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Sample records for monocyte oxidative metabolism

  1. Transcellular lipoxygenase metabolism between monocytes and platelets

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    Bigby, T.D.; Meslier, N. (Univ. of California, San Francisco (USA))

    1989-09-15

    We have examined the effects of co-culture and in vitro co-stimulation on lipoxygenase metabolism in monocytes and platelets. Monocytes were obtained from the peripheral blood of normal volunteers by discontinuous gradient centrifugation and adherence to tissue culture plastic. Platelets were obtained from the platelet-rich plasma of the same donor. When 10(9) platelets and 2.5 x 10(6) monocytes were co-stimulated with 1 microM A23187, these preparations released greater quantities of 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid, 5(S),12-(S)dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid, and leukotriene C4, 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic (LTC4) when compared with monocytes alone. Release of arachidonic acid, 5-HETE, delta 6-trans-LTB4, and delta 6-trans-12-epi-LTB4 from monocytes was decreased in the presence of platelets. A dose-response curve was constructed and revealed that the above changes became evident when the platelet number exceeded 10(7). Dual radiolabeling experiments with 3H- and 14C-arachidonic acid revealed that monocytes provided arachidonic acid, 5-HETE, and LTA4 for further metabolism by the platelet. Monocytes did not metabolize platelet intermediates detectably. In addition, as much as 1.2 microM 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid and 12(S)-hydroperoxy-10-trans-5,8,14-cis-eicosatetraenoic acid had no effect on monocyte lipoxygenase metabolism. Platelets were capable of converting LTA4 to LTC4, but conversion of LTA4 to LTB4 was not detected. We conclude that the monocyte and platelet lipoxygenase pathways undergo a transcellular lipoxygenase interaction that differs from the interaction of the neutrophil and platelet lipoxygenase pathways. In this interaction monocytes provide intermediate substrates for further metabolic conversion by platelets in an unidirectional manner.

  2. Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis.

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    Domínguez-Andrés, Jorge; Arts, Rob J W; Ter Horst, Rob; Gresnigt, Mark S; Smeekens, Sanne P; Ratter, Jacqueline M; Lachmandas, Ekta; Boutens, Lily; van de Veerdonk, Frank L; Joosten, Leo A B; Notebaart, Richard A; Ardavín, Carlos; Netea, Mihai G

    2017-09-01

    Monocytes are innate immune cells that play a pivotal role in antifungal immunity, but little is known regarding the cellular metabolic events that regulate their function during infection. Using complementary transcriptomic and immunological studies in human primary monocytes, we show that activation of monocytes by Candida albicans yeast and hyphae was accompanied by metabolic rewiring induced through C-type lectin-signaling pathways. We describe that the innate immune responses against Candida yeast are energy-demanding processes that lead to the mobilization of intracellular metabolite pools and require induction of glucose metabolism, oxidative phosphorylation and glutaminolysis, while responses to hyphae primarily rely on glycolysis. Experimental models of systemic candidiasis models validated a central role for glucose metabolism in anti-Candida immunity, as the impairment of glycolysis led to increased susceptibility in mice. Collectively, these data highlight the importance of understanding the complex network of metabolic responses triggered during infections, and unveil new potential targets for therapeutic approaches against fungal diseases.

  3. Postprandial Monocyte Activation in Individuals With Metabolic Syndrome

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    Khan, Ilvira M.; Pokharel, Yashashwi; Dadu, Razvan T.; Lewis, Dorothy E.; Hoogeveen, Ron C.; Wu, Huaizhu

