partitioning between dysoxic and suboxic waters. The numerical abundance of SUP05 proteins mediating inorganic carbon fixation under anoxic conditions suggests that SUP05 will become increasingly important in global ocean carbon and nutrient cycling as OMZs expand. PMID:25053816

  12. Metaproteomics reveals differential modes of metabolic coupling among ubiquitous oxygen minimum zone microbes.

    PubMed

    Hawley, Alyse K; Brewer, Heather M; Norbeck, Angela D; Paša-Tolić, Ljiljana; Hallam, Steven J

    2014-08-01

    Marine oxygen minimum zones (OMZs) are intrinsic water column features arising from respiratory oxygen demand during organic matter degradation in stratified waters. Currently OMZs are expanding due to global climate change with resulting feedback on marine ecosystem function. Here we use metaproteomics to chart spatial and temporal patterns of gene expression along defined redox gradients in a seasonally stratified fjord to better understand microbial community responses to OMZ expansion. The expression of metabolic pathway components for nitrification, anaerobic ammonium oxidation (anammox), denitrification, and inorganic carbon fixation were differentially expressed across the redoxcline and covaried with distribution patterns of ubiquitous OMZ microbes including Thaumarchaeota, Nitrospina, Nitrospira, Planctomycetes, and SUP05/ARCTIC96BD-19 Gammaproteobacteria. Nitrification and inorganic carbon fixation pathways affiliated with Thaumarchaeota dominated dysoxic waters, and denitrification, sulfur oxidation, and inorganic carbon fixation pathways affiliated with the SUP05 group of nitrate-reducing sulfur oxidizers dominated suboxic and anoxic waters. Nitrifier nitrite oxidation and anammox pathways affiliated with Nirospina, Nitrospira, and Planctomycetes, respectively, also exhibited redox partitioning between dysoxic and suboxic waters. The numerical abundance of SUP05 proteins mediating inorganic carbon fixation under anoxic conditions suggests that SUP05 will become increasingly important in global ocean carbon and nutrient cycling as OMZs expand. PMID:25053816

  13. Obesity, Metabolic Syndrome, and Physical Activity.

    ERIC Educational Resources Information Center

    Yeater, Rachel

    2000-01-01

    Discusses the scope of the problem of obesity in the United States, noting the health risks associated with being overweight or obese (e.g., gallstones, osteoarthritis, sleep apnea, and colon cancer); discussing the association of type-II diabetes mellitus with obesity; examining the effects of exercise on metabolic disease; and looking at…

  14. High altitude may alter oxygen availability and renal metabolism in diabetics as measured by hyperpolarized [1-(13)C]pyruvate magnetic resonance imaging.

    PubMed

    Laustsen, Christoffer; Lycke, Sara; Palm, Fredrik; Østergaard, Jakob A; Bibby, Bo M; Nørregaard, Rikke; Flyvbjerg, Allan; Pedersen, Michael; Ardenkjaer-Larsen, Jan H

    2014-07-01

    The kidneys account for about 10% of the whole body oxygen consumption, whereas only 0.5% of the total body mass. It is known that intrarenal hypoxia is present in several diseases associated with development of kidney disease, including diabetes, and when renal blood flow is unaffected. The importance of deranged oxygen metabolism is further supported by deterioration of kidney function in patients with diabetes living at high altitude. Thus, we argue that reduced oxygen availability alters renal energy metabolism. Here, we introduce a novel magnetic resonance imaging (MRI) approach to monitor metabolic changes associated with diabetes and oxygen availability. Streptozotocin diabetic and control rats were given reduced, normal, or increased inspired oxygen in order to alter tissue oxygenation. The effects on kidney oxygen metabolism were studied using hyperpolarized [1-(13)C]pyruvate MRI. Reduced inspired oxygen did not alter renal metabolism in the control group. Reduced oxygen availability in the diabetic kidney altered energy metabolism by increasing lactate and alanine formation by 23% and 34%, respectively, whereas the bicarbonate flux was unchanged. Thus, the increased prevalence and severity of nephropathy in patients with diabetes at high altitudes may originate from the increased sensitivity toward inspired oxygen. This increased lactate production shifts the metabolic routs toward hypoxic pathways. PMID:24352155

  15. Integrating the pulse of the riverscape and landscape: modelling stream metabolism using continuous dissolved oxygen measurements

    NASA Astrophysics Data System (ADS)

    Soulsby, C.; Birkel, C.; Malcolm, I.; Tetzlaff, D.

    2013-12-01

    Stream metabolism is a fundamental pulse of the watershed which reflects both the in-stream environment and its connectivity with the wider landscape. We used high quality, continuous (15 minute), long-term (>3 years) measurement of stream dissolved oxygen (DO) concentrations to estimate photosynthetic productivity (P) and system respiration (R) in forest and moorland reaches of an upland stream with peaty soils. We calibrated a simple five parameter numerical oxygen mass balance model driven by radiation, stream and air temperature, stream depth and re-aeration capacity. This used continuous 24-hour periods for the whole time series to identify behavioural simulations where DO simulations were re-produced sufficiently well to be considered reasonable representations of ecosystem functioning. Results were evaluated using a seasonal Regional Sensitivity Analysis and a co-linearity index for parameter sensitivity. This showed that >95 % of the behavioural models for the moorland and forest sites were identifiable and able to infer in-stream processes from the DO time series for almost half of all measured days at both sites. Days when the model failed to simulate DO levels successfully provided invaluable insight into time periods when other factors are likely to disrupt in-stream metabolic processes; these include (a) flood events when scour reduces the biomass of benthic primary producers, (b) periods of high water colour in higher summer/autumn flows and (c) low flow periods when hyporheic respiration is evident. Monthly P/R ratios <1 indicate a heterotrophic system with both sites exhibiting similar temporal patterns; with a maximum in February and a second peak during summer months. However, the estimated net ecosystem productivity (NPP) suggests that the moorland reach without riparian tree cover is likely to be a much larger source of carbon to the atmosphere (122 mmol C m-2 d-1) compared to the forested reach (64 mmol C m-2 d-1). The study indicates the value

  16. A novel Bayesian approach to accounting for uncertainty in fMRI-derived estimates of cerebral oxygen metabolism fluctuations.

    PubMed

    Simon, Aaron B; Dubowitz, David J; Blockley, Nicholas P; Buxton, Richard B

    2016-04-01

    Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2' as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2', we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2'-based estimate of the metabolic response to CO2 of 1.4%, and R2'- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2'-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2. PMID:26790354

  17. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling

    PubMed Central

    Sena, Laura A.; Li, Sha; Jairaman, Amit; Prakriya, Murali; Ezponda, Teresa; Hildeman, David A.; Wang, Chyung-Ru; Schumacker, Paul T.; Licht, Jonathan D.; Perlman, Harris; Bryce, Paul J.; Chandel, Navdeep S.

    2013-01-01

    SUMMARY It is widely appreciated that T cells increase glycolytic flux during activation, however the role of mitochondrial flux is unclear. Here we have shown that mitochondrial metabolism, in the absence of glucose metabolism, was sufficient to support interleukin-2 (IL-2) induction. Furthermore, we used mice with reduced mitochondrial reactive oxygen species (mROS) production in T cells (T-Uqcrfs−/− mice) to show that mitochondria are required for T cell activation to produce mROS for activation of nuclear factor of activated T cells (NFAT) and subsequent IL-2 induction. These mice could not induce antigen-specific expansion of T cells in vivo, however Uqcrfs1−/− T cells retained the ability to proliferate in vivo under lymphopenic conditions. This suggests that Uqcrfs1−/− T cells were not lacking bioenergetically, but rather lacked specific ROS-dependent signaling events needed for antigen-specific expansion. Thus, mitochondrial metabolism is a critical component of T cell activation through production of complex III ROS. PMID:23415911

  18. Metabolically-Derived Human Ventilation Rates: A Revised Approach Based Upon Oxygen Consumption Rates (External Review Draft)

    EPA Science Inventory

    EPA has released a draft report entitled, Metabolically-Derived Human Ventilation Rates: A Revised Approach Based Upon Oxygen Consumption Rates, for independent external peer review and public comment. NCEA published the Exposure Factors Handbook in 1997. This comprehens...

  19. Plankton community respiration, net ecosystem metabolism, and oxygen dynamics on the Louisiana continental shelf: implications for hypoxia

    EPA Science Inventory

    We conducted a multi-year study of the Louisiana continental shelf (LCS) to better understand the linkages between water column metabolism and the formation of hypoxia (dissolved oxygen <2 mg L-1) in the region. Water column community respiration rates (WR) were measured on 10 cr...

  20. Improving estimates of ecosystem metabolism by reducing effects of tidal advection on dissolved oxygen time series-Abstract

    EPA Science Inventory

    Continuous time series of dissolved oxygen (DO) have been used to compute estimates of metabolism in aquatic ecosystems. Central to this open water or "Odum" method is the assumption that the DO time is not strongly affected by advection and that effects due to advection or mixin...

  1. Vinpocetine modulates metabolic activity and function during retinal ischemia.

    PubMed

    Nivison-Smith, Lisa; O'Brien, Brendan J; Truong, Mai; Guo, Cindy X; Kalloniatis, Michael; Acosta, Monica L

    2015-05-01

    Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues. PMID:25696811

  2. Chemoprotective activity of boldine: modulation of drug-metabolizing enzymes.

    PubMed

    Kubínová, R; Machala, M; Minksová, K; Neca, J; Suchý, V

    2001-03-01

    Possible chemoprotective effects of the naturally occurring alkaloid boldine, a major alkaloid of boldo (Peumus boldus Mol.) leaves and bark, including in vitro modulations of drug-metabolizing enzymes in mouse hepatoma Hepa-1 cell line and mouse hepatic microsomes, were investigated. Boldine manifested inhibition activity on hepatic microsomal CYP1A-dependent 7-ethoxyresorufin O-deethylase and CYP3A-dependent testosterone 6 beta-hydroxylase activities and stimulated glutathione S-transferase activity in Hepa-1 cells. In addition to the known antioxidant activity, boldine could decrease the metabolic activation of other xenobiotics including chemical mutagens. PMID:11265593

  3. Slowed muscle oxygen uptake kinetics with raised metabolism are not dependent on blood flow or recruitment dynamics.

    PubMed

    Wüst, Rob C I; McDonald, James R; Sun, Yi; Ferguson, Brian S; Rogatzki, Matthew J; Spires, Jessica; Kowalchuk, John M; Gladden, L Bruce; Rossiter, Harry B

    2014-04-15

    Oxygen uptake kinetics (τVO2) are slowed when exercise is initiated from a raised metabolic rate. Whether this reflects the recruitment of muscle fibres differing in oxidative capacity, or slowed blood flow (Q) kinetics is unclear. This study determined τVO2 in canine muscle in situ, with experimental control over muscle activation and Q during contractions initiated from rest and a raised metabolic rate. The gastrocnemius complex of nine anaesthetised, ventilated dogs was isolated and attached to a force transducer. Isometric tetanic contractions (50 Hz; 200 ms duration) via supramaximal sciatic nerve stimulation were used to manipulate metabolic rate: 3 min stimulation at 0.33 Hz (S1), followed by 3 min at 0.67 Hz (S2). Circulation was initially intact (SPON), and subsequently isolated for pump-perfusion (PUMP) above the greatest value in SPON. Muscle VO2 was determined contraction-by-contraction using an ultrasonic flowmeter and venous oximeter, and normalised to tension-time integral (TTI). τVO2/TTI and τQ were less in S1SPON (mean ± s.d.: 13 ± 3 s and 12 ± 4 s, respectively) than in S2SPON (29 ± 19 s and 31 ± 13 s, respectively; P < 0.05). τVO2/TTI was unchanged by pump-perfusion (S1PUMP, 12 ± 4 s; S2PUMP, 24 ± 6 s; P < 0.001) despite increased O2 delivery; at S2 onset, venous O2 saturation was 21 ± 4% and 65 ± 5% in SPON and PUMP, respectively. VO2 kinetics remained slowed when contractions were initiated from a raised metabolic rate despite uniform muscle stimulation and increased O2 delivery. The intracellular mechanism may relate to a falling energy state, approaching saturating ADP concentration, and/or slowed mitochondrial activation; but further study is required. These data add to the evidence that muscle VO2 control is more complex than previously suggested. PMID:24469073

  4. Metabolic activity, experiment M171. [space flight effects on human metabolism

    NASA Technical Reports Server (NTRS)

    Michel, E. L.; Rummel, J. A.

    1973-01-01

    The Skylab metabolic activity experiment determines if man's metabolic effectiveness in doing mechanical work is progressively altered by a simulated Skylab environment, including environmental factors such as slightly increased pCO2. This test identified several hardware/procedural anomalies. The most important of these were: (1) the metabolic analyzer measured carbon dioxide production and expired water too high; (2) the ergometer load module failed under continuous high workload conditions; (3) a higher than desirable number of erroneous blood pressure measurements were recorded; (4) vital capacity measurements were unreliable; and (5) anticipated crew personal exercise needs to be more structured.

  5. Quiescence in Artemia franciscana embryos: reversible arrest of metabolism and gene expression at low oxygen levels.

    PubMed

    Hand, S C

    1998-04-01

    Depression of the production and consumption of cellular energy appears to be a prerequisite for the survival of prolonged bouts of anoxia. A correlation exists between the degree of metabolic depression under anoxia and the duration of anoxia tolerance. In the case of brine shrimp (Artemia franciscana) embryos, oxygen deprivation induces a reversible quiescent state that can be tolerated for several years with substantial survivorship. A global arrest of cytoplasmic translation accompanies the transition into anoxia, and rates of protein synthesis in mitochondria from these embryos appears to be markedly reduced in response to anoxia. Previous evidence suggests that the acute acidification of intracellular pH (pHi) by over 1.0 unit during the transition into anoxia contributes to the depression of biosynthesis, but message limitation does not appear to play a role in the down-regulation in either cellular compartment. The ontogenetic increase in mRNA levels for a mitochondrial-encoded subunit of cytochrome c oxidase (COX I) and for nuclear-encoded actin is blocked by anoxia and aerobic acidosis (artificial quiescence imposed by intracellular acidification under aerobic conditions). Further, the levels of COX I and actin mRNA do not decline appreciably during 6 h bouts of quiescence, even though protein synthesis is acutely arrested across this same period. Thus, the constancy of mRNA levels during quiescence indicates that reduced protein synthesis is not caused by message limitation but, instead, is probably controlled at the translational level. This apparent stabilization of mRNA under anoxia is mirrored in an extension of protein half-life. The ubiquitin-dependent pathway for protein degradation is depressed under anoxia and aerobic acidosis, as judged by the acute drop in levels of ubiquitin-conjugated proteins. Mitochondrial protein synthesis is responsive to both acidification of pHi and removal of oxygen per se. Matrix pH declines in parallel with pHi, and

  6. Metabolic physiology of the Humboldt squid, Dosidicus gigas: Implications for vertical migration in a pronounced oxygen minimum zone

    NASA Astrophysics Data System (ADS)

    Rosa, Rui; Seibel, Brad A.

    2010-07-01

    The Humboldt (or jumbo) squid, Dosidicus gigas, is an active predator endemic to the Eastern Pacific that undergoes diel vertical migrations into a pronounced oxygen minimum layer (OML). Here, we investigate the physiological mechanisms that facilitate these migrations and assess the associated costs and benefits. Exposure to hypoxic conditions equivalent to those found in the OML (∼10 μM O 2 at 10 °C) led to a significant reduction in the squid’s routine metabolic rate (RMR), from 8.9 to 1.6 μmol O 2 g -1 h -1 ( p < 0.05), and a concomitant increase in mantle muscle octopine levels (from 0.50 to 5.24 μmol g -1 tissue, p < 0.05). Enhanced glycolitic ATP production accounted for only 7.0% and 2.8% at 10 °C and 20 °C, respectively, of the energy deficit that resulted from the decline in aerobic respiration. The observed metabolic suppression presumably extends survival time in the OML by conserving the finite stores of fermentable substrate and avoiding the accumulation of the deleterious anaerobic end products in the tissues. RMR increased significantly with temperature ( p < 0.05), from 8.9 (at 10 °C) to 49.85 μmol O 2 g -1 h -1 (at 25 °C) which yielded a Q10 of 2.0 between 10 and 20 °C and 7.9 between 20 and 25 °C ( p < 0.05). These results suggest that 25 °C, although within the normal surface temperature range in the Gulf of California, is outside this species’ normal temperature range. By following the scattering layer into oxygen-enriched shallow water at night, D. gigas may repay any oxygen debt accumulated during the daytime. The dive to deeper water may minimize exposure to stressful surface temperatures when most prey have migrated to depth during the daytime. The physiological and ecological strategies demonstrated here may have facilitated the recent range expansion of this species into northern waters where expanding hypoxic zones prohibit competing top predators.

  7. Activated oxygen alters cerebral microvascular responses in newborn pigs

    SciTech Connect

    Leffler, C.W.; Busiia, D.W.; Armstead, W.M.; Mirro, R.; Thelin, O. )

    1990-02-26

    In piglets, cerebral ischemia/reperfusion blocks prostanoid dependent cerebral vasodilation to hypercapnia (CO{sub 2}) and hypotension but not prostanoid independent dilation to isoproterenol (Isu) or constriction to norepinephrine (NE). Ischemia/reperfusion increases activated-O{sub 2} production by piglet brains. Using cranial windows in piglets, the authors investigated the hypothesis that activated oxygen can block prostanoid dependent cerebral vasodilator responses to CO{sub 2} and hypotension without altering responses to Isu and NE. Exposure to an activated oxygen generating system of xanthine oxidase, hypoxanthine, and Fe that made about 3 times the activated-O{sub 2} on the brain surface as ischemia/reperfusion caused reversible pial arteriolar dilation. After exposure, pial arteriolar dilation was reduced to CO{sub 2} and hypotension but not to Isu. NE constrictor responses were also unaltered. H{sub 2}O{sub 2} or H{sub 2}O{sub 2} + Fe caused constriction followed by reversible dilation. After exposure, pial arteriolar dilation in response to CO{sub 2} and hypotension was not altered. However, addition of xanthine oxidase and hypoxanthine with H{sub 2}O{sub 2} and Fe totally eliminated pial arteriolar dilator responses to CO{sub 2} and hypotension but did not decrease dilation caused by Isu or constriction caused by NE. The authors conclude that activated oxygen could produce the altered prostanoid dependent pial arteriolar responses observed following ischemia in piglets.

  8. Preliminary Insights Into the Interplay Among Oxygen, Organic Carbon, and Microbial Metabolism in North Atlantic Subseafloor Sediment Communities

    NASA Astrophysics Data System (ADS)

    Amenabar, M. J.; Dore, J. E.; Spivack, A. J.; Murray, R. W.; D'Hondt, S.; Boyd, E. S.

    2015-12-01

    Deep marine sediments harbor abundant microbial cells that, if active, are likely to exert a strong influence on element biogeochemical cycling. However, our understanding of the fraction of cells that are active in situ and the metabolic processes that sustain them remain underexplored. Here we describe recent results of our studies aimed at unraveling the links between geochemical heterogeneity, cellular viability and synthesis, and metabolism along a vertical depth profile in sediment from four deep sites (>5 km beneath ocean surface) cored by R/V KNORR Expedition KN-223 in the North Atlantic (2014). These sediment columns exhibit varying levels of organic carbon and different vertical extents of oxygen (O2) penetration, which we hypothesize is due to variation in the extent of heterotrophic metabolism. We prepared most probable number (MPN) assays with acetate or peptone as electron donor and carbon source, and five different terminal electron acceptors (O2, NO3, SO4, MnO2, and ferrihydrite) with sediments from 4 to 5 depths in each of the four cores MPNs were similar for acetate- and peptone-amended cultures, regardless of electron acceptor, and generally decreased with depth in the sediment column. MPNs amended with O2 as electron acceptor were greater than MPNs amended with NO3, SO4, MnO2, and ferrihydrite in samples from all depths. Moreover, MPNs were higher for assays amended with O2 from cores where the depth of O2 penetration was shallow when compared to cores where O2 is predicted to penetrate to basement rock. These results are consistent with aerobic heterotrophs limiting the penetration of O2 in deep marine sediments, and thereby provide a mechanism to explain the relationship between low O2 penetrations in sediment cores with elevated organic carbon contents. We will also present results of our ongoing isotopic labeling experiments aimed at determining rates of DNA and protein synthesis as proxies for cell replication and productivity, respectively

  9. Metabolic profiling reveals ethylene mediated metabolic changes and a coordinated adaptive mechanism of 'Jonagold' apple to low oxygen stress.

    PubMed

    Bekele, Elias A; Beshir, Wasiye F; Hertog, Maarten L A T M; Nicolai, Bart M; Geeraerd, Annemie H

    2015-11-01

    Apples are predominantly stored in controlled atmosphere (CA) storage to delay ripening and prolong their storage life. Profiling the dynamics of metabolic changes during ripening and CA storage is vital for understanding the governing molecular mechanism. In this study, the dynamics of the primary metabolism of 'Jonagold' apples during ripening in regular air (RA) storage and initiation of CA storage was profiled. 1-Methylcyclopropene (1-MCP) was exploited to block ethylene receptors and to get insight into ethylene mediated metabolic changes during ripening of the fruit and in response to hypoxic stress. Metabolic changes were quantified in glycolysis, the tricarboxylic acid (TCA) cycle, the Yang cycle and synthesis of the main amino acids branching from these metabolic pathways. Partial least square discriminant analysis of the metabolic profiles of 1-MCP treated and control apples revealed a metabolic divergence in ethylene, organic acid, sugar and amino acid metabolism. During RA storage at 18°C, most amino acids were higher in 1-MCP treated apples, whereas 1-aminocyclopropane-1-carboxylic acid (ACC) was higher in the control apples. The initial response of the fruit to CA initiation was accompanied by an increase of alanine, succinate and glutamate, but a decline in aspartate. Furthermore, alanine and succinate accumulated to higher levels in control apples than 1-MCP treated apples. The observed metabolic changes in these interlinked metabolites may indicate a coordinated adaptive strategy to maximize energy production. PMID:26031836

  10. Optically based quantification of absolute cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution in rodents

    NASA Astrophysics Data System (ADS)

    Yaseen, Mohammad A.; Srinivasan, Vivek J.; Sakadžić, Sava; Vinogradov, Sergei A.; Boas, David A.

    2010-02-01

    Measuring oxygen delivery in brain tissue is important for identifying the pathophysiological changes associated with brain injury and various diseases such as cancer, stroke, and Alzheimer's disease. We have developed a multi-modal imaging system for minimally invasive measurement of cerebral oxygenation and blood flow in small animals with high spatial resolution. The system allows for simultaneous measurement of blood flow using Fourier-domain optical coherence tomography, and oxygen partial pressure (pO2) using either confocal or multiphoton phosphorescence lifetime imaging with exogenous porphyrin-based dyes sensitive to dissolved oxygen. Here we present the changes in pO2 and blood flow in superficial cortical vessels of Sprague Dawley rats in response to conditions such as hypoxia, hyperoxia, and functional stimulation. pO2 measurements display considerable heterogeneity over distances that cannot be resolved with more widely used oxygen-monitoring techniques such as BOLD-fMRI. Large increases in blood flow are observed in response to functional stimulation and hypoxia. Our system allows for quantification of cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution, providing a better understanding of metabolic dynamics during functional stimulation and under various neuropathologies. Ultimately, better insight into the underlying mechanisms of neuropathologies will facilitate the development of improved therapeutic strategies to minimize damage to brain tissue.

  11. Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis

    PubMed Central

    2010-01-01

    Background Metabolic flux profiling based on the analysis of distribution of stable isotope tracer in metabolites is an important method widely used in cancer research to understand the regulation of cell metabolism and elaborate new therapeutic strategies. Recently, we developed software Isodyn, which extends the methodology of kinetic modeling to the analysis of isotopic isomer distribution for the evaluation of cellular metabolic flux profile under relevant conditions. This tool can be applied to reveal the metabolic effect of proapoptotic drug edelfosine in leukemia Jurkat cell line, uncovering the mechanisms of induction of apoptosis in cancer cells. Results The study of 13C distribution of Jukat cells exposed to low edelfosine concentration, which induces apoptosis in ≤5% of cells, revealed metabolic changes previous to the development of apoptotic program. Specifically, it was found that low dose of edelfosine stimulates the TCA cycle. These metabolic perturbations were coupled with an increase of nucleic acid synthesis de novo, which indicates acceleration of biosynthetic and reparative processes. The further increase of the TCA cycle fluxes, when higher doses of drug applied, eventually enhance reactive oxygen species (ROS) production and trigger apoptotic program. Conclusion The application of Isodyn to the analysis of mechanism of edelfosine-induced apoptosis revealed primary drug-induced metabolic changes, which are important for the subsequent initiation of apoptotic program. Initiation of such metabolic changes could be exploited in anticancer therapy. PMID:20925932

  12. Localized hypothermia: impact on oxygenation, microregional perfusion, metabolic and bioenergetic status of subcutaneous rat tumours.

    PubMed Central

    Kelleher, D. K.; Nauth, C.; Thews, O.; Krueger, W.; Vaupel, P.

    1998-01-01

    The effect of localized hypothermia on microcirculatory and metabolic parameters in s.c. DS sarcomas on the hind foot dorsum of Sprague-Dawley rats was investigated. Tumours were cooled by superfusion of the tumour surface with cooled saline solution to 25 degrees C or 15 degrees C. Control tumours remained at 35 degrees C. These temperatures were maintained for 30 min. In tumour oxygenation measurements, hypothermia at 25 degrees C and 15 degrees C caused progressive decreases in the size of the fraction of pO2 measurements between 0 and 2.5 mmHg together with a reduction in pO2 variability. No significant changes in median or mean pO2 or in the fraction of pO2 measurements between 0 and 5 mmHg, and 0 and 10 mmHg were observed. Using laser Doppler flowmetry, red blood cell flux was found to decrease significantly upon 25 degrees C or 15 degrees C hypothermia treatment to 67% and 37% of starting values respectively, whereas no significant changes were seen in control tumours over the whole observation period. Viscosity was measured in blood and plasma samples over a range of temperatures and was found to increase with decreasing temperature. Assessment of tumour glucose levels showed an increased concentration of glucose following 15 degrees C hypothermia, an observation consistent with a 'slowing down' of glycolysis. No changes in lactate or adenylate phosphate levels were observed. As a way of improving tumour oxygenation, localized hypothermia may therefore be a useful means of radiosensitization. PMID:9662251

  13. Activation of molecular oxygen and the nature of the active oxygen species for CO oxidation on oxide supported Au catalysts.

    PubMed

    Widmann, D; Behm, R J

    2014-03-18

    Although highly dispersed Au catalysts with Au nanoparticles (NPs) of a few nanometers in diameter are well-known for their high catalytic activity for several oxidation and reduction reactions already at rather low temperatures for almost 30 years, central aspects of the reaction mechanism are still unresolved. While most studies focused on the active site, the active Au species, and the effect of the support material, the most crucial step during oxidation reactions, the activation of molecular oxygen and the nature of the resulting active oxygen species (Oact), received more attention just recently. This is topic of this Account, which focuses on the formation, location, and nature of the Oact species present on metal oxide supported Au catalysts under typical reaction conditions, at room temperature and above. It is mainly based on quantitative temporal analysis of products (TAP) reactor measurements, which different from most spectroscopic techniques are able to detect and quantify these species even at the extremely low concentrations present under realistic reaction conditions. Different types of pulse experiments were performed, during which the highly dispersed, realistic powder catalysts are exposed to very low amounts of reactants, CO and/or O2, in order to form and reactively remove Oact species and gain information on their formation, nature, and the active site for Oact formation. Our investigations have shown that the active oxygen species for CO oxidation on Au/TiO2 for reaction at 80 °C and higher is a highly stable atomic species, which at 80 °C is formed only at the perimeter of the Au-oxide interface and whose reactive removal by CO is activated, but not its formation. From these findings, it is concluded that surface lattice oxygen represents the Oact species for the CO oxidation. Accordingly, the CO oxidation proceeds via a Au-assisted Mars-van Krevelen mechanism, during which surface lattice oxygen close to the Au NPs is removed by reaction

  14. Removal of Biologically Active Organic Contaminants using Atomic Oxygen

    NASA Technical Reports Server (NTRS)

    Banks, Bruce A. (Inventor); Banks, Michael A. (Inventor); Banks, Eric B. (Inventor)

    2003-01-01

    Biomedical devices that are to come into contact with living tissue, such as prosthetic and other implants for the human body and the containers used to store and transport them, are together cleaned of non-living, but biologically active organic materials, including endotoxins such as lipopolysaccharides, and assembled into a hermetically sealed package without recontamination. This is achieved by cleaning both the device and package components together in an apparatus, which includes a hermetically sealed chamber, in which they are contacted with atomic oxygen which biocleans them, by oxidizing the biologically active organic materials. The apparatus also includes means for manipulating the device and container and hermetically sealing the cleaned device into the cleaned container to form the package. A calibrated witness coupon visually indicates whether or not the device and container have received enough exposure to the atomic oxygen to have removed the organic materials from their surfaces. Gamma radiation is then used to sterilize the device in the sealed container.

  15. Anatomical Grading for Metabolic Activity of Brown Adipose Tissue

    PubMed Central

    Becker, Anton S.; Nagel, Hannes W.; Wolfrum, Christian; Burger, Irene A.

    2016-01-01

    Background Recent advances in obesity research suggest that BAT activity, or absence thereof, may be an important factor in the growing epidemic of obesity and its manifold complications. It is thus important to assess larger populations for BAT-activating and deactivating factors. 18FDG-PET/CT is the standard method to detect and quantify metabolic BAT activity, however, the manual measurement is not suitable for large studies due to its time-consuming nature and poor reproducibility across different software and devices. Methodology/Main Findings In a retrospective study, 1060 consecutive scans of 1031 patients receiving a diagnostic 18FDG-PET/CT were examined for the presence of active BAT. Patients were classified according to a 3-tier system (supraclavicular, mediastinal, infradiaphragmatic) depending on the anatomical location of their active BAT depots, with the most caudal location being the decisive factor. The metabolic parameters (maximum activity, total volume and total glycolysis) were measured on a standard PET/CT workstation. Mean age of the population was 60±14.6y. 41.61% of patients were female. Metabolically active BAT was found in 53 patients (5.1%). Female, younger and leaner patients tended to have more active BAT, higher metabolic activity and more caudally active BAT. In total, 15 patients showed only supraclavicular, 27 additional mediastinal, and 11 infradiaphragmal activity. Interestingly, the activation of BAT always followed a cranio-caudal gradient. This anatomical pattern correlated with age and BMI as well as with all metabolic parameters, including maximum and total glycolysis (p<0.001). Conclusion Based on our data we propose a simple method to grade or quantify the degree of BAT amount/activity in patients based on the most caudally activated depot. As new modalities for BAT visualization may arise in the future, this system would allow direct comparability with other modalities, in contrary to the PET-metrics, which are

  16. Metabolic Agents that Enhance ATP can Improve Cognitive Functioning: A Review of the Evidence for Glucose, Oxygen, Pyruvate, Creatine, and L-Carnitine

    PubMed Central

    Owen, Lauren; Sunram-Lea, Sandra I.

    2011-01-01

    Over the past four or five decades, there has been increasing interest in the neurochemical regulation of cognition. This field received considerable attention in the 1980s, with the identification of possible cognition enhancing agents or “smart drugs”. Even though many of the optimistic claims for some agents have proven premature, evidence suggests that several metabolic agents may prove to be effective in improving and preserving cognitive performance and may lead to better cognitive aging through the lifespan. Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. There are a number of agents with the potential to improve metabolic activity. Research is now beginning to identify these various agents and delineate their potential usefulness for improving cognition in health and disease. This review provides a brief overview of the metabolic agents glucose, oxygen, pyruvate, creatine, and L-carnitine and their beneficial effects on cognitive function. These agents are directly responsible for generating ATP (adenosine triphosphate) the main cellular currency of energy. The brain is the most metabolically active organ in the body and as such is particularly vulnerable to disruption of energy resources. Therefore interventions that sustain adenosine triphosphate (ATP) levels may have importance for improving neuronal dysfunction and loss. Moreover, recently, it has been observed that environmental conditions and diet can affect transgenerational gene expression via epigenetic mechanisms. Metabolic agents might play a role in regulation of nutritional epigenetic effects. In summary, the reviewed metabolic agents represent a promising strategy for improving cognitive function and possibly slowing or preventing cognitive decline. PMID:22254121

  17. Charge transfer induced activity of graphene for oxygen reduction

    NASA Astrophysics Data System (ADS)

    Shen, Anli; Xia, Weijun; Zhang, Lipeng; Dou, Shuo; Xia, Zhenhai; Wang, Shuangyin

    2016-05-01

    Tetracyanoethylene (TCNE), with its strong electron-accepting ability, was used to dope graphene as a metal-free electrocatalyst for the oxygen reduction reaction (ORR). The charge transfer process was observed from graphene to TCNE by x-ray photoelectron spectroscopy and Raman characterizations. Our density functional theory calculations found that the charge transfer behavior led to an enhancement of the electrocatalytic activity for the ORR.

  18. Effects of MCI-186 upon neutrophil-derived active oxygens.

    PubMed

    Sumitomo, K; Shishido, N; Aizawa, H; Hasebe, N; Kikuchi, K; Nakamura, M

    2007-01-01

    Reactions of 3-methyl-1-phenyl-2-pyrazoline-5-one (MCI-186) with hypochlorous acid and superoxide were analysed by spectrophotometry and mass spectrometry. The results were applied to the neutrophil system to evaluate the scavenging activity of neutrophil-derived active oxygen species by MCI-186. MCI-186 reacted rapidly with hypochlorous acid (1 x 10(6) M(-1)s(-1)) to form a chlorinated intermediate, followed by a slow conversion to a new spectrum. MCI-186 consumed 3 moles of hypochlorous acid and did not react with superoxide. The newly synthesized fluorescence probes, 2-[6-(4'-amino)-phenoxy-3H-xanthen-3-on-9-yl]benzoic acid (APF) and 2-[6-(4'-hydroxy)phenoxy-3H-anthen-3-on-9-yl]benzoic acid (HPF) successfully detected neutrophil-derived active oxygens (Setsukinai K, Urano Y, Kakinuma K, Majima HJ, Nagano T. Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J Biol Chem 2003; 278: 3170-3175). The rate constants for the reaction of hypochlorous acid with MCI-186 and fluorescence probes was in the order of MCI-186 > APF > HPF. Fluorescence due to the oxidation of APF and HPF was observed with the stimulated neutrophils. The result that the intensity from APF oxidation was higher than that from HPF oxidation is compatible with reports that APF selectively reacts with hypochlorous acid. Fluorescence due to oxidation of both APF and HPF decreased when the reactions were carried out in the presence of a fluorescence probe and MCI-186 in a dose-dependent manner. These results indicate that MCI-186 effectively scavenges neutrophil-derived hypochlorous acid and other active oxygens. PMID:17705989

  19. [Relationships between reactive oxygen metabolism and endodormancy release of peach bud under short-term heating].

    PubMed

    Wang, Xiao-di; Wang, Hai-bo; Gao, Dong-sheng; Li, Jiang; Wang, Bao-liang; Liu, Feng-zhi

    2010-11-01

    Taking the 6-year-old peach "Shuguang" as test object, this paper studied the effects of short-term heating at 40 degrees C, 45 degrees C, and 50 degrees C on the bud livability, bud burst, reactive oxygen content, and activities of related enzymes in peach bud, aimed to investigate the regulation effect of short-term heating on the endodormancy release of peach bud. The results indicated that the effects of short-tern heating on the endodormancy release of peach bud were advanced by the postponement of treatment date, the increase of treatment temperature, and the prolonging of treatment time. On November 30, the regulation effect of heating at 40 degrees C was negative. Comparing with those under no-heating (CK), the date of endodormancy release was postponed, the bud burst, the O2-* and * OH production rates, the H2O2 content, and the activities of CAT and POD were lowered, and the SOD activity was improved. It was adverse under heating at 45 degrees C and 50 degrees C. On December 10, heating at 40 degrees C nearly had no obvious effect on the endodormancy release, while heating at 45 degrees C and 50 degrees C had the same effect as that on November 30, with the former being more superior to the latter. Correlation analysis indicated that the rapid increase of reactive oxygen might be the critical reason for the endodormancy release of peach bud. PMID:21360995

  20. Sequential activation of metabolic pathways: a dynamic optimization approach.

    PubMed

    Oyarzún, Diego A; Ingalls, Brian P; Middleton, Richard H; Kalamatianos, Dimitrios

    2009-11-01

    The regulation of cellular metabolism facilitates robust cellular operation in the face of changing external conditions. The cellular response to this varying environment may include the activation or inactivation of appropriate metabolic pathways. Experimental and numerical observations of sequential timing in pathway activation have been reported in the literature. It has been argued that such patterns can be rationalized by means of an underlying optimal metabolic design. In this paper we pose a dynamic optimization problem that accounts for time-resource minimization in pathway activation under constrained total enzyme abundance. The optimized variables are time-dependent enzyme concentrations that drive the pathway to a steady state characterized by a prescribed metabolic flux. The problem formulation addresses unbranched pathways with irreversible kinetics. Neither specific reaction kinetics nor fixed pathway length are assumed.In the optimal solution, each enzyme follows a switching profile between zero and maximum concentration, following a temporal sequence that matches the pathway topology. This result provides an analytic justification of the sequential activation previously described in the literature. In contrast with the existent numerical approaches, the activation sequence is proven to be optimal for a generic class of monomolecular kinetics. This class includes, but is not limited to, Mass Action, Michaelis-Menten, Hill, and some Power-law models. This suggests that sequential enzyme expression may be a common feature of metabolic regulation, as it is a robust property of optimal pathway activation. PMID:19412635

  1. The measurement of sequential changes in cerebral blood flow and oxygen metabolism by positron computed tomography with continuous inhalation of oxygen-15 labeled gases

    SciTech Connect

    Tanada, S.; Yonekura, Y.; Senda, M.; Nishimura, K.; Tamaki, N.; Saji, H.; Fujita, T.; Kobayashi, A.; Taki, W.; Ishikawa, M.

    1984-01-01

    The use of continuous inhalation of oxygen-15 labeled gases is a widely accepted method to measure regional cerebral blood flow (CBF) and oxygen metabolism (CMRO/sub 2/) with positron computed tomography (PCT). The purpose of this study is to evaluate the feasibility to measure sequential changes in CBF and CMRO/sub 2/ by PCT. The functional images of CBF, oxygen extraction fraction (OEF), and CMRO/sub 2/ were obtained using continuous inhalation of oxygen-15 labeled carbon dioxide and oxygen. The effects of spinal drainage in CBF and CMRO/sub 2/ were studied in patients with hydrocephalus following subarachnoid hemorrhage due to the rupture of intracranial aneurysm. Following the measurement in control state, 20 ml of cerebrospinal fluid (CSF) were withdrawn gradually through lumbar puncture, and sequential PCT scans were performed. CBF and CMRO/sub 2/ were markedly depressed in the case with hydrocephalus. The drainage of CSF significantly improved OEF and CMRO/sub 2/, whereas CBF remained depressed. In patients with chronic cerebrovascular disease, the changes in CBF were studied with inhalation of 5% carbon dioxide (CO/sub 2/). CO/sub 2/ loading demonstrated the increase in CBF, while poor regional increase was observed in ''moyamoya'' disease, which permitted the assessment of vascular response to the elevation of plasma CO/sub 2/. The authors preliminary work indicated the potential usefulness of sequential PCT to study the changes in CBF and CMRO/sub 2/ with various interventions.

  2. Adaptation of cerebral oxygen metabolism and blood flow and modulation of neurovascular coupling with prolonged stimulation in human visual cortex

    PubMed Central

    Moradi, Farshad; Buxton, Richard B

    2013-01-01

    Prolonged visual stimulation results in neurophysiologic and hemodynamic adaptation. However, the hemodynamic adaptation appears to be small compared to neural adaptation. It is not clear how the cerebral metabolic rate of oxygen (CMRO2) is affected by adaptation. We measured cerebral blood flow (CBF) and CMRO2 change in responses to peripheral stimulation either continuously, or intermittently (on/off cycles). A linear system’s response to the continuous input should be equal to the sum of the original response to the intermittent input and a version of that response shifted by half a cycle. The CMRO2 response showed a large non-linearity consistent with adaptation, the CBF response adapted to a lesser degree, and the blood oxygenation level dependent (BOLD) response was nearly linear. The metabolic response was coupled with a larger flow in the continuous condition than in the intermittent condition. Our results suggest that contrast adaptation improves energy economy of visual processing. However BOLD modulations may not accurately represent the underlying metabolic nonlinearity due to modulation of the coupling of blood flow and oxygen metabolism changes. PMID:23732885

  3. Heterogeneity in a Suburban River Network: Understanding the Impact of Fluvial Wetlands on Dissolved Oxygen and Metabolism in Headwater Streams

    NASA Astrophysics Data System (ADS)

    Cain, J. S.; Wollheim, W. M.; Sheehan, K.; Lightbody, A.

    2014-12-01

    Low dissolved oxygen content in rivers threatens fish populations, aquatic organisms, and the health of entire ecosystems. River systems with high fluvial wetland abundance and organic matter, may result in high metabolism that in conjunction with low re-aeration rates, lead to low oxygen conditions. Increasing abundance of beaver ponds in many areas may exacerbate this phenomenon. This research aims to understand the impact of fluvial wetlands, including beaver ponds, on dissolved oxygen (D.O.) and metabolism throughout the headwaters of the Ipswich R. watershed, MA, USA. In several fluvial wetland dominated systems, we measured diel D.O. and metabolism in the upstream inflow, the surface water transient storage zones of fluvial wetland sidepools, and at the outflow to understand how the wetlands modify dissolved oxygen. D.O. was also measured longitudinally along entire surface water flow paths (x-y km long) to determine how low levels of D.O. propagate downstream. Nutrient samples were also collected to understand how their behavior was related to D.O. behavior. Results show that D.O. in fluvial wetlands has large swings with periods of very low D.O. at night. D.O. swings were also seen in downstream outflow, though lagged and somewhat attenuated. Flow conditions affect the level of inundation and the subsequent effects of fluvial wetlands on main channel D.O.. Understanding the D.O. behavior throughout river systems has important implications for the ability of river systems to remove anthropogenic nitrogen.

  4. Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex.

    PubMed

    Mayhew, J; Johnston, D; Martindale, J; Jones, M; Berwick, J; Zheng, Y

    2001-06-01

    indicated changes in the diffusivity of the capillary bed, but in this case the changes were negative; i.e., oxygen transport from the capillary decreased relative to baseline under hypercapnia. Neither of the models could account for the differences between the hypercapnia and activation data when matched for equivalent flow changes. A modification to the models to allow non-null tissue oxygen concentrations that can be moderated by changes due to increased metabolic demand following increased neural activity is proposed. This modification would allow modulation of oxygen transport from the capillary bed (e.g., changes in diffusivity) by tissue oxygen tension and would allow a degree of decoupling of flow and oxygen delivery, which can encompass both the data from stimulation and from hypercapnia. PMID:11352604

  5. Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats.

    PubMed

    Hansen, M B; Olsen, N V; Hyldegaard, O

    2013-11-01

    Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose concentrations. HBOT has been shown to induce a delayed increase in whole blood CN concentrations, whereas OHCob may act as an intravascular CN scavenger. Additionally, HBOT may prevent respiratory distress and restore blood pressure during CN intoxication, an effect not seen with OHCob administration. In this report, we evaluated the combined effects of HBOT and OHCob on interstitial lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations, as well as in low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with subsequent stabilization of mean arterial blood pressure. The present findings indicate that a combined administration of OHCob and HBOT has a beneficial and persistent effect on the cerebral metabolism during CN intoxication. PMID:23970528

  6. Estrogen receptor alpha activation enhances mitochondrial function and systemic metabolism in high-fat-fed ovariectomized mice.

    PubMed

    Hamilton, Dale J; Minze, Laurie J; Kumar, Tanvi; Cao, Tram N; Lyon, Christopher J; Geiger, Paige C; Hsueh, Willa A; Gupte, Anisha A

    2016-09-01

    Estrogen impacts insulin action and cardiac metabolism, and menopause dramatically increases cardiometabolic risk in women. However, the mechanism(s) of cardiometabolic protection by estrogen remain incompletely understood. Here, we tested the effects of selective activation of E2 receptor alpha (ERα) on systemic metabolism, insulin action, and cardiac mitochondrial function in a mouse model of metabolic dysfunction (ovariectomy [OVX], insulin resistance, hyperlipidemia, and advanced age). Middle-aged (12-month-old) female low-density lipoprotein receptor (Ldlr)(-/-) mice were subjected to OVX or sham surgery and fed "western" high-fat diet (WHFD) for 3 months. Selective ERα activation with 4,4',4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl) (PPT), prevented weight gain, improved insulin action, and reduced visceral fat accumulation in WHFD-fed OVX mice. PPT treatment also elevated systemic metabolism, increasing oxygen consumption and core body temperature, induced expression of several metabolic genes such as peroxisome proliferator-activated receptor gamma, coactivator 1 alpha, and nuclear respiratory factor 1 in heart, liver, skeletal muscle, and adipose tissue, and increased cardiac mitochondrial function. Taken together, selective activation of ERα with PPT enhances metabolic effects including insulin resistance, whole body energy metabolism, and mitochondrial function in OVX mice with metabolic syndrome. PMID:27582063

  7. FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression

    PubMed Central

    Ferber, E C; Peck, B; Delpuech, O; Bell, G P; East, P; Schulze, A

    2012-01-01

    Forkhead transcription factors of the O class (FOXOs) are important targets of the phosphatidylinositol 3-kinase/Akt pathway, and are key regulators of the cell cycle, apoptosis and response to oxidative stress. FOXOs have been shown to have tumour suppressor function and are important for stem cell maintenance. We have performed a detailed analysis of the transcriptional programme induced in response to Forkhead-box protein O3a (FOXO3a) activation. We observed that FOXO3a activation results in the repression of a large number of nuclear-encoded genes with mitochondrial function. Repression of these genes was mediated by FOXO3a-dependent inhibition of c-Myc. FOXO3a activation also caused a reduction in mitochondrial DNA copy number, expression of mitochondrial proteins, respiratory complexes and mitochondrial respiratory activity. FOXO3a has been previously implicated in the detoxification of reactive oxygen species (ROS) through induction of manganese-containing superoxide dismutase (SOD2). We observed that reduction in ROS levels following FOXO3a activation was independent of SOD2, but required c-Myc inhibition. Hypoxia increases ROS production from the mitochondria, which is required for stabilisation of the hypoxia-inducible factor-1α (HIF-1α). FOXO3a activation blocked the hypoxia-dependent increase in ROS and prevented HIF-1α stabilisation. Our data suggest that FOXO factors regulate mitochondrial activity through inhibition of c-Myc function and alter the hypoxia response. PMID:22139133

  8. FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression.

    PubMed

    Ferber, E C; Peck, B; Delpuech, O; Bell, G P; East, P; Schulze, A

    2012-06-01

    Forkhead transcription factors of the O class (FOXOs) are important targets of the phosphatidylinositol 3-kinase/Akt pathway, and are key regulators of the cell cycle, apoptosis and response to oxidative stress. FOXOs have been shown to have tumour suppressor function and are important for stem cell maintenance. We have performed a detailed analysis of the transcriptional programme induced in response to Forkhead-box protein O3a (FOXO3a) activation. We observed that FOXO3a activation results in the repression of a large number of nuclear-encoded genes with mitochondrial function. Repression of these genes was mediated by FOXO3a-dependent inhibition of c-Myc. FOXO3a activation also caused a reduction in mitochondrial DNA copy number, expression of mitochondrial proteins, respiratory complexes and mitochondrial respiratory activity. FOXO3a has been previously implicated in the detoxification of reactive oxygen species (ROS) through induction of manganese-containing superoxide dismutase (SOD2). We observed that reduction in ROS levels following FOXO3a activation was independent of SOD2, but required c-Myc inhibition. Hypoxia increases ROS production from the mitochondria, which is required for stabilisation of the hypoxia-inducible factor-1α (HIF-1α). FOXO3a activation blocked the hypoxia-dependent increase in ROS and prevented HIF-1α stabilisation. Our data suggest that FOXO factors regulate mitochondrial activity through inhibition of c-Myc function and alter the hypoxia response. PMID:22139133

  9. Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming

    PubMed Central

    Li, Heng-Hong; Wang, Yi-wen; Chen, Renxiang; Zhou, Bin; Ashwell, Jonathan D.; Fornace, Albert J.

    2015-01-01

    Ionizing radiation has a variety of acute and long-lasting adverse effects on the immune system. Whereas measureable effects of radiation on immune cell cytotoxicity and population change have been well studied in human and animal models, little is known about the functional alterations of the surviving immune cells after ionizing radiation. The objective of this study was to delineate the effects of radiation on T cell function by studying the alterations of T cell receptor activation and metabolic changes in activated T cells isolated from previously irradiated animals. Using a global metabolomics profiling approach, for the first time we demonstrate that ionizing radiation impairs metabolic reprogramming of T cell activation, which leads to substantial decreases in the efficiency of key metabolic processes required for activation, such as glucose uptake, glycolysis, and energy metabolism. In-depth understanding of how radiation impacts T cell function highlighting modulation of metabolism during activation is not only a novel approach to investigate the pivotal processes in the shift of T cell homeostasis after radiation, it also may lead to new targets for therapeutic manipulation in the combination of radiotherapy and immune therapy. Given that appreciable effects were observed with as low as 10 cGy, our results also have implications for low dose environmental exposures. PMID:26078715

  10. Physical Activity, Metabolic Syndrome, and Overweight in Rural Youth

    ERIC Educational Resources Information Center

    Moore, Justin B.; Davis, Catherine L.; Baxter, Suzanne Domel; Lewis, Richard D.; Yin, Zenong

    2008-01-01

    Background: Research suggests significant health differences between rural dwelling youth and their urban counterparts with relation to cardiovascular risk factors. This study was conducted to (1) determine relationships between physical activity and markers of metabolic syndrome, and (2) to explore factors relating to physical activity in a…

  11. Size-fraction partitioning of community gene transcription and nitrogen metabolism in a marine oxygen minimum zone.

    PubMed

    Ganesh, Sangita; Bristow, Laura A; Larsen, Morten; Sarode, Neha; Thamdrup, Bo; Stewart, Frank J

    2015-12-01

    The genetic composition of marine microbial communities varies at the microscale between particle-associated (PA; >1.6 μm) and free-living (FL; 0.2-1.6 μm) niches. It remains unclear, however, how metabolic activities differ between PA and FL fractions. We combined rate measurements with metatranscriptomics to quantify PA and FL microbial activity in the oxygen minimum zone (OMZ) of the Eastern Tropical North Pacific, focusing on dissimilatory processes of the nitrogen (N) cycle. Bacterial gene counts were 8- to 15-fold higher in the FL compared with the PA fraction. However, rates of all measured N cycle processes, excluding ammonia oxidation, declined significantly following particle (>1.6 μm) removal. Without particles, rates of nitrate reduction to nitrite (1.5-9.4nMNd(-1)) fell to zero and N2 production by denitrification (0.5-1.7nMNd(-1)) and anammox (0.3-1.9nMNd(-1)) declined by 53-85%. The proportional representation of major microbial taxa and N cycle gene transcripts in metatranscriptomes followed fraction-specific trends. Transcripts encoding nitrate reductase were uniform among PA and FL fractions, whereas anammox-associated transcripts were proportionately enriched up to 15-fold in the FL fraction. In contrast, transcripts encoding enzymes for N2O and N2 production by denitrification were enriched up to 28-fold in PA samples. These patterns suggest that the majority of N cycle activity, excluding N2O and N2 production by denitrification, is confined to a FL majority that is critically dependent on access to particles, likely as a source of organic carbon and inorganic N. Variable particle distributions may drive heterogeneity in N cycle activity and gene expression in OMZs. PMID:25848875

  12. [Active forms of oxygen: cytotoxic effects and methodological approaches to laboratory control of liver lesions (literature review)].

    PubMed

    Matiushin, B N; Loginov, A S

    1996-01-01

    The injurious effects of active oxygen forms (AOF) on the cell caused by destruction of its membranous structures and impairment of their functional characteristics are discussed. Disorders of the processes of formation and inactivation of AOF in hepatocytes may be the metabolic mechanisms mediating the status and development of the pathological process in the liver. The problem of prospective approaches to assessing chronic diseases of the liver at the level of "free-radical pathology" is discussed. PMID:8963562

  13. Support nanostructure boosts oxygen transfer to catalytically active platinum nanoparticles.

    PubMed

    Vayssilov, Georgi N; Lykhach, Yaroslava; Migani, Annapaola; Staudt, Thorsten; Petrova, Galina P; Tsud, Nataliya; Skála, Tomáš; Bruix, Albert; Illas, Francesc; Prince, Kevin C; Matolín, Vladimír; Neyman, Konstantin M; Libuda, Jörg

    2011-04-01

    Interactions of metal particles with oxide supports can radically enhance the performance of supported catalysts. At the microscopic level, the details of such metal-oxide interactions usually remain obscure. This study identifies two types of oxidative metal-oxide interaction on well-defined models of technologically important Pt-ceria catalysts: (1) electron transfer from the Pt nanoparticle to the support, and (2) oxygen transfer from ceria to Pt. The electron transfer is favourable on ceria supports, irrespective of their morphology. Remarkably, the oxygen transfer is shown to require the presence of nanostructured ceria in close contact with Pt and, thus, is inherently a nanoscale effect. Our findings enable us to detail the formation mechanism of the catalytically indispensable Pt-O species on ceria and to elucidate the extraordinary structure-activity dependence of ceria-based catalysts in general. PMID:21423188

  14. Support nanostructure boosts oxygen transfer to catalytically active platinum nanoparticles

    NASA Astrophysics Data System (ADS)

    Vayssilov, Georgi N.; Lykhach, Yaroslava; Migani, Annapaola; Staudt, Thorsten; Petrova, Galina P.; Tsud, Nataliya; Skála, Tomáš; Bruix, Albert; Illas, Francesc; Prince, Kevin C.; MatolíN, VladimíR.; Neyman, Konstantin M.; Libuda, Jörg

    2011-04-01

    Interactions of metal particles with oxide supports can radically enhance the performance of supported catalysts. At the microscopic level, the details of such metal-oxide interactions usually remain obscure. This study identifies two types of oxidative metal-oxide interaction on well-defined models of technologically important Pt-ceria catalysts: (1) electron transfer from the Pt nanoparticle to the support, and (2) oxygen transfer from ceria to Pt. The electron transfer is favourable on ceria supports, irrespective of their morphology. Remarkably, the oxygen transfer is shown to require the presence of nanostructured ceria in close contact with Pt and, thus, is inherently a nanoscale effect. Our findings enable us to detail the formation mechanism of the catalytically indispensable Pt-O species on ceria and to elucidate the extraordinary structure-activity dependence of ceria-based catalysts in general.

  15. Selection of quiescent Escherichia coli with high metabolic activity.

    PubMed

    Sonderegger, Marco; Schümperli, Michael; Sauer, Uwe

    2005-01-01

    Sustained metabolic activity in non-growing, quiescent cells can increase the operational life-span of bio-processes and improve process economics by decoupling production from cell growth. Because of the ill-defined molecular nature of this phenotype, we developed selection protocols for the evolution of quiescent Escherichia coli mutants that exhibit high metabolic activity in ammonium starvation-induced stationary phase. The best enrichment procedures were continuously or discontinuously fed ammonium-limited chemostat cultures with a very low dilution rate of 0.03 h(-1). After 40 generations of selection, improved mutants with up to doubled catabolic rates in stationary phase were isolated. The metabolically most active clones were identified by screening for high specific glucose uptake rates during ammonium starvation-induced stationary phase in deep-well microtiter plates. PMID:15721805

  16. Regulation of metabolic flux in Lactobacillus casei for lactic acid production by overexpressed ldhL gene with two-stage oxygen supply strategy.

    PubMed

    Ge, Xiang-Yang; Xu, Yan; Chen, Xiang; Zhang, Long-Yun

    2015-01-01

    This study describes a novel strategy to regulate the metabolic flux for lactic acid production in Lactobacillus casei. The ldhL gene encoding L-lactate dehydrogenase (L-LDH) was overexpressed in L. casei, and a two-stage oxygen supply strategy (TOS) that maintained a medium oxygen supply level during the early fermentation phase, and a low oxygen supply level in the later phase was carried out. As a consequence, a maximum L-LDH activity of 95.6 U/ml was obtained in the recombinant strain, which was over 4-fold higher than that of the initial strain. Under the TOS for L. casei (pMG-ldhL), the maximum lactic acid concentration of 159.6 g/l was obtained in 36 h, corresponding to a 62.8% increase. The results presented here provide a novel way to regulate the metabolic flux of L. casei for lactic acid production in different fermentation stages, which is available to enhance organic acid production in other strains. PMID:25179900

  17. Antitumor activity of DMAKO-05, a novel shikonin derivative, and its metabolism in rat liver microsome.

    PubMed

    Zhang, Xu; Wang, Ru-Bing; Zhou, Wen; Xiao, Sui; Meng, Qing-Qing; Li, Shao-Shun

    2015-04-01

    The antitumor activity of shikonin derivatives is largely dependent on the generation of superoxide radicals and the alkylation activity of their naphthoquinone moiety. However, our recent study showed that 1,4-dioxime-5,8-dimethoxynaphthalene (DMAKO-05), a novel shikonin derivative, displayed more potential antitumor activity and less toxicity compared to fluorouracil (5-FU) both in vitro and in vivo, even though the hydroxyl and carbonyl groups of its naphthoquinone structure were shielded. To understand the underlying mechanisms, we investigated the metabolism of DMAKO-05 in rat liver microsomes. The kinetic analysis indicated that DMAKO-05 underwent a biphasic metabolism in rat liver microsomes. The inhibition experiments showed that CYP1A and CYP3A were the major enzymes in the metabolism of DMAKO-05, along with partial contribution from CYP2A. In addition, the structures of eight DMAKO-05 metabolites, which were characterized by accurate mass and MS/MS fragmentograms, implied that DMAKO-05 was mainly metabolized through the oxygenation of its naphthoquinone nucleus and the hydrolysis of its side chain, instead of the oxidation of hydroxyimine to ketone. Therefore, DMAKO-05 should not be considered as a traditional naphthoquinone prodrug. PMID:25273027

  18. Dual and Opposing Roles of Xanthine Dehydrogenase in Defense-Associated Reactive Oxygen Species Metabolism in Arabidopsis.

    PubMed

    Ma, Xianfeng; Wang, Wenming; Bittner, Florian; Schmidt, Nadine; Berkey, Robert; Zhang, Lingli; King, Harlan; Zhang, Yi; Feng, Jiayue; Wen, Yinqiang; Tan, Liqiang; Li, Yue; Zhang, Qiong; Deng, Ziniu; Xiong, Xingyao; Xiao, Shunyuan

    2016-05-01

    While plants produce reactive oxygen species (ROS) for stress signaling and pathogen defense, they need to remove excessive ROS induced during stress responses in order to minimize oxidative damage. How can plants fine-tune this balance and meet such conflicting needs? Here, we show that XANTHINE DEHYDROGENASE1 (XDH1) in Arabidopsis thaliana appears to play spatially opposite roles to serve this purpose. Through a large-scale genetic screen, we identified three missense mutations in XDH1 that impair XDH1's enzymatic functions and consequently affect the powdery mildew resistance mediated by RESISTANCE TO POWDERY MILDEW8 (RPW8) in epidermal cells and formation of xanthine-enriched autofluorescent objects in mesophyll cells. Further analyses revealed that in leaf epidermal cells, XDH1 likely functions as an oxidase, along with the NADPH oxidases RbohD and RbohF, to generate superoxide, which is dismutated into H2O2 The resulting enrichment of H2O2 in the fungal haustorial complex within infected epidermal cells helps to constrain the haustorium, thereby contributing to RPW8-dependent and RPW8-independent powdery mildew resistance. By contrast, in leaf mesophyll cells, XDH1 carries out xanthine dehydrogenase activity to produce uric acid in local and systemic tissues to scavenge H2O2 from stressed chloroplasts, thereby protecting plants from stress-induced oxidative damage. Thus, XDH1 plays spatially specified dual and opposing roles in modulation of ROS metabolism during defense responses in Arabidopsis. PMID:27152019

  19. Oxygen metabolism and water mass mixing in the northern Gulf of Mexico hypoxic zone in 2010

    NASA Astrophysics Data System (ADS)

    Ostrom, Nathaniel E.; Gandhi, Hasand; Kamphuis, Ben; DeCamp, Sam; Liu, Zhanfei; McCarthy, Mark J.; Gardner, Wayne S.

    2014-09-01

    We evaluated O2 metabolism and mixing of river and seawater in the northern Gulf of Mexico (NGOMEX) in May and August of 2010. A strong correlation between the δ2H and δ18O of water and salinity indicated simple mixing of the two water sources. The isotope values for the freshwater source suggested that Mississippi River water predominated over the Atchafalaya River water in at our study sites in both May and August. Knowledge of the δ18O of water is required for determination of the ratio of primary production to respiration (P:R) from the δ18O and concentration of O2. We observed a strong correlation between δ18O of water and salinity, which indicates that subsequent studies of P:R may simply be able to predict the isotopic composition of water from salinity in this region. P:R values were determined from the concentration and isotopic composition of O2 and varied from 0.88 to 1.10. The range in P:R and progression from high values in May to net heterotrophy in August is consistent with enhanced primary production in spring followed by respiration in excess of production in summer. Averages of -5.8‰ and -3.4‰ were observed for the isotopic enrichment factor, εobs, for sub-pycnocline respiration in May and August, respectively. In contrast to previous studies we found that εobs is not an effective indicator of the proportion of water column to sediment respiration, but rather reflects the total rate of sub-pycnocline respiration (water column plus sediment respiration). Nonetheless, as εobs is an indication of total sub-pycnocline respiration insight into oxygen-removal can be obtained without the need for incubation. Even though our research cruises occurred approximately three weeks after the initiation and one month after cessation of the Deepwater Horizon oil spill, P:R and εobs values were each within ranges reported previously in NGOMEX. Thus, a direct link between the oil spill and O2 metabolism or hypoxia development was not apparent.

  20. On the determination of oxygen abundances in chromospherically active stars

    NASA Astrophysics Data System (ADS)

    Morel, T.; Micela, G.

    2004-08-01

    We discuss oxygen abundances derived from [O I] λ6300s and the O I triplet in stars spanning a wide range in chromospheric activity level, and show that these two indicators yield increasingly discrepant results with higher chromospheric/coronal activity measures. While the forbidden and permitted lines give fairly consistent results for solar-type disk dwarfs, spuriously high O I triplet abundances are observed in young Hyades and Pleiades stars, as well as in individual components of RS CVn binaries (up to 1.8 dex). The distinct behaviour of the [O I]-based abundances which consistently remain near-solar suggests that this phenomenon mostly results from large departures from LTE affecting the O I triplet at high activity level that are currently unaccounted for, but also possibly from a failure to adequately model the atmospheres of K-type stars. These results suggest that some caution should be exercised when interpreting oxygen abundances in active binaries or young open cluster stars. Based on observations collected at the European Southern Observatory, Chile (Proposals 64.L-0249 and 071.D-0260). Table \\ref{tab_data} is only available in electronic form at http://www.edpsciences.org

  1. Fate of oxygen losses from Typha domingensis (Typhaceae) and Cladium jamaicense (Cyperaceae) and consequences for root metabolism

    USGS Publications Warehouse

    Chabbi, A.; McKee, K.L.; Mendelssohn, I.A.

    2000-01-01

    The objective of this work was to determine whether radial oxygen loss (ROL) from roots of Typha domingensis and Cladium jamaicense creates an internal oxygen deficiency or, conversely, indicates adequate internal aeration and leakage of excess oxygen to the rhizosphere. Methylene blue in agar was used to quantify oxygen leakage. Typha's roots had a higher porosity than Cladium's and responded to flooding treatment by increasing cortical air space, particularly near the root tips. A greater oxygen release, which occurred along the subapical root axis, and an increase in rhizosphere redox potential (Eh) over time were associated with the well-developed aerenchyma system in Typha. Typha roots, regardless of oxygen release pattern, showed low or undetectable alcohol dehydrogenage (ADH) activity or ethanol concentrations, indicating that ROL did not cause internal deficiencies. Cladium roots also releases oxygen, but this loss primarily occurred at the root tips and was accompanied by increased root ADH activity and ethanol concentrations. These results support the hypothesis that oxygen release by Cladium is accompanied by internal deficiencies of oxygen sufficient to stimulate alcoholic fermentation and helps explain Cladium's lesser flood tolerance in comparison with Typha.

  2. Metabolic activation of efferent pathways from the rat area postrema.

    PubMed

    Gross, P M; Wainman, D S; Shaver, S W; Wall, K M; Ferguson, A V

    1990-03-01

    We used the quantitative [14C]deoxyglucose method and autoradiography to evaluate metabolic activity in 47 individual cerebral structures or subregions that are part of neural pathways emanating from the brain stem circumventricular organ, area postrema. Electrical stimulation of the dorsocentral area postrema in halothane-ventilated rats produced hypotension and increased glucose metabolism by several structures within the ascending trajectories of efferent neural projections from the nucleus. Structures in the caudal medulla oblongata, including three subnuclei of the nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and nucleus ambiguus-A1 noradrenergic region, had increases of metabolism during stimulation of 32-62%. Pontine activation occurred specifically in the locus coeruleus and lateral parabrachial nuclei (increases of 24-36%). Magnocellular and parvocellular subdivisions of the hypothalamic paraventricular nucleus, supraoptic and suprachiasmatic nuclei, and median eminence showed increases in metabolism of 22-34%. An 89% elevation of glucose metabolism by the pituitary neural lobe resulted. The findings are evidence for functional activation of specific structures within ascending neural pathways from area postrema to forebrain mechanisms regulating blood pressure and fluid balance. PMID:2316724

  3. Copper oxide nanoparticles inhibit the metabolic activity of Saccharomyces cerevisiae.

    PubMed

    Mashock, Michael J; Kappell, Anthony D; Hallaj, Nadia; Hristova, Krassimira R

    2016-01-01

    Copper oxide nanoparticles (CuO NPs) are used increasingly in industrial applications and consumer products and thus may pose risk to human and environmental health. The interaction of CuO NPs with complex media and the impact on cell metabolism when exposed to sublethal concentrations are largely unknown. In the present study, the short-term effects of 2 different sized manufactured CuO NPs on metabolic activity of Saccharomyces cerevisiae were studied. The role of released Cu(2+) during dissolution of NPs in the growth media and the CuO nanostructure were considered. Characterization showed that the 28 nm and 64 nm CuO NPs used in the present study have different primary diameter, similar hydrodynamic diameter, and significantly different concentrations of dissolved Cu(2+) ions in the growth media released from the same initial NP mass. Exposures to CuO NPs or the released Cu(2+) fraction, at doses that do not have impact on cell viability, showed significant inhibition on S. cerevisiae cellular metabolic activity. A greater CuO NP effect on the metabolic activity of S. cerevisiae growth under respiring conditions was observed. Under the tested conditions the observed metabolic inhibition from the NPs was not explained fully by the released Cu ions from the dissolving NPs. PMID:26178758

  4. [Oxygen metabolism in the body during substitution of nitrogen by helium in the air].

    PubMed

    Troshikhin, G V; Isaakian, L A; Bekirova, G G

    1975-01-01

    The total gas exchange, body temperature, content of free oxygen in the quadriceps muscle and its changes upon oxygen inhalation of a known dosage (oxygen test) were measured in the Wistar rats during their one-hour exposure to a helium-oxygen atmosphere (21%) at 25 degrees C. In this atmosphere the animals displayed a 1.8 degrees decline in the body temperature, a 20.5% increase in the gas exchange and a 26% decrease of oxygen in the muscular tissue as compared with the respective parameters in the air. After the experiment during the first 20 min exposure to the normal atmosphere oxygen tests were 10-15% lower than before the experiment. These findings give evidence for an increase of oxygen exchange in the muscles of animals exposed to the helium-oxygen atmosphere at a temperature below the comfortable level. PMID:1214483

  5. Pyruvate modifies metabolic flux and nutrient sensing during extracorporeal membrane oxygenation in an immature swine model

    SciTech Connect

    Ledee, Dolena R.; Kajimoto, Masaki; O'Kelly-Priddy, Colleen M.; Olson, Aaron; Isern, Nancy G.; Robillard Frayne, Isabelle; Des Rosiers, Christine; Portman, Michael A.

    2015-07-01

    Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support for infants and children with postoperative cardiopulmonary failure. Nutritional support is mandatory during ECMO, although specific actions for substrates on the heart have not been delineated. Prior work shows that enhancing pyruvate oxidation promotes successful weaning from ECMO. Accordingly, we closely examined the role of prolonged systemic pyruvate supplementation in modifying metabolic parameters during the unique conditions of ventricular unloading provided by ECMO. Twelve male mixed breed Yorkshire piglets (age 30-49 days) received systemic infusion of either normal saline (Group C) or pyruvate (Group P) during ECMO for 8 hours. Over the final hour piglets received [2-13C] pyruvate, and [13C6]-L-leucine, as an indicator for oxidation and protein synthesis. A significant increase in lactate and pyruvate concentrations occurred, along with an increase in the absolute concentration of all measured CAC intermediates. Group P showed greater anaplerotic flux through pyruvate carboxylation although pyruvate oxidation relative to citrate synthase flux was similar to Group C. The groups demonstrated similar leucine fractional contributions to acetyl-CoA and fractional protein synthesis rates. Pyruvate also promoted an increase in the phosphorylation state of several nutrient sensitive enzymes, such as AMPK and ACC, and promoted O-GlcNAcylation through the hexosamine biosynthetic pathway (HBP). In conclusion, prolonged pyruvate supplementation during ECMO modified anaplerotic pyruvate flux and elicited changes in important nutrient and energy sensitive pathways, while preserving protein synthesis. Therefore, the observed results support the further study of nutritional supplementation and its downstream effects on cardiac adaptation during ventricular unloading.

  6. Reactive oxygen species metabolism during the cadmium hyperaccumulation of a new hyperaccumulator Sedum alfredii (Crassulaceae).

    PubMed

    Zhang, Zhong-chun; Qiu, Bao-Sheng

    2007-01-01

    Sedum alfredii Hance, a newly discovered hyperaccumulator, could serve as a good material for phytoremediation of Cd polluted sites. Malondialdehyde (MDA), reactive oxygen species (ROS) and antioxidases (catalase (CAT); superoxide dismutase (SOD); peroxidase (POD)) in the leaf were determined when S. alfredii was treated for 15 d with various CdCl2 concentrations ranging from 0 to 800 micromol/L. The results showed that the production rate of 2',7'-dichlorofluorescein (DCF), which is an indicator of ROS level, reached up to the maximum at 400 micromol/L CdCl2 and then declined with the increase of CdCl2 concentration, while MDA accumulation tended to increase. CAT activity was significantly inhibited at all tested CdCl2 concentrations and SOD activity was sharply suppressed at 800 micromol/L CdCl2. However, the enhancement of POD activity was observed when CdCl2 concentration was higher than 400 micromol/L. In addition, its activity increased when treated with 600 micromol/L CdCl2 for more than 5 d. When sodium benzoate, a free radical scavenger, was added, S. alfredii was a little more sensitive to Cd toxicity than that exposed to Cd alone, and the Cd accumulation tended to decline with the increase of sodium benzoate concentration. It came to the conclusions that POD played an important role during Cd hyperaccumulation, and the accumulation of ROS induced by Cd treatment might be involved in Cd hyperaccumulation. PMID:18232224

  7. Metabolic responses of novel cellulolytic and saccharolytic agricultural soil Bacteria to oxygen.

    PubMed

    Schellenberger, Stefanie; Kolb, Steffen; Drake, Harold L

    2010-04-01

    Cellulose is the most abundant biopolymer in terrestrial ecosystems and is degraded by microbial communities in soils. However, relatively little is known about the diversity and function of soil prokaryotes that might participate in the overall degradation of this biopolymer. The active cellulolytic and saccharolytic Bacteria in an agricultural soil were evaluated by 16S rRNA (13)C-based stable isotope probing. Cellulose, cellobiose and glucose were mineralized under oxic conditions in soil slurries to carbon dioxide. Under anoxic conditions, these substrates were converted primarily to acetate, butyrate, carbon dioxide, hydrogen and traces of propionate and iso-butyrate; the production of these fermentation end-products was concomitant with the apparent reduction of iron(III). [(13)C]-cellulose was mainly degraded under oxic conditions by novel family-level taxa of the Bacteroidetes and Chloroflexi, and a known family-level taxon of Planctomycetes, whereas degradation under anoxic conditions was facilitated by the Kineosporiaceae (Actinobacteria) and cluster III Clostridiaceae and novel clusters within Bacteroidetes. Active aerobic sub-communities in oxic [(13)C]-cellobiose and [(13)C]-glucose treatments were dominated by Intrasporangiaceae and Micrococcaceae (Actinobacteria) whereas active cluster I Clostridiaceae (Firmicutes) were prevalent in anoxic treatments. A very large number (i.e. 28) of the detected taxa did not closely affiliate with known families, and active Archaea were not detected in any of the treatments. These collective findings suggest that: (i) a large uncultured diversity of soil Bacteria was involved in the utilization of cellulose and products of its hydrolysis, (ii) the active saccharolytic community differed phylogenetically from the active cellulolytic community, (iii) oxygen availability impacted differentially on the activity of taxa and (iv) different redox guilds (e.g. fermenters and iron reducers) compete or interact during

  8. Effect of 6-day hypokinesia on oxygen metabolism indices in elderly and senile subjects

    NASA Technical Reports Server (NTRS)

    Ivanov, L. A.; Orlov, P. A.

    1978-01-01

    After a strict 6 day confinement to bed of elderly and senile subjects the oxygen supply of the subcutaneous cellular tissue was impaired, and the intensity of its tissue respiration was somewhat reduced. The vacat-oxygen of the blood and urine, the coefficient of incomplete oxidation, and the oxygen deficiency in the organism were increased.

  9. Molecular Evidence for Metabolically Active Bacteria in the Atmosphere

    PubMed Central

    Klein, Ann M.; Bohannan, Brendan J. M.; Jaffe, Daniel A.; Levin, David A.; Green, Jessica L.

    2016-01-01

    Bacterial metabolisms are responsible for critical chemical transformations in nearly all environments, including oceans, freshwater, and soil. Despite the ubiquity of bacteria in the atmosphere, little is known about the metabolic functioning of atmospheric bacterial communities. To gain a better understanding of the metabolism of bacterial communities in the atmosphere, we used a combined empirical and model-based approach to investigate the structure and composition of potentially active bacterial communities in air sampled at a high elevation research station. We found that the composition of the putatively active bacterial community (assayed via rRNA) differed significantly from the total bacterial community (assayed via rDNA). Rare taxa in the total (rDNA) community were disproportionately active relative to abundant taxa, and members of the order Rhodospirillales had the highest potential for activity. We developed theory to explore the effects of random sampling from the rRNA and rDNA communities on observed differences between the communities. We found that random sampling, particularly in cases where active taxa are rare in the rDNA community, will give rise to observed differences in community composition including the occurrence of “phantom taxa”, taxa which are detected in the rRNA community but not the rDNA community. We show that the use of comparative rRNA/rDNA techniques can reveal the structure and composition of the metabolically active portion of bacterial communities. Our observations suggest that metabolically active bacteria exist in the atmosphere and that these communities may be involved in the cycling of organic compounds in the atmosphere. PMID:27252689

  10. Device for measuring oxygen activity in liquid sodium

    DOEpatents

    Roy, P.; Young, R.S.