    2016-01-01

    Context: Postprandial hyperlipidemia has been suggested to contribute to atherogenesis by inducing proinflammatory changes in monocytes. Individuals with metabolic syndrome (MS), shown to have higher blood triglyceride concentration and delayed triglyceride clearance, may thus have increased risk for development of atherosclerosis. Objective: Our objective was to examine fasting levels and effects of a high-fat meal on phenotypes of monocyte subsets in individuals with obesity and MS and in healthy controls. Design, Setting, Participants, Intervention: Individuals with obesity and MS and gender- and age-matched healthy controls were recruited. Blood was collected from participants after an overnight fast (baseline) and at 3 and 5 hours after ingestion of a high-fat meal. At each time point, monocyte phenotypes were examined by multiparameter flow cytometry. Main Outcome Measures: Baseline levels of activation markers and postprandial inflammatory response in each of the three monocyte subsets were measured. Results: At baseline, individuals with obesity and MS had higher proportions of circulating lipid-laden foamy monocytes than controls, which were positively correlated with fasting triglyceride levels. Additionally, the MS group had increased counts of nonclassical monocytes, higher CD11c, CX3CR1, and human leukocyte antigen-DR levels on intermediate monocytes, and higher CCR5 and tumor necrosis factor-α levels on classical monocytes in the circulation. Postprandial triglyceride increases in both groups were paralleled by upregulation of lipid-laden foamy monocytes. MS, but not control, subjects had significant postprandial increases of CD11c and percentages of IL-1β+ and tumor necrosis factor-α+ cells in nonclassical monocytes. Conclusions: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation. PMID:27575945

  4. Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism

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    Soufi Muhidien

    2008-11-01

    Full Text Available Abstract Background Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH with those from healthy individuals. Methods Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography – mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p Results Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells. Conclusion Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.

  5. Blood monocyte oxidative burst activity in acute P. falciparum malaria

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    Nielsen, H; Theander, T G

    1989-01-01

    The release of superoxide anion from blood monocytes was studied in eight patients with acute primary attack P. falciparum malaria. Before treatment a significant enhancement of the oxidative burst prevailed, which contrasts with previous findings of a depressed monocyte chemotactic responsiveness...

  6. Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes

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    Nora Raulien

    2017-05-01

    Full Text Available Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect. Experiments using the Seahorse Extracellular Flux Analyzer revealed that limited glucose supply shifts monocyte metabolism toward oxidative phosphorylation, fueled largely by fatty acid oxidation at the expense of lipid droplets. While this metabolic state appears to provide sufficient energy to sustain functional properties like cytokine secretion, migration, and phagocytosis, it cannot prevent a rise in the AMP/ATP ratio and a decreased respiratory burst. The molecular trigger mediating the metabolic shift and the functional consequences is activation of AMP-activated protein kinase (AMPK. Taken together, our results indicate that monocytes are sufficiently metabolically flexible to perform pro-inflammatory functions at sites of inflammation despite glucose deprivation and inhibition of the LPS-induced Warburg effect. AMPK seems to play a pivotal role in orchestrating these processes during glucose deprivation in monocytes.

  7. Oxidative Mechanisms of Monocyte-Mediated Cytotoxicity

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    Weiss, Stephen J.; Lobuglio, Albert F.; Kessler, Howard B.

    1980-01-01

    Human monocytes stimulated with phorbol myristate acetate were able to rapidly destroy autologous erythrocyte targets. Monocyte-mediated cytotoxicity was related to phorbol myristate acetate concentration and monocyte number. Purified preparations of lymphocytes were incapable of mediating erythrocyte lysis in this system. The ability of phorbol myristate acetate-stimulated monocytes to lyse erythrocyte targets was markedly impaired by catalase or superoxide dismutase but not by heat-inactivated enzymes or albumin. Despite a simultaneous requirement for superoxide anion and hydrogen peroxide in the cytotoxic event, a variety of hydroxyl radical and singlet oxygen scavengers did not effect cytolysis. However, tryptophan significantly inhibited cytotoxicity. The myeloperoxidase inhibitor cyanide enhanced erythrocyte destruction, whereas azide reduced it modestly. The inability of cyanide to reduce cytotoxicity coupled with the protective effect of superoxide dismutase suggests that cytotoxicity is independent of the classic myeloperoxidase system. We conclude that monocytes, stimulated with phorbol myristate acetate, generate superoxide anion and hydrogen peroxide, which together play an integral role in this cytotoxic mechanism.