    1973-12-01

    A composite ceramic electrolyte in a configuration (such as a closed end tube or a plate) suitable to separate liquid sodium from a reference electrode with a high impedance voltmeter connected to measure EMF between the sodium and the reference electrode as a measure of oxygen activity in the sodium is described. The composite electrolyte consists of zirconiacalcia with a bonded layer of thoria-yttria. The device is used with a gaseous reference electrode on the zirconia-calcia side and liquid sodium on the thoria-yttria side of the electrolyte. (Official Gazette)

  11. Bioreductively Activated Reactive Oxygen Species (ROS) Generators as MRSA Inhibitors.

    PubMed

    Khodade, Vinayak S; Sharath Chandra, Mallojjala; Banerjee, Ankita; Lahiri, Surobhi; Pulipeta, Mallikarjuna; Rangarajan, Radha; Chakrapani, Harinath

    2014-07-10

    The number of cases of drug resistant Staphylococcus aureus infections is on the rise globally and new strategies to identify drug candidates with novel mechanisms of action are in urgent need. Here, we report the synthesis and evaluation of a series of benzo[b]phenanthridine-5,7,12(6H)-triones, which were designed based on redox-active natural products. We find that the in vitro inhibitory activity of 6-(prop-2-ynyl)benzo[b]phenanthridine-5,7,12(6H)-trione (1f) against methicillin-resistant Staphylococcus aureus (MRSA), including a panel of patient-derived strains, is comparable or better than vancomycin. We show that the lead compound generates reactive oxygen species (ROS) in the cell, contributing to its antibacterial activity. PMID:25050164

  12. Spontaneous ultraweak photon emission imaging of oxidative metabolic processes in human skin: effect of molecular oxygen and antioxidant defense system

    NASA Astrophysics Data System (ADS)

    Rastogi, Anshu; Pospíšil, Pavel

    2011-09-01

    All living organisms emit spontaneous ultraweak photon emission as a result of cellular metabolic processes. In this study, the involvement of reactive oxygen species (ROS) formed as the byproduct of oxidative metabolic processes in spontaneous ultraweak photon emission was studied in human hand skin. The effect of molecular oxygen and ROS scavengers on spontaneous ultraweak photon emission from human skin was monitored using a highly sensitive photomultiplier tube and charged coupled device camera. When spontaneous ultraweak photon emission was measured under anaerobic conditions, the photon emission was decreased, whereas under hyperaerobic condition the enhancement in photon emission was observed. Spontaneous ultraweak photon emission measured after topical application of glutathione, α-tocopherol, ascorbate, and coenzyme Q10 was observed to be decreased. These results reveal that ROS formed during the cellular metabolic processes in the epidermal cells play a significant role in the spontaneous ultraweak photon emission. It is proposed that spontaneous ultraweak photon emission can be used as a noninvasive tool for the temporal and spatial monitoring of the oxidative metabolic processes and intrinsic antioxidant system in human skin.

  13. [Metabolic shift of Corynebacterium acetoacidophilum-deltaldh under oxygen deprivation conditions].

    PubMed

    Yang, Qian; Zheng, Pu; Yu, Fang; Liu, Wei; Sun, Zhihao

    2014-03-01

    Lactate and succinate were produced by Corynebacterium acetoacidophilum from glucose under oxygen deprivation conditions. To construct knockout mutant, lactate dehydrogenase gene (ldh) of C. acetoacidophilum was deleted by double-crossover chromosome replacement with sacB gene. Comparing with the wild strain ATCC13870, ldhA-deficent mutant produced no lactate with glucose consumption rate decreased by 29.3%, while succinate and acetate concentrations were increased by 45.6% and 182%, respectively. Moreover, the NADH/NAD+ rate was less than 1 (about 0.7), and the activities of phosphoenolpyruvate carboxylase and acetate kinase of the ldhA-deficent mutant were enhanced by 84% and 12 times, respectively. Our studies show that succinicate and acetate production pathways are strengthened by blocking lactate synthesis. It also suggests that improving NADH supply and eliminating acetate generation are alternative strategies to get high succinate-producer. PMID:25007579

  14. Metabolic correlates of pallidal neuronal activity in Parkinson's disease.

    PubMed

    Eidelberg, D; Moeller, J R; Kazumata, K; Antonini, A; Sterio, D; Dhawan, V; Spetsieris, P; Alterman, R; Kelly, P J; Dogali, M; Fazzini, E; Beric, A

    1997-08-01

    We have used [18F]fluorodeoxyglucose and PET to identify specific metabolic covariance patterns associated with Parkinson's disease and related disorders previously. Nonetheless, the physiological correlates of these abnormal patterns are unknown. In this study we used PET to measure resting state glucose metabolism in 42 awake unmedicated Parkinson's disease patients prior to unilateral stereotaxic pallidotomy for relief of symptoms. Spontaneous single unit activity of the internal segment of the globus pallidus (GPi) was recorded intraoperatively in the same patients under identical conditions. The first 24 patients (Group A) were scanned on an intermediate resolution tomograph (full width at half maximum, 8 mm); the subsequent 18 patients (Group B) were scanned on a higher resolution tomograph (full width half maximum, 4.2 mm). We found significant positive correlations between GPi firing rates and thalamic glucose metabolism in both patient groups (Group A: r = 0.41, P < 0.05; Group B: r = 0.69, P < 0.005). In Group B, pixel-based analysis disclosed a significant focus of physiological-metabolic correlation involving the ventral thalamus and the GPi (statistical parametric map: P < 0.05, corrected). Regional covariance analysis demonstrated that internal pallidal neuronal activity correlated significantly (r = 0.65, P < 0.005) with the expression of a unique network characterized by covarying pallidothalamic and brainstem metabolic activity. Our findings suggest that the variability in pallidal neuronal firing rates in Parkinson's disease patients is associated with individual differences in the metabolic activity of efferent projection systems. PMID:9278625

  15. Molecular changes in mitochondrial respiratory activity and metabolic enzyme activity in muscle of four pig breeds with distinct metabolic types.

    PubMed

    Liu, Xuan; Trakooljul, Nares; Muráni, Eduard; Krischek, Carsten; Schellander, Karl; Wicke, Michael; Wimmers, Klaus; Ponsuksili, Siriluck

    2016-02-01

    Skeletal muscles are metabolically active and have market value in meat-producing farm animals. A better understanding of biological pathways affecting energy metabolism in skeletal muscle could advance the science of skeletal muscle. In this study, comparative pathway-focused gene expression profiling in conjunction with muscle fiber typing were analyzed in skeletal muscles from Duroc, Pietrain, and Duroc-Pietrain crossbred pigs. Each breed type displayed a distinct muscle fiber-type composition. Mitochondrial respiratory activity and glycolytic and oxidative enzyme activities were comparable among genotypes, except for significantly lower complex I activity in Pietrain pigs homozygous-positive for malignant hyperthermia syndrome. At the transcriptional level, lactate dehydrogenase B showed breed specificity, with significantly lower expression in Pietrain pigs homozygous-positive for malignant hyperthermia syndrome. A similar mRNA expression pattern was shown for several subunits of oxidative phosphorylation complexes, including complex I, complex II, complex IV, and ATP synthase. Significant correlations were observed between mRNA expression of genes in focused pathways and enzyme activities in a breed-dependent manner. Moreover, expression patterns of pathway-focused genes were well correlated with muscle fiber-type composition. These results stress the importance of regulation of transcriptional rate of genes related to oxidative and glycolytic pathways in the metabolic capacity of muscle fibers. Overall, the results further the breed-specific understanding of the molecular basis of metabolic enzyme activities, which directly impact meat quality. PMID:26759028

  16. Spatial and temporal regulation of the metabolism of reactive oxygen and nitrogen species during the early development of pepper (Capsicum annuum) seedlings

    PubMed Central

    Airaki, Morad; Leterrier, Marina; Valderrama, Raquel; Chaki, Mounira; Begara-Morales, Juan C.; Barroso, Juan B.; del Río, Luis A.; Palma, José M.; Corpas, Francisco J.

    2015-01-01

    Background and Aims The development of seedlings involves many morphological, physiological and biochemical processes, which are controlled by many factors. Some reactive oxygen and nitrogen species (ROS and RNS, respectively) are implicated as signal molecules in physiological and phytopathological processes. Pepper (Capsicum annuum) is a very important crop and the goal of this work was to provide a framework of the behaviour of the key elements in the metabolism of ROS and RNS in the main organs of pepper during its development. Methods The main seedling organs (roots, hypocotyls and green cotyledons) of pepper seedlings were analysed 7, 10 and 14 d after germination. Activity and gene expression of the main enzymatic antioxidants (catalase, ascorbate–glutathione cycle enzymes), NADP-generating dehydrogenases and S-nitrosoglutathione reductase were determined. Cellular distribution of nitric oxide (·NO), superoxide radical (O2·–) and peroxynitrite (ONOO–) was investigated using confocal laser scanning microscopy. Key Results The metabolism of ROS and RNS during pepper seedling development was highly regulated and showed significant plasticity, which was co-ordinated among the main seedling organs, resulting in correct development. Catalase showed higher activity in the aerial parts of the seedling (hypocotyls and green cotyledons) whereas roots of 7-d-old seedlings contained higher activity of the enzymatic components of the ascorbate glutathione cycle, NADP-isocitrate dehydrogenase and NADP-malic enzyme. Conclusions There is differential regulation of the metabolism of ROS, nitric oxide and NADP dehydrogenases in the different plant organs during seedling development in pepper in the absence of stress. The metabolism of ROS and RNS seems to contribute significantly to plant development since their components are involved directly or indirectly in many metabolic pathways. Thus, specific molecules such as H2O2 and NO have implications for signalling

  17. The Effect of Sustained Compression on Oxygen Metabolic Transport in the Intervertebral Disc Decreases with Degenerative Changes

    PubMed Central

    Malandrino, Andrea; Noailly, Jérôme; Lacroix, Damien

    2011-01-01

    Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance. Disc degenerative changes alter the tissue mechanics, but interactions between mechanical loading and disc transport are still an open issue. A poromechanical finite element model of the human disc was coupled with oxygen and lactate transport models. Deformations and fluid flow were linked to transport predictions by including strain-dependent diffusion and advection. The two solute transport models were also coupled to account for cell metabolism. With this approach, the relevance of metabolic and mechano-transport couplings were assessed in the healthy disc under loading-recovery daily compression. Disc height, cell density and material degenerative changes were parametrically simulated to study their influence on the calculated solute concentrations. The effects of load frequency and amplitude were also studied in the healthy disc by considering short periods of cyclic compression. Results indicate that external loads influence the oxygen and lactate regional distributions within the disc when large volume changes modify diffusion distances and diffusivities, especially when healthy disc properties are simulated. Advection was negligible under both sustained and cyclic compression. Simulating degeneration, mechanical changes inhibited the mechanical effect on transport while disc height, fluid content, nucleus pressure and overall cell density reductions affected significantly transport predictions. For the healthy disc, nutrient concentration patterns depended mostly on the time of sustained compression and recovery. The relevant effect of cell density on the metabolic transport indicates the disturbance of cell number as a possible onset for disc degeneration via alteration of the metabolic balance. Results also suggest that healthy disc properties have a positive effect of loading on metabolic transport. Such

  18. Deep-sea echinoderm oxygen consumption rates and an interclass comparison of metabolic rates in Asteroidea, Crinoidea, Echinoidea, Holothuroidea and Ophiuroidea.

    PubMed

    Hughes, Sarah Jane Murty; Ruhl, Henry A; Hawkins, Lawrence E; Hauton, Chris; Boorman, Ben; Billett, David S M

    2011-08-01

    Echinoderms are important components of deep-sea communities because of their abundance and the fact that their activities contribute to carbon cycling. Estimating the echinoderm contribution to food webs and carbon cycling is important to our understanding of the functioning of the deep-sea environment and how this may alter in the future as climatic changes take place. Metabolic rate data from deep-sea echinoderm species are, however, scarce. To obtain such data from abyssal echinoderms, a novel in situ respirometer system, the benthic incubation chamber system (BICS), was deployed by remotely operated vehicle (ROV) at depths ranging from 2200 to 3600 m. Oxygen consumption rates were obtained in situ from four species of abyssal echinoderm (Ophiuroidea and Holothuroidea). The design and operation of two versions of BICS are presented here, together with the in situ respirometry measurements. These results were then incorporated into a larger echinoderm metabolic rate data set, which included the metabolic rates of 84 echinoderm species from all five classes (Asteroidea, Crinoidea, Echinoidea, Holothuroidea and Ophiuroidea). The allometric scaling relationships between metabolic rate and body mass derived in this study for each echinoderm class were found to vary. Analysis of the data set indicated no change in echinoderm metabolic rate with depth (by class or phylum). The allometric scaling relationships presented here provide updated information for mass-dependent deep-sea echinoderm metabolic rate for use in ecosystem models, which will contribute to the study of both shallow water and deep-sea ecosystem functioning and biogeochemistry. PMID:21753044

  19. Metabolic Cost of Daily Activities and Effect of Mobility Impairment in Older Adults

    PubMed Central

    Knaggs, Jeffrey D; Larkin, Kelly A; Manini, Todd M

    2013-01-01

    OBJECTIVES There is a shortage of information on metabolic costs of daily physical activities in older adults and the effect of having mobility impairments. The primary purpose of this study was to evaluate metabolic equivalent (MET) values on common daily tasks in men and women aged > 70 years compared to normative criteria. A secondary purpose was to determine the effect of having mobility impairments. DESIGN Cross-sectional observational study. SETTING University based research clinic PARTICIPANTS Forty-five participants aged 70 to 90 years of age (mean: 76.3 ± 5.1) volunteered to complete 17 daily activities, each lasting 10 minutes. MEASUREMENTS Oxygen consumption (VO2 = ml•kg−1•min−1) was measured through a mask by a portable gas analyzer and MET values were calculated as measured VO2/3.5 ml•kg−1•min−1. Values were compared to both normative values and between participants with and without mobility impairments. RESULTS Compared to the established normative criteria, measured METs were different in 14 of 17 tasks performed. Compared to measured METs, normative values underestimated walking leisurely (0.87 ± 0.12 METs) walking briskly (0.87 ± 0.12 METs ), and bed making (1.07 ± 0.10 METs ), but overestimated gardening (1.46 ± 0.12 METs) and climbing stairs (0.73 ± 0.18). Participants with impairments had significantly lower METs while gardening, vacuuming/sweeping, stair climbing, and walking briskly. However, when METs were adjusted for performance speed the metabolic costs were 16–27% higher for those with mobility impairments. CONCLUSION Compared to normative values, metabolic costs of daily activities are substantially different in older adults and having mobility impairments increases this metabolic cost. These results may have implications for practitioners to appropriately prescribe daily physical activities for healthy and mobility impaired older adults. PMID:22091979

  20. Biophysical model for integrating neuronal activity, EEG, fMRI and metabolism.

    PubMed

    Sotero, Roberto C; Trujillo-Barreto, Nelson J

    2008-01-01

    Our goal is to model the coupling between neuronal activity, cerebral metabolic rates of glucose and oxygen consumption, cerebral blood flow (CBF), electroencephalography (EEG) and blood oxygenation level-dependent (BOLD) responses. In order to accomplish this, two previous models are coupled: a metabolic/hemodynamic model (MHM) for a voxel, linking BOLD signals and neuronal activity, and a neural mass model describing the neuronal dynamics within a voxel and its interactions with voxels of the same area (short-range interactions) and other areas (long-range interactions). For coupling both models, we take as the input to the BOLD model, the number of active synapses within the voxel, that is, the average number of synapses that will receive an action potential within the time unit. This is obtained by considering the action potentials transmitted between neuronal populations within the voxel, as well as those arriving from other voxels. Simulations are carried out for testing the integrated model. Results show that realistic evoked potentials (EP) at electrodes on the scalp surface and the corresponding BOLD signals for each voxel are produced by the model. In another simulation, the alpha rhythm was reproduced and reasonable similarities with experimental data were obtained when calculating correlations between BOLD signals and the alpha power curve. The origin of negative BOLD responses and the characteristics of EEG, PET and BOLD signals in Alzheimer's disease were also studied. PMID:17919931

  1. Biogeography of Metabolically Active Microbial Populations within the Subseafloor Biosphere

    NASA Astrophysics Data System (ADS)

    Reese, B. K.; Shepard, A.; St. Peter, C.; Mills, H. J.

    2011-12-01

    Microbial life in deep marine sediments is widespread, metabolically active and diverse. Evidence of prokaryotic communities in sediments as deep as 800 m below the seafloor (mbsf) have been found. By recycling carbon and nutrients through biological and geochemical processes, the deep subsurface has the potential to remain metabolically active over geologic time scales. While a vast majority of the subsurface biosphere remains under studied, recent advances in molecular techniques and an increased focus on microbiological sampling during IODP expeditions have provided the initial steps toward better characterizations of the microbial communities. Coupling of geochemistry and RNA-based molecular analysis is essential to the description of the active microbial populations within the subsurface biosphere. Studies based on DNA may describe the taxa and metabolic pathways from the total microbial community within the sediment, whether the cells sampled were metabolically active, quiescent or dead. Due to a short lifespan within a cell, only an RNA-based analysis can be used to identify linkages between active populations and observed geochemistry. This study will coalesce and compare RNA sequence and geochemical data from Expeditions 316 (Nankai Trough), 320 (Pacific Equatorial Age Transect), 325 (Great Barrier Reef) and 329 (South Pacific Gyre) to evaluate the biogeography of microbial lineages actively altering the deep subsurface. The grouping of sediments allows for a wide range of geochemical environments to be compared, including two environments limited in organic carbon. Significant to this study is the use of similar extraction, amplification and simultaneous 454 pyrosequencing on all sediment populations allowing for robust comparisons with similar protocol strengths and biases. Initial trends support previously described reduction of diversity with increasing depth. The co-localization of active reductive and oxidative lineages suggests a potential cryptic

  2. Post-hypoxic hypoperfusion is associated with suppression of cerebral metabolism and increased tissue oxygenation in near-term fetal sheep

    PubMed Central

    Jensen, E C; Bennet, L; Hunter, C J; Power, G C; Gunn, A J

    2006-01-01

    Secondary cerebral hypoperfusion is common following perinatal hypoxia–ischaemia. However, it remains unclear whether this represents a true failure to provide sufficient oxygen and nutrients to tissues, or whether it is simply a consequence of reduced cerebral metabolic demand. We therefore examined the hypothesis that cerebral oxygenation would be reduced during hypoperfusion after severe asphyxia, and further, that the greater neural injury associated with blockade of the adenosine A1 receptor during the insult would be associated with greater hypoperfusion and deoxygenation. Sixteen near-term fetal sheep received either vehicle or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) for 1 h, followed by 10 min of severe asphyxia induced by complete occlusion of the umbilical cord. Infusions were discontinued at the end of the occlusion and data were analysed for the following 8 h. A transient, secondary fall in carotid artery blood flow and laser Doppler flow was seen from approximately 1–4 h after occlusion (P < 0.001), with no significant differences between vehicle and DPCPX. Changes in laser Doppler blood flow were highly correlated with carotid blood flow (r2 = 0.81, P < 0.001). Cortical metabolism was suppressed, reaching a nadir 1 h after occlusion and then resolving. Cortical tissue PO2 was significantly increased at 1, 2 and 3 h after occlusion compared to baseline, and inversely correlated with carotid blood flow (r2 = 0.69, P < 0.001). In conclusion, contrary to our initial hypothesis, delayed posthypoxic hypoperfusion was associated with suppression of cerebral metabolism and increased tissue PO2, and was not significantly affected by preceding adenosine A1 blockade. These data suggest that posthypoxic hypoperfusion is actively mediated and reflects suppressed cerebral metabolism. PMID:16484307

  3. Breakpoints in ventilation, cerebral and muscle oxygenation, and muscle activity during an incremental cycling exercise

    PubMed Central

    Racinais, Sebastien; Buchheit, Martin; Girard, Olivier

    2014-01-01

    The aim of this study was to locate the breakpoints of cerebral and muscle oxygenation and muscle electrical activity during a ramp exercise in reference to the first and second ventilatory thresholds. Twenty-five cyclists completed a maximal ramp test on an electromagnetically braked cycle-ergometer with a rate of increment of 25 W/min. Expired gazes (breath-by-breath), prefrontal cortex and vastus lateralis (VL) oxygenation [Near-infrared spectroscopy (NIRS)] together with electromyographic (EMG) Root Mean Square (RMS) activity for the VL, rectus femoris (RF), and biceps femoris (BF) muscles were continuously assessed. There was a non-linear increase in both cerebral deoxyhemoglobin (at 56 ± 13% of the exercise) and oxyhemoglobin (56 ± 8% of exercise) concomitantly to the first ventilatory threshold (57 ± 6% of exercise, p > 0.86, Cohen's d < 0.1). Cerebral deoxyhemoglobin further increased (87 ± 10% of exercise) while oxyhemoglobin reached a plateau/decreased (86 ± 8% of exercise) after the second ventilatory threshold (81 ± 6% of exercise, p < 0.05, d > 0.8). We identified one threshold only for muscle parameters with a non-linear decrease in muscle oxyhemoglobin (78 ± 9% of exercise), attenuation in muscle deoxyhemoglobin (80 ± 8% of exercise), and increase in EMG activity of VL (89 ± 5% of exercise), RF (82 ± 14% of exercise), and BF (85 ± 9% of exercise). The thresholds in BF and VL EMG activity occurred after the second ventilatory threshold (p < 0.05, d > 0.6). Our results suggest that the metabolic and ventilatory events characterizing this latter cardiopulmonary threshold may affect both cerebral and muscle oxygenation levels, and in turn, muscle recruitment responses. PMID:24782786

  4. A universal molecular clock of protein folds and its power in tracing the early history of aerobic metabolism and planet oxygenation.

    PubMed

    Wang, Minglei; Jiang, Ying-Ying; Kim, Kyung Mo; Qu, Ge; Ji, Hong-Fang; Mittenthal, Jay E; Zhang, Hong-Yu; Caetano-Anollés, Gustavo

    2011-01-01

    The standard molecular clock describes a constant rate of molecular evolution and provides a powerful framework for evolutionary timescales. Here, we describe the existence and implications of a molecular clock of folds, a universal recurrence in the discovery of new structures in the world of proteins. Using a phylogenomic structural census in hundreds of proteomes, we build phylogenies and time lines of domains at fold and fold superfamily levels of structural complexity. These time lines correlate approximately linearly with geological timescales and were here used to date two crucial events in life history, planet oxygenation and organism diversification. We first dissected the structures and functions of enzymes in simulated metabolic networks. The placement of anaerobic and aerobic enzymes in the time line revealed that aerobic metabolism emerged about 2.9 billion years (giga-annum; Ga) ago and expanded during a period of about 400 My, reaching what is known as the Great Oxidation Event. During this period, enzymes recruited old and new folds for oxygen-mediated enzymatic activities. Remarkably, the first fold lost by a superkingdom disappeared in Archaea 2.6 Ga ago, within the span of oxygen rise, suggesting that oxygen also triggered diversification of life. The implications of a molecular clock of folds are many and important for the neutral theory of molecular evolution and for understanding the growth and diversity of the protein world. The clock also extends the standard concept that was specific to molecules and their timescales and turns it into a universal timescale-generating tool. PMID:20805191

  5. Multi-timescale Modeling of Activity-Dependent Metabolic Coupling in the Neuron-Glia-Vasculature Ensemble

    PubMed Central

    Jolivet, Renaud; Coggan, Jay S.; Allaman, Igor; Magistretti, Pierre J.

    2015-01-01

    Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain’s metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging. PMID:25719367

  6. Multi-timescale modeling of activity-dependent metabolic coupling in the neuron-glia-vasculature ensemble.

    PubMed

    Jolivet, Renaud; Coggan, Jay S; Allaman, Igor; Magistretti, Pierre J

    2015-02-01

    Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain's metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging. PMID:25719367

  7. The interrelationship between muscle oxygenation, muscle activation, and pulmonary oxygen uptake to incremental ramp exercise: influence of aerobic fitness.

    PubMed

    Boone, Jan; Barstow, Thomas J; Celie, Bert; Prieur, Fabrice; Bourgois, Jan

    2016-01-01

    We investigated whether muscle and ventilatory responses to incremental ramp exercise would be influenced by aerobic fitness status by means of a cross-sectional study with a large subject population. Sixty-four male students (age: 21.2 ± 3.2 years) with a heterogeneous peak oxygen uptake (51.9 ± 6.3 mL·min(-1)·kg(-1), range 39.7-66.2 mL·min(-1)·kg(-1)) performed an incremental ramp cycle test (20-35 W·min(-1)) to exhaustion. Breath-by-breath gas exchange was recorded, and muscle activation and oxygenation were measured with surface electromyography and near-infrared spectroscopy, respectively. The integrated electromyography (iEMG), mean power frequency (MPF), deoxygenated [hemoglobin and myoglobin] (deoxy[Hb+Mb]), and total[Hb+Mb] responses were set out as functions of work rate and fitted with a double linear function. The respiratory compensation point (RCP) was compared and correlated with the breakpoints (BPs) (as percentage of peak oxygen uptake) in muscle activation and oxygenation. The BP in total[Hb+Mb] (83.2% ± 3.0% peak oxygen uptake) preceded (P < 0.001) the BP in iEMG (86.7% ± 4.0% peak oxygen uptake) and MPF (86.3% ± 4.1% peak oxygen uptake), which in turn preceded (P < 0.01) the BP in deoxy[Hb+Mb] (88.2% ± 4.5% peak oxygen uptake) and RCP (87.4% ± 4.5% peak oxygen uptake). Furthermore, the peak oxygen uptake was significantly (P < 0.001) positively correlated to the BPs and RCP, indicating that the BPs in total[Hb+Mb] (r = 0.66; P < 0.001), deoxy[Hb+Mb] (r = 0.76; P < 0.001), iEMG (r = 0.61; P < 0.001), MPF (r = 0.63; P < 0.001), and RCP (r = 0.75; P < 0.001) occurred at a higher percentage of peak oxygen uptake in subjects with a higher peak oxygen uptake. In this study a close relationship between muscle oxygenation, activation, and pulmonary oxygen uptake was found, occurring in a cascade of events. In subjects with a higher aerobic fitness level this cascade occurred at a higher relative intensity. PMID:26701120

  8. Reactive oxygen species regulate alkaloid metabolism in undifferentiated N. tabacum cells.

    PubMed

    Sachan, Nita; Rogers, Dennis T; Yun, Kil-Young; Littleton, John M; Falcone, Deane L

    2010-05-01

    Plants produce an immense number of natural products and undifferentiated cells from various plant tissues have long been considered an ideal source for their synthesis. However, undifferentiated plant cells often either lose their biosynthetic capacity over time or exhibit immediate repression of the required pathways once dedifferentiated. In this study, freshly prepared callus tissue was employed to further investigate the regulation of a natural product pathway in undifferentiated tobacco cells. Putrescine N-methyltransferase (PMT) is a pathway-specific enzyme required in nicotinic alkaloid production in Nicotiana species. Callus derived from transgenic Nicotiana tabacum plants harboring PMT promoter-GUS fusions were used to study factors that influence PMT expression. Under normal callus growth conditions in the presence of light and auxin, PMT promoter activity was strongly repressed. Conversely, dark conditions and the absence of auxin were found to upregulate PMT promoter activity, with light being dominant to the repressive effects of auxin. Since reactive oxygen species (ROS) are known by-products of photosynthesis and have been implicated in signaling, their involvement was investigated in transgenic callus by treatment with the ROS scavenger, dimethylthiourea, or catalase. Under highly repressive conditions for alkaloid synthesis, including normal culture conditions in the light, both ROS scavengers resulted in significant induction of PMT promoter activity. Moreover, treatment of callus with catalase resulted in the upregulation of PMT promoter activity and alkaloid accumulation in this tissue. These results suggest that ROS impact the regulation of the alkaloid pathway in undifferentiated cells and have implications for regulation of the pathway in other plant tissues. PMID:20217418

  9. Physiological community ecology: variation in metabolic activity of ecologically important rocky intertidal invertebrates along environmental gradients.

    PubMed

    Dahlhoff, Elizabeth P; Stillman, Jonathon H; Menge, Bruce A

    2002-08-01

    Rocky intertidal invertebrates live in heterogeneous habitats characterized by steep gradients in wave activity, tidal flux, temperature, food quality and food availability. These environmental factors impact metabolic activity via changes in energy input and stress-induced alteration of energetic demands. For keystone species, small environmentally induced shifts in metabolic activity may lead to disproportionately large impacts on community structure via changes in growth or survival of these key species. Here we use biochemical indicators to assess how natural differences in wave exposure, temperature and food availability may affect metabolic activity of mussels, barnacles, whelks and sea stars living at rocky intertidal sites with different physical and oceanographic characteristics. We show that oxygen consumption rate is correlated with the activity of key metabolic enzymes (e.g., citrate synthase and malate dehydrogenase) for some intertidal species, and concentrations of these enzymes in certain tissues are lower for starved individuals than for those that are well fed. We also show that the ratio of RNA to DNA (an index of protein synthetic capacity) is highly variable in nature and correlates with short-term changes in food availability. We also observed striking patterns in enzyme activity and RNA/DNA in nature, which are related to differences in rocky intertidal community structure. Differences among species and habitats are most pronounced in summer and are linked to high nearshore productivity at sites favored by suspension feeders and to exposure to stressful low-tide air temperatures in areas of low wave splash. These studies illustrate the great promise of using biochemical indicators to test ecological models, which predict changes in community structure along environmental gradients. Our results also suggest that biochemical indices must be carefully validated with laboratory studies, so that the indicator selected is likely to respond to the

  10. Regulation of Primary Metabolism in Response to Low Oxygen Availability as Revealed by Carbon and Nitrogen Isotope Redistribution1[OPEN

    PubMed Central

    Päpke, Carola; Diab, Houssein; Fernie, Alisdair R.

    2016-01-01

    Based on enzyme activity assays and metabolic responses to waterlogging of the legume Lotus japonicus, it was previously suggested that, during hypoxia, the tricarboxylic acid cycle switches to a noncyclic operation mode. Hypotheses were postulated to explain the alternative metabolic pathways involved, but as yet, a direct analysis of the relative redistribution of label through the corresponding pathways was not made. Here, we describe the use of stable isotope-labeling experiments for studying metabolism under hypoxia using wild-type roots of the crop legume soybean (Glycine max). [13C]Pyruvate labeling was performed to compare metabolism through the tricarboxylic acid cycle, fermentation, alanine metabolism, and the γ-aminobutyric acid shunt, while [13C]glutamate and [15N]ammonium labeling were performed to address the metabolism via glutamate to succinate. Following these labelings, the time course for the redistribution of the 13C/15N label throughout the metabolic network was evaluated with gas chromatography-time of flight-mass spectrometry. Our combined labeling data suggest the inhibition of the tricarboxylic acid cycle enzyme succinate dehydrogenase, also known as complex II of the mitochondrial electron transport chain, providing support for the bifurcation of the cycle and the down-regulation of the rate of respiration measured during hypoxic stress. Moreover, up-regulation of the γ-aminobutyric acid shunt and alanine metabolism explained the accumulation of succinate and alanine during hypoxia. PMID:26553649

  11. Dynamic model for selective metabolic activation in chemical carcinogenesis

    SciTech Connect

    Selkirk, J.K.; MacLeod, M.C.

    1980-01-01

    Theoretical calculations predict the relative ease of formation of carbonium ions from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene-9,10-oxide or from either of the 2 symmetrical bay regions of B(e)P, and suggest their attraction to cellular nucleophiles. When both isomers were metabolized by hamster embryo fibroblasts (HEF) and the products analyzed, the results showed that the probable reason for benzo(e)pyrene's lack of carcinogenicity was its metabolic preference to attack the molecule away from the bay-region area. Particularly striking was the absence of any evidence for the formation of a significant amount of B(e)P-9,10-dihydrodiol. This suggests a metabolic basis for the relative lack of carcinogenic and mutagenic activity of B(e)P. The reason for this is not clear but may be due to physical or chemical factors such as membrane solubility or stereochemical requirements of the active site of the enzyme. The bay-region theory of PAH carcinogenesis predicts that carbonium ion formation from 9,10-dihydro-9,10-dihydroxybenzo(e)pyrene-11, 12-oxide, if formed, would be energetically favorable. Thus, the inability of HEF and microcomes to form B(e)P-9,10-dihydrodiol, the precursor of its potentially highly reactive diol-epoxide, would explain the relative inertness of B(e)P in several biological systems. As the subtle biochemical interactions of the various carcinogen intermediates become clarified, it becomes apparent that susceptibility and resistance to malignant transformation are based on a complex set of both chemical and physical parameters. It is becoming clear that metabolism kinetics, membrane interaction, and the role of nuclear metabolism help dictate the passage of the carcinogen and its reactive intermediates into and through the metabolic machinery of the cell. (ERB)

  12. Activated carbon becomes active for oxygen reduction and hydrogen evolution reactions.

    PubMed

    Yan, Xuecheng; Jia, Yi; Odedairo, Taiwo; Zhao, Xiaojun; Jin, Zhao; Zhu, Zhonghua; Yao, Xiangdong

    2016-06-21

    We utilized a facile method for creating unique defects in the activated carbon (AC), which makes it highly active for the oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER). The ORR activity of the defective AC (D-AC) is comparable to the commercial Pt/C in alkaline medium, and the D-AC also exhibits excellent HER activity in acidic solution. PMID:27277286

  13. Microbial metabolic activity in soil as measured by dehydrogenase determinations

    NASA Technical Reports Server (NTRS)

    Casida, L. E., Jr.

    1977-01-01

    The dehydrogenase technique for measuring the metabolic activity of microorganisms in soil was modified to use a 6-h, 37 C incubation with either glucose or yeast extract as the electron-donating substrate. The rate of formazan production remained constant during this time interval, and cellular multiplication apparently did not occur. The technique was used to follow changes in the overall metabolic activities of microorganisms in soil undergoing incubation with a limiting concentration of added nutrient. The sequence of events was similar to that obtained by using the Warburg respirometer to measure O2 consumption. However, the major peaks of activity occurred earlier with the respirometer. This possibly is due to the lack of atmospheric CO2 during the O2 consumption measurements.

  14. Metabolic, autophagic, and mitophagic activities in cancer initiation and progression.

    PubMed

    Hjelmeland, Anita; Zhang, Jianhua

    2016-04-01

    Cancer is a complex disease marked by uncontrolled cell growth and invasion. These processes are driven by the accumulation of genetic and epigenetic alterations that promote cancer initiation and progression. Contributing to genome changes are the regulation of oxidative stress and reactive species-induced damage to molecules and organelles. Redox regulation, metabolic plasticity, autophagy, and mitophagy play important and interactive roles in cancer hallmarks including sustained proliferation, activated invasion, and replicative immortality. However, the impact of these processes can differ depending on the signaling pathways altered in cancer, tumor type, tumor stage, and/or the differentiation state. Here, we highlight some of the representative studies on the impact of oxidative and nitrosative activities, mitochondrial bioenergetics, metabolism, and autophagy and mitophagy in the context of tumorigenesis. We discuss the implications of these processes for cellular activities in cancer for anti-cancer-based therapeutics. PMID:27372165

  15. Novel TPP-riboswitch activators bypass metabolic enzyme dependency

    NASA Astrophysics Data System (ADS)

    Mayer, Günter; Lünse, Christina; Suckling, Colin; Scott, Fraser

    2014-07-01

    Riboswitches are conserved regions within mRNA molecules that bind specific metabolites and regulate gene expression. TPP-riboswitches, which respond to thiamine pyrophosphate (TPP), are involved in the regulation of thiamine metabolism in numerous bacteria. As these regulatory RNAs are often modulating essential biosynthesis pathways they have become increasingly interesting as promising antibacterial targets. Here, we describe thiamine analogs containing a central 1,2,3-triazole group to induce repression of thiM-riboswitch dependent gene expression in different E. coli strains. Additionally, we show that compound activation is dependent on proteins involved in the metabolic pathways of thiamine uptake and synthesis. The most promising molecule, triazolethiamine (TT), shows concentration dependent reporter gene repression that is dependent on the presence of thiamine kinase ThiK, whereas the effect of pyrithiamine (PT), a known TPP-riboswitch modulator, is ThiK independent. We further show that this dependence can be bypassed by triazolethiamine-derivatives that bear phosphate-mimicking moieties. As triazolethiamine reveals superior activity compared to pyrithiamine, it represents a very promising starting point for developing novel antibacterial compounds that target TPP-riboswitches. Riboswitch-targeting compounds engage diverse endogenous mechanisms to attain in vivo activity. These findings are of importance for the understanding of compounds that require metabolic activation to achieve effective riboswitch modulation and they enable the design of novel compound generations that are independent of endogenous activation mechanisms.

  16. Glucose deprivation activates a metabolic and signaling amplification loop leading to cell death

    PubMed Central

    Graham, Nicholas A; Tahmasian, Martik; Kohli, Bitika; Komisopoulou, Evangelia; Zhu, Maggie; Vivanco, Igor; Teitell, Michael A; Wu, Hong; Ribas, Antoni; Lo, Roger S; Mellinghoff, Ingo K; Mischel, Paul S; Graeber, Thomas G

    2012-01-01

    The altered metabolism of cancer can render cells dependent on the availability of metabolic substrates for viability. Investigating the signaling mechanisms underlying cell death in cells dependent upon glucose for survival, we demonstrate that glucose withdrawal rapidly induces supra-physiological levels of phospho-tyrosine signaling, even in cells expressing constitutively active tyrosine kinases. Using unbiased mass spectrometry-based phospho-proteomics, we show that glucose withdrawal initiates a unique signature of phospho-tyrosine activation that is associated with focal adhesions. Building upon this observation, we demonstrate that glucose withdrawal activates a positive feedback loop involving generation of reactive oxygen species (ROS) by NADPH oxidase and mitochondria, inhibition of protein tyrosine phosphatases by oxidation, and increased tyrosine kinase signaling. In cells dependent on glucose for survival, glucose withdrawal-induced ROS generation and tyrosine kinase signaling synergize to amplify ROS levels, ultimately resulting in ROS-mediated cell death. Taken together, these findings illustrate the systems-level cross-talk between metabolism and signaling in the maintenance of cancer cell homeostasis. PMID:22735335

  17. Metabolic activity in dormant conidia of Aspergillus niger and developmental changes during conidial outgrowth.

    PubMed

    Novodvorska, Michaela; Stratford, Malcolm; Blythe, Martin J; Wilson, Raymond; Beniston, Richard G; Archer, David B

    2016-09-01

    The early stages of development of Aspergillus niger conidia during outgrowth were explored by combining genome-wide gene expression analysis (RNAseq), proteomics, Warburg manometry and uptake studies. Resting conidia suspended in water were demonstrated for the first time to be metabolically active as low levels of oxygen uptake and the generation of carbon dioxide were detected, suggesting that low-level respiratory metabolism occurs in conidia for maintenance. Upon triggering of spore germination, generation of CO2 increased dramatically. For a short period, which coincided with mobilisation of the intracellular polyol, trehalose, there was no increase in uptake of O2 indicating that trehalose was metabolised by fermentation. Data from genome-wide mRNA profiling showed the presence of transcripts associated with fermentative and respiratory metabolism in resting conidia. Following triggering of conidial outgrowth, there was a clear switch to respiration after 25min, confirmed by cyanide inhibition. No effect of SHAM, salicylhydroxamic acid, on respiration suggests electron flow via cytochrome c oxidase. Glucose entry into spores was not detectable before 1h after triggering germination. The impact of sorbic acid on germination was examined and we showed that it inhibits glucose uptake. O2 uptake was also inhibited, delaying the onset of respiration and extending the period of fermentation. In conclusion, we show that conidia suspended in water are not completely dormant and that conidial outgrowth involves fermentative metabolism that precedes respiration. PMID:27378203

  18. Quantifying the cerebral metabolic rate of oxygen by combining diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Verdecchia, Kyle; Diop, Mamadou; Lee, Ting-Yim; St. Lawrence, Keith

    2013-02-01

    Preterm infants are highly susceptible to ischemic brain injury; consequently, continuous bedside monitoring to detect ischemia before irreversible damage occurs would improve patient outcome. In addition to monitoring cerebral blood flow (CBF), assessing the cerebral metabolic rate of oxygen (CMRO2) would be beneficial considering that metabolic thresholds can be used to evaluate tissue viability. The purpose of this study was to demonstrate that changes in absolute CMRO2 could be measured by combining diffuse correlation spectroscopy (DCS) with time-resolved near-infrared spectroscopy (TR-NIRS). Absolute CBF was determined using bolus-tracking TR-NIRS to calibrate the DCS measurements. Cerebral venous blood oxygenation (SvO2) was determined by multiwavelength TR-NIRS measurements, the accuracy of which was assessed by directly measuring the oxygenation of sagittal sinus blood. In eight newborn piglets, CMRO2 was manipulated by varying the anesthetics and by injecting sodium cyanide. No significant differences were found between the two sets of SvO2 measurements obtained by TR-NIRS or sagittal sinus blood samples and the corresponding CMRO2 measurements. Bland-Altman analysis showed a mean CMRO2 difference of 0.0268±0.8340 mL O2/100 g/min between the two techniques over a range from 0.3 to 4 mL O2/100 g/min.

  19. Relationship Between Cerebral Oxygenation and Metabolism During Rewarming in Newborn Infants After Therapeutic Hypothermia Following Hypoxic-Ischemic Brain Injury.

    PubMed

    Mitra, Subhabrata; Bale, Gemma; Meek, Judith; Uria-Avellanal, Cristina; Robertson, Nicola J; Tachtsidis, Ilias

    2016-01-01

    Therapeutic hypothermia (TH) has become a standard of care following hypoxic ischemic encephalopathy (HIE). After TH, body temperature is brought back to 37 °C over 14 h. Lactate/N-acetylasperatate (Lac/NAA) peak area ratio on proton magnetic resonance spectroscopy ((1)H MRS) is the best available outcome biomarker following HIE. We hypothesized that broadband near infrared spectroscopy (NIRS) measured changes in the oxidation state of cytochrome-c-oxidase concentration (Δ[oxCCO]) and cerebral hemodynamics during rewarming would relate to Lac/NAA. Broadband NIRS and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. (1)H MRS was performed on day 5-9. Heart rate increased by 20/min during rewarming while blood pressure and peripheral oxygen saturation (SpO2) remained stable. The relationship between mitochondrial metabolism and oxygenation (measured as Δ[oxCCO] and Δ[HbD], respectively) was calculated by linear regression analysis. This was reviewed in three groups: Lac/NAA values <0.5, 0.5-1, >1. Mean regression coefficient (r (2)) values in these groups were 0.41 (±0.27), 0.22 (±0.21) and 0.01, respectively. The relationship between mitochondrial metabolism and oxygenation became impaired with rising Lac/NAA. Cardiovascular parameters remained stable during rewarming. PMID:27526150

  20. Pyruvate modifies metabolic flux and nutrient sensing during extracorporeal membrane oxygenation in an immature swine model

    PubMed Central

    Ledee, Dolena R.; Kajimoto, Masaki; O'Kelly Priddy, Colleen M.; Olson, Aaron K.; Isern, Nancy; Robillard-Frayne, Isabelle; Des Rosiers, Christine

    2015-01-01

    Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support for infants and children with postoperative cardiopulmonary failure. Nutritional support is mandatory during ECMO although specific actions for substrates on the heart have not been delineated. Prior work shows that enhancing pyruvate oxidation promotes successful weaning from ECMO. Accordingly, we tested the hypothesis that prolonged systemic pyruvate supplementation activates pyruvate oxidation in an immature swine model in vivo. Twelve male mixed-breed Yorkshire piglets (age 30–49 days) received systemic infusion of either normal saline (group C) or pyruvate (group P) during the final 6 h of 8 h of ECMO. Over the final hour, piglets received [2-13C] pyruvate, as a reference substrate for oxidation, and [13C6]-l-leucine, as an indicator for amino acid oxidation and protein synthesis. A significant increase in lactate and pyruvate concentrations occurred, along with an increase in the absolute concentration of the citric acid cycle intermediates. An increase in anaplerotic flux through pyruvate carboxylation in group P occurred compared with no change in pyruvate oxidation. Additionally, pyruvate promoted an increase in the phosphorylation state of several nutrient-sensitive enzymes, like AMP-activated protein kinase and acetyl CoA carboxylase, suggesting activation for fatty acid oxidation. Pyruvate also promoted O-GlcNAcylation through the hexosamine biosynthetic pathway. In conclusion, although prolonged pyruvate supplementation did not alter pyruvate oxidation, it did elicit changes in nutrient- and energy-sensitive pathways. Therefore, the observed results support the further study of pyruvate and its downstream effect on cardiac function. PMID:25910802

  1. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease

    PubMed Central

    Azhar, Salman

    2011-01-01

    Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/β and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. PMID:20932114

  2. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease.

    PubMed

    Azhar, Salman

    2010-09-01

    Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/ß and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. PMID:20932114

  3. Metabolic correlates of subthalamic nucleus activity in Parkinson's disease.

    PubMed

    Lin, Tanya P; Carbon, Maren; Tang, Chengke; Mogilner, Alon Y; Sterio, Djordje; Beric, Aleksandar; Dhawan, Vijay; Eidelberg, David

    2008-05-01

    Overactivity of subthalamic nucleus (STN) neurons is a consistent feature of Parkinson's disease (PD) and is a target of therapy for this disorder. However, the relationship of STN firing rate to regional brain function is not known. We scanned 17 PD patients with (18)F-fluorodeoxyglucose (FDG) PET to measure resting glucose metabolism before the implantation of STN deep brain stimulation electrodes. Spontaneous STN firing rates were recorded during surgery and correlated with preoperative regional glucose metabolism on a voxel-by-voxel basis. We also examined the relationship between firing rate and the activity of metabolic brain networks associated with the motor and cognitive manifestations of the disease. Mean firing rates were 47.2 +/- 6.1 and 48.7 +/- 8.5 Hz for the left and right hemispheres, respectively. These measures correlated (P < 0.007) with glucose metabolism in the putamen and globus pallidus, which receive projections from this structure. Significant correlations (P < 0.0005) were also evident in the primary motor (BA4) and dorsolateral prefrontal (BA46/10) cortical areas. The activity of both the motor (P < 0.0001) and the cognitive (P < 0.006) PD-related metabolic networks was elevated in these patients. STN firing rates correlated with the activity of the former (P < 0.007) but not the latter network (P = 0.39). The findings suggest that the functional pathways associated with motor disability in PD are linked to the STN firing rate. These pathways are likely to mediate the clinical benefit that is seen following targeted STN interventions for this disease. PMID:18400841

  4. Human Aldo-Keto Reductases and the Metabolic Activation of Polycyclic Aromatic Hydrocarbons

    PubMed Central

    2015-01-01

    Aldo-keto reductases (AKRs) are promiscuous NAD(P)(H) dependent oxidoreductases implicated in the metabolic activation of polycyclic aromatic hydrocarbons (PAH). These enzymes catalyze the oxidation of non-K-region trans-dihydrodiols to the corresponding o-quinones with the concomitant production of reactive oxygen species (ROS). The PAH o-quinones are Michael acceptors and can form adducts but are also redox-active and enter into futile redox cycles to amplify ROS formation. Evidence exists to support this metabolic pathway in humans. The human recombinant AKR1A1 and AKR1C1–AKR1C4 enzymes all catalyze the oxidation of PAH trans-dihydrodiols to PAH o-quinones. Many human AKRs also catalyze the NADPH-dependent reduction of the o-quinone products to air-sensitive catechols, exacerbating ROS formation. Moreover, this pathway of PAH activation occurs in a panel of human lung cell lines, resulting in the production of ROS and oxidative DNA damage in the form of 8-oxo-2′-deoxyguanosine. Using stable-isotope dilution liquid chromatography tandem mass spectrometry, this pathway of benzo[a]pyrene (B[a]P) metabolism was found to contribute equally with the diol-epoxide pathway to the activation of this human carcinogen in human lung cells. Evaluation of the mutagenicity of anti-B[a]P-diol epoxide with B[a]P-7,8-dione on p53 showed that the o-quinone produced by AKRs was the more potent mutagen, provided that it was permitted to redox cycle, and that the mutations observed were G to T transversions, reminiscent of those observed in human lung cancer. It is concluded that there is sufficient evidence to support the role of human AKRs in the metabolic activation of PAH in human lung cell lines and that they may contribute to the causation of human lung cancer. PMID:25279998

  5. Human aldo-keto reductases and the metabolic activation of polycyclic aromatic hydrocarbons.

    PubMed

    Penning, Trevor M

    2014-11-17

    Aldo-keto reductases (AKRs) are promiscuous NAD(P)(H) dependent oxidoreductases implicated in the metabolic activation of polycyclic aromatic hydrocarbons (PAH). These enzymes catalyze the oxidation of non-K-region trans-dihydrodiols to the corresponding o-quinones with the concomitant production of reactive oxygen species (ROS). The PAH o-quinones are Michael acceptors and can form adducts but are also redox-active and enter into futile redox cycles to amplify ROS formation. Evidence exists to support this metabolic pathway in humans. The human recombinant AKR1A1 and AKR1C1-AKR1C4 enzymes all catalyze the oxidation of PAH trans-dihydrodiols to PAH o-quinones. Many human AKRs also catalyze the NADPH-dependent reduction of the o-quinone products to air-sensitive catechols, exacerbating ROS formation. Moreover, this pathway of PAH activation occurs in a panel of human lung cell lines, resulting in the production of ROS and oxidative DNA damage in the form of 8-oxo-2'-deoxyguanosine. Using stable-isotope dilution liquid chromatography tandem mass spectrometry, this pathway of benzo[a]pyrene (B[a]P) metabolism was found to contribute equally with the diol-epoxide pathway to the activation of this human carcinogen in human lung cells. Evaluation of the mutagenicity of anti-B[a]P-diol epoxide with B[a]P-7,8-dione on p53 showed that the o-quinone produced by AKRs was the more potent mutagen, provided that it was permitted to redox cycle, and that the mutations observed were G to T transversions, reminiscent of those observed in human lung cancer. It is concluded that there is sufficient evidence to support the role of human AKRs in the metabolic activation of PAH in human lung cell lines and that they may contribute to the causation of human lung cancer. PMID:25279998

  6. Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production.

    PubMed

    Carnagarin, Revathy; Carlessi, Rodrigo; Newsholme, Philip; Dharmarajan, Arun M; Dass, Crispin R

    2016-09-01

    Pigment epithelium-derived factor is a multifunctional serpin implicated in insulin resistance in metabolic disorders. Recent evidence suggests that exposure of peripheral tissues such as skeletal muscle to PEDF has profound metabolic consequences with predisposition towards chronic conditions such as obesity, type 2 diabetes, metabolic syndrome and polycystic ovarian syndrome. Chronic inflammation shifts muscle metabolism towards increased glycolysis and decreased oxidative metabolism. In the present study, we demonstrate a novel effect of PEDF on cellular metabolism in mouse cell line (C2C12) and human primary skeletal muscle cells. PEDF addition to skeletal muscle cells induced enhanced phospholipase A2 activity. This was accompanied with increased production of reactive oxygen species in a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent manner that triggered a shift towards a more glycolytic phenotype. Extracellular flux analysis and glucose consumption assays demonstrated that PEDF treatment resulted in enhanced glycolysis but did not change mitochondrial respiration. Our results demonstrate that skeletal muscle cells express a PEDF-inducible oxidant generating system that enhances glycolysis but is sensitive to antioxidants and NADPH oxidase inhibition. PMID:27343430

  7. Oxygen metabolism in the northern Gulf of Mexico in the vicinity of the Deepwater Horizon oil spill

    NASA Astrophysics Data System (ADS)

    Ostrom, N. E.; Gandhi, H.; Kamphuis, B.; Decamp, S.; Liu, Z.; Gardner, W. S.

    2010-12-01

    Oxygen metabolism was evaluated in the northern Gulf of Mexico hypoxia region in May and August of 2010. Sampling initially occurred approximately one month after the initiation of the Deepwater Horizon oil spill and 6 stations were sampled within approximately 100 km of the drill site (Figure 1). Nearly or hypoxic (< 2 mg O2/L) conditions were evident in the bottom waters of 4 of the stations including one station east of the Mississippi River where hypoxia has rarely been observed. Strong supersaturation in oxygen (up to 142%) was evident in the surface waters at several stations. Oxygen isotope values (with respect to the air standard) in May varied between -3.5 and 9.8 per mil. Negative values are indicative of oxygen derived primarily from primary production where as positive values are associated with oxygen consumption by respiration and were most evident in near bottom waters. Oxygen concentration and isotope values were modeled to determine the ratio of respiration to primary production and ratios above the pycnocline varied between 0.4 and 1.8. The study site with the highest R:P ratio was a site in which an oil sheen and tarballs were clearly evident at the surface. Further, this station was characterized by a distinct mid-water column oxygen minimum and high R:P ratio at the base of the pycnocline reflecting enhanced respiration. Fractionation factors associated with oxygen consumption during respiration were determined for samples beneath the pycnocline and ranged from 3.6 to 10.3 per mil. Our observation of low fractionation factors at our stations indicates that respiration in sediments consumes more oxygen than that in the water column. Based on the expected fractionation factors for oxygen consumption in sediments (3 per mil) and that in the water column (23.5 per mil) we found that sediment respiration was 64.3 to 97.1 % of total respiration beneath the pycnocline. This result indicates hypoxia in this area is largely driven by respiration in

  8. Active metabolism of thyroid hormone during metamorphosis of amphioxus.

    PubMed

    Paris, Mathilde; Hillenweck, Anne; Bertrand, Stéphanie; Delous, Georges; Escriva, Hector; Zalko, Daniel; Cravedi, Jean-Pierre; Laudet, Vincent

    2010-07-01

    Thyroid hormones (THs), and more precisely the 3,3',5-triiodo-l-thyronine (T(3)) acetic derivative 3,3',5-triiodothyroacetic acid (TRIAC), have been shown to activate metamorphosis in amphioxus. However, it remains unknown whether TRIAC is endogenously synthesized in amphioxus and more generally whether an active TH metabolism is regulating metamorphosis. Here we show that amphioxus naturally produces TRIAC from its precursors T(3) and l-thyroxine (T(4)), supporting its possible role as the active TH in amphioxus larvae. In addition, we show that blocking TH production inhibits metamorphosis and that this effect is compensated by exogenous T(3), suggesting that a peak of TH production is important for advancement of proper metamorphosis. Moreover, several amphioxus genes encoding proteins previously proposed to be involved in the TH signaling pathway display expression profiles correlated with metamorphosis. In particular, thyroid hormone receptor (TR) and deiodinases gene expressions are either up- or down-regulated during metamorphosis and by TH treatments. Overall, these results suggest that an active TH metabolism controls metamorphosis in amphioxus, and that endogenous TH production and metabolism as well as TH-regulated metamorphosis are ancestral in the chordate lineage. PMID:21558188

  9. Marine Omega-3 Phospholipids: Metabolism and Biological Activities

    PubMed Central

    Burri, Lena; Hoem, Nils; Banni, Sebastiano; Berge, Kjetil

    2012-01-01

    The biological activities of omega-3 fatty acids (n-3 FAs) have been under extensive study for several decades. However, not much attention has been paid to differences of dietary forms, such as triglycerides (TGs) versus ethyl esters or phospholipids (PLs). New innovative marine raw materials, like krill and fish by-products, present n-3 FAs mainly in the PL form. With their increasing availability, new evidence has emerged on n-3 PL biological activities and differences to n-3 TGs. In this review, we describe the recently discovered nutritional properties of n-3 PLs on different parameters of metabolic syndrome and highlight their different metabolic bioavailability in comparison to other dietary forms of n-3 FAs. PMID:23203133

  10. [An electrochemical method for measuring metabolic activity and counting cells].

    PubMed

    Kuznetsov, B a; Khlupova, M e; Shleev, S V; Kaprel'iants, A S; Iaropolov, A I

    2006-01-01

    An express electrochemical method for determining the metabolic activity of live cells based on the possibility of an electron exchange between an electrode and elements of the biological electron transfer chain in the presence of a mediator is proposed. This method is useful for studying any live cells (animal, plant, and microbial), including anaerobic, dormant, and spore cells. The sample preparation and measurement itself does not take more than 30 min. The detection limit in a volume of 15 ml amounts to 10-5 cells/ml. The applicability of the assessment method of the metabolic activity level during the transition of the bacteria Mycobacterium smegmatis into an uncultivable dormant state was demonstrated. This method is of special value for medicine and environmental control, detecting latent forms of pathogens. An optimal combination of the methods for the express analysis of latent pathogens is proposed. PMID:17066962

  11. Activating and Elucidating Metabolism of Complex Sugars in Yarrowia lipolytica.

    PubMed

    Ryu, Seunghyun; Hipp, Julie; Trinh, Cong T

    2016-02-01

    The oleaginous yeast Yarrowia lipolytica is an industrially important host for production of organic acids, oleochemicals, lipids, and proteins with broad biotechnological applications. Albeit known for decades, the unique native metabolism of Y. lipolytica for using complex fermentable sugars, which are abundant in lignocellulosic biomass, is poorly understood. In this study, we activated and elucidated the native sugar metabolism in Y. lipolytica for cell growth on xylose and cellobiose as well as their mixtures with glucose through comprehensive metabolic and transcriptomic analyses. We identified 7 putative glucose-specific transporters, 16 putative xylose-specific transporters, and 4 putative cellobiose-specific transporters that are transcriptionally upregulated for growth on respective single sugars. Y. lipolytica is capable of using xylose as a carbon source, but xylose dehydrogenase is the key bottleneck of xylose assimilation and is transcriptionally repressed by glucose. Y. lipolytica has a set of 5 extracellular and 6 intracellular β-glucosidases and is capable of assimilating cellobiose via extra- and intracellular mechanisms, the latter being dominant for growth on cellobiose as a sole carbon source. Strikingly, Y. lipolytica exhibited enhanced sugar utilization for growth in mixed sugars, with strong carbon catabolite activation for growth on the mixture of xylose and cellobiose and with mild carbon catabolite repression of glucose on xylose and cellobiose. The results of this study shed light on fundamental understanding of the complex native sugar metabolism of Y. lipolytica and will help guide inverse metabolic engineering of Y. lipolytica for enhanced conversion of biomass-derived fermentable sugars to chemicals and fuels. PMID:26682853

  12. Activating and Elucidating Metabolism of Complex Sugars in Yarrowia lipolytica

    PubMed Central

    Ryu, Seunghyun; Hipp, Julie

    2015-01-01

    The oleaginous yeast Yarrowia lipolytica is an industrially important host for production of organic acids, oleochemicals, lipids, and proteins with broad biotechnological applications. Albeit known for decades, the unique native metabolism of Y. lipolytica for using complex fermentable sugars, which are abundant in lignocellulosic biomass, is poorly understood. In this study, we activated and elucidated the native sugar metabolism in Y. lipolytica for cell growth on xylose and cellobiose as well as their mixtures with glucose through comprehensive metabolic and transcriptomic analyses. We identified 7 putative glucose-specific transporters, 16 putative xylose-specific transporters, and 4 putative cellobiose-specific transporters that are transcriptionally upregulated for growth on respective single sugars. Y. lipolytica is capable of using xylose as a carbon source, but xylose dehydrogenase is the key bottleneck of xylose assimilation and is transcriptionally repressed by glucose. Y. lipolytica has a set of 5 extracellular and 6 intracellular β-glucosidases and is capable of assimilating cellobiose via extra- and intracellular mechanisms, the latter being dominant for growth on cellobiose as a sole carbon source. Strikingly, Y. lipolytica exhibited enhanced sugar utilization for growth in mixed sugars, with strong carbon catabolite activation for growth on the mixture of xylose and cellobiose and with mild carbon catabolite repression of glucose on xylose and cellobiose. The results of this study shed light on fundamental understanding of the complex native sugar metabolism of Y. lipolytica and will help guide inverse metabolic engineering of Y. lipolytica for enhanced conversion of biomass-derived fermentable sugars to chemicals and fuels. PMID:26682853

  13. Production and Characterization of Active Transparent PET Films for Oxygen Sensitive Foods Packaging

    NASA Astrophysics Data System (ADS)

    Rosaria Galdi, Maria; Incarnato, Loredana

    2010-06-01

    The aim of this work is to investigate possible solutions to realize active, transparent PET film suitable for packaging oxygen sensitive foods. At this purpose, monolayer active PET films at different oxygen scavenger concentrations and multilayer active ones were produced by cast extrusion laboratory scale equipments. To assess their activity and to verify the efficacy of such solutions, O2 absorption analyses were carried out in continuous by an innovative oxygen meter.

  14. Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides. The involvement of sulphur metabolism

    PubMed Central

    Neuberger, Albert; Sandy, John D.; Tait, George H.

    1973-01-01

    1. The `initial' 5-aminolaevulinate synthetase activity, that is the activity observed immediately after cell disruption, in extracts prepared from unharvested semianaerobically grown Rhodopseudomonas spheroides, was twice that observed under the same assay conditions in extracts prepared from harvested cells. 2. The effect of oxygenation of a culture on the `maximum' aminolaevulinate synthetase activity, that is the activity observed 1h after disruption of harvested cells, is markedly influenced by the contents of the growth medium. Oxygenation of organisms for 1h in the medium in which they have grown produces an 80–90% decrease in maximum activity, whereas similar treatment of organisms resuspended in fresh medium produces less than a 40% decrease. 3. This protective effect of fresh medium is absolutely dependent on the presence of sulphate. When cells are suspended in sulphate-deficient fresh medium, the maximum activity falls by 65–75% even without oxygenation. A high maximum activity is regenerated when sulphate is resupplied. 4. When organisms are oxygenated in the medium in which they have grown, the cellular contents of GSH+GSSG and cysteine+cystine fall very markedly and homolanthionine is formed. Both the fall in aminolaevulinate synthetase activity and the changes in sulphur metabolism are largely prevented by the addition of compounds which stimulate synthesis of cysteine de novo or inhibit the conversion of cysteine S into homocysteine S. 5. The maximum aminolaevulinate synthetase activity was directly proportional to the GSH+GSSG content of all cell preparations. In glutathione-depleted extracts the `low'-activity enzyme could be re-activated in vitro by the addition of GSH, GSSG, cysteine or cystine, whereas in extracts with a high glutathione content the `high'-activity enzyme was unaffected by these sulphur compounds. 6. The activation of low-activity enzyme with exogenous sulphur compounds was prevented by excluding air or by adding NADH

  15. A combined method to quantify the retinal metabolic rate of oxygen using photoacoustic ophthalmoscopy and optical coherence tomography

    PubMed Central

    Song, Wei; Wei, Qing; Liu, Wenzhong; Liu, Tan; Yi, Ji; Sheibani, Nader; Fawzi, Amani A.; Linsenmeier, Robert A.; Jiao, Shuliang; Zhang, Hao F.

    2014-01-01

    Quantitatively determining physiological parameters at a microscopic level in the retina furthers the understanding of the molecular pathways of blinding diseases, such as diabetic retinopathy and glaucoma. An essential parameter, which has yet to be quantified noninvasively, is the retinal oxygen metabolic rate (rMRO2). Quantifying rMRO2 is challenging because two parameters, the blood flow rate and hemoglobin oxygen saturation (sO2), must be measured together. We combined photoacoustic ophthalmoscopy (PAOM) with spectral domain-optical coherence tomography (SD-OCT) to tackle this challenge, in which PAOM measured the sO2 and SD-OCT mapped the blood flow rate. We tested the integrated system on normal wild-type rats, in which the measured rMRO2 was 297.86 ± 70.23 nl/minute. This quantitative method may shed new light on both fundamental research and clinical care in ophthalmology in the future. PMID:25283870

  16. BMP7 drives human adipogenic stem cells into metabolically active beige adipocytes

    PubMed Central

    Okla, Meshail; Ha, Jung-Heun; Temel, Ryan E.; Chung, Soonkyu

    2014-01-01

    Adult humans have a substantial amount of inducible-brown (or beige) fat, which is associated with increased energy expenditure and reduced weight gain via thermogenesis. Despite the identification of key regulators of beige adipogenesis, impacts of dietary factors on adaptive thermogenesis are largely unknown, partly due to a lack of validated human cell models. Bone morphogenetic protein 7 (BMP7) is known to promote brown adipogenesis in rodent and human progenitor cells. However, controversy still surrounds the cellular identity in BMP7-mediated transition of white to brown adipocytes. The aim of this study is to confirm BMP7-derived human adipocytes as a relevant in vitro model of human beige adipocyte by verifying the cellular lineage and metabolic activity. In this study, we hypothesized that pre-exposure of stromal vascular (SV) fraction of primary human adipogenic precursor cells (hASC) to BMP7 would convert metabolically active brown adipocytes. Our results showed that exposure of hASC to human BMP7 was associated with significant escalation of 1) UCP1 gene expression, a signature gene of brown adipocytes, 2) beige specific marker gene expression (i.e., CD137 and TMEM26), 3) glucose and fatty acid uptake, and 4) basal and cAMP-stimulated oxygen consumption rate compared to white adipocyte control. Taken together, we demonstrated that BMP7 mediates conversion of hASC into metabolically active beige adipocytes. By confirming the cellular identity and metabolic activity, this BMP7-induced human beige adipocytes from hASC should aid in the discovery and assessment of bioactive molecules to promote adaptive thermogenesis. PMID:25534037

  17. BMP7 drives human adipogenic stem cells into metabolically active beige adipocytes.

    PubMed

    Okla, Meshail; Ha, Jung-Heun; Temel, Ryan E; Chung, Soonkyu

    2015-02-01

    Adult humans have a substantial amount of inducible-brown (or beige) fat, which is associated with increased energy expenditure and reduced weight gain via thermogenesis. Despite the identification of key regulators of beige adipogenesis, impacts of dietary factors on adaptive thermogenesis are largely unknown, partly due to a lack of validated human cell models. Bone morphogenetic protein 7 (BMP7) is known to promote brown adipogenesis in rodent and human progenitor cells. However, controversy still surrounds the cellular identity in BMP7-mediated transition of white to brown adipocytes. The aim of this study was to confirm BMP7-derived human adipocytes as a relevant in vitro model of human beige adipocyte by verifying the cellular lineage and metabolic activity. In this study, we hypothesized that pre-exposure of the stromal vascular (SV) fraction of primary human adipogenic precursor cells (hASC) to BMP7 would convert metabolically active brown adipocytes. Our results showed that exposure of hASC to human BMP7 was associated with significant escalation of (1) UCP1 gene expression, a signature gene of brown adipocytes, (2) beige specific marker gene expression (i.e., CD137 and TMEM26), (3) glucose and fatty acid uptake, and (4) basal and cAMP-stimulated oxygen consumption rate compared to white adipocyte control. Taken together, we demonstrated that BMP7 mediates conversion of hASC into metabolically active beige adipocytes. By confirming the cellular identity and metabolic activity, this BMP7-induced human beige adipocytes from hASC should aid in the discovery and assessment of bioactive molecules to promote adaptive thermogenesis. PMID:25534037

  18. Metabolic oxygen consumption measurement with a single-cell biosensor after particle microbeam irradiation.

    PubMed

    Xu, Yanping; Zhang, Bo; Messerli, Mark; Randers-Pehrson, Gerhard; Hei, Tom K; Brenner, David J

    2015-03-01

    A noninvasive, self-referencing biosensor/probe system has been integrated into the Columbia University Radiological Research Accelerator Facility Microbeam II end station. A single-cell oxygen consumption measurement has been conducted with this type of oxygen probe in 37° C Krebs-Ringer Bicarbonate buffer immediately before and after a single-cell microbeam irradiation. It is the first such measurement made for a microbeam irradiation, and a six fold increment of oxygen flux induced during a 15-s period of time has been observed following radiation exposure. The experimental procedure and the results are discussed. PMID:25335641

  19. Metabolic oxygen consumption measurement with a single-cell biosensor after particle microbeam irradiation

    PubMed Central

    Zhang, Bo; Messerli, Mark; Randers-Pehrson, Gerhard; Hei, Tom K.; Brenner, David J.

    2015-01-01

    A noninvasive, self-referencing biosensor/probe system has been integrated into the Columbia University Radiological Research Accelerator Facility Microbeam II end station. A single-cell oxygen consumption measurement has been conducted with this type of oxygen probe in 37°C Krebs–Ringer Bicarbonate buffer immediately before and after a single-cell microbeam irradiation. It is the first such measurement made for a microbeam irradiation, and a six fold increment of oxygen flux induced during a 15-s period of time has been observed following radiation exposure. The experimental procedure and the results are discussed. PMID:25335641

  20. Metabolic activation of carcinogenic ethylbenzene leads to oxidative DNA damage.

    PubMed

    Midorikawa, Kaoru; Uchida, Takafumi; Okamoto, Yoshinori; Toda, Chitose; Sakai, Yoshie; Ueda, Koji; Hiraku, Yusuke; Murata, Mariko; Kawanishi, Shosuke; Kojima, Nakao

    2004-12-01

    Ethylbenzene is carcinogenic to rats and mice, while it has no mutagenic activity. We have investigated whether ethylbenzene undergoes metabolic activation, leading to DNA damage. Ethylbenzene was metabolized to 1-phenylethanol, acetophenone, 2-ethylphenol and 4-ethylphenol by rat liver microsomes. Furthermore, 2-ethylphenol and 4-ethylphenol were metabolically transformed to ring-dihydroxylated metabolites such as ethylhydroquinone and 4-ethylcatechol, respectively. Experiment with 32P-labeled DNA fragment revealed that both ethylhydroquinone and 4-ethylcatechol caused DNA damage in the presence of Cu(II). These dihydroxylated compounds also induced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in calf thymus DNA in the presence of Cu(II). Catalase, methional and Cu(I)-specific chelator, bathocuproine, significantly (P<0.05) inhibited oxidative DNA damage, whereas free hydroxyl radical scavenger and superoxide dismutase did not. These results suggest that Cu(I) and H2O2 produced via oxidation of ethylhydroquinone and 4-ethylcatechol are involved in oxidative DNA damage. Addition of an endogenous reductant NADH dramatically enhanced 4-ethylcatechol-induced oxidative DNA damage, whereas ethylhydroquinone-induced DNA damage was slightly enhanced. Enhancing effect of NADH on oxidative DNA damage by 4-ethylcatechol may be explained by assuming that reactive species are generated from the redox cycle. In conclusion, these active dihydroxylated metabolites would be involved in the mechanism of carcinogenesis by ethylbenzene. PMID:15560893

  1. Carbohydrate-active enzymes exemplify entropic principles in metabolism

    PubMed Central

    Kartal, Önder; Mahlow, Sebastian; Skupin, Alexander; Ebenhöh, Oliver

    2011-01-01

    Glycans comprise ubiquitous and essential biopolymers, which usually occur as highly diverse mixtures. The myriad different structures are generated by a limited number of carbohydrate-active enzymes (CAZymes), which are unusual in that they catalyze multiple reactions by being relatively unspecific with respect to substrate size. Existing experimental and theoretical descriptions of CAZyme-mediated reaction systems neither comprehensively explain observed action patterns nor suggest biological functions of polydisperse pools in metabolism. Here, we overcome these limitations with a novel theoretical description of this important class of biological systems in which the mixing entropy of polydisperse pools emerges as an important system variable. In vitro assays of three CAZymes essential for central carbon metabolism confirm the power of our approach to predict equilibrium distributions and non-equilibrium dynamics. A computational study of the turnover of the soluble heteroglycan pool exemplifies how entropy-driven reactions establish a metabolic buffer in vivo that attenuates fluctuations in carbohydrate availability. We argue that this interplay between energy- and entropy-driven processes represents an important regulatory design principle of metabolic systems. PMID:22027553

  2. Physical Activity, Body Composition and Metabolic Syndrome in Young Adults

    PubMed Central

    Salonen, Minna K.; Wasenius, Niko; Kajantie, Eero; Lano, Aulikki; Lahti, Jari; Heinonen, Kati; Räikkönen, Katri; Eriksson, Johan G.

    2015-01-01

    Objective Low physical activity (PA) is a major risk factor for cardiovascular and metabolic disorders in all age groups. We measured intensity and volume of PA and examined the associations between PA and the metabolic syndrome (MS), its components and body composition among young Finnish adults. Research Design and Methods The study comprises 991 men and women born 1985-86, who participated in a clinical study during the years 2009-11 which included assessments of metabolism, body composition and PA. Objectively measured (SenseWear Armband) five-day PA data was available from 737 participants and was expressed in metabolic equivalents of task (MET). Results The prevalence of MS ranged between 8-10%. Higher total mean volume (MET-hours) or intensity (MET) were negatively associated with the risk of MS and separate components of MS, while the time spent at sedentary level of PA was positively associated with MS. Conclusions MS was prevalent in approximately every tenth of the young adults at the age of 24 years. Higher total mean intensity and volume rates as well as longer duration spent at moderate and vigorous PA level had a beneficial impact on the risk of MS. Longer time spent at the sedentary level of PA increased the risk of MS. PMID:25992848

  3. Metabolic pathway of Propionibacterium growing with oxygen: enzymes, 13C NMR analysis, and its application for vitamin B12 production with periodic fermentation.

    PubMed

    Ye, K; Shijo, M; Miyano, K; Shimizu, K

    1999-01-01

    The metabolic pathway of Propionibacterium grown under an aerobic condition is still not clear so far. In this work, cell growth, organic acid formation, vitamin B12 synthesis, and enzyme activities were determined in different aerobic cultivation systems. It was found that the propionate, which is accumulated during anaerobic cultivation, was completely decomposed when the cultivation was shifted to an aerobic condition. Moreover, pyruvate was formed in accordance with the decomposition of the propionate. Besides, more acetate was produced and a large amount of malate was formed during the aerobic cultivation. Such phenomena could be repeatedly observed in a periodic cultivation in which the dissolved oxygen concentration was alternatively controlled at 0 or 1 ppm. Enzyme analysis indicates that the regulation of organic acid formation depends on which molecule, i.e., oxygen or fumarate, serves as an electron acceptor in the respiratory chain reactions. No tricarboxylic acid cycle was found to exist in this species grown under an aerobic condition. It is evident that the randomizing pathway worked in a reversed direction in the presence of oxygen, through which the propionate is oxidized to pyruvate. The 13C NMR spectral analysis confirmed this observation. PMID:10194395

  4. EPR oxygen imaging and hyperpolarized 13C MRI of pyruvate metabolism as noninvasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate.

    PubMed

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu; Morris, H Douglas; Munasinghe, Jeeva P; Lizak, Martin; Merkle, Hellmut; Ardenkjaer-Larsen, Jan Henrik; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Koretsky, Alan P; Mitchell, James B; Krishna, Murali C

    2013-05-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation and promote glycolysis for energy production. Thereby, inhibition of glycolysis has the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate blocks glycolysis pathway by inhibiting hypoxia inducible enzymes and enhanced cytotoxicity of 3-bromopyruvate under hypoxic conditions has been reported in vitro. However, the efficacy of 3-bromopyruvate was substantially attenuated in hypoxic tumor regions (pO2<10 mmHg) in vivo using squamous cell carcinoma (SCCVII)-bearing mouse model. Metabolic MRI studies using hyperpolarized 13C-labeled pyruvate showed that monocarboxylate transporter-1 is the major transporter for pyruvate and the analog 3-bromopyruvate in SCCVII tumor. The discrepant results between in vitro and in vivo data were attributed to biphasic oxygen dependent expression of monocarboxylate transporter-1 in vivo. Expression of monocarboxylate transporter-1 was enhanced in moderately hypoxic (8-15 mmHg) tumor regions but down regulated in severely hypoxic (<5 mmHg) tumor regions. These results emphasize the importance of noninvasive imaging biomarkers to confirm the action of hypoxia-activated drugs. PMID:22692861

  5. Metabolically activated steviol, the aglycone of stevioside, is mutagenic.

    PubMed Central

    Pezzuto, J M; Compadre, C M; Swanson, S M; Nanayakkara, D; Kinghorn, A D

    1985-01-01

    Stevioside, a constituent of Stevia rebaudiana, is commonly used as a noncaloric sugar substitute in Japan. Consistent with reports in the literature, we have found that stevioside is not mutagenic as judged by utilization of Salmonella typhimurium strain TM677, either in the presence or in the absence of a metabolic activating system. Similar negative results were obtained with several structurally related sweet-tasting glycosides. However, steviol, the aglycone of stevioside, was found to be highly mutagenic when evaluated in the presence of a 9000 X g supernatant fraction derived from the livers of Aroclor 1254-pretreated rats. Expression of mutagenic activity was dependent on both pretreatment of the rats with Aroclor 1254 and addition of NADPH; unmetabolized steviol was not active. The structurally related species, isosteviol, was not active regardless of metabolic activation. Similarly, chemical reduction of the unsaturated bond linking the carbon-16 and -17 positions of steviol resulted in the generation of two isomeric products, dihydrosteviol A and B, that were not mutagenic. In addition, ent-kaurenoic acid was found to be inactive. It is therefore clear that a metabolite of an integral component of stevioside is mutagenic; structural features of requisite importance for the expression of mutagenic activity include a hydroxy group at position 13 and an unsaturated bond joining the carbon atoms at positions 16 and 17. A potential metabolite of steviol, steviol-16 alpha,17-epoxide, was synthesized chemically and found to be ineffective as a direct-acting mutagen. Thus, although stevioside itself appears innocuous, it would seem prudent to expeditiously and unequivocally establish the human metabolic disposition of this substance. PMID:3887402

  6. Effect of oxygen on the microbial activities of thermophilic anaerobic biomass.

    PubMed

    Pedizzi, C; Regueiro, L; Rodriguez-Verde, I; Lema, J M; Carballa, M

    2016-07-01

    Low oxygen levels (μgO2L(-1)) in anaerobic reactors are quite common and no relevant consequences are expected. On the contrary, higher concentrations could affect the process. This work aimed to study the influence of oxygen (4.3 and 8.8mgO2L(-1), respectively) on the different microbial activities (hydrolytic, acidogenic and methanogenic) of thermophilic anaerobic biomass and on the methanogenic community structure. Batch tests in presence of oxygen were conducted using specific substrates for each biological activity and a blank (with minimum oxygen) was included. No effect of oxygen was observed on the hydrolytic and acidogenic activities. In contrast, the methane production rate decreased by 40% in all oxygenated batches and the development of active archaeal community was slower in presence of 8.8mgO2L(-1). However, despite this sensitivity of methanogens to oxygen at saturation levels, the inhibition was reversible. PMID:27020398

  7. Analytic Models of Oxygen and Nutrient Diffusion, Metabolism Dynamics, and Architecture Optimization in Three-Dimensional Tissue Constructs with Applications and Insights in Cerebral Organoids.

    PubMed

    McMurtrey, Richard J

    2016-03-01

    Diffusion models are important in tissue engineering as they enable an understanding of gas, nutrient, and signaling molecule delivery to cells in cell cultures and tissue constructs. As three-dimensional (3D) tissue constructs become larger, more intricate, and more clinically applicable, it will be essential to understand internal dynamics and signaling molecule concentrations throughout the tissue and whether cells are receiving appropriate nutrient delivery. Diffusion characteristics present a significant limitation in many engineered tissues, particularly for avascular tissues and for cells whose viability, differentiation, or function are affected by concentrations of oxygen and nutrients. This article seeks to provide novel analytic solutions for certain cases of steady-state and nonsteady-state diffusion and metabolism in basic 3D construct designs (planar, cylindrical, and spherical forms), solutions that would otherwise require mathematical approximations achieved through numerical methods. This model is applied to cerebral organoids, where it is shown that limitations in diffusion and organoid size can be partially overcome by localizing metabolically active cells to an outer layer in a sphere, a regionalization process that is known to occur through neuroglial precursor migration both in organoids and in early brain development. The given prototypical solutions include a review of metabolic information for many cell types and can be broadly applied to many forms of tissue constructs. This work enables researchers to model oxygen and nutrient delivery to cells, predict cell viability, study dynamics of mass transport in 3D tissue constructs, design constructs with improved diffusion capabilities, and accurately control molecular concentrations in tissue constructs that may be used in studying models of development and disease or for conditioning cells to enhance survival after insults like ischemia or implantation into the body, thereby providing a

  8. Validity of using a 3-dimensional PET scanner during inhalation of 15O-labeled oxygen for quantitative assessment of regional metabolic rate of oxygen in man

    NASA Astrophysics Data System (ADS)

    Hori, Yuki; Hirano, Yoshiyuki; Koshino, Kazuhiro; Moriguchi, Tetsuaki; Iguchi, Satoshi; Yamamoto, Akihide; Enmi, Junichiro; Kawashima, Hidekazu; Zeniya, Tsutomu; Morita, Naomi; Nakagawara, Jyoji; Casey, Michael E.; Iida, Hidehiro

    2014-09-01

    Use of 15O labeled oxygen (15O2) and positron emission tomography (PET) allows quantitative assessment of the regional metabolic rate of oxygen (CMRO2) in vivo, which is essential to understanding the pathological status of patients with cerebral vascular and neurological disorders. The method has, however, been challenging, when a 3D PET scanner is employed, largely attributed to the presence of gaseous radioactivity in the trachea and the inhalation system, which results in a large amount of scatter and random events in the PET assessment. The present study was intended to evaluate the adequacy of using a recently available commercial 3D PET scanner in the assessment of regional cerebral radioactivity distribution during an inhalation of 15O2. Systematic experiments were carried out on a brain phantom. Experiments were also performed on a healthy volunteer following a recently developed protocol for simultaneous assessment of CMRO2 and cerebral blood flow, which involves sequential administration of 15O2 and C15O2. A particular intention was to evaluate the adequacy of the scatter-correction procedures. The phantom experiment demonstrated that errors were within 3% at the practically maximum radioactivity in the face mask, with the greatest radioactivity in the lung. The volunteer experiment demonstrated that the counting rate was at peak during the 15O gas inhalation period, within a verified range. Tomographic images represented good quality over the entire FOV, including the lower part of the cerebral structures and the carotid artery regions. The scatter-correction procedures appeared to be important, particularly in the process to compensate for the scatter originating outside the FOV. Reconstructed images dramatically changed if the correction was carried out using inappropriate procedures. This study demonstrated that accurate reconstruction could be obtained when the scatter compensation was appropriately carried out. This study also suggested the

  9. Base substitution mutations induced by metabolically activated aflatoxin B1.

    PubMed

    Foster, P L; Eisenstadt, E; Miller, J H

    1983-05-01

    We have determined the base substitutions generated by metabolically activated aflatoxin B1 in the lacI gene of a uvrB- strain of Escherichia coli. By monitoring over 70 different nonsense mutation sites, we show that activated aflatoxin B1 specifically induced GxC leads to TxA transversions. One possible pathway leading to this base change involves depurination at guanine residues. We consider this mechanism of mutagenesis in the light of our other findings that the carcinogens benzo[a]pyrene diol epoxide and N-acetoxyacetylaminofluorene also specifically induce GxC leads to TxA transversions. PMID:6405385

  10. Lithium protection against oxygen toxicity in rats: ammonia and amino acid metabolism.

    PubMed Central

    Banister, E W; Bhakthan, N M; Singh, A K

    1976-01-01

    1. The use of Li pre-treatment in rats before high pressure oxygen exposure has been reported effective in controlling convulsions. This is an effect which is better demonstrated if exposure to oxygen follows shortly after Li injection than exposure following several hours later. 2. This study has investigated the hypothesis that the protective action of Li may be exerted, in the short term, by its removing ammonia from the blood and alleviating the latter's known toxic action. 3. A normal Li distribution time profile in unstressed rat brain and blood following intraperitoneal injection has been established. Brain and blood ammonia, amino acids and Li concentrations were also measured in Li-treated animals exposed and convulsed by oxygen. These measurements were made both shortly (15 min) and also several hours after (24 hr) Li treatment. Ammonia and amino acid values in Li-protected groups were compared to normal unstressed animal values and also to values in animals convulsed by oxygen unprotected by Li pre-treatment. 4. In rat brain abd blood significant (P less than 0-001) elevation of ammonia and glutamine and depression of gamma-amino butyric acid (brain only) and glutamate was noted following oxygen treatment in unprotected animals. Prior injection of Li 15 min before high pressure oxygen exposure delayed convulsions twice as long. Additionally if these animals were only exposed to oxygen for a period of time equal to that which would normally produce convulsions in unprotected animals, brain and blood ammonia and amino acids were maintained near to unstressed animal levels. Concomitantly, blood Li concentrations were considerably depressed below the values one would expect from the previously determined Li distribution time profile. 5. In rats exposed to high pressure oxygen 24 hr after Li treatment there was no protective action against high pressure oxygen convulsion, rather a potentiating effect for convulsion was seen. 6. These data present compelling

  11. [Response of reactive oxygen metabolism in melon chloroplasts to short-term salinity-alkalinity stress regulated by exogenous γ-aminobutyric acid].

    PubMed

    Xiang, Li-xia; Hu, Li-pan; Hu, Xiao-hui; Pan, Xiong-bo; Ren, Wen-qi

    2015-12-01

    The regulatory effect of exogenous γ-aminobutyric acid (GABA) on metabolism of reactive oxygen species (ROS) in melon chloroplasts under short-term salinity-alkalinity stress were investigated in melon variety 'Jinhui No. 1', which was cultured with deep flow hydroponics. The result showed that under salinity-alkalinity stress, the photosynthetic pigment content, MDA content, superoxide anion (O₂·) production rate and hydrogen peroxide (H₂O₂) content in chloroplast increased significantly, the contents of antioxidants ascorbic acid (AsA) and glutathione (GSH) increased, and the activities of H⁺-ATPase and H⁺-PPiase were inhibited obviously. With exogenous GABA application, the accumulations of O₂·, MDA and H₂O₂ induced by salinity-alkalinity stress were inhibited. Exogenous GABA alleviated the increase of photosynthetic pigment content, improved the activity of SOD, enzymes of AsA-GSH cycle, total AsA and total GSH while decreased the AsA/DHA ratio and GSH/GSSH ratio. Foliar GABA could enhance the H⁺-ATPase and H⁺-PPiase activities. Our results suggested that the exogenous GABA could accelerate the ROS metabolism in chloroplast, promote the recycle of AsA-GSH, and maintain the permeability of cell membrane to improve the ability of melon chloroplast against salinity-alkalinity stress. PMID:27112014

  12. Metabolic Plasticity in Resting and Thrombin Activated Platelets

    PubMed Central

    Ravi, Saranya; Chacko, Balu; Sawada, Hirotaka; Kramer, Philip A.; Johnson, Michelle S.; Benavides, Gloria A.; O’Donnell, Valerie; Marques, Marisa B.; Darley-Usmar, Victor M.

    2015-01-01

    Platelet thrombus formation includes several integrated processes involving aggregation, secretion of granules, release of arachidonic acid and clot retraction, but it is not clear which metabolic fuels are required to support these events. We hypothesized that there is flexibility in the fuels that can be utilized to serve the energetic and metabolic needs for resting and thrombin-dependent platelet aggregation. Using platelets from healthy human donors, we found that there was a rapid thrombin-dependent increase in oxidative phosphorylation which required both glutamine and fatty acids but not glucose. Inhibition of fatty acid oxidation or glutamine utilization could be compensated for by increased glycolytic flux. No evidence for significant mitochondrial dysfunction was found, and ATP/ADP ratios were maintained following the addition of thrombin, indicating the presence of functional and active mitochondrial oxidative phosphorylation during the early stages of aggregation. Interestingly, inhibition of fatty acid oxidation and glutaminolysis alone or in combination is not sufficient to prevent platelet aggregation, due to compensation from glycolysis, whereas inhibitors of glycolysis inhibited aggregation approximately 50%. The combined effects of inhibitors of glycolysis and oxidative phosphorylation were synergistic in the inhibition of platelet aggregation. In summary, both glycolysis and oxidative phosphorylation contribute to platelet metabolism in the resting and activated state, with fatty acid oxidation and to a smaller extent glutaminolysis contributing to the increased energy demand. PMID:25875958

  13. Probing Saltern Brines with an Oxygen Electrode: What Can We Learn about the Community Metabolism in Hypersaline Systems?

    PubMed

    Oren, Aharon

    2016-01-01

    We have explored the use of optical oxygen electrodes to study oxygenic photosynthesis and heterotrophic activities in crystallizer brines of the salterns in Eilat, Israel. Monitoring oxygen uptake rates in the dark enables the identification of organic substrates that are preferentially used by the community. Addition of glycerol (the osmotic solute synthesized by Dunaliella) or dihydroxyacetone (produced from glycerol by Salinibacter) enhanced respiration rates. Pyruvate, produced from glycerol or from some sugars by certain halophilic Archaea also stimulated community respiration. Fumarate had a sparing effect on respiration, possibly as many halophilic Archaea can use fumarate as a terminal electron acceptor in respiration. Calculating the photosynthetic activity of Dunaliella by monitoring oxygen concentration changes during light/dark incubations is not straightforward as light also affects respiration of some halophilic Archaea and Bacteria due to action of light-driven proton pumps. When illuminated, community respiration of brine samples in which oxygenic photosynthesis was inhibited by DCMU decreased by ~40%. This effect was interpreted as the result of competition between two energy yielding systems: the bacteriorhodopsin proton pump and the respiratory chain of the prokaryotes. These findings have important implications for the interpretation of other published data on photosynthetic and respiratory activities in hypersaline environments. PMID:27338478

  14. Metabolic, anabolic, and mitogenic insulin responses: A tissue-specific perspective for insulin receptor activators

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin acts as the major regulator of the fasting-to-fed metabolic transition by altering substrate metabolism, promoting energy storage, and helping activate protein synthesis. In addition to its glucoregulatory and other metabolic properties, insulin can also act as a growth factor. The metabolic...

  15. Influence of metabolism on endocrine activities of bisphenol S.

    PubMed

    Skledar, Darja Gramec; Schmidt, Jan; Fic, Anja; Klopčič, Ivana; Trontelj, Jurij; Dolenc, Marija Sollner; Finel, Moshe; Mašič, Lucija Peterlin

    2016-08-01

    Bisphenol S (BPS; bis[4-hydroxyphenyl]sulfone) is commonly used as a replacement for bisphenol A in numerous consumer products. The main goal of this study was to examine the influence of different metabolic reactions that BPS undergoes on the endocrine activity. We demonstrate that hydroxylation of the aromatic ring of BPS, catalyzed mainly by the cytochrome P450 enzymes CYP3A4 and CYP2C9, is its major in-vitro phase I biotransformation. Nevertheless, coupled oxidative-conjugative reactions analyses revealed that glucuronidation and formation of BPS glucuronide is the predominant BPS metabolic pathway. BPS reactive metabolites that can be tracked as glutathione conjugates were not detected in the present study. Two in-vitro systems were used to evaluate the endocrine activity of BPS and its two main metabolites, BPS glucuronide and hydroxylated BPS 4-(4-hydroxy-benzenesulfonyl)-benzene-1,2-diol (BPSM1). In addition, we have tested two structural analogs of BPS, bis[4-(2-hydroxyetoxy)phenyl]sulfone (BHEPS) and 4,4-sulfonylbis(2-methylphenol) (dBPS). The test systems were yeast cells, for evaluating estrogenic and androgenic activities, and the GH3.TRE-Luc reporter cell line for measuring thyroid hormone activity. BPS and BPSM1 were weak agonists of the estrogen receptor, EC50 values of 8.4 × 10(-5) M and 6.7 × 10(-4) M, respectively. Additionally, BPSM1 exhibited weak antagonistic activity toward the thyroid hormone receptor, with an IC50 of 4.3 × 10(-5) M. In contrast to BPSM1, BPS glucuronide was inactive in these assays, inhibiting neither the estrogen nor the thyroid hormone receptors. Hence, glucuronidation appears to be the most important pathway for both BPS metabolism and detoxification. PMID:27213244

  16. The effect of intravitreal vascular endothelial growth factor on inner retinal oxygen delivery and metabolism in rats.

    PubMed

    Blair, Norman P; Wanek, Justin; Teng, Pang-yu; Shahidi, Mahnaz

    2016-02-01

    Vascular endothelial growth factor (VEGF) is stimulated by hypoxia and plays an important role in pathologic vascular leakage and neovascularization. Increased VEGF may affect inner retinal oxygen delivery (DO2) and oxygen metabolism (MO2), however, quantitative information is lacking. We tested the hypotheses that VEGF increases DO2, but does not alter MO2. In 10 rats, VEGF was injected intravitreally into one eye, whereas balanced salt solution (BSS) was injected into the fellow eye, 24 h prior to imaging. Vessel diameters and blood velocities were determined by red-free and fluorescent microsphere imaging, respectively. Vascular PO2 values were derived by phosphorescence lifetime imaging of an intravascular oxyphor. Retinal blood flow, vascular oxygen content, DO2 and MO2 were calculated. Retinal arterial and venous diameters were larger in VEGF-injected eyes compared to control eyes (P < 0.03), however no significant difference was observed in blood velocity (P = 0.21). Thus, retinal blood flow was greater in VEGF-injected eyes (P = 0.007). Retinal vascular PO2 and oxygen content were similar between control and VEGF-injected eyes (P > 0.11), while the arteriovenous oxygen content difference was marginally lower in VEGF-injected eyes (P = 0.05). DO2 was 950 ± 340 and 1380 ± 650 nL O2/min in control and VEGF-injected eyes, respectively (P = 0.005). MO2 was 440 ± 150 and 490 ± 190 nL O2/min in control and VEGF-injected eyes, respectively (P = 0.31). Intravitreally administered VEGF did not alter MO2 but increased DO2, suggesting VEGF may play an offsetting role in conditions characterized by retinal hypoxia. PMID:26518179

  17. The influence of carbon dioxide on brain activity and metabolism in conscious humans

    PubMed Central

    Xu, Feng; Uh, Jinsoo; Brier, Matthew R; Hart, John; Yezhuvath, Uma S; Gu, Hong; Yang, Yihong; Lu, Hanzhang

    2011-01-01

    A better understanding of carbon dioxide (CO2) effect on brain activity may have a profound impact on clinical studies using CO2 manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO2, via inhalation of 5% CO2, may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO2) by 13.4%±2.3% (N=14) and, furthermore, the CMRO2 change was proportional to the subject's end-tidal CO2 (Et-CO2) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visual-evoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO2 inhalation. PMID:20842164

  18. [Drug with a high metabolic activity, cocarnit, in the treatment of diabetic cardiac autonomic neuropathy].

    PubMed

    Popov, S V; Melekhovets', O K; Demikhova, N V; Vynnychenko, L B

    2012-01-01

    Left ventricular diastolic dysfunction in patients with diabetes is formed in the absence of atherosclerotic changes as a consequence of diabetic cardiac autonomic neuropathy in the early stages of diabetes. Progression of autonomic cardiac neuropathy in cardio-vascular type is associated with the violation of energy supply of cells, protein synthesis, electrolyte exchange, the exchange of trace elements, oxidation reduction processes, oxygen-transport function of blood, so that metabolic therapy is carried out to optimize the processes of formation and energy costs. The drug cocarnit activates processes of aerobic oxidation of glucose, as well as providing regulatory influence on the oxidation of fatty acids. Applying of cocarnit in complex therapy in patients with diabetic cardiac autonomic neuropathy found improvement of left ventricular diastolic function, and positive dynamics in the efferent activity balance of the sympathetic and parasympathetic control of heart rate variability, which provides the regression of clinical symptoms. PMID:23356142

  19. Effects of intermittent 60-Hz high voltage electric fields on metabolism, activity, and temperature in mice

    SciTech Connect

    Rosenbergy, R.S; Duffy, P.H.; Sacher, G.A.

    1981-01-01

    Transient effects of 100-kV/m extremely low frequency electric fields were studied in the white footed deermouse, Peromyscus leucopus. Gross motor activity, carbon dioxide production, oxygen consumption, and core body temperature were monitored before, during, and after intermittent field exposures (four hour-long exposures, at one-hour intervals). Thirty-four mice were exposed in cages with plastic floors floating above ground potential, and 21 mice were exposed in cages with grounded metal floor plates. The first field exposure produced an immediate, transient increase of activity and gas measures during the inactive phase of the circadian cycle. All measures returned to baseline levels before the second exposure and were not significantly changed throughout the remainder of the exposures. The rapid habituation of field-induced arousal suggests that significant metabolic changes will not be measured in experiments in which the interval between exposure and measurement is greater than two hours.

  20. Hibernating myocardium retains metabolic and contractile reserve despite regional reductions in flow, function, and oxygen consumption at rest.

    PubMed

    Fallavollita, James A; Malm, Brian J; Canty, John M

    2003-01-10

    Hibernating myocardium, characterized by reductions in flow and function at rest, has limited contractile reserve in response to increases in external workload. We hypothesized that this attenuation of function reflects an adaptive downregulation that prevents the development of metabolic evidence of ischemia during stress. To test this hypothesis, pigs were chronically instrumented with a proximal left anterior descending artery stenosis for 3 months, resulting in severe anteroapical hypokinesis with reduced resting perfusion (0.78+/-0.05 versus 0.94+/-0.07 mL x min(-1)x g(-1) in remote, P<0.01; and 0.99+/-0.08 in controls, P<0.05). Open-chest studies confirmed resting dysfunction compared with normal controls (segment shortening 9.2+/-2.2% versus 23.5+/-1.1%, P<0.05). Resting myocardial oxygen consumption was reduced (63+/-3 versus 77+/-6 microL x g(-1) x min(-1) in controls, P<0.05), yet lactate consumption was normal. Although subendocardial perfusion failed to increase during graded, intravenous epinephrine infusion (n=8), peak segment shortening (to 17.3+/-3.1%, P<0.05) and oxygen consumption (to 90+/-6 microL x g(-1) x min(-1), P<0.01) increased from the depressed resting levels. There was no lactate production in hibernating myocardium, and lactate uptake increased during stress (0.7+/-0.1 to 1.2+/-0.1 micromol x g(-1) x min(-1), P<0.05). The absence of metabolic evidence of ischemia was also confirmed during atrial pacing to a rate of 120 bpm (n=8). Thus, despite reductions in function and oxygen consumption at rest, hibernating myocardium retains the ability to increase metabolism without the development of acute ischemia. This supports the hypothesis that the downregulation of oxygen consumption and function in hibernating myocardium is an adaptive response that prevents a supply-demand imbalance during submaximal increases in cardiac workload when coronary flow reserve is limited. PMID:12522120

  1. Probing the metabolic water contribution to intracellular water using oxygen isotope ratios of PO4.

    PubMed

    Li, Hui; Yu, Chan; Wang, Fei; Chang, Sae Jung; Yao, Jun; Blake, Ruth E

    2016-05-24

    Knowledge of the relative contributions of different water sources to intracellular fluids and body water is important for many fields of study, ranging from animal physiology to paleoclimate. The intracellular fluid environment of cells is challenging to study due to the difficulties of accessing and sampling the contents of intact cells. Previous studies of multicelled organisms, mostly mammals, have estimated body water composition-including metabolic water produced as a byproduct of metabolism-based on indirect measurements of fluids averaged over the whole organism (e.g., blood) combined with modeling calculations. In microbial cells and aquatic organisms, metabolic water is not generally considered to be a significant component of intracellular water, due to the assumed unimpeded diffusion of water across cell membranes. Here we show that the (18)O/(16)O ratio of PO4 in intracellular biomolecules (e.g., DNA) directly reflects the O isotopic composition of intracellular water and thus may serve as a probe allowing direct sampling of the intracellular environment. We present two independent lines of evidence showing a significant contribution of metabolic water to the intracellular water of three environmentally diverse strains of bacteria. Our results indicate that ∼30-40% of O in PO4 comprising DNA/biomass in early stationary phase cells is derived from metabolic water, which bolsters previous results and also further suggests a constant metabolic water value for cells grown under similar conditions. These results suggest that previous studies assuming identical isotopic compositions for intracellular/extracellular water may need to be reconsidered. PMID:27170190

  2. A ligand field chemistry of oxygen generation by the oxygen-evolving complex and synthetic active sites

    PubMed Central

    Betley, Theodore A; Surendranath, Yogesh; Childress, Montana V; Alliger, Glen E; Fu, Ross; Cummins, Christopher C; Nocera, Daniel G

    2007-01-01

    Oxygen–oxygen bond formation and O2 generation occur from the S4 state of the oxygen-evolving complex (OEC). Several mechanistic possibilities have been proposed for water oxidation, depending on the formal oxidation state of the Mn atoms. All fall under two general classifications: the AB mechanism in which nucleophilic oxygen (base, B) attacks electrophilic oxygen (acid, A) of the Mn4Ca cluster or the RC mechanism in which radical-like oxygen species couple within OEC. The critical intermediate in either mechanism involves a metal oxo, though the nature of this oxo for AB and RC mechanisms is disparate. In the case of the AB mechanism, assembly of an even-electron count, high-valent metal-oxo proximate to a hydroxide is needed whereas, in an RC mechanism, two odd-electron count, high-valent metal oxos are required. Thus the two mechanisms give rise to very different design criteria for functional models of the OEC active site. This discussion presents the electron counts and ligand geometries that support metal oxos for AB and RC O–O bond-forming reactions. The construction of architectures that bring two oxygen functionalities together under the purview of the AB and RC scenarios are described. PMID:17971328

  3. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme

    PubMed Central

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  4. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme.

    PubMed

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  5. Metabolic transistor strategy for controlling electron transfer chain activity in Escherichia coli

    PubMed Central

    Wu, Hui; Tuli, Leepika; Bennett, George N.; San, Ka-Yiu

    2015-01-01

    A novel strategy to finely control a large metabolic flux by using a “metabolic transistor” approach was established. In this approach a small change in the level or availability of an essential component for the process is controlled by adding a competitive reaction that affects a precursor or an intermediate in its biosynthetic pathway. The change of the basal level of the essential component, considered as a base current in a transistor, has a large effect on the flux through the major pathway. In this way, the fine-tuning of a large flux can be accomplished. The “metabolic transistor” strategy was applied to controlling electron transfer chain function by manipulation of the quinone synthesis pathway in Escherichia coli. The achievement of a theoretical yield of lactate production under aerobic conditions via this strategy upon manipulation of the biosynthetic pathway of the key participant, ubiquinone-8 (Q8), in an E. coli strain provides an in vivo, genetically tunable means to control the activity of the electron transfer chain and manipulate the production of reduced products while limiting consumption of oxygen to a defined amount. PMID:25596510

  6. Oxygen reduction reaction activity on Pt{111} surface alloys.

    PubMed

    Attard, Gary A; Brew, Ashley; Ye, Jin-Yu; Morgan, David; Sun, Shi-Gang

    2014-07-21

    PtM overlayers (where M=Fe, Co or Ni) supported on Pt{111} are prepared via thermal annealing in either a nitrogen/water or hydrogen ambient of dilute aqueous droplets containing M(Z+) cations directly attached to the electrode. Two different PtM phases are detected depending on the nature of the post-annealing cooling environment. The first of these consists of small (<20 nm), closely packed microcrystals comprised of a central metallic core and a shell (several monolayers thick) of mixed metal oxides/hydroxides. The second type of PtM phase is prepared by cooling in a stream of hydrogen gas. Although this second phase also consists of numerous microcrystals covering the Pt{111} electrode surface, these are both flatter than before and moreover are entirely metallic in character. A positive shift in the onset of PtM oxide formation correlates with increased activity towards the oxygen reduction reaction (ORR), which we ascribe to the greater availability of platinum metallic sites under ORR conditions. PMID:24986646

  7. Bench-to-bedside review: Oxygen debt and its metabolic correlates as quantifiers of the severity of hemorrhagic and post-traumatic shock

    PubMed Central

    Rixen, Dieter; Siegel, John H

    2005-01-01

    Evidence is increasing that oxygen debt and its metabolic correlates are important quantifiers of the severity of hemorrhagic and post-traumatic shock and and may serve as useful guides in the treatment of these conditions. The aim of this review is to demonstrate the similarity between experimental oxygen debt in animals and human hemorrhage/post-traumatic conditions, and to examine metabolic oxygen debt correlates, namely base deficit and lactate, as indices of shock severity and adequacy of volume resuscitation. Relevant studies in the medical literature were identified using Medline and Cochrane Library searches. Findings in both experimental animals (dog/pig) and humans suggest that oxygen debt or its metabolic correlates may be more useful quantifiers of hemorrhagic shock than estimates of blood loss, volume replacement, blood pressure, or heart rate. This is evidenced by the oxygen debt/probability of death curves for the animals, and by the consistency of lethal dose (LD)25,50 points for base deficit across all three species. Quantifying human post-traumatic shock based on base deficit and adjusting for Glasgow Coma Scale score, prothrombin time, Injury Severity Score and age is demonstrated to be superior to anatomic injury severity alone or in combination with Trauma and Injury Severity Score. The data examined in this review indicate that estimates of oxygen debt and its metabolic correlates should be included in studies of experimental shock and in the management of patients suffering from hemorrhagic shock. PMID:16277731

  8. Metabolically Derived human ventilation rates: A revised approach based upon oxygen consumption rates (Final Report) 2009

    EPA Science Inventory

    The purpose of this report is to provide a revised approach for calculating an individual's ventilation rate directly from their oxygen consumption rate. This revised approach will be used to update the ventilation rate information in the Exposure Factors Handbook, which serve as...

  9. Routine Metabolic Rate and Limiting Oxygen Concentration of Freshwater Prawn Macrobrachium rosenbergii Larvae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Malaysian prawns, Macrobrachium rosenbergii, are hatched and raised indoors in small tanks. Prawns may be raised and shipped at high densities which could result in low dissolved oxygen (DO) conditions. Because DO may play an important role in prawn development and survival, we measured routine me...

  10. Modeling Diel Oxygen Dynamics and Ecosystem Metabolism in Weeks Bay, Alabama.

    EPA Science Inventory

    Weeks Bay is a shallow eutrophic estuary that exhibits frequent summertime diel-cycling hypoxia and periods of dissolved oxygen (DO) oversaturation during the day. Diel DO dynamics in shallow estuaries like Weeks Bay are complex, and may be influenced by wind forcing, vertical an...

  11. Probing the metabolic water contribution to intracellular water using oxygen isotope ratios of PO4

    NASA Astrophysics Data System (ADS)

    Li, Hui; Yu, Chan; Wang, Fei; Chang, Sae Jung; Yao, Jun; Blake, Ruth E.

    2016-05-01

    Knowledge of the relative contributions of different water sources to intracellular fluids and body water is important for many fields of study, ranging from animal physiology to paleoclimate. The intracellular fluid environment of cells is challenging to study due to the difficulties of accessing and sampling the contents of intact cells. Previous studies of multicelled organisms, mostly mammals, have estimated body water composition—including metabolic water produced as a byproduct of metabolism—based on indirect measurements of fluids averaged over the whole organism (e.g., blood) combined with modeling calculations. In microbial cells and aquatic organisms, metabolic water is not generally considered to be a significant component of intracellular water, due to the assumed unimpeded diffusion of water across cell membranes. Here we show that the 18O/16O ratio of PO4 in intracellular biomolecules (e.g., DNA) directly reflects the O isotopic composition of intracellular water and thus may serve as a probe allowing direct sampling of the intracellular environment. We present two independent lines of evidence showing a significant contribution of metabolic water to the intracellular water of three environmentally diverse strains of bacteria. Our results indicate that ˜30–40% of O in PO4 comprising DNA/biomass in early stationary phase cells is derived from metabolic water, which bolsters previous results and also further suggests a constant metabolic water value for cells grown under similar conditions. These results suggest that previous studies assuming identical isotopic compositions for intracellular/extracellular water may need to be reconsidered.

  12. Dopaminergic correlates of metabolic network activity in Parkinson's disease.

    PubMed

    Holtbernd, Florian; Ma, Yilong; Peng, Shichun; Schwartz, Frank; Timmermann, Lars; Kracht, Lutz; Fink, Gereon R; Tang, Chris C; Eidelberg, David; Eggers, Carsten

    2015-09-01

    Parkinson's disease (PD) is associated with distinct metabolic covariance patterns that relate to the motor and cognitive manifestations of the disorder. It is not known, however, how the expression of these patterns relates to measurements of nigrostriatal dopaminergic activity from the same individuals. To explore these associations, we studied 106 PD subjects who underwent cerebral PET with both (18) F-fluorodeoxyglucose (FDG) and (18) F-fluoro-L-dopa (FDOPA). Expression values for the PD motor- and cognition-related metabolic patterns (PDRP and PDCP, respectively) were computed for each subject; these measures were correlated with FDOPA uptake on a voxel-by-voxel basis. To explore the relationship between dopaminergic function and local metabolic activity, caudate and putamen FDOPA PET signal was correlated voxel-wise with FDG uptake over the entire brain. PDRP expression correlated with FDOPA uptake in caudate and putamen (P < 0.001), while PDCP expression correlated with uptake in the anterior striatum (P < 0.001). While statistically significant, the correlations were only of modest size, accounting for less than 20% of the overall variation in these measures. After controlling for PDCP expression, PDRP correlations were significant only in the posterior putamen. Of note, voxel-wise correlations between caudate/putamen FDOPA uptake and whole-brain FDG uptake were significant almost exclusively in PDRP regions. Overall, the data indicate that PDRP and PDCP expression correlates significantly with PET indices of presynaptic dopaminergic functioning obtained in the same individuals. Even so, the modest size of these correlations suggests that in PD patients, individual differences in network activity cannot be explained solely by nigrostriatal dopamine loss. PMID:26037537

  13. The Emerging Nexus of Active DNA Demethylation and Mitochondrial Oxidative Metabolism in Post-Mitotic Neurons

    PubMed Central

    Meng, Huan; Chen, Guiquan; Gao, Hui-Ming; Song, Xiaoyu; Shi, Yun; Cao, Liu

    2014-01-01

    The variable patterns of DNA methylation in mammals have been linked to a number of physiological processes, including normal embryonic development and disease pathogenesis. Active removal of DNA methylation, which potentially regulates neuronal gene expression both globally and gene specifically, has been recently implicated in neuronal plasticity, learning and memory processes. Model pathways of active DNA demethylation involve ten-eleven translocation (TET) methylcytosine dioxygenases that are dependent on oxidative metabolites. In addition, reactive oxygen species (ROS) and oxidizing agents generate oxidative modifications of DNA bases that can be removed by base excision repair proteins. These potentially link the two processes of active DNA demethylation and mitochondrial oxidative metabolism in post-mitotic neurons. We review the current biochemical understanding of the DNA demethylation process and discuss its potential interaction with oxidative metabolism. We then summarise the emerging roles of both processes and their interaction in neural plasticity and memory formation and the pathophysiology of neurodegeneration. Finally, possible therapeutic approaches for neurodegenerative diseases are proposed, including reprogramming therapy by global DNA demethylation and mitohormesis therapy for locus-specific DNA demethylation in post-mitotic neurons. PMID:25490140

  14. Lipid metabolizing enzyme activities modulated by phospholipid substrate lateral distribution.

    PubMed

    Salinas, Dino G; Reyes, Juan G; De la Fuente, Milton

    2011-09-01

    Biological membranes contain many domains enriched in phospholipid lipids and there is not yet clear explanation about how these domains can control the activity of phospholipid metabolizing enzymes. Here we used the surface dilution kinetic theory to derive general equations describing how complex substrate distributions affect the activity of enzymes following either the phospholipid binding kinetic model (which assumes that the enzyme molecules directly bind the phospholipid substrate molecules), or the surface-binding kinetic model (which assumes that the enzyme molecules bind to the membrane before binding the phospholipid substrate). Our results strongly suggest that, if the enzyme follows the phospholipid binding kinetic model, any substrate redistribution would increase the enzyme activity over than observed for a homogeneous distribution of substrate. Besides, enzymes following the surface-binding model would be independent of the substrate distribution. Given that the distribution of substrate in a population of micelles (each of them a lipid domain) should follow a Poisson law, we demonstrate that the general equations give an excellent fit to experimental data of lipases acting on micelles, providing reasonable values for kinetic parameters--without invoking special effects such as cooperative phenomena. Our theory will allow a better understanding of the cellular-metabolism control in membranes, as well as a more simple analysis of the mechanisms of membrane acting enzymes. PMID:21108012

  15. In vivo enzyme activity in inborn errors of metabolism

    SciTech Connect

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. )

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  16. Growth enhancement and gene expression of Arabidopsis thaliana irradiated with active oxygen species

    NASA Astrophysics Data System (ADS)

    Watanabe, Satoshi; Ono, Reoto; Hayashi, Nobuya; Shiratani, Masaharu; Tashiro, Kosuke; Kuhara, Satoru; Inoue, Asami; Yasuda, Kaori; Hagiwara, Hiroko

    2016-07-01

    The characteristics of plant growth enhancement effect and the mechanism of the enhancement induced by plasma irradiation are investigated using various active species in plasma. Active oxygen species in oxygen plasma are effective for growth enhancement of plants. DNA microarray analysis of Arabidopsis thaliana indicates that the genes coding proteins that counter oxidative stresses by eliminating active oxygen species are expressed at significantly high levels. The size of plant cells increases owing to oxygen plasma irradiation. The increases in gene expression levels and cell size suggest that the increase in the expression level of the expansin protein is essential for plant growth enhancement phenomena.

  17. Effects of increased temperature on metabolic activity and oxidative stress in the first life stages of marble trout (Salmo marmoratus).

    PubMed

    Simčič, Tatjana; Jesenšek, Dušan; Brancelj, Anton

    2015-08-01

    Climate change may result in future alterations in thermal regime which could markedly affect the early developmental stages of cold water fish due to their expected high sensitivity to increasing temperature. In the present study, the effect of temperature increase of 2, 4 and 6°C on the oxygen consumption rate (R), the activity of respiratory electron transport system (ETS) and oxidative stress have been studied in four developmental stages of the marble trout (Salmo marmoratus)-eyed eggs, yolk-sac larvae and juveniles of 1 and 3 months. Oxygen consumption rate and ETS activity increased with level of development and with temperature in all four stages. ETS/R ratios decreased during development and correlated with temperature in eyed eggs, larvae and juveniles of 1 month, but not in juveniles of 3 months. Low ETS/R ratios at higher temperatures indicate stress response in eyed eggs, the most temperature sensitive developmental stage. Catalase (CAT) and glutathione reductase (GR) activities increased during development, but responded differently to elevated temperature in the different developmental stages. Stress in eyed eggs, caused by higher temperatures, resulted in increased oxygen consumption rate and increased activities of CAT and GR. Larvae were sensitive to increased temperature only at the highest experimental temperature of 16°C. Increased temperature did not stress the metabolism of the juveniles, since they were able to compensate their metabolic activity. The earlier developmental stages of marble trout are thus more sensitive to temperature increase than juveniles and therefore more endangered by higher water temperatures. This is the first report connecting oxygen consumption, ETS activity and ETS/R ratio with the activities of antioxidant enzymes in relation to increased temperature in salmonids. PMID:25935664

  18. Treatment benefits on metabolic syndrome with diet and physical activity.

    PubMed

    Dragusha, Gani; Elezi, Abdulla; Dragusha, Shpend; Gorani, Daut; Begolli, Luljeta

    2010-05-01

    The research has included 422 patients aged between 25 to 60, of whom 341 were men and 81 women. The purpose of research was to determine impact of diet and physical activity in the treatment of metabolic syndrome during the six month period. Processing of results through descriptive and discriminative analysis have indicated that 6 month treatment with diet and physical activity have had an impact in the: waistline decrease by 6.05 cm or 5.50% among males, and 4.92 cm or 5.10% among females; body mass index (BMI) decrease by 1.78 or 6.20% among males, and 2.3 or 8.16% among females; decrease of blood triglycerides levels by 0.35 mmol/L or 16.28% among males, and 0.27 mmol/L or 13.30% among females; increase of blood cholesterol HDL-C by 0.48 mmol/L or 34.78% among males, and 0.06 mmol/L or 4.28% among females; systolic arterial pressure decreased by 15 mmHg or 10.18%, and diastolic blood pressure by 8.74 mmHg or 9.47% among males, and systolic arterial pressure decreased by 7.39 mmHg or 5.17%, and diastolic blood pressure decreased by 5.18 mmHg or 5.75% among females; the level of blood glucose decreased by 0.45 mmol/L or 7.04% among males, and by 0.64 mmol/L or 9.92% decreased among females. The results show that physical exercise and diet are important factors in reducing the values symptoms of metabolic syndrome. In order to improve symptoms of metabolic syndrome, it is necessary to keep on with healthy diet and physical exercise that means the change of lifestyle. PMID:20507300

  19. Modeling the dynamics of metabolism in montane streams using continuous dissolved oxygen measurements

    NASA Astrophysics Data System (ADS)

    Birkel, Christian; Soulsby, Chris; Malcolm, Iain; Tetzlaff, Doerthe

    2013-09-01

    We inferred in-stream ecosystem processes in terms of photosynthetic productivity (P), system respiration (R), and reaeration capacity (RC) from a five parameter numerical oxygen mass balance model driven by radiation, stream and air temperature, and stream depth. This was calibrated to high-resolution (15 min), long-term (2.5 years) dissolved oxygen (DO) time series for moorland and forest reaches of a third-order montane stream in Scotland. The model was multicriteria calibrated to continuous 24 h periods within the time series to identify behavioral simulations representative of ecosystem functioning. Results were evaluated using a seasonal regional sensitivity analysis and a colinearity index for parameter sensitivity. This showed that >95 % of the behavioral models for the moorland and forest sites were identifiable and able to infer in-stream processes from the DO time series for around 40% and 32% of the time period, respectively. Monthly P/R ratios <1 indicate a heterotrophic system with both sites exhibiting similar temporal patterns; with a maximum in February and a second peak during summer months. However, the estimated net ecosystem productivity suggests that the moorland reach without riparian tree cover is likely to be a much larger source of carbon to the atmosphere (122 mmol C m-2 d-1) compared to the forested reach (64 mmol C m-2 d-1). We conclude that such process-based oxygen mass balance models may be transferable tools for investigating other systems; specifically, well-oxygenated upland channels with high hydraulic roughness and lacking reaeration measurements.

  20. Indole generates quiescent and metabolically active Escherichia coli cultures.

    PubMed

    Chen, Chih-Chin; Walia, Rupali; Mukherjee, Krishna J; Mahalik, Subhashree; Summers, David K

    2015-04-01

    An inherent problem with bacterial cell factories used to produce recombinant proteins or metabolites is that resources are channeled into unwanted biomass as well as product. Over several years, attempts have been made to increase efficiency by unlinking biomass and product generation. One example was the quiescent cell (Q-Cell) expression system that generated non-growing but metabolically active Escherichia coli by over-expressing a regulatory RNA (Rcd) in a defined genetic background. Although effective at increasing the efficiency with which resources are converted to product, the technical complexity of the Rcd-based Q-Cell system limited its use. We describe here an alternative method for generating Q-Cells by the direct addition of indole, or related indole derivatives, to the culture medium of an E. coli strain carrying defined mutations in the hns gene. This simple and effective approach is shown to be functional in both shake-flask and fermenter culture. The cells remain metabolically active and analysis of their performance in the fermenter suggests that they may be particularly suitable for the production of cellular metabolites. PMID:25594833

  1. Sleep slow-wave activity regulates cerebral glycolytic metabolism.

    PubMed

    Wisor, Jonathan P; Rempe, Michael J; Schmidt, Michelle A; Moore, Michele E; Clegern, William C

    2013-08-01

    Non-rapid eye movement sleep (NREMS) onset is characterized by a reduction in cerebral metabolism and an increase in slow waves, 1-4-Hz oscillations between relatively depolarized and hyperpolarized states in the cerebral cortex. The metabolic consequences of slow-wave activity (SWA) at the cellular level remain uncertain. We sought to determine whether SWA modulates the rate of glycolysis within the cerebral cortex. The real-time measurement of lactate concentration in the mouse cerebral cortex demonstrates that it increases during enforced wakefulness. In spontaneous sleep/wake cycles, lactate concentration builds during wakefulness and rapid eye movement sleep and declines during NREMS. The rate at which lactate concentration declines during NREMS is proportional to the magnitude of electroencephalographic (EEG) activity at frequencies of <10 Hz. The induction of 1-Hz oscillations, but not 10-Hz oscillations, in the electroencephalogram by optogenetic stimulation of cortical pyramidal cells during wakefulness triggers a decline in lactate concentration. We conclude that cerebral SWA promotes a decline in the rate of glycolysis in the cerebral cortex. These results demonstrate a cellular energetic function for sleep SWA, which may contribute to its restorative effects on brain function. PMID:22767634

  2. Metabolism of a highly selective gelatinase inhibitor generates active metabolite.

    PubMed

    Lee, Mijoon; Villegas-Estrada, Adriel; Celenza, Giuseppe; Boggess, Bill; Toth, Marta; Kreitinger, Gloria; Forbes, Christopher; Fridman, Rafael; Mobashery, Shahriar; Chang, Mayland

    2007-11-01

    (4-Phenoxyphenylsulfonyl)methylthiirane (inhibitor 1) is a highly selective inhibitor of gelatinases (matrix metalloproteinases 2 and 9), which is showing considerable promise in animal models for cancer and stroke. Despite demonstrated potent, selective, and effective inhibition of gelatinases both in vitro and in vivo, the compound is rapidly metabolized, implying that the likely activity in vivo is due to a metabolite rather than the compound itself. To this end, metabolism of inhibitor 1 was investigated in in vitro systems. Four metabolites were identified by LC/MS-MS and the structures of three of them were further validated by comparison with authentic synthetic samples. One metabolite, 4-(4-thiiranylmethanesulfonylphenoxy)phenol (compound 21), was generated by hydroxylation of the terminal phenyl group of 1. This compound was investigated in kinetics of inhibition of several matrix metalloproteinases. This metabolite was a more potent slow-binding inhibitor of gelatinases (matrix metalloproteinase-2 and matrix metalloproteinase-9) than the parent compound 1, but it also served as a slow-binding inhibitor of matrix metalloproteinase-14, the upstream activator of matrix metalloproteinase-2. PMID:17927722

  3. Metabolic clearance of biologically active luteinizing hormone in man.

    PubMed Central

    Veldhuis, J D; Fraioli, F; Rogol, A D; Dufau, M L

    1986-01-01

    The plasma metabolic clearance of biologically active luteinizing hormone (bioactive LH) was studied using the rat interstitial cell testosterone (RICT) bioassay in six hypogonadotropic men after single bolus injection of highly purified human LH and during continuous steady-state infusions of three graded doses of LH. The LH bolus disappearance curves provided estimates of metabolic clearance rates (MCR) of 24.1 +/- 4.7 (+/- SD) ml/min for bioactive LH vs. 56.2 +/- 12 ml/min for immunoactive LH in the same men (P = 0.03). A lower MCR of bioactive LH compared with immunoactive LH was also observed during continuous infusions of physiological doses of LH; for example, the mean steady-state MCRs for bioactive and immunoactive LH were, respectively, 26.1 +/- 3.1 and 34.2 +/- 3.2 ml/min (P = 0.02). Moreover, the stepped-dose infusion regimens permitted us to demonstrate that increasing doses of pure human LH resulted in progressive and parallel decreases in the apparent MCRs of both bioactive and immunoactive LH. Based on the respective steady-state MCRs calculated at physiological plasma concentrations of immunoactive and bioactive LH, we estimate a mean endogenous production rate for bioactive hormone of 1,937 IU/24 h, and for immunoactive LH of 589 IU/24 h in normal men. These results indicate that previous estimates of LH production rates from immunoassay data alone markedly underestimate the quantity of biologically active hormone secreted in man. PMID:3958184

  4. Selective metabolic activation of the hippocampus during lidocaine-induced pre-seizure activity.

    PubMed

    Ingvar, M; Shapiro, H M

    1981-01-01

    Neurophysiologic studies indicate that local anesthetic-induced seizures are generated in subcortical brain structures. The authors utilized a quantitative autoradiographic technique to measure cerebral metabolism during lidocaine-induced seizure activity in rats anesthetized with nitrous oxide. Local cerebral metabolic rate for glucose (l-CMRg) was determined when lidocaine infusion resulted in sustained electroencephalographic patterns consisting of approximately 100--125-mu volt discharges with a frequency of about 9 Hz, lasting 1-2 sec, and superimposed upon almost isoelectric periods lasting 1-3 sec. Significant reductions in 1-CMRg (30-70 per cent decreases) occurred in 19 of 26 regions surveyed. All areas of cerebral cortex had decreased glucose uptake following lidocaine administration. The hippocampus developed a striking increase in 1-CMRg of 237 per cent, while the amygdala and other related nuclei sustained metabolic rates similar to those present before lidocaine was given. This study demonstrates a coupling of metabolic activity with functional activity in subcortical structures recognized to be involved in the generation of local anesthetic seizure activity. Additionally, it reveals a heterogeneous response of cerebral metabolism to lidocaine infusion in the presence of subcortically localized seizures. PMID:7457980

  5. Detection of reactive oxygen species via endogenous oxidative pentose phosphate cycle activity in response to oxygen concentration: implications for the mechanism of HIF-1alpha stabilization under moderate hypoxia.

    PubMed

    Tuttle, Stephen W; Maity, Amit; Oprysko, Patricia R; Kachur, Alexander V; Ayene, Iraimoudi S; Biaglow, John E; Koch, Cameron J

    2007-12-21

    The oxidative pentose phosphate cycle (OPPC) is necessary to maintain cellular reducing capacity during periods of increased oxidative stress. Metabolic flux through the OPPC increases stoichiometrically in response to a broad range of chemical oxidants, including those that generate reactive oxygen species (ROS). Here we show that OPPC sensitivity is sufficient to detect low levels of ROS produced metabolically as a function of the percentage of O2. We observe a significant decrease in OPPC activity in cells incubated under severe and moderate hypoxia (ranging from <0.01 to 4% O2), whereas hyperoxia (95% O2) results in a significant increase in OPPC activity. These data indicate that metabolic ROS production is directly dependent on oxygen concentration. Moreover, we have found no evidence to suggest that ROS, produced by mitochondria, are needed to stabilize hypoxia-inducible factor 1alpha (HIF-1alpha) under moderate hypoxia. Myxothiazol, an inhibitor of mitochondrial electron transfer, did not prevent HIF-1alpha stabilization under moderate hypoxia. Moreover, the levels of HIF-1alpha that we observed after exposure to moderate hypoxia were comparable between rho0 cells, which lack functional mitochondria, and the wild-type cells. Finally, we find no evidence for stabilization of HIF-1alpha in response to the non-toxic levels of H2O2 generated by the enzyme glucose oxidase. Therefore, we conclude that the oxygen dependence of the prolyl hydroxylase reaction is sufficient to mediate HIF-1alpha stability under moderate as well as severe hypoxia. PMID:17666400

  6. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson BH. Principles of Anatomy and Physiology . 14th ed. Hoboken, NJ: John H Wiley and Sons; 2013: ...

  7. Simvastatin Inhibits Glucose Metabolism and Legumain Activity in Human Myotubes

    PubMed Central

    Smith, Robert; Solberg, Rigmor; Jacobsen, Linn Løkken; Voreland, Anette Larsen; Rustan, Arild Christian; Thoresen, G. Hege; Johansen, Harald Thidemann

    2014-01-01

    Simvastatin, a HMG-CoA reductase inhibitor, is prescribed worldwide to patients with hypercholesterolemia. Although simvastatin is well tolerated, side effects like myotoxicity are reported. The mechanism for statin-induced myotoxicity is still poorly understood. Reports have suggested impaired mitochondrial dysfunction as a contributor to the observed myotoxicity. In this regard, we wanted to study the effects of simvastatin on glucose metabolism and the activity of legumain, a cysteine protease. Legumain, being the only known asparaginyl endopeptidase, has caspase-like properties and is described to be involved in apoptosis. Recent evidences indicate a regulatory role of both glucose and statins on cysteine proteases in monocytes. Satellite cells were isolated from the Musculus obliquus internus abdominis of healthy human donors, proliferated and differentiated into polynuclear myotubes. Simvastatin with or without mevalonolactone, farnesyl pyrophosphate or geranylgeranyl pyrophosphate were introduced on day 5 of differentiation. After 48 h, cells were either harvested for immunoblotting, ELISA, cell viability assay, confocal imaging or enzyme activity analysis, or placed in a fuel handling system with [14C]glucose or [3H]deoxyglucose for uptake and oxidation studies. A dose-dependent decrease in both glucose uptake and oxidation were observed in mature myotubes after exposure to simvastatin in concentrations not influencing cell viability. In addition, simvastatin caused a decrease in maturation and activity of legumain. Dysregulation of glucose metabolism and decreased legumain activity by simvastatin points out new knowledge about the effects of statins on skeletal muscle, and may contribute to the understanding of the myotoxicity observed by statins. PMID:24416446

  8. Oxygen Dependence and Extravascular Transport of Hypoxia-Activated Prodrugs: Comparison of the Dinitrobenzamide Mustard PR-104A and Tirapazamine

    SciTech Connect

    Hicks, Kevin O. Myint, Hilary; Patterson, Adam V.; Pruijn, Frederik B.; Siim, Bronwyn G.; Patel, Kashyap; Wilson, William R.

    2007-10-01

    Purpose: To compare oxygen dependence and tissue transport properties of a new hypoxia-activated prodrug, PR-104A, with tirapazamine, and to evaluate the implications for antitumor activity when combined with radiotherapy. Methods and Materials: Oxygen dependence of cytotoxicity was measured by clonogenic assay in SiHa cell suspensions. Tissue transport parameters were determined using SiHa multicellular layers. Spatially resolved pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to predict cell killing in SiHa tumors and tested by clonogenic assay 18 h after treatment with the corresponding phosphate ester, PR-104. Results: The K-value (oxygen concentration to halve cytotoxic potency) of PR-104A was 0.126 {+-} 0.021 {mu}M (10-fold lower than tirapazamine at 1.30 {+-} 0.28 {mu}M). The diffusion coefficient of PR-104A in multicellular layers (4.42 {+-} 0.15 x 10{sup -7} cm{sup 2} s{sup -1}) was lower than that of tirapazamine (1.30 {+-} 0.05 x 10{sup -6} cm{sup 2} s{sup -1}) but PK modeling predicted better penetration to hypoxic cells in tumors because of its slower metabolism. The tirapazamine PK/PD model successfully predicted the measured activity in combination with single-dose radiation against SiHa tumors, and the PR-104A model underpredicted the activity, which was greater for PR-104 than for tirapazamine (at equivalent host toxicity) both with radiation and as a single agent. Conclusion: PR-104/PR-104A has different PK/PD properties from tirapazamine and superior activity with single-dose radiotherapy against SiHa xenografts. We have inferred that PR-104A is better able to kill cells at intermediate partial pressure of oxygen in tumors than implied by the PK/PD model, most likely because of a bystander effect resulting from diffusion of its activated metabolites from severely hypoxic zones.

  9. Activated Macrophages as a Novel Determinant of Tumor Cell Radioresponse: The Role of Nitric Oxide-Mediated Inhibition of Cellular Respiration and Oxygen Sparing

    SciTech Connect

    Jiang Heng; De Ridder, Mark; Verovski, Valeri N.; Sonveaux, Pierre; Jordan, Benedicte F.; Law, Kalun; Monsaert, Christinne; Van den Berge, Dirk L.; Verellen, Dirk; Feron, Olivier; Gallez, Bernard; Storme, Guy A.

    2010-04-15

    Purpose: Nitric oxide (NO), synthesized by the inducible nitric oxide synthase (iNOS), is known to inhibit metabolic oxygen consumption because of interference with mitochondrial respiratory activity. This study examined whether activation of iNOS (a) directly in tumor cells or (b) in bystander macrophages may improve radioresponse through sparing of oxygen. Methods and Materials: EMT-6 tumor cells and RAW 264.7 macrophages were exposed to bacterial lipopolysaccharide plus interferon-gamma, and examined for iNOS expression by reverse transcription polymerase chain reaction, Western blotting and enzymatic activity. Tumor cells alone, or combined with macrophages were subjected to metabolic hypoxia and analyzed for radiosensitivity by clonogenic assay, and for oxygen consumption by electron paramagnetic resonance and a Clark-type electrode. Results: Both tumor cells and macrophages displayed a coherent picture of iNOS induction at transcriptional/translational levels and NO/nitrite production, whereas macrophages showed also co-induction of the inducible heme oxygenase-1, which is associated with carbon monoxide (CO) and bilirubin production. Activation of iNOS in tumor cells resulted in a profound oxygen sparing and a 2.3-fold radiosensitization. Bystander NO-producing, but not CO-producing, macrophages were able to block oxygen consumption by 1.9-fold and to radiosensitize tumor cells by 2.2-fold. Both effects could be neutralized by aminoguanidine, a metabolic iNOS inhibitor. An improved radioresponse was clearly observed at macrophages to tumor cells ratios ranging between 1:16 to 1:1. Conclusions: Our study is the first, as far as we are aware, to provide evidence that iNOS may induce radiosensitization through oxygen sparing, and illuminates NO-producing macrophages as a novel determinant of tumor cell radioresponse within the hypoxic tumor microenvironment.

  10. Metabolic rates, enzyme activities and chemical compositions of some deep-sea pelagic worms, particularly Nectonemertes mirabilis (Nemertea; Hoplonemertinea) and Poeobius meseres (Annelida; Polychaeta)

    NASA Astrophysics Data System (ADS)

    Thuesen, Erik V.; Childress, James J.

    1993-05-01

    Investigations of metabolic rate, enzyme activity and chemical composition were undertaken on two abundant deep-sea pelagic worms: Nectonemertes mirabilis (Nemertea; Hoplonemertinea) and Poeobius meseres (Annelida; Polychaeta). Six other species of worms ( Pelagonemertes brinkmanni (Nemertea) and the following polychaetes: Pelagobia species A, Tomopteris nisseni, Tomopteris pacifica, Tomopteris species A, and Traviopsis lobifera) were captured in smaller numbers and used for comparison in the physiological and biochemical measurements. Polychaete worms had the highest oxygen consumption rates and, along with N. mirabilis, displayed significant size effects on metabolic rate. Poeobius meseres had the lowest rates of oxygen consumption and displayed no significant relationship of oxygen consumption rate to wet weight. No significant effect of size on the activities of citrate synthase, lactate dehydrogenase or pyruvate kinase was observed in P. meseres or N. mirabilis. Lipid content was higher than protein content for all the worms in this study. Carbohydrate was of little significance in these worms and was usually <0.01% of the total weight. Citrate synthase activities of pelagic worms showed excellent correlation with metabolic rates. It appears that polychaete worms as a group have higher metabolic rates than bathypelagic shrimps, copepods and fishes, and may be the animals with the highest metabolic rates in the bathypelagic regions of the world's oceans.

  11. No effect of acute beetroot juice ingestion on oxygen consumption, glucose kinetics, or skeletal muscle metabolism during submaximal exercise in males.

    PubMed

    Betteridge, Scott; Bescós, Raúl; Martorell, Miquel; Pons, Antoni; Garnham, Andrew P; Stathis, Christos C; McConell, Glenn K

    2016-02-15

    Beetroot juice, which is rich in nitrate (NO3 (-)), has been shown in some studies to decrease oxygen consumption (V̇o2) for a given exercise workload, i.e., increasing efficiency and exercise tolerance. Few studies have examined the effect of beetroot juice or nitrate supplementation on exercise metabolism. Eight healthy recreationally active males participated in three trials involving ingestion of either beetroot juice (Beet; ∼8 mmol NO3 (-)), Placebo (nitrate-depleted Beet), or Beet + mouthwash (Beet+MW), all of which were performed in a randomized single-blind crossover design. Two-and-a-half hours later, participants cycled for 60 min on an ergometer at 65% of V̇o2 peak. [6,6-(2)H]glucose was infused to determine glucose kinetics, blood samples obtained throughout exercise, and skeletal muscle biopsies that were obtained pre- and postexercise. Plasma nitrite [NO2 (-)] increased significantly (∼130%) with Beet, and this was attenuated in MW+Beet. Beet and Beet+MW had no significant effect on oxygen consumption, blood glucose, blood lactate, plasma nonesterified fatty acids, or plasma insulin during exercise. Beet and Beet+MW also had no significant effect on the increase in glucose disposal during exercise. In addition, Beet and Beet+MW had no significant effect on the decrease in muscle glycogen and phosphocreatine and the increase in muscle creatine, lactate, and phosphorylated acetyl CoA carboxylase during exercise. In conclusion, at the dose used, acute ingestion of beetroot juice had little effect on skeletal muscle metabolism during exercise. PMID:26635348

  12. Molecular dioxygen enters the active site of 12/15-lipoxygenase via dynamic oxygen access channels.

    PubMed

    Saam, Jan; Ivanov, Igor; Walther, Matthias; Holzhütter, Hermann-Georg; Kuhn, Hartmut

    2007-08-14

    Cells contain numerous enzymes that use molecular oxygen for their reactions. Often, their active sites are buried deeply inside the protein, which raises the question whether there are specific access channels guiding oxygen to the site of catalysis. Choosing 12/15-lipoxygenase as a typical example for such oxygen-dependent enzymes, we determined the oxygen distribution within the protein and defined potential routes for oxygen access. For this purpose, we have applied an integrated strategy of structural modeling, molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements. First, we computed the 3D free-energy distribution for oxygen, which led to identification of four oxygen channels in the protein. All channels connect the protein surface with a region of high oxygen affinity at the active site. This region is localized opposite to the nonheme iron providing a structural explanation for the reaction specificity of this lipoxygenase isoform. The catalytically most relevant path can be obstructed by L367F exchange, which leads to a strongly increased Michaelis constant for oxygen. The blocking mechanism is explained in detail by reordering the hydrogen-bonding network of water molecules. Our results provide strong evidence that the main route for oxygen access to the active site of the enzyme follows a channel formed by transiently interconnected cavities whereby the opening and closure are governed by side chain dynamics. PMID:17675410

  13. PHYTOALEXIN DEFICIENT 4 affects reactive oxygen species metabolism, cell wall and wood properties in hybrid aspen (Populus tremula L. × tremuloides).

    PubMed

    Ślesak, Ireneusz; Szechyńska-Hebda, Magdalena; Fedak, Halina; Sidoruk, Natalia; Dąbrowska-Bronk, Joanna; Witoń, Damian; Rusaczonek, Anna; Antczak, Andrzej; Drożdżek, Michał; Karpińska, Barbara; Karpiński, Stanisław

    2015-07-01

    The phytoalexin deficient 4 (PAD4) gene in Arabidopsis thaliana (AtPAD4) is involved in the regulation of plant--pathogen interactions. The role of PAD4 in woody plants is not known; therefore, we characterized its function in hybrid aspen and its role in reactive oxygen species (ROS)-dependent signalling and wood development. Three independent transgenic lines with different suppression levels of poplar PAD expression were generated. All these lines displayed deregulated ROS metabolism, which was manifested by an increased H2O2 level in the leaves and shoots, and higher activities of manganese superoxide dismutase (MnSOD) and catalase (CAT) in the leaves in comparison to the wild-type plants. However, no changes in non-photochemical quenching (NPQ) between the transgenic lines and wild type were observed in the leaves. Moreover, changes in the ROS metabolism in the pad4 transgenic lines positively correlated with wood formation. A higher rate of cell division, decreased tracheid average size and numbers, and increased cell wall thickness were observed. The results presented here suggest that the Populus tremula × tremuloides PAD gene might be involved in the regulation of cellular ROS homeostasis and in the cell division--cell death balance that is associated with wood development. PMID:24943986

  14. Ethanol metabolism and oxidative stress are required for unfolded protein response activation and steatosis in zebrafish with alcoholic liver disease

    PubMed Central

    Tsedensodnom, Orkhontuya; Vacaru, Ana M.; Howarth, Deanna L.; Yin, Chunyue; Sadler, Kirsten C.

    2013-01-01

    SUMMARY Secretory pathway dysfunction and lipid accumulation (steatosis) are the two most common responses of hepatocytes to ethanol exposure and are major factors in the pathophysiology of alcoholic liver disease (ALD). However, the mechanisms by which ethanol elicits these cellular responses are not fully understood. Recent data indicates that activation of the unfolded protein response (UPR) in response to secretory pathway dysfunction can cause steatosis. Here, we examined the relationship between alcohol metabolism, oxidative stress, secretory pathway stress and steatosis using zebrafish larvae. We found that ethanol was immediately internalized and metabolized by larvae, such that the internal ethanol concentration in 4-day-old larvae equilibrated to 160 mM after 1 hour of exposure to 350 mM ethanol, with an average ethanol metabolism rate of 56 μmol/larva/hour over 32 hours. Blocking alcohol dehydrogenase 1 (Adh1) and cytochrome P450 2E1 (Cyp2e1), the major enzymes that metabolize ethanol, prevented alcohol-induced steatosis and reduced induction of the UPR in the liver. Thus, we conclude that ethanol metabolism causes ALD in zebrafish. Oxidative stress generated by Cyp2e1-mediated ethanol metabolism is proposed to be a major culprit in ALD pathology. We found that production of reactive oxygen species (ROS) increased in larvae exposed to ethanol, whereas inhibition of the zebrafish CYP2E1 homolog or administration of antioxidants reduced ROS levels. Importantly, these treatments also blocked ethanol-induced steatosis and reduced UPR activation, whereas hydrogen peroxide (H2O2) acted as a pro-oxidant that synergized with low doses of ethanol to induce the UPR. Collectively, these data demonstrate that ethanol metabolism and oxidative stress are conserved mechanisms required for the development of steatosis and hepatic dysfunction in ALD, and that these processes contribute to ethanol-induced UPR activation and secretory pathway stress in hepatocytes. PMID

  15. Metabolic analyzer

    NASA Technical Reports Server (NTRS)

    Lem, J. D.

    1977-01-01

    The metabolic analyzer was designed to support experiment M171. It operates on the so-called open circuit method to measure a subject's metabolic activity in terms of oxygen consumed, carbon dioxide produced, minute volume, respiratory exchange ratio, and tidal volume or vital capacity. The system operates in either of two modes. (1) In Mode I, inhaled respiratory volumes are actually measured by a piston spirometer. (2) In Mode II, inhaled volumes are calculated from the exhaled volume and the measured inhaled and exhaled nitrogen concentrations. This second mode was the prime mode for Skylab. Following is a brief description of the various subsystems and their operation.

  16. Vampires, Pasteur and reactive oxygen species. Is the switch from aerobic to anaerobic metabolism a preventive antioxidant defence in blood-feeding parasites?

    PubMed

    Oliveira, Pedro L; Oliveira, Marcus F

    2002-08-14

    Several species of parasites show a reduction of their respiratory activity along their developmental cycles after they start to feed on vertebrate blood, relying on anaerobic degradation of carbohydrates to achieve their energy requirements. Usually, these parasites choose not to breathe despite of living in an environment of high oxygen availability such as vertebrate blood. Absence of the 'Pasteur effect' in most of these parasites has been well documented. Interestingly, together with the switch from aerobic to anaerobic metabolism in these parasites, there is clear evidence pointing to an increase in their antioxidant defences. As the respiratory chain in mitochondria is a major site of production of reactive oxygen species (ROS), we propose here that the arrest of respiration constitutes an adaptation to avoid the toxic effects of ROS. This situation would be especially critical for blood-feeding parasites because ROS produced in mitochondria would interact with pro-oxidant products of blood digestion, such as haem and/or iron, and increase the oxidative damage to the parasite's cells. PMID:12163151

  17. A mechanism of oxygen sensing in yeast. Multiple oxygen-responsive steps in the heme biosynthetic pathway affect Hap1 activity.

    PubMed

    Hon, Thomas; Dodd, Athena; Dirmeier, Reinhard; Gorman, Nadia; Sinclair, Peter R; Zhang, Li; Poyton, Robert O

    2003-12-12

    Heme plays central roles in oxygen sensing and utilization in many living organisms. In yeast, heme mediates the effect of oxygen on the expression of many genes involved in using or detoxifying oxygen. However, a direct link between intracellular heme level and oxygen concentration has not been vigorously established. In this report, we have examined the relationships among oxygen levels, heme levels, Hap1 activity, and HAP1 expression. We found that Hap1 activity is controlled in vivo by heme and not by its precursors and that heme activates Hap1 even in anoxic cells. We also found that Hap1 activity exhibits the same oxygen dose-response curves as Hap1-dependent aerobic genes and that these dose-response curves have a sharp break at approximately 1 microM O2. The results show that the intracellular signaling heme level, reflected as Hap1 activity, is closely correlated with oxygen concentration. Furthermore, we found that bypass of all heme synthetic steps but ferrochelatase by deuteroporphyrin IX does not circumvent the need for oxygen in Hap1 full activation by heme, suggesting that the last step of heme synthesis, catalyzed by ferrochelatase, is also subjected to oxygen control. Our results show that multiple heme synthetic steps can sense oxygen concentration and provide significant insights into the mechanism of oxygen sensing in yeast. PMID:14512429

  18. Metabolic Tumor Profiling with pH, Oxygen, and Glucose Chemosensors on a Quantum Dot Scaffold

    PubMed Central

    Lemon, Christopher M.; Curtin, Peter N.; Somers, Rebecca C.; Greytak, Andrew B.; Lanning, Ryan M.; Jain, Rakesh K.; Bawendi, Moungi G.; Nocera, Daniel G.

    2013-01-01

    Synopsis Acidity, hypoxia and glucose levels characterize the tumor microenvironment rendering pH, pO2 and pGlucose, respectively, important indicators of tumor health. To this end, understanding how these parameters change can be a powerful tool for the development of novel and effective therapeutics. We have designed optical chemosensors that feature a quantum dot and an analyte-responsive dye. These non-invasive chemosensors permit pH, oxygen, and glucose to be monitored dynamically within the tumor microenvironment by using multiphoton imaging. PMID:24143874

  19. Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.

    PubMed

    Shabalina, Irina G; Kalinovich, Anastasia V; Cannon, Barbara; Nedergaard, Jan

    2016-05-01

    The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fatty acids. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization or to ROS production. Thus, metabolic effects of perfluorinated fatty acids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA-/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged. PMID:26041126

  20. Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage

    NASA Astrophysics Data System (ADS)

    Lin, Pei-Yi; Hagan, Katherine; Fenoglio, Angela; Grant, P. Ellen; Franceschini, Maria Angela

    2016-05-01

    Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant’s bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFi and CMRO2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO2 does not differ between groups. Thus, CBFi and CMRO2i may have better sensitivity than SO2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response, and potentially predicting neurodevelopmental outcome.

  1. Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage.

    PubMed

    Lin, Pei-Yi; Hagan, Katherine; Fenoglio, Angela; Grant, P Ellen; Franceschini, Maria Angela

    2016-01-01

    Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant's bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFi and CMRO2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO2 does not differ between groups. Thus, CBFi and CMRO2i may have better sensitivity than SO2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response, and potentially predicting neurodevelopmental outcome. PMID:27181339

  2. Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage

    PubMed Central

    Lin, Pei-Yi; Hagan, Katherine; Fenoglio, Angela; Grant, P. Ellen; Franceschini, Maria Angela

    2016-01-01

    Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant’s bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFi and CMRO2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO2 does not differ between groups. Thus, CBFi and CMRO2i may have better sensitivity than SO2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response, and potentially predicting neurodevelopmental outcome. PMID:27181339

  3. Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning.

    PubMed

    Linnman, Clas; Zeidan, Mohamed A; Pitman, Roger K; Milad, Mohammed R

    2012-02-01

    We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differentially conditioned skin conductance responses. Midbrain and insula resting metabolism negatively predicted midbrain and insula functional reactivity, while dorsal anterior cingulate resting metabolism positively predicted midbrain functional reactivity. We conclude that resting metabolism in limbic areas can predict some aspects of psychophysiological and neuronal reactivity during fear learning. PMID:22207247

  4. Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning

    PubMed Central

    Linnman, Clas; Zeidan, Mohamed A.; Pitman, Roger K; Milad, Mohammed R.

    2011-01-01

    We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differentially conditioned skin conductance responses. Midbrain and insula resting metabolism negatively predicted midbrain and insula functional reactivity, while dorsal anterior cingulate resting metabolism positively predicted midbrain functional reactivity. We conclude that resting metabolism in limbic areas can predict some aspects of psychophysiological and neuronal reactivity during fear learning. PMID:22207247

  5. Hepatically-metabolized and -excreted artificial oxygen carrier, hemoglobin vesicles, can be safely used under conditions of hepatic impairment

    SciTech Connect

    Taguchi, Kazuaki; Miyasato, Mayumi; Ujihira, Hayato; Watanabe, Hiroshi; Kadowaki, Daisuke; Sakai, Hiromi; Tsuchida, Eishun; Horinouchi, Hirohisa; Kobayashi, Koichi; Maruyama, Toru; Otagiri, Masaki

    2010-11-01

    The hemoglobin vesicle (HbV) is an artificial oxygen carrier in which a concentrated Hb solution is encapsulated in lipid vesicles. Our previous studies demonstrated that HbV is metabolized by the mononuclear phagocyte system, and the lipid components are excreted from the liver. It is well-known that many hepatically-metabolized and -excreted drugs show altered pharmaceutics under conditions of liver impairment, which results in adverse effects. The aim of this study was to determine whether the administration of HbV causes toxicity in rats with carbon tetrachloride induced liver cirrhosis. Changes in plasma biochemical parameters, histological staining and the pharmacokinetic distribution of HbV were evaluated after an HbV injection of the above model rats at a putative clinical dose (1400 mgHb/kg). Plasma biochemical parameters were not significantly affected, except for a transient elevation of lipase, lipid components and bilirubin, which recovered within 14 days after an HbV infusion. Negligible morphological changes were observed in the kidney, liver, spleen, lung and heart. Hemosiderin, a marker of iron accumulation in organs, was observed in the liver and spleen up to 14 days after HbV treatment, but no evidence of oxidative stress in the plasma and liver were observed. HbV is mainly distributed in the liver and spleen, and the lipid components are excreted into feces within 7 days. In conclusion, even under conditions of hepatic cirrhosis, HbV and its components exhibit the favorable metabolic and excretion profile at the putative clinical dose. These findings provide further support for the safety and effectiveness of HbV in clinical settings.

  6. The effects of hyperammonemia in learning and brain metabolic activity.

    PubMed

    Arias, Natalia; Fidalgo, Camino; Felipo, Vicente; Arias, Jorge L

    2014-03-01

    Ammonia is thought to be central in the development of hepatic encephalopathy. However, the specific relation of ammonia with brain energy depletions and learning has not been studied. Our work attempts to reproduce an increase in rat cerebral ammonia level, study the hyperamonemic animals' performance of two learning tasks, an allocentric (ALLO) and a cue guided (CG) task, and elucidate the contribution of hyperammonemia to the differential energy requirements of the brain limbic system regions involved in these tasks. To assess these goals, four groups of animals were used: a control (CHA) CG group (n = 10), a CHA ALLO group (n = 9), a hyperammonemia (HA) CG group (n = 7), and HA ALLO group (n = 8). Oxidative metabolism of the target brain regions were assessed by histochemical labelling of cytochrome oxidase (C.O.). The behavioural results revealed that the hyperammonemic rats were not able to reach the behavioural criterion in either of the two tasks, in contrast to the CHA groups. The metabolic brain consumption revealed increased C.O. activity in the anterodorsal thalamus when comparing the HA ALLO group with the CHA ALLO group. Significant differences between animals trained in the CG task were observed in the prelimbic, infralimbic, parietal, entorhinal and perirhinal cortices, the anterolateral and anteromedial striatum, and the basolateral and central amygdala. Our findings may provide fresh insights to reveal how the differential damage to the brain limbic structures involved in these tasks differs according to the degree of task difficulty. PMID:24415107

  7. Correlates of average daily metabolism of field-active zebra-tailed lizards (Callisaurus draconoides).

    PubMed

    Karasov, W H; Anderson, R A

    1998-01-01

    The extent of variation in reptile field metabolism, and its causal bases, are poorly understood. We studied the energetics of the insectivorous lizard Callisaurus draconoides at a site in the California Desert (Desert Center) and at a site at the southern tip of the Baja Peninsula (Cabo San Lucas; hereafter, Cabo). Reproducing Callisaurus were smaller at Cabo than at Desert Center. The allometry of metabolism with body mass can account for most differences in whole-animal metabolism. There was no significant effect of sex or source population on mass-adjusted metabolic rate in the laboratory (resting metabolism, measured by closed-system respirometry) or in the field (field metabolism, measured with doubly labeled water). The mass-adjusted resting metabolism and field metabolism of gravid females and the field metabolism of juvenile lizards were not significantly different from those of nonreproductive adults. Temperature had a significant effect on resting metabolism (Q10 = 2.7); fed lizards had resting metabolism that was 22% higher than that of fasted lizards; field metabolism was positively correlated with growth rate in juveniles; and field metabolism of adults increased from spring to late summer at Desert Center by 25%, probably because of longer activity period length and slightly higher activity period body temperature. We calculated from water influx and field metabolism that juveniles allocated 18% of their metabolizable energy intake to growth and that most energy deposited into eggs was transferred from energy stores rather than ingested in the weeks prior to laying. PMID:9472817

  8. Cell death induced by direct laser activation of singlet oxygen at 1270 nm

    NASA Astrophysics Data System (ADS)

    Anquez, F.; El Yazidi Belkoura, I.; Suret, P.; Randoux, S.; Courtade, E.

    2013-02-01

    Singlet oxygen plays a major role in many chemical and biological photo-oxidation processes. It has a high chemical reactivity, which is commonly harnessed for therapeutic issues. Indeed, singlet oxygen is recognized as the major cytotoxic agent in photodynamic therapy. In this treatment of cancer, singlet oxygen is created, among other reactive species, by an indirect transfer of energy from light to molecular oxygen via excitation of a photosensitizer. In this paper, we show that the conventional singlet oxygen production scheme can be simplified. Production of singlet oxygen is achieved in living cells from photosensitizer-free 1270 nm laser excitation of the electronic ground state of molecular oxygen. The quantity of singlet oxygen produced in this way is sufficient to induce an oxidative stress leading to cell death. Other effects such as thermal stress are discriminated, and we conclude that cell death is only due to singlet oxygen creation. This new simplified scheme of singlet oxygen activation can be seen as a breakthrough for phototherapies of malignant diseases and/or as a non-invasive possibility to generate reactive oxygen species in a tightly controlled manner.

  9. Metabolic responses of Glossina pallidipes (Diptera: Glossinidae) puparia exposed to oxygen and temperature variation: implications for population dynamics and subterranean life.

    PubMed

    Basson, C Helene; Terblanche, John S

    2010-12-01

    Understanding the factors affecting insect gas exchange in subterranean environments is critical to understanding energy budgets and predicting mortality under field conditions. Here, we examine the metabolic rate (MR) responses of tsetse puparia, which remain underground for ca. 1 month in this life-stage, to varying oxygen and temperature. First, the effects of temperature and oxygen on puparial MR were investigated by ramping temperature from 15 to 35°C under 10, 21 or 40% O(2). Overall, temperature was the dominant effect on puparial MR although O(2) had small but significant impacts. Second, critical O(2) concentration (P(CRIT)) for MR of puparia was examined across a range of oxygen concentrations (0-40%). P(CRIT) was 6% O(2) which is similar to P(CRIT) in other basal arthropods but relatively high for inactive or subterranean insects. Third, we asked if puparia exposed to anoxia might experience oxygen debt, potentially indicative of anaerobic metabolism or cellular repair. Metabolic responses to anoxia were limited or insignificant, but MR was marginally elevated (∼ 15%) in anoxia-exposed (4h) puparia by 12h post-anoxia. Finally, we examined the ability of puparia to withstand water submersion, thus simulating flooding conditions frequently experienced in tropical soil habitats. Puparia were unable to survive submersion for >24h suggesting limited flooding tolerance. These novel results suggest that soil conditions experienced by puparia should not be limiting for MR, except possibly under high temperature-low O(2) conditions. Due to a large safety margin between P(CRIT) and soil oxygen levels and limited effects of oxygen on metabolism during temperature ramping experiments, we suggest that Glossina pallidipes puparia are not particularly susceptible to oxygen availability in their natural environment. However, soil flooding associated with tropical rainfall likely imposes strong selection on tsetse populations and may have had important effects for

  10. Unwinding activity of cold shock proteins and RNA metabolism.

    PubMed

    Phadtare, Sangita

    2011-01-01

    Temperature downshift from 37 °C to 15 °C results in the exertion of cold shock response in Escherichia coli, which induces cold shock proteins, such as CsdA. Previously, we showed that the helicase activity of CsdA is critical for its function in the cold acclimation of cells and its primary role is mRNA degradation. Only RhlE (helicase), CspA (RNA chaperone) and RNase R (exoribonuclease) were found to complement the cold shock function of CsdA. RNase R has two independent activities, helicase and ribonuclease, only helicase being essential for the functional complementation of CsdA. Here, we discuss the significance of above findings as these emphasize the importance of the unwinding activity of cold-shock-inducible proteins in the RNA metabolism at low temperature, which may be different than that at 37 °C. It requires assistance of proteins to destabilize the secondary structures in mRNAs that are stabilized upon temperature downshift, hindering the activity of ribonucleases. PMID:21445001

  11. Effects of blood flow restriction duration on muscle activation and microvascular oxygenation during low-volume isometric exercise.

    PubMed

    Cayot, Trent E; Lauver, Jakob D; Silette, Christopher R; Scheuermann, Barry W

    2016-07-01

    The purpose of the investigation was to observe how varying occlusion durations affected neuromuscular activation and microvascular oxygenation during low-volume isometric knee extension exercise. Healthy, recreationally active males performed isometric knee extension at a variety of submaximal intensities under different blood flow restriction (BFR) occlusion durations. The occlusion pressure (130% SBP) was applied either 5 min prior to exercise (PO), immediately prior to exercise (IO) or not during exercise (CON). Surface electromyography (sEMG) and near-infrared spectroscopy (NIRS) was used to record the neuromuscular activation and microvascular oxygenation of the knee extensors during exercise. No difference in sEMG was observed in the vastus lateralis or vastus medialis during any exercise condition or any submaximal intensity. PO elicited greater microvascular deoxygenation (deoxy-[Hb + Mb]) compared to CON (P≤0·05) at all submaximal intensities and also compared to IO at 20% maximal voluntary contraction (MVC). IO resulted in a greater deoxy-[Hb + Mb] response during low-intensity exercise (20% and 40% MVC) compared to CON (P≤0·05). These findings suggest that applying BFR 5 min before exercise can enhance the exercise-induced metabolic stress (i.e. deoxy-[Hb + Mb]), measured via NIRS, during low-intensity exercise (20% MVC) compared to applying BFR immediately prior to exercise. Furthermore, the increased metabolic stress observed during IO is attenuated during high-intensity (60% MVC, 80% MVC) exercise when compared to CON conditions. Knowledge of the changes in exercise-induced metabolic stress between the various occlusion durations may assist in developing efficient BFR exercise programmes. PMID:25564998

  12. Evolution of the metabolic and regulatory networks associated with oxygen availability in two phytopathogenic enterobacteria

    PubMed Central

    2012-01-01

    Background Dickeya dadantii and Pectobacterium atrosepticum are phytopathogenic enterobacteria capable of facultative anaerobic growth in a wide range of O2 concentrations found in plant and natural environments. The transcriptional response to O2 remains under-explored for these and other phytopathogenic enterobacteria although it has been well characterized for animal-associated genera including Escherichia coli and Salmonella enterica. Knowledge of the extent of conservation of the transcriptional response across orthologous genes in more distantly related species is useful to identify rates and patterns of regulon evolution. Evolutionary events such as loss and acquisition of genes by lateral transfer events along each evolutionary branch results in lineage-specific genes, some of which may have been subsequently incorporated into the O2-responsive stimulon. Here we present a comparison of transcriptional profiles measured using densely tiled oligonucleotide arrays for two phytopathogens, Dickeya dadantii 3937 and Pectobacterium atrosepticum SCRI1043, grown to mid-log phase in MOPS minimal medium (0.1% glucose) with and without O2. Results More than 7% of the genes of each phytopathogen are differentially expressed with greater than 3-fold changes under anaerobic conditions. In addition to anaerobic metabolism genes, the O2 responsive stimulon includes a variety of virulence and pathogenicity-genes. Few of these genes overlap with orthologous genes in the anaerobic stimulon of E. coli. We define these as the conserved core, in which the transcriptional pattern as well as genetic architecture are well preserved. This conserved core includes previously described anaerobic metabolic pathways such as fermentation. Other components of the anaerobic stimulon show variation in genetic content, genome architecture and regulation. Notably formate metabolism, nitrate/nitrite metabolism, and fermentative butanediol production, differ between E. coli and the phytopathogens

  13. Control of macrophage metabolism and activation by mTOR and Akt signaling

    PubMed Central

    Covarrubias, Anthony J.; Aksoylar, H. Ibrahim; Horng, Tiffany

    2015-01-01

    Macrophages are pleiotropic cells that assume a variety of functions depending on their tissue of residence and tissue state. They maintain homeostasis as well as coordinate responses to stresses such as infection and metabolic challenge. The ability of macrophages to acquire diverse, context-dependent activities requires their activation (or polarization) to distinct functional states. While macrophage activation is well understood at the level of signal transduction and transcriptional regulation, the metabolic underpinnings are poorly understood. Importantly, emerging studies indicate that metabolic shifts play a pivotal role in control of macrophage activation and acquisition of context-dependent effector activities. The signals that drive macrophage activation impinge on metabolic pathways, allowing for coordinate control of macrophage activation and metabolism. Here we discuss how mTOR and Akt, major metabolic regulators and targets of such activation signals, control macrophage metabolism and activation. Dysregulated macrophage activities contribute to many diseases, including infectious, inflammatory, and metabolic diseases and cancer, thus a better understanding of metabolic control of macrophage activation could pave the way to the development of new therapeutic strategies. PMID:26360589

  14. Mechanical and metabolic reflex activation of the sympathetic nervous system in younger adults with metabolic syndrome

    PubMed Central

    Limberg, Jacqueline; Morgan, Barbara; Schrage, William

    2014-01-01

    Aim Based on reports of exaggerated blood pressure responses to whole-body exercise in patients with metabolic syndrome (MetSyn), we tested the hypothesis that MetSyn adults would exhibit augmented sympathetic and pressor responses to mechanoreflex and metaboreflex activation when compared with healthy, age-matched control subjects. Methods We studied 12 adults with MetSyn (34±3 years) and 12 healthy control subjects (34±3 years). Heart rate (HR; ECG), blood pressure (BP; finger photoplethysmography), and MSNA (microneurography of the peroneal nerve) were measured during: (1) Static handgrip exercise at 15% of maximal voluntary contraction (MVC), and (2) Static handgrip exercise at 30% MVC to fatigue, followed by post-exercise ischemia (PEI). Increases in MSNA, HR, and BP were assessed. Results During static exercise at both 15 and 30% MVC, increases in MSNA, HR, and BP were not different between groups. MSNA remained significantly elevated from baseline during PEI and responses were not different between groups. Conclusion Sympathetic and pressor responses to mechanoreflex and metaboreflex activation are not augmented in younger adults with MetSyn. PMID:24680829

  15. The ancestral activation promiscuity of ADP-glucose pyrophosphorylases from oxygenic photosynthetic organisms

    PubMed Central

    2013-01-01

    Background ADP-glucose pyrophosphorylase (ADP-Glc PPase) catalyzes the first committed step in the synthesis of glycogen in bacteria and starch in algae and plants. In oxygenic photosynthetic organisms, ADP-Glc PPase is mainly activated by 3-phosphoglycerate (3-PGA) and to a lesser extent by other metabolites. In this work, we analyzed the activation promiscuity of ADP-Glc PPase subunits from the cyanobacterium Anabaena PCC 7120, the green alga Ostreococcus tauri, and potato (Solanum tuberosum) tuber by comparing a specificity constant for 3-PGA, fructose-1,6-bisphosphate (FBP), fructose-6-phosphate, and glucose-6-phosphate. Results The 3-PGA specificity constant for the enzymes from Anabaena (homotetramer), O. tauri, and potato tuber was considerably higher than for other activators. O. tauri and potato tuber enzymes were heterotetramers comprising homologous small and large subunits. Conversely, the O. tauri small subunit (OtaS) homotetramer was more promiscuous because its FBP specificity constant was similar to that for 3-PGA. To explore the role of both OtaS and OtaL (O. tauri large subunit) in determining the specificity of the heterotetramer, we knocked out the catalytic activity of each subunit individually by site-directed mutagenesis. Interestingly, the mutants OtaSD148A/OtaL and OtaS/OtaLD171A had higher specificity constants for 3-PGA than for FBP. Conclusions After gene duplication, OtaS seemed to have lost specificity for 3-PGA compared to FBP. This was physiologically and evolutionarily feasible because co-expression of both subunits restored the specificity for 3-PGA of the resulting heterotetrameric wild type enzyme. This widespread promiscuity seems to be ancestral and intrinsic to the enzyme family. Its presence could constitute an efficient evolutionary mechanism to accommodate the ADP-Glc PPase regulation to different metabolic needs. PMID:23433303

  16. Parallel activation of mitochondrial oxidative metabolism with increased cardiac energy expenditure is not dependent on fatty acid oxidation in pigs

    PubMed Central

    Zhou, Lufang; Cabrera, Marco E; Huang, Hazel; Yuan, Celvie L; Monika, Duda K; Sharma, Naveen; Bian, Fang; Stanley, William C

    2007-01-01

    Steady state concentrations of ATP and ADP in vivo are similar at low and high cardiac workloads; however, the mechanisms that regulate the activation of substrate metabolism and oxidative phosphorylation that supports this stability are poorly understood. We tested the hypotheses that (1) there is parallel activation of mitochondrial and cytosolic dehydrogenases in the transition from low to high workload, which increases NADH/NAD+ ratio in both compartments, and (2) this response does not require an increase in fatty acid oxidation (FAO). Anaesthetized pigs were subjected to either sham treatment, or an abrupt increase in cardiac workload for 5 min with dobutamine infusion and aortic constriction. Myocardial oxygen consumption and FAO were increased 3- and 2-fold, respectively, but ATP and ADP concentrations did not change. NADH-generating pathways were rapidly activated in both the cytosol and mitochondria, as seen in a 40% depletion in glycogen stores, a 3.6-fold activation of pyruvate dehydrogenase, and a 50% increase in tissue NADH/NAD+. Simulations from a multicompartmental computational model of cardiac energy metabolism predicted that parallel activation of glycolysis and mitochondrial metabolism results in an increase in the NADH/NAD+ ratio in both cytosol and mitochondria. FAO was blocked by 75% in a third group of pigs, and a similar increase in and the NAHD/NAD+ ratio was observed. In conclusion, in the transition to a high cardiac workload there is rapid parallel activation of substrate oxidation that results in an increase in the NADH/NAD+ ratio. PMID:17185335

  17. Estimation of the regional cerebral metabolic rate of oxygen consumption with proton detected 17O MRI during precision 17O2 inhalation in swine

    PubMed Central

    Mellon, Eric A.; Beesam, R. Shashank; Baumgardner, James E.; Borthakur, Arijitt; Witschey, Walter R.; Reddy, Ravinder

    2009-01-01

    Despite the importance of metabolic disturbances in many diseases, there are currently no clinically used methods for the detection of oxidative metabolism in vivo. To address this deficiency, 17O MRI techniques are scaled from small animals to swine as a large animal model of human inhalation and circulation. The hemispheric cerebral metabolic rate of oxygen consumption (CMRO2) is estimated in swine by detection of metabolically produced H217O by rapid T1ρ-weighted proton magnetic resonance imaging on a 1.5 Tesla clinical scanner. The 17O is delivered as oxygen gas by a custom, minimal-loss, precision-delivery breathing circuit and converted to H217O by oxidative metabolism. A model for gas arterial input is presented for the deeply breathing large animal. The arterial input function for recirculation of metabolic water is measured by arterial blood sampling and high field 17O spectroscopy. It is found that minimal metabolic water “wash-in” occurs before 60 seconds. A high temporal resolution pulse sequence is employed to measure CMRO2 during those 60 seconds after delivery begins. Only about one tidal volume of 17O enriched oxygen gas is used per measurement. Proton measurements of signal change due to metabolically produced water are correlated with 17O in vivo spectroscopy. Using these techniques, the hemispheric CMRO2 in swine is estimated to be 1.23 ± 0.26 μmol/g/min, consistent with existing literature values. All of the technology used to perform these CMRO2 estimates can easily be adapted to clinical MR scanners, and it is hoped that this work will lead to future studies of human disease. PMID:19428508

  18. Effect of Oxygen Concentration on Viability and Metabolism in a Fluidized-Bed Bioartificial Liver Using 31P and 13C NMR Spectroscopy

    PubMed Central

    Jeffries, Rex E.; Gamcsik, Michael P.; Keshari, Kayvan R.; Pediaditakis, Peter; Tikunov, Andrey P.; Young, Gregory B.; Lee, Haakil; Watkins, Paul B.

    2013-01-01

    Many oxygen mass-transfer modeling studies have been performed for various bioartificial liver (BAL) encapsulation types; yet, to our knowledge, there is no experimental study that directly and noninvasively measures viability and metabolism as a function of time and oxygen concentration. We report the effect of oxygen concentration on viability and metabolism in a fluidized-bed NMR-compatible BAL using in vivo 31P and 13C NMR spectroscopy, respectively, by monitoring nucleotide triphosphate (NTP) and 13C-labeled nutrient metabolites, respectively. Fluidized-bed bioreactors eliminate the potential channeling that occurs with packed-bed bioreactors and serve as an ideal experimental model for homogeneous oxygen distribution. Hepatocytes were electrostatically encapsulated in alginate (avg. diameter, 500 μm; 3.5×107 cells/mL) and perfused at 3 mL/min in a 9-cm (inner diameter) cylindrical glass NMR tube. Four oxygen treatments were tested and validated by an in-line oxygen electrode: (1) 95:5 oxygen:carbon dioxide (carbogen), (2) 75:20:5 nitrogen:oxygen:carbon dioxide, (3) 60:35:5 nitrogen:oxygen:carbon dioxide, and (4) 45:50:5 nitrogen:oxygen:carbon dioxide. With 20% oxygen, β-NTP steadily decreased until it was no longer detected at 11 h. The 35%, 50%, and 95% oxygen treatments resulted in steady β-NTP levels throughout the 28-h experimental period. For the 50% and 95% oxygen treatment, a 13C NMR time course (∼5 h) revealed 2-13C-glycine and 2-13C-glucose to be incorporated into [2-13C-glycyl]glutathione (GSH) and 2-13C-lactate, respectively, with 95% having a lower rate of lactate formation. 31P and 13C NMR spectroscopy is a noninvasive method for determining viability and metabolic rates. Modifying tissue-engineered devices to be NMR compatible is a relatively easy and inexpensive process depending on the bioreactor shape. PMID:22835003

  19. Effect of oxygen concentration on viability and metabolism in a fluidized-bed bioartificial liver using ³¹P and ¹³C NMR spectroscopy.

    PubMed

    Jeffries, Rex E; Gamcsik, Michael P; Keshari, Kayvan R; Pediaditakis, Peter; Tikunov, Andrey P; Young, Gregory B; Lee, Haakil; Watkins, Paul B; Macdonald, Jeffrey M

    2013-02-01

    Many oxygen mass-transfer modeling studies have been performed for various bioartificial liver (BAL) encapsulation types; yet, to our knowledge, there is no experimental study that directly and noninvasively measures viability and metabolism as a function of time and oxygen concentration. We report the effect of oxygen concentration on viability and metabolism in a fluidized-bed NMR-compatible BAL using in vivo ³¹P and ¹³C NMR spectroscopy, respectively, by monitoring nucleotide triphosphate (NTP) and ¹³C-labeled nutrient metabolites, respectively. Fluidized-bed bioreactors eliminate the potential channeling that occurs with packed-bed bioreactors and serve as an ideal experimental model for homogeneous oxygen distribution. Hepatocytes were electrostatically encapsulated in alginate (avg. diameter, 500 μm; 3.5×10⁷ cells/mL) and perfused at 3 mL/min in a 9-cm (inner diameter) cylindrical glass NMR tube. Four oxygen treatments were tested and validated by an in-line oxygen electrode: (1) 95:5 oxygen:carbon dioxide (carbogen), (2) 75:20:5 nitrogen:oxygen:carbon dioxide, (3) 60:35:5 nitrogen:oxygen:carbon dioxide, and (4) 45:50:5 nitrogen:oxygen:carbon dioxide. With 20% oxygen, β-NTP steadily decreased until it was no longer detected at 11 h. The 35%, 50%, and 95% oxygen treatments resulted in steady β-NTP levels throughout the 28-h experimental period. For the 50% and 95% oxygen treatment, a ¹³C NMR time course (∼5 h) revealed 2-¹³C-glycine and 2-¹³C-glucose to be incorporated into [2-¹³C-glycyl]glutathione (GSH) and 2-¹³C-lactate, respectively, with 95% having a lower rate of lactate formation. ³¹P and ¹³C NMR spectroscopy is a noninvasive method for determining viability and metabolic rates. Modifying tissue-engineered devices to be NMR compatible is a relatively easy and inexpensive process depending on the bioreactor shape. PMID:22835003

  20. Method of Separating Oxygen From Spacecraft Cabin Air to Enable Extravehicular Activities

    NASA Technical Reports Server (NTRS)

    Graf, John C.

    2013-01-01

    Extravehicular activities (EVAs) require high-pressure, high-purity oxygen. Shuttle EVAs use oxygen that is stored and transported as a cryogenic fluid. EVAs on the International Space Station (ISS) presently use the Shuttle cryo O2, which is transported to the ISS using a transfer hose. The fluid is compressed to elevated pressures and stored as a high-pressure gas. With the retirement of the shuttle, NASA has been searching for ways to deliver oxygen to fill the highpressure oxygen tanks on the ISS. A method was developed using low-pressure oxygen generated onboard the ISS and released into ISS cabin air, filtering the oxygen from ISS cabin air using a pressure swing absorber to generate a low-pressure (high-purity) oxygen stream, compressing the oxygen with a mechanical compressor, and transferring the high-pressure, high-purity oxygen to ISS storage tanks. The pressure swing absorber (PSA) can be either a two-stage device, or a single-stage device, depending on the type of sorbent used. The key is to produce a stream with oxygen purity greater than 99.5 percent. The separator can be a PSA device, or a VPSA device (that uses both vacuum and pressure for the gas separation). The compressor is a multi-stage mechanical compressor. If the gas flow rates are on the order of 5 to 10 lb (.2.3 to 4.6 kg) per day, the compressor can be relatively small [3 16 16 in. (.8 41 41 cm)]. Any spacecraft system, or other remote location that has a supply of lowpressure oxygen, a method of separating oxygen from cabin air, and a method of compressing the enriched oxygen stream, has the possibility of having a regenerable supply of highpressure, high-purity oxygen that is compact, simple, and safe. If cabin air is modified so there is very little argon, the separator can be smaller, simpler, and use less power.

  1. Effective Presentation of Metabolic Rate Information for Lunar Extravehicular Activity (EVA)

    NASA Technical Reports Server (NTRS)

    Mackin, Michael A.; Gonia, Philip; Lombay-Gonzalez, Jose

    2010-01-01

    During human exploration of the lunar surface, a suited crewmember needs effective and accurate information about consumable levels remaining in their life support system. The information must be presented in a manner that supports real-time consumable monitoring and route planning. Since consumable usage is closely tied to metabolic rate, the lunar suit must estimate metabolic rate from life support sensors, such as oxygen tank pressures, carbon dioxide partial pressure, and cooling water inlet and outlet temperatures. To provide adequate warnings that account for traverse time for a crewmember to return to a safe haven, accurate forecasts of consumable depletion rates are required. The forecasts must be presented to the crewmember in a straightforward, effective manner. In order to evaluate methods for displaying consumable forecasts, a desktop-based simulation of a lunar Extravehicular Activity (EVA) has been developed for the Constellation lunar suite s life-support system. The program was used to compare the effectiveness of several different data presentation methods.

  2. The Effect of 30% Oxygen on Visuospatial Performance and Brain Activation: An Fmri Study

    ERIC Educational Resources Information Center

    Chung, S.C.; Tack, G.R.; Lee, B.; Eom, G.M.; Lee, S.Y.; Sohn, J.H.

    2004-01-01

    This study aimed to investigate the hypothesis that administration of the air with 30% oxygen compared with normal air (21% oxygen) enhances cognitive functioning through increased activation in the brain. A visuospatial task was presented while brain images were scanned by a 3 T fMRI system. The results showed that there was an improvement in…

  3. Metaproteomic analysis reveals microbial metabolic activities in the deep ocean

    NASA Astrophysics Data System (ADS)

    Wang, Da-Zhi; Xie, Zhang-Xian; Zhang, Shu-Feng; Wang, Ming-Hua; Zhang, Hao; Kong, Ling-Fen; Lin, Lin

    2016-04-01

    The deep sea is the largest habitat on earth and holds many and varied microbial life forms. However, little is known about their metabolic activities in the deep ocean. Here, we characterized protein profiles of particulate (>0.22 μm) and dissolved (between 10 kDa and 0.22 μm) fractions collected from the deep South China Sea using a shotgun proteomic approach. SAR324, Alteromonadales and SAR11 were the most abundant groups, while Prasinophyte contributed most to eukaryotes and cyanophage to viruses. The dominant heterotrophic activity was evidenced by the abundant transporters (33%). Proteins participating in nitrification, methanogenesis, methyltrophy and CO2 fixation were detected. Notably, the predominance of unique cellular proteins in dissolved fraction suggested the presence of membrane structures. Moreover, the detection of translation proteins related to phytoplankton indicated that other process rather than sinking particles might be the downward export of living cells. Our study implied that novel extracellular activities and the interaction of deep water with its overlying water could be crucial to the microbial world of deep sea.

  4. Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia

    SciTech Connect

    Volkow, N.D.; Wolf, A.P.; Van Gelder, P.; Brodie, J.D.; Overall, J.E.; Cancro, R.; Gomez-Mont, F.

    1987-02-01

    Using (11C)-deoxy-D-glucose and positron emission tomography (PET), the authors measured brain metabolism in 18 patients with chronic schizophrenia to assess which of the metabolic measures from two test conditions was more closely related to the patients' differing clinical characteristics. The two conditions were resting and activation, and an eye tracking task was used. Patients with more negative symptoms showed lower global metabolic rates and more severe hypofrontality than did the patients with fewer negative symptoms. Differences among the patients were distinguished by the task: sicker patients failed to show a metabolic activation response. These findings suggest that cerebral metabolic patterns reflect clinical characteristics of schizophrenic patients.

  5. Atmospheric oxygen plasma activation of silicon (100) surfaces

    SciTech Connect

    Habib, Sara B.; Gonzalez, Eleazar II; Hicks, Robert F.

    2010-05-15

    Silicon (100) surfaces were converted to a hydrophilic state with a water contact angle of <5 deg. by treatment with a radio frequency, atmospheric pressure helium, and oxygen plasma. A 2 in. wide plasma beam, operating at 250 W, 1.0 l/min O{sub 2}, 30 l/min He, and a source-to-sample distance of 3{+-}0.1 mm, was scanned over the sample at 100{+-}2 mm/s. Plasma oxidation of HF-etched silicon caused the dispersive component of the surface energy to decrease from 55.1 to 25.8 dyn/cm, whereas the polar component of the surface energy increased from 0.3 to 42.1 dyn/cm. X-ray photoelectron spectroscopy revealed that the treatment generated a monolayer of covalently bonded oxygen on the Si(100) surface 0.15{+-}0.10 nm thick. The surface oxidation kinetics have been measured by monitoring the change in water contact angle with treatment time, and are consistent with a process that is limited by the mass transfer of ground-state oxygen atoms to the silicon surface.

  6. 4-Methylcoumarin Derivatives Inhibit Human Neutrophil Oxidative Metabolism and Elastase Activity

    PubMed Central

    Fuzissaki, Carolina N.; Andrade, Micássio F.; Azzolini, Ana Elisa C.S.; Taleb-Contini, Silvia H.; Vermelho, Roberta B.; Lopes, João Luis C.; Lucisano-Valim, Yara Maria

    2013-01-01

    Abstract Increased neutrophil activation significantly contributes to the tissue damage in inflammatory illnesses; this phenomenon has motivated the search for new compounds to modulate their effector functions. Coumarins are natural products that are widely consumed in the human diet. We have evaluated the antioxidant and immunomodulator potential of five 4-methylcoumarin derivatives. We found that the 4-methylcoumarin derivatives inhibited the generation of reactive oxygen species by human neutrophils triggered by serum-opsonized zymosan or phorbol-12-myristate-13-acetate; this inhibition occurred in a concentration-dependent manner, as revealed by lucigenin- and luminol-enhanced chemiluminescence assays. Cytotoxicity did not mediate this inhibitory effect. The 7,8-dihydroxy-4-methylcoumarin suppressed the neutrophil oxidative metabolism more effectively than the 6,7- and 5,7-dihydroxy-4-methylcoumarins, but the 5,7- and 7,8-diacetoxy-4-methylcoumarins were less effective than their hydroxylated counterparts. An analysis of the biochemical pathways suggested that the 6,7- and 7,8-dihydroxy-4-methylcoumarins inhibit the protein kinase C-mediated signaling pathway, but 5,7-dihydroxy-4-methylcoumarin, as well as 5,7- and 7,8-diacetoxy-4-methylcoumarins do not significantly interfere in this pathway of the activation of the human neutrophil oxidative metabolism. The 4-methylcoumarin derivatives bearing the catechol group suppressed the elastase and myeloperoxidase activity and reduced the 1,1-diphenyl-2-picrylhydrazyl free radical the most strongly. Interestingly, the 5,7-dihydroxy-4-methylcoumarin scavenged hypochlorous acid more effectively than the o-dihydroxy-substituted 4-methylcoumarin derivatives, and the diacetoxylated 4-methylcoumarin derivatives scavenged hypochlorous acid as effectively as the 7,8-dihydroxy-4-methylcoumarin. The significant influence of small structural modifications in the inhibitory potential of 4-methylcoumarin derivatives on the

  7. The relationship between body temperature, heart rate, breathing rate, and rate of oxygen consumption, in the tegu lizard (Tupinambis merianae) at various levels of activity.

    PubMed

    Piercy, Joanna; Rogers, Kip; Reichert, Michelle; Andrade, Denis V; Abe, Augusto S; Tattersall, Glenn J; Milsom, William K

    2015-12-01

    The present study determined whether EEG and/or EMG recordings could be used to reliably define activity states in the Brazilian black and white tegu lizard (Tupinambis merianae) and then examined the interactive effects of temperature and activity states on strategies for matching O2 supply and demand. In a first series of experiments, the rate of oxygen consumption (VO2), breathing frequency (fR), heart rate (fH), and EEG and EMG (neck muscle) activity were measured in different sleep/wake states (sleeping, awake but quiet, alert, or moving). In general, metabolic and cardio-respiratory changes were better indictors of the transition from sleep to wake than were changes in the EEG and EMG. In a second series of experiments, the interactive effects of temperature (17, 27 and 37 °C) and activity states on fR, tidal volume (VT), the fraction of oxygen extracted from the lung per breath (FIO2-FEO2), fH, and the cardiac O2 pulse were quantified to determine the relative roles of each of these variables in accommodating changes in VO2. The increases in oxygen supply to meet temperature- and activity-induced increases in oxygen demand were produced almost exclusively by increases in fH and fR. Regression analysis showed that the effects of temperature and activity state on the relationships between fH, fR and VO2 was to extend a common relationship along a single curve, rather than separate relationships for each metabolic state. For these lizards, the predictive powers of fR and fH were maximized when the effects of changes in temperature, digestive state and activity were pooled. However, the best r(2) values obtained were 0.63 and 0.74 using fR and fH as predictors of metabolic rate, respectively. PMID:26285591

  8. Oxygen Effects on Photosynthesis and 14C Metabolism in Desert Plants

    PubMed Central

    Glacoleva, Tatyana A.; Zalensky, Oleg V.; Mokronosov, Adolf T.

    1978-01-01

    The effect of 1% and 21% O2 upon 14CO2 assimilation by desert plants exposed for 10 to 90 seconds has been studied. The plants studied can be divided into three groups with respect to O2. The C3 plants display the usual Warburg effect. No changes could be observed in the intensity of photosynthesis as a function of O2 content in another group of plants (showing signs of Crassulacean acid metabolism). In still another group of plants (C4 plants) the stimulating effect of O2 on photosynthesis could be detected. In C3 plants, O2 inhibits the processing of carbon through the Calvin cycle intermediates. The involvement of carbon in the glycolate pathway fails to explain completely the inhibiting effect of O2 on photosynthesis. It is assumed that O2 inhibits the enzymes of the Calvin cycle. In C4 plants O2 stimulates the incorporation of 14C into malate and aspartate. The incorporation of 14C into the intermediates of the Calvin cycle in C4 plants is inhibited much like that in typical C3 plants. PMID:16660486

  9. Design of high pressure oxygen filter for extravehicular activity life support system, volume 1

    NASA Technical Reports Server (NTRS)

    Wilson, B. A.

    1977-01-01

    The experience of the National Aeronautics and Space Administration (NASA) with extravehicular activity life support emergency oxygen supply subsystems has shown a large number of problems associated with particulate contamination. These problems have resulted in failures of high pressure oxygen component sealing surfaces. A high pressure oxygen filter was designed which would (a) control the particulate contamination level in the oxygen system to a five-micron glass bead rating, ten-micron absolute condition (b) withstand the dynamic shock condition resulting from the sudden opening of 8000 psi oxygen system shutoff valve. Results of the following program tasks are reported: (1) contaminant source identification tests, (2) dynamic system tests, (3) high pressure oxygen filter concept evaluation, (4) design, (5) fabrication, (6) test, and (7) application demonstration.

  10. HEALTHY Intervention: Fitness, Physical Activity, and Metabolic Syndrome Results

    PubMed Central

    Jago, Russell; McMurray, Robert G.; Drews, Kimberly L.; Moe, Esther L.; Murray, Tinker; Pham, Trang H.; Venditti, Elizabeth M.; Volpe, Stella L.

    2013-01-01

    Purpose This study aimed to assess the effect of the HEALTHY intervention on the metabolic syndrome (Met-S), fitness, and physical activity levels of US middle-school students. Methods Cluster randomized controlled trial conducted in 42 (21 intervention) US middle schools. Participants were recruited at the start of sixth grade (2006) when baseline assessments were made, with post-assessments made 2.5 yr later at the end of eighth grade (2009). The HEALTHY intervention had four components: 1) improved school food environment, 2) physical activity and eating educational sessions, 3) social marketing, and 4) revised physical education curriculum. Met-S risk factors, 20-m shuttle run (fitness), and self-reported moderate to vigorous physical activity (MVPA) were assessed at each time point. Ethnicity and gender were self-reported. Obesity status (normal weight, overweight, or obese) was also assessed. Results At baseline, 5% of the participants were classified with Met-S, with two-thirds of the males and one-third of the females recording below average baseline fitness levels. Control group participants reported 96 min of MVPA at baseline with 103 min reported by the intervention group. There were no statistically significant (P < 0.05) differences in Met-S, fitness, or MVPA levels at the end of the study after adjustment for baseline values and confounders. There were no differences in any ethnic, obesity, or ethnic × obesity subgroups for either gender. Conclusions The HEALTHY intervention had no effect on the Met-S, fitness, or physical activity levels. Approaches that focus on how to change physical activity, fitness, and Met-S using nonschool or perhaps in addition to school based components need to be developed. PMID:21233778

  11. The metabolic activator FOXO1 binds hepatitis B virus DNA and activates its transcription

    SciTech Connect

    Shlomai, Amir; Shaul, Yosef

    2009-04-17

    Hepatitis B virus (HBV) is a small DNA virus that targets the liver and infects humans worldwide. Recently we have shown that the metabolic regulator PGC-1{alpha} coactivates HBV transcription thereby rendering the virus susceptible to fluctuations in the nutritional status of the liver. PGC-1{alpha} coactivation of HBV is mediated through the liver-enriched nuclear receptor HNF4{alpha} and through another yet unknown transcription factor(s). Here we show that the forkhead transcription factor FOXO1, a known target for PGC-1{alpha} coactivation and a central mediator of glucose metabolism in the liver, binds HBV core promoter and activates its transcription. This activation is further enhanced in the presence of PGC-1{alpha}, implying that FOXO1 is a target for PGC-1{alpha} coactivation of HBV transcription. Thus, our results identify another key metabolic regulator as an activator of HBV transcription, thereby supporting the principle that HBV gene expression is regulated in a similar way to key hepatic metabolic genes.

  12. Benzene's metabolites alter c-MYB activity via reactive oxygen species in HD3 cells

    SciTech Connect

    Wan, Joanne; Winn, Louise M. . E-mail: winnl@queensu.ca

    2007-07-15

    Benzene is a known leukemogen that is metabolized to form reactive intermediates and reactive oxygen species (ROS). The c-Myb oncoprotein is a transcription factor that has a critical role in hematopoiesis. c-Myb transcript and protein have been overexpressed in a number of leukemias and cancers. Given c-Myb's role in hematopoiesis and leukemias, it is hypothesized that benzene interferes with the c-Myb signaling pathway and that this involves ROS. To investigate our hypothesis, we evaluated whether benzene, 1,4-benzoquinone, hydroquinone, phenol, and catechol generated ROS in chicken erythroblast HD3 cells, as measured by 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (DCFDA) and dihydrorhodamine-123 (DHR-123), and whether the addition of 100 U/ml of the antioxidating enzyme superoxide dismutase (SOD) could prevent ROS generation. Reduced to oxidized glutathione ratios (GSH:GSSG) were also assessed as well as hydroquinone and benzoquinone's effects on c-Myb protein levels and activation of a transiently transfected reporter construct. Finally we attempted to abrogate benzene metabolite mediated increases in c-Myb activity with the use of SOD. We found that benzoquinone, hydroquinone, and catechol increased DCFDA fluorescence, increased DHR-123 fluorescence, decreased GSH:GSSG ratios, and increased reporter construct expression after 24 h of exposure. SOD was able to prevent DCFDA fluorescence and c-Myb activity caused by benzoquinone and hydroquinone only. These results are consistent with other studies, which suggest metabolite differences in benzene-mediated toxicity. More importantly, this study supports the hypothesis that benzene may mediate its toxicity through ROS-mediated alterations in the c-Myb signaling pathway.

  13. Reactive oxygen scavenging activity of matured whiskey and its active polyphenols.

    PubMed

    Koga, K; Taguchi, A; Koshimizu, S; Suwa, Y; Yamada, Y; Shirasaka, N; Yoshizumi, H

    2007-04-01

    The quality of whiskey is known to improve remarkably by its storage over many years. This process is commonly termed "maturing." In this process, polyphenols derived from lignin and tannin of the barrel have an important role in not only forming the matured flavor and taste but also contributing to the advance of clustering ethanol and water in whiskey. It is also likely that polyphenols generally possess reactive oxygen (RO) scavenging activity. The present study evaluated the RO scavenging activity (free-radical scavenging activity, H(2)O(2) reduction activity under peroxidase coculture, and H(2)O(2)scavenging activity) of 24 single malt whiskeys with a maturation age of 10 to 30 y produced in Japanese, Scotch (Islay), or Scotch (Speyside and Highland) regions. Single malt whiskey not only showed RO scavenging activity but there was also a positive correlation between this activity and the maturation age of whiskey exceeding the difference resulting from the manufacturing region. A nonvolatile fraction derived from the barrel was responsible for RO scavenging activity. In particular, the contents of ellagic and gallic acids and lyoniresinol, the main polyphenolic compounds in whiskey, increased with maturation age. For the free-radical scavenging activity per molecule, each compound was 1.68 to 3.14 times that of trolox (a water-soluble vitamin E). The activities of ellagic acid, gallic acid, and lyoniresinol in the whiskey (Yamazaki 18) were equivalent to that of 80.3, 31.2, and 11.1 ppm trolox, respectively. Accordingly, the total activity of these 3 compounds accounted for about 20% of the activity of the whiskey (630.7 ppm trolox). PMID:17995817

  14. Oxygen-18 incorporation studies of the metabolism of phenytoin to the catechol.

    PubMed

    Billings, R E; Fischer, L J

    1985-01-01

    Phenytoin (PHT) is metabolized primarily to 5-(4-hydroxyphenyl)-5-phenylhydantoin (4-HPPH), a 3,4-dihydrodiol metabolite (DHD), and a catechol, 5-(3,4-dihydroxyphenyl)-5-phenylhydantoin (Cat). The objective of the present studies was to determine the mechanism of Cat formation. The experiments were conducted with isolated rat hepatocytes and the 9000g supernatant fraction of mouse liver. Incubations of PHT were done under an 18O2 atmosphere and the incorporation of 18O into 4-HPPH and Cat was determined by mass spectrometry. It was found that the amount of Cat formed relative to the amount of 4-HPPH and DHD formed varied among the enzyme sources employed. However, in all cases, most of Cat formed from PHT contained two atoms of 18O. These results show that PHT is converted to Cat primarily by hydroxylation of 4-HPPH rather than by oxidation of DHD. Cat formation via DHD would add an 16O atom from hydrolysis of a 3,4-epoxide. Only 14-36% of the Cat formed contained one atom of 18O and one atom of 16O. Kinetic studies of Cat formation from 4-HPPH and DHD with rat liver subcellular fractions showed that the Vmax is higher and the Km is an order of magnitude lower with 4-HPPH than with DHD. These data suggest that DHD is only slowly converted to Cat and provide an explanation for the paucity of Cat formation via DHD when PHT is incubated with intact cells. PMID:2861989

  15. Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation

    PubMed Central

    Yaseen, Mohammad A; Srinivasan, Vivek J; Sakadžić, Sava; Radhakrishnan, Harsha; Gorczynska, Iwona; Wu, Weicheng; Fujimoto, James G; Boas, David A

    2011-01-01

    Measuring cerebral oxygen delivery and metabolism microscopically is important for interpreting macroscopic functional magnetic resonance imaging (fMRI) data and identifying pathological changes associated with stroke, Alzheimer's disease, and brain injury. Here, we present simultaneous, microscopic measurements of cerebral blood flow (CBF) and oxygen partial pressure (pO2) in cortical microvessels of anesthetized rats under baseline conditions and during somatosensory stimulation. Using a custom-built imaging system, we measured CBF with Fourier-domain optical coherence tomography (OCT), and vascular pO2 with confocal phosphorescence lifetime microscopy. Cerebral blood flow and pO2 measurements displayed heterogeneity over distances irresolvable with fMRI and positron emission tomography. Baseline measurements indicate O2 extraction from pial arterioles and homogeneity of ascending venule pO2 despite large variation in microvessel flows. Oxygen extraction is linearly related to flow in ascending venules, suggesting that flow in ascending venules closely matches oxygen demand of the drained territory. Oxygen partial pressure and relative CBF transients during somatosensory stimulation further indicate arteriolar O2 extraction and suggest that arterioles contribute to the fMRI blood oxygen level dependent response. Understanding O2 supply on a microscopic level will yield better insight into brain function and the underlying mechanisms of various neuropathologies. PMID:21179069

  16. Metabolic activity of permafrost bacteria below the freezing point

    NASA Technical Reports Server (NTRS)

    Rivkina, E. M.; Friedmann, E. I.; McKay, C. P.; Gilichinsky, D. A.

    2000-01-01

    Metabolic activity was measured in the laboratory at temperatures between 5 and -20 degrees C on the basis of incorporation of (14)C-labeled acetate into lipids by samples of a natural population of bacteria from Siberian permafrost (permanently frozen soil). Incorporation followed a sigmoidal pattern similar to growth curves. At all temperatures, the log phase was followed, within 200 to 350 days, by a stationary phase, which was monitored until the 550th day of activity. The minimum doubling times ranged from 1 day (5 degrees C) to 20 days (-10 degrees C) to ca. 160 days (-20 degrees C). The curves reached the stationary phase at different levels, depending on the incubation temperature. We suggest that the stationary phase, which is generally considered to be reached when the availability of nutrients becomes limiting, was brought on under our conditions by the formation of diffusion barriers in the thin layers of unfrozen water known to be present in permafrost soils, the thickness of which depends on temperature.

  17. Metabolic Activity of Permafrost Bacteria below the Freezing Point

    PubMed Central

    Rivkina, E. M.; Friedmann, E. I.; McKay, C. P.; Gilichinsky, D. A.

    2000-01-01

    Metabolic activity was measured in the laboratory at temperatures between 5 and −20°C on the basis of incorporation of 14C-labeled acetate into lipids by samples of a natural population of bacteria from Siberian permafrost (permanently frozen soil). Incorporation followed a sigmoidal pattern similar to growth curves. At all temperatures, the log phase was followed, within 200 to 350 days, by a stationary phase, which was monitored until the 550th day of activity. The minimum doubling times ranged from 1 day (5°C) to 20 days (−10°C) to ca. 160 days (−20°C). The curves reached the stationary phase at different levels, depending on the incubation temperature. We suggest that the stationary phase, which is generally considered to be reached when the availability of nutrients becomes limiting, was brought on under our conditions by the formation of diffusion barriers in the thin layers of unfrozen water known to be present in permafrost soils, the thickness of which depends on temperature. PMID:10919774

  18. Metabolic signals and innate immune activation in obesity and exercise.

    PubMed

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. PMID:25825956

  19. Effects of carbohydrate on the internal oxygen concentration, oxygen uptake, and nitrogenase activity in detached pea nodules

    SciTech Connect

    Monroe, J.D. ); LaRue, T.A. )

    1989-10-01

    The interaction between carbon substrates and O{sub 2} and their effects on nitrogenase activity (C{sub 2}H{sub 2}) were examined in detached nodules of pea (Pisum sativum L. cv Sparkle). The internal O{sub 2} concentration was estimated from the fractional oxygenation of leghemoglobin measured by reflectance spectroscopy. Lowering the endogenous carbohydrate content of nodules by excising the shoots 16 hours before nodule harvest or by incubating detached nodules at 100 kPa O{sub 2} for 2 hours resulted in a 2- to 10-fold increase in internal O{sub 2}, and a decline in nitrogenase activity. Conversely, when detached nodules were supplied with 100 millimolar succinate, the internal O{sub 2} was lowered. Nitrogenase activity was stimulated by succinate but only at high external O{sub 2}. Oxygen uptake increased linearly with external O{sub 2} but was affected only slightly by the carbon treatments. The apparent diffusion resistance in the nodule cortex was similar in all of the treatments. Carbon substrates can thus affect nitrogenase activity indirectly by affecting the O{sub 2} concentration within detached nodules.

  20. The oxygen-18 isotope approach for measuring aquatic metabolism in high-productivity waters

    USGS Publications Warehouse

    Tobias, C.R.; Böhlke, J.K.; Harvey, J.W.

    2007-01-01

    We examined the utility of ??18O2 measurements in estimating gross primary production (P), community respiration (R), and net metabolism (P:R) through diel cycles in a productive agricultural stream located in the midwestern U.S.A. Large diel swings in O2 (??200 ??mol L-1) were accompanied by large diel variation in ??18O2 (??10???). Simultaneous gas transfer measurements and laboratory-derived isotopic fractionation factors for O2 during respiration (??r) were used in conjunction with the diel monitoring of O2 and ??18O2 to calculate P, R, and P:R using three independent isotope-based methods. These estimates were compared to each other and against the traditional "open-channel diel O2-change" technique that lacked ??18O2. A principal advantage of the ??18O2 measurements was quantification of diel variation in R, which increased by up to 30% during the day, and the diel pattern in R was variable and not necessarily predictable from assumed temperature effects on R. The P, R, and P:R estimates calculated using the isotope-based approaches showed high sensitivity to the assumed system fractionation factor (??r). The optimum modeled ??r values (0.986-0.989) were roughly consistent with the laboratory-derived values, but larger (i.e., less fractionation) than ??r values typically reported for enzyme-limited respiration in open water environments. Because of large diel variation in O2, P:R could not be estimated by directly applying the typical steady-state solution to the O2 and 18O-O2 mass balance equations in the absence of gas transfer data. Instead, our results indicate that a modified steady-state solution (the daily mean value approach) could be used with time-averaged O2 and ??18O2 measurements to calculate P:R independent of gas transfer. This approach was applicable under specifically defined, net heterotrophic conditions. The diel cycle of increasing daytime R and decreasing nighttime R was only partially explained by temperature variation, but could be

  1. Study of oxygen scavenging PET-based films activated by water

    NASA Astrophysics Data System (ADS)

    Rossi, Gabriella; Scarfato, Paola; Incarnato, Loredana

    2016-05-01

    In this work an active barrier system consisting of a thin and transparent film based on polyethylene terephthalate (PET) was studied. Dynamic oxygen absorption measurements were performed at different values of relative humidity and temperature, pointing out that humidity is a key factor in activating the oxidation of the polymer sample. Moreover, the thermal and optical properties of the films were investigated and a good correlation was found between the crystallinity increase and the consequent transparency reduction occurring after the oxygen absorption.

  2. Oxygen requirements for formation and activity of the squalene expoxidase in Saccharomyces cerevisiae

    NASA Technical Reports Server (NTRS)

    Jahnke, L.; Klein, H. P.

    1983-01-01

    The effect of oxygen on squalene epoxidase activity in Saccharomyces cerevisiae was investigated. In cells grown in standing cultures, the epoxidase was localized mainly in the 'mitochondrial' fraction. Upon aeration, enzyme activity increased and the newly formed enzyme was associated with the 'microsomal' fraction. At 0.03 percent (vol/vol) oxygen, epoxidase levels doubled, whereas the ergosterol level was only slightly increased. Cycloheximide inhibited the increase in epoxidase under these conditions. An apparent K sub m for oxygen of 0.38 percent (vol/vol) was determined from a crude particulate preparation for the epoxidase.

  3. The role of beaded activated carbon's surface oxygen groups on irreversible adsorption of organic vapors.

    PubMed

    Jahandar Lashaki, Masoud; Atkinson, John D; Hashisho, Zaher; Phillips, John H; Anderson, James E; Nichols, Mark

    2016-11-01

    The objective of this study is to determine the contribution of surface oxygen groups to irreversible adsorption (aka heel formation) during cyclic adsorption/regeneration of organic vapors commonly found in industrial systems, including vehicle-painting operations. For this purpose, three chemically modified activated carbon samples, including two oxygen-deficient (hydrogen-treated and heat-treated) and one oxygen-rich sample (nitric acid-treated) were prepared. The samples were tested for 5 adsorption/regeneration cycles using a mixture of nine organic compounds. For the different samples, mass balance cumulative heel was 14 and 20% higher for oxygen functionalized and hydrogen-treated samples, respectively, relative to heat-treated sample. Thermal analysis results showed heel formation due to physisorption for the oxygen-deficient samples, and weakened physisorption combined with chemisorption for the oxygen-rich sample. Chemisorption was attributed to consumption of surface oxygen groups by adsorbed species, resulting in formation of high boiling point oxidation byproducts or bonding between the adsorbates and the surface groups. Pore size distributions indicated that different pore sizes contributed to heel formation - narrow micropores (<7Å) in the oxygen-deficient samples and midsize micropores (7-12Å) in the oxygen-rich sample. The results from this study help explain the heel formation mechanism and how it relates to chemically tailored adsorbent materials. PMID:27295065

  4. Antimicrobial activity of Amazon Astrocaryum aculeatum extracts and its association to oxidative metabolism.

    PubMed

    Jobim, Micheli Lamberti; Santos, Roberto Christ Vianna; dos Santos Alves, Camilla Filippi; Oliveira, Raul Moreira; Mostardeiro, Clarice Pinheiro; Sagrillo, Michele Rorato; de Souza Filho, Olmiro Cezimbra; Garcia, Luiz Filipe Machado; Manica-Cattani, Maria Fernanda; Ribeiro, Euler Esteves; da Cruz, Ivana Beatrice Mânica

    2014-04-01

    Several compounds present in fruits as polyphenols are able to kill or inhibit the growth of microorganisms. These proprieties are relevant mainly in tropical areas, as Amazonian region where infectious are highly prevalent. Therefore, this study investigated the antimicrobial activity of tucumã Amazonian fruit against 37 microorganisms. The potential role of oxidative metabolism imbalance was also studied as causal mechanism of antimicrobial activity. The results showed antibacterial effect of pulp and peel tucumã hydro-alcoholic extracts on three Gram-positive bacteria (Enterococcus faecalis, Bacillus cereus, Listeria monocytogenes) and antifungal effect against Candida albicans. The antimicrobial contribution of main chemical compounds (quercetin, rutin, β-carotene and gallic, caffeic and chlorogenic acids) found in tucumã extracts was also investigated showing an inhibitory effect depending of the organism mainly by quercetin in bacteria and rutin in C. albicans. Analysis of kinetic of DNA releasing in extracellular medium by fluorescence using DNA Pico Green assay(®) and reactive oxygen species production (ROS) showed potential oxidative imbalance contribution on tucumã inhibitory effect. In B. cereus and C. albicans this effect was clear since after 24h the ROS levels were higher when compared to negative control group. In conclusion, tucumã extracts present antimicrobial activity to four microorganisms that have large problems of drug resistance, and the possible mechanism of action of this Amazon fruit is related to REDOX imbalance. PMID:23870852

  5. Effects of reactive oxygen species on metabolism monitored by longitudinal 1H single voxel MRS follow-up in patients with mitochondrial disease or cerebral tumors

    NASA Astrophysics Data System (ADS)

    Constans, J. M.; Collet, S.; Guillamo, J. S.; Hossu, G.; Lacombe, S.; Gauduel, Y. A.; Houée Levin, C.; Dou, W.; Ruan, S.; Barré, L.; Rioult, F.; Derlon, J. M.; Lechapt-Zalcman, E.; Valable, S.; Chapon, F.; Courtheoux, P.; Fong, V.; Kauffmann, F.

    2011-01-01

    Free radicals, or Reactive Oxygen Species (ROS), have an effect on energy and glycolytic metabolism, mitochondrial function, lipid metabolism, necrosis and apoptosis, cell proliferation, and infiltration. These changes could be monitored longitudinally (every 4 months over 6 years) in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI) and spectroscopy (MRS) and MR perfusion. Some examples of early clinical data from longitudinal follow-up monitoring in humans of energy and glycolytic metabolism, lipid metabolism, necrosis, proliferation, and infiltration measured by conventional MRI, MRS and perfusion, and positron emission tomography (PET) are shown in glial brain tumors after therapy. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and therapeutic response.

  6. Lysine-specific demethylase-1 contributes to malignant behavior by regulation of invasive activity and metabolic shift in esophageal cancer.

    PubMed

    Kosumi, Keisuke; Baba, Yoshifumi; Sakamoto, Akihisa; Ishimoto, Takatsugu; Harada, Kazuto; Nakamura, Kenichi; Kurashige, Junji; Hiyoshi, Yukiharu; Iwatsuki, Masaaki; Iwagami, Shiro; Sakamoto, Yasuo; Miyamoto, Yuji; Yoshida, Naoya; Oki, Eiji; Watanabe, Masayuki; Hino, Shinjiro; Nakao, Mitsuyoshi; Baba, Hideo

    2016-01-15

    Lysine-specific demethylase-1 (LSD1) removes the methyl groups from mono- and di-methylated lysine 4 of histone H3. Previous studies have linked LSD1 to malignancy in several human tumors, and LSD1 is considered to epigenetically regulate the energy metabolism genes in adipocytes and hepatocellular carcinoma. This study investigates the function of LSD1 in the invasive activity and the metabolism of esophageal cancer cells. We investigated whether LSD1 immunohistochemical expression levels are related to clinical and pathological features, including the maximum standard uptake value in fluorodeoxyglucose positron emission tomography assay. The influence of LSD1 on cell proliferation, invasion and glucose uptake was evaluated in vitro by using specific small interfering RNA for LSD1, and an LSD1 inhibitor. We also evaluated two major energy pathways (glycolytic pathway and mitochondrial respiration) by measuring the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) with an extracellular flux analyzer. High LSD1 immunohistochemical expression was significantly associated with high tumor stage, lymphovascular invasion, poor prognosis, and high maximum standard uptake value in esophageal cancer patients. In the in vitro analysis, LSD1 knockdown significantly suppressed the invasive activity and glucose uptake of cancerous cells, reduced their ECAR and increased their OCR and OCR/ECAR. LSD1 may contribute to malignant behavior by regulating the invasive activity and metabolism, activating the glycolytic pathway and inhibiting the mitochondrial respiration of esophageal cancer cells. The results support LSD1 as a potential therapeutic target. PMID:26240060

  7. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR

    PubMed Central

    2013-01-01

    Nuclear receptors are integrators of hormonal and nutritional signals, mediating changes to metabolic pathways within the body. Given that modulation of lipid and glucose metabolism has been linked to diseases including type 2 diabetes, obesity and atherosclerosis, a greater understanding of pathways that regulate metabolism in physiology and disease is crucial. The liver X receptors (LXRs) and the farnesoid X receptors (FXRs) are activated by oxysterols and bile acids, respectively. Mounting evidence indicates that these nuclear receptors have essential roles, not only in the regulation of cholesterol and bile acid metabolism but also in the integration of sterol, fatty acid and glucose metabolism. PMID:22414897

  8. Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

    SciTech Connect

    Bordbar, Aarash; Mo, Monica L.; Nakayasu, Ernesto S.; Rutledge, Alexandra C.; Kim, Young-Mo; Metz, Thomas O.; Jones, Marcus B.; Frank, Bryan C.; Smith, Richard D.; Peterson, Scott N.; Hyduke, Daniel R.; Adkins, Joshua N.; Palsson, Bernhard O.

    2012-06-26

    Macrophages are central players in the immune response, manifesting divergent phenotypes to control inflammation and innate immunity through the release of cytokines and other regulatory factor-dependent signaling pathways. In recent years, the focus on metabolism has been reemphasized as critical signaling and regulatory pathways of human pathophysiology, ranging from cancer to aging, often converge on metabolic responses. Here, we used genome-scale modeling and multi-omics (transcriptomics, proteomics, and metabolomics) analysis to assess metabolic features critical for macrophage functions. We constructed a genome-scale metabolic network for the RAW 264.7 cell line to determine metabolic modulators of macrophage activation. Metabolites well-known to be associated with immunoactivation (e.g., glucose and arginine) and immunosuppression (e.g., tryptophan and vitamin D3) were amongst the most critical effectors. Intracellular metabolic mechanisms linked to critical suppressive effectors were then assessed, identifying a suppressive role for de novo nucleotide synthesis. Finally, the underlying metabolic mechanisms of macrophage activation are identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. Our study demonstrates metabolism's role in regulating activation may be greater than previously anticipated and elucidates underlying metabolic connections between activation and metabolic effectors.

  9. Oxygen activation with transition metal complexes in aqueous solution

    SciTech Connect

    Bakac, Andreja

    2010-04-12

    Coordination to transition-metal complexes changes both the thermodynamics and kinetics of oxygen reduction. Some of the intermediates (superoxo, hydroperoxo, and oxo species) are close analogues of organic oxygen-centered radicals and peroxides (ROO{sm_bullet}, ROOH, and RO{sm_bullet}). Metal-based intermediates are typically less reactive, but more persistent, than organic radicals, which makes the two types of intermediates similarly effective in their reactions with various substrates. The self-exchange rate constant for hydrogen-atom transfer for the couples Cr{sub aq}OO{sup 2+}/Cr{sub aq}OOH{sup 2+} and L{sup 1}(H{sub 2}O)RhOO{sup 2+}/L{sup 1}(H{sub 2}O)RhOOH{sup 2+} was estimated to be 10{sup 1 {+-} 1} M{sup -1} s{sup -1}. The use of this value in the simplified Marcus equation for the Cr{sub aq}O{sup 2+}/Cr{sub aq}OOH{sup 2+} cross reaction provided an upper limit k{sub CrO,CrOH} {le} 10{sup (-2{+-}1)} M{sup -1} s{sup -1} for Cr{sub aq}O{sup 2+}/Cr{sub aq}OH{sup 2+} self-exchange. Even though superoxo complexes react very slowly in bimolecular self-reactions, extremely fast cross reactions with organic counterparts, i.e., acylperoxyl radicals, have been observed. Many of the intermediates generated by the interaction of O{sub 2} with reduced metal complexes can also be accessed by alternative routes, both thermal and photochemical.

  10. TRANSPORT AND DEPOSITION OF METABOLICALLY ACTIVE AND STATIONARY PHASE DEINOCOCCUS RADIODURANS IN UNSATURATED POROUS MEDIA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bioremediation is a cost efficient clean-up technique that involves the use of metabolically active bacteria to degrade recalcitrant pollutants. To further develop this technique it is important to understand the migration and deposition behaviour of metabolically active bacteria in unsaturated soil...

  11. Spatially distinct and metabolically active membrane domain in mycobacteria.

    PubMed

    Hayashi, Jennifer M; Luo, Chu-Yuan; Mayfield, Jacob A; Hsu, Tsungda; Fukuda, Takeshi; Walfield, Andrew L; Giffen, Samantha R; Leszyk, John D; Baer, Christina E; Bennion, Owen T; Madduri, Ashoka; Shaffer, Scott A; Aldridge, Bree B; Sassetti, Christopher M; Sandler, Steven J; Kinoshita, Taroh; Moody, D Branch; Morita, Yasu S

    2016-05-10

    Protected from host immune attack and antibiotic penetration by their unique cell envelope, mycobacterial pathogens cause devastating human diseases such as tuberculosis. Seamless coordination of cell growth with cell envelope elongation at the pole maintains this barrier. Unraveling this spatiotemporal regulation is a potential strategy for controlling mycobacterial infections. Our biochemical analysis previously revealed two functionally distinct membrane fractions in Mycobacterium smegmatis cell lysates: plasma membrane tightly associated with the cell wall (PM-CW) and a distinct fraction of pure membrane free of cell wall components (PMf). To provide further insight into the functions of these membrane fractions, we took the approach of comparative proteomics and identified more than 300 proteins specifically associated with the PMf, including essential enzymes involved in cell envelope synthesis such as a mannosyltransferase, Ppm1, and a galactosyltransferase, GlfT2. Furthermore, comparative lipidomics revealed the distinct lipid composition of the PMf, with specific association of key cell envelope biosynthetic precursors. Live-imaging fluorescence microscopy visualized the PMf as patches of membrane spatially distinct from the PM-CW and notably enriched in the pole of the growing cells. Taken together, our study provides the basis for assigning the PMf as a spatiotemporally distinct and metabolically active membrane domain involved in cell envelope biogenesis. PMID:27114527

  12. Activation of AMP-kinase by Policosanol Requires Peroxisomal Metabolism

    PubMed Central

    Banerjee, Subhashis; Ghoshal, Sarbani

    2011-01-01

    Policosanol, a well-defined mixture of very long chain primary alcohols that is available as a nutraceutical product, has been reported to lower blood cholesterol levels. The present studies demonstrate that policosanol promotes the phosphorylation of AMP-kinase and HMG-CoA reductase in hepatoma cells and in mouse liver after intragastric administration, providing a possible means by which policosanol might lower blood cholesterol levels. Treatment of hepatoma cells with policosanol produced a 2.5-fold or greater increase in the phosphorylation of AMP-kinase and HMG-CoA reductase, and increased the phosphorylation of Ca++/calmodulin-dependent kinase kinase (CaMKK), an upstream AMP-kinase kinase. Intra-gastric administration of policosanol to mice similarly increased the phosphorylation of hepatic HMG-CoA reductase and AMP-kinase by greater than 2-fold. siRNA-mediated suppression of fatty aldehyde dehydrogenase, fatty acyl-CoA synthetase 4, and acyl-CoA acetyltransferase expression in hepatoma cells prevented the phosphorylation of AMP-kinase and HMG-CoA reductase by policosanol, indicating that metabolism of these very long chain alcohols to activated fatty acids is necessary for the suppression of cholesterol synthesis, presumably by increasing cellular AMP levels. Subsequent peroxisomal β-oxidation probably augments this effect. PMID:21359855

  13. Rice alcohol dehydrogenase 1 promotes survival and has a major impact on carbohydrate metabolism in the embryo and endosperm when seeds are germinated in partially oxygenated water

    PubMed Central

    Takahashi, Hirokazu; Greenway, Hank; Matsumura, Hideo; Tsutsumi, Nobuhiro; Nakazono, Mikio

    2014-01-01

    Background and Aims Rice (Oryza sativa) has the rare ability to germinate and elongate a coleoptile under oxygen-deficient conditions, which include both hypoxia and anoxia. It has previously been shown that ALCOHOL DEHYDROGENASE 1 (ADH1) is required for cell division and cell elongation in the coleoptile of submerged rice seedlings by means of studies using a rice ADH1-deficient mutant, reduced adh activity (rad). The aim of this study was to understand how low ADH1 in rice affects carbohydrate metabolism in the embryo and endosperm, and lactate and alanine synthesis in the embryo during germination and subsequent coleoptile growth in submerged seedlings. Methods Wild-type and rad mutant rice seeds were germinated and grown under complete submergence. At 1, 3, 5 and 7 d after imbibition, the embryo and endosperm were separated and several of their metabolites were measured and compared. Key results In the rad embryo, the rate of ethanol fermentation was halved, while lactate and alanine concentrations were 2·4- and 5·7- fold higher in the mutant than in the wild type. Glucose and fructose concentrations in the embryos increased with time in the wild type, but not in the rad mutant. The rad mutant endosperm had lower amounts of the α-amylases RAMY1A and RAMY3D, resulting in less starch degradation and lower glucose concentrations. Conclusions These results suggest that ADH1 is essential for sugar metabolism via glycolysis to ethanol fermentation in both the embryo and endosperm. In the endosperm, energy is presumably needed for synthesis of the amylases and for sucrose synthesis in the endosperm, as well as for sugar transport to the embryo. PMID:24431339

  14. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy

    PubMed Central

    Poff, A. M.; Ward, N.; Seyfried, T. N.; Arnold, P.; D’Agostino, D. P.

    2015-01-01

    The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies – the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT) and dietary ketone supplementation – could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control), low glucose (LG), ketone supplementation (βHB), hyperbaric oxygen (HBOT), or combination therapy (LG+βHB+HBOT) on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers. PMID:26061868

  15. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy.

    PubMed

    Poff, A M; Ward, N; Seyfried, T N; Arnold, P; D'Agostino, D P

    2015-01-01

    The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT) and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control), low glucose (LG), ketone supplementation (βHB), hyperbaric oxygen (HBOT), or combination therapy (LG+βHB+HBOT) on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers. PMID:26061868

  16. Effects of a helium/oxygen mixture on individuals’ lung function and metabolic cost during submaximal exercise for participants with obstructive lung diseases

    PubMed Central

    Häussermann, Sabine; Schulze, Anja; Katz, Ira M; Martin, Andrew R; Herpich, Christiane; Hunger, Theresa; Texereau, Joëlle

    2015-01-01

    Background Helium/oxygen therapies have been studied as a means to reduce the symptoms of obstructive lung diseases with inconclusive results in clinical trials. To better understand this variability in results, an exploratory physiological study was performed comparing the effects of helium/oxygen mixture (78%/22%) to that of medical air. Methods The gas mixtures were administered to healthy, asthmatic, and chronic obstructive pulmonary disease (COPD) participants, both moderate and severe (6 participants in each disease group, a total of 30); at rest and during submaximal cycling exercise with equivalent work rates. Measurements of ventilatory parameters, forced spirometry, and ergospirometry were obtained. Results There was no statistical difference in ventilatory and cardiac responses to breathing helium/oxygen during submaximal exercise. For asthmatics, but not for the COPD participants, there was a statistically significant benefit in reduced metabolic cost, determined through measurement of oxygen uptake, for the same exercise work rate. However, the individual data show that there were a mixture of responders and nonresponders to helium/oxygen in all of the groups. Conclusion The inconsistent response to helium/oxygen between individuals is perhaps the key drawback to the more effective and widespread use of helium/oxygen to increase exercise capacity and for other therapeutic applications. PMID:26451096

  17. The effect of mayfly (Hexagenia spp.) burrowing activity on sediment oxygen demand in western Lake Erie

    USGS Publications Warehouse

    Edwards, William J.; Soster, Frederick M.; Matisoff, Gerald; Schloesser, Donald W.

    2009-01-01

    Previous studies support the hypothesis that large numbers of infaunal burrow-irrigating organisms in the western basin of Lake Erie may increase significantly the sediment oxygen demand, thus enhancing the rate of hypolimnetic oxygen depletion. We conducted laboratory experiments to quantify burrow oxygen dynamics and increased oxygen demand resulting from burrow irrigation using two different year classes of Hexagenia spp. nymphs from western Lake Erie during summer, 2006. Using oxygen microelectrodes and hot film anemometry, we simultaneously determined oxygen concentrations and burrow water flow velocities. Burrow oxygen depletion rates ranged from 21.7 mg/nymph/mo for 15 mm nymphs at 23 °C to 240.7 mg/nymph/mo for 23 mm nymphs at 13 °C. Sealed microcosm experiments demonstrated that mayflies increase the rate of oxygen depletion by 2-5 times that of controls, depending on size of nymph and water temperature, with colder waters having greater impact. At natural population densities, nymph pumping activity increased total sediment oxygen demand 0.3-2.5 times compared to sediments with no mayflies and accounted for 22-71% of the total sediment oxygen demand. Extrapolating laboratory results to the natural system suggest that Hexagenia spp. populations may exert a significant control on oxygen depletion during intermittent stratification. This finding may help explain some of the fluctuations in Hexagenia spp. population densities in western Lake Erie and suggests that mayflies, by causing their own population collapse irrespective of other environmental conditions, may need longer term averages when used as a bio-indicator of the success of pollution-abatement programs in western Lake Erie and possibly throughout the Great Lakes.

  18. Diverse Activities of Histone Acylations Connect Metabolism to Chromatin Function.

    PubMed

    Dutta, Arnob; Abmayr, Susan M; Workman, Jerry L

    2016-08-18

    Modifications of histones play important roles in balancing transcriptional output. The discovery of acyl marks, besides histone acetylation, has added to the functional diversity of histone modifications. Since all modifications use metabolic intermediates as substrates for chromatin-modifying enzymes, the prevalent landscape of histone modifications in any cell type is a snapshot of its metabolic status. Here, we review some of the current findings of how differential use of histone acylations regulates gene expression as response to metabolic changes and differentiation programs. PMID:27540855

  19. Use of the liver activity index and other metabolic variables in the assessment of metabolic health in dairy herds.

    PubMed

    Bertoni, Giuseppe; Trevisi, Erminio

    2013-07-01

    The usefulness of the metabolic profile in dairy cows has been questioned because of poor standardization of procedures, high cost of analysis, and perceived inefficiency of the approach. Composite indices based on multiple variables, namely the Liver Activity Index and the Liver Functionality Index, which consider the pattern of changes of some negative acute-phase proteins in the first month of lactation, appear promising in the assessment of metabolic health status and the prediction of lactational and reproductive performance. The application of such indices depends on their reliability and on making them practical and economical regarding test cost and number of sampling points required. PMID:23809898

  20. AMP-activated Protein Kinase Signaling Activation by Resveratrol Modulates Amyloid-β Peptide Metabolism*

    PubMed Central

    Vingtdeux, Valérie; Giliberto, Luca; Zhao, Haitian; Chandakkar, Pallavi; Wu, Qingli; Simon, James E.; Janle, Elsa M.; Lobo, Jessica; Ferruzzi, Mario G.; Davies, Peter; Marambaud, Philippe

    2010-01-01

    Alzheimer disease is an age-related neurodegenerative disorder characterized by amyloid-β (Aβ) peptide deposition into cerebral amyloid plaques. The natural polyphenol resveratrol promotes anti-aging pathways via the activation of several metabolic sensors, including the AMP-activated protein kinase (AMPK). Resveratrol also lowers Aβ levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Moreover, the bioavailability of resveratrol in the brain remains uncertain. Here we show that AMPK signaling controls Aβ metabolism and mediates the anti-amyloidogenic effect of resveratrol in non-neuronal and neuronal cells, including in mouse primary neurons. Resveratrol increased cytosolic calcium levels and promoted AMPK activation by the calcium/calmodulin-dependent protein kinase kinase-β. Direct pharmacological and genetic activation of AMPK lowered extracellular Aβ accumulation, whereas AMPK inhibition reduced the effect of resveratrol on Aβ levels. Furthermore, resveratrol inhibited the AMPK target mTOR (mammalian target of rapamycin) to trigger autophagy and lysosomal degradation of Aβ. Finally, orally administered resveratrol in mice was detected in the brain where it activated AMPK and reduced cerebral Aβ levels and deposition in the cortex. These data suggest that resveratrol and pharmacological activation of AMPK have therapeutic potential against Alzheimer disease. PMID:20080969

  1. Physical Activity and Sedentary Behavior Associated with Components of Metabolic Syndrome among People in Rural China

    PubMed Central

    Xiao, Jing; Shen, Chong; Chu, Min J.; Gao, Yue X.; Xu, Guang F.; Huang, Jian P.; Xu, Qiong Q.; Cai, Hui

    2016-01-01

    Background Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China. Methods The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed. Results Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15–40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15–30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids. Conclusions Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also

  2. Correction for intravascular activity in the oxygen-15 steady-state technique is independent of the regional hematocrit

    SciTech Connect

    Lammertsma, A.A.; Baron, J.C.; Jones, T.

    1987-06-01

    The oxygen-15 steady-state technique to measure the regional cerebral metabolic rate for oxygen requires a correction for the nonextracted intravascular molecular oxygen-15. To perform this correction, an additional procedure is carried out using RBCs labeled with /sup 11/CO or C/sup 15/O. The previously reported correction method, however, required knowledge of the regional cerebral to large vessel hematocrit ratio. A closer examination of the underlying model eliminated this ratio. Both molecular oxygen and carbon monoxide are carried by RBCs and are therefore similarly affected by a change in hematocrit.

  3. Inactivation of Pathogenic Bacteria on Seeds by Active Oxygen Species Generated in Low-Pressure Plasma

    NASA Astrophysics Data System (ADS)

    Ono, Reoto; Uchida, Shohei; Hayashi, Nobuya; Kosaka, Rina; Soeda, Yasutaka

    2015-09-01

    The inactivation of bacteria on seeds by active oxygen species generated by a low-pressure oxygen plasma is investigated. Species of active oxygen contributing to the inactivation of bacteria are attempted to be identified. Cylindrical stainless chamber with the internal volume of 17 L is used and RF antenna is set inside the chamber. The oxygen gas pressure is 20-100 Pa. RF power of 13.56 MHz is supplied to RF antenna and CCP is generated. After irradiation, bacteria are extracted from seeds and cultivated on nutrient agars. The number of colonies on these agars is counted after 48 h incubation. The number of bacteria on seeds decreases to less than 10-3 after plasma irradiation for 45 min comparing with that of control. The tendency of the reduction rate of bacteria on seeds has positive correlation with that of the light emission intensity of the singlet excited oxygen molecule as the oxygen gas pressure is varied. It is supposed that the singlet excited oxygen molecule would be one of the major factors for the inactivation of bacteria on seeds.

  4. Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels

    PubMed Central

    Smith, M. Ryan; Vayalil, Praveen K.; Zhou, Fen; Benavides, Gloria A.; Beggs, Reena R.; Golzarian, Hafez; Nijampatnam, Bhavitavya; Oliver, Patsy G.; Smith, Robin A.J.; Murphy, Michael P.; Velu, Sadanandan E.; Landar, Aimee

    2016-01-01

    Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compound, iodobutyl triphenylphosphonium (IBTP), decreased mitochondrial metabolism and ATP in MDA-MB 231 (MB231) breast adenocarcinoma cells up to 6 days after an initial 24 h treatment. Mitochondrial thiol modification also depressed oxygen consumption rates (OCR) in a dose-dependent manner to a greater extent than a non-thiol modifying analog, suggesting that thiol reactivity is an important factor in the inhibition of cancer cell metabolism. In non-tumorigenic MCF-10A cells, IBTP also decreased OCR; however the extracellular acidification rate was significantly increased at all but the highest concentration (10 µM) of IBTP indicating that thiol modification can have significantly different effects on bioenergetics in tumorigenic versus non-tumorigenic cells. ATP and other adenonucleotide levels were also decreased by thiol modification up to 6 days post-treatment, indicating a decreased overall energetic state in MB231 cells. Cellular proliferation of MB231 cells was also inhibited up to 6 days post-treatment with little change to cell viability. Targeted metabolomic analyses revealed that thiol modification caused depletion of both Krebs cycle and glutaminolysis intermediates. Further experiments revealed that the activity of the Krebs cycle enzyme, aconitase, was attenuated in response to thiol modification. Additionally, the inhibition of glutaminolysis corresponded to decreased glutaminase C (GAC) protein levels, although other protein levels were unaffected. This study

  5. Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels.

    PubMed

    Smith, M Ryan; Vayalil, Praveen K; Zhou, Fen; Benavides, Gloria A; Beggs, Reena R; Golzarian, Hafez; Nijampatnam, Bhavitavya; Oliver, Patsy G; Smith, Robin A J; Murphy, Michael P; Velu, Sadanandan E; Landar, Aimee

    2016-08-01

    Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In t