  8. High-Density Lipoprotein Reduction Differentially Modulates to Classical and Nonclassical Monocyte Subpopulations in Metabolic Syndrome Patients and in LPS-Stimulated Primary Human Monocytes In Vitro

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    Grün, Johanna L.; Manjarrez-Reyna, Aaron N.; Gómez-Arauz, Angélica Y.; Leon-Cabrera, Sonia; Bueno-Hernández, Nallely; Islas-Andrade, Sergio

    2018-01-01

    The effect of metabolic syndrome on human monocyte subpopulations has not yet been studied. Our main goal was to examine monocyte subpopulations in metabolic syndrome patients, while also identifying the risk factors that could directly influence these cells. Eighty-six subjects were divided into metabolic syndrome patients and controls. Monocyte subpopulations were quantified by flow cytometry, and interleukin- (IL-) 1β secretion levels were measured by ELISA. Primary human monocytes were cultured in low or elevated concentrations of high-density lipoprotein (HDL) and stimulated with lipopolysaccharide (LPS). The nonclassical monocyte (NCM) percentage was significantly increased in metabolic syndrome patients as compared to controls, whereas classical monocytes (CM) were reduced. Among all metabolic syndrome risk factors, HDL reduction exhibited the most important correlation with monocyte subpopulations and then was studied in vitro. Low HDL concentration reduced the CM percentage, whereas it increased the NCM percentage and IL-1β secretion in LPS-treated monocytes. The LPS effect was abolished when monocytes were cultured in elevated HDL concentrations. Concurring with in vitro results, IL-1β serum values significantly increased in metabolic syndrome patients with low HDL levels as compared to metabolic syndrome patients without HDL reduction. Our data demonstrate that HDL directly modulates monocyte subpopulations in metabolic syndrome. PMID:29850624

  9. High-Density Lipoprotein Reduction Differentially Modulates to Classical and Nonclassical Monocyte Subpopulations in Metabolic Syndrome Patients and in LPS-Stimulated Primary Human Monocytes In Vitro

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    Johanna L. Grün

    2018-01-01

    Full Text Available The effect of metabolic syndrome on human monocyte subpopulations has not yet been studied. Our main goal was to examine monocyte subpopulations in metabolic syndrome patients, while also identifying the risk factors that could directly influence these cells. Eighty-six subjects were divided into metabolic syndrome patients and controls. Monocyte subpopulations were quantified by flow cytometry, and interleukin- (IL- 1β secretion levels were measured by ELISA. Primary human monocytes were cultured in low or elevated concentrations of high-density lipoprotein (HDL and stimulated with lipopolysaccharide (LPS. The nonclassical monocyte (NCM percentage was significantly increased in metabolic syndrome patients as compared to controls, whereas classical monocytes (CM were reduced. Among all metabolic syndrome risk factors, HDL reduction exhibited the most important correlation with monocyte subpopulations and then was studied in vitro. Low HDL concentration reduced the CM percentage, whereas it increased the NCM percentage and IL-1β secretion in LPS-treated monocytes. The LPS effect was abolished when monocytes were cultured in elevated HDL concentrations. Concurring with in vitro results, IL-1β serum values significantly increased in metabolic syndrome patients with low HDL levels as compared to metabolic syndrome patients without HDL reduction. Our data demonstrate that HDL directly modulates monocyte subpopulations in metabolic syndrome.

  10. Mitochondrial Sirtuin 4 Resolves Immune Tolerance in Monocytes by Rebalancing Glycolysis and Glucose Oxidation Homeostasis

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    Jie Tao

    2018-03-01

    Full Text Available The goal of this investigation was to define the molecular mechanism underlying physiologic conversion of immune tolerance to resolution of the acute inflammatory response, which is unknown. An example of this knowledge gap and its clinical importance is the broad-based energy deficit and immunometabolic paralysis in blood monocytes from non-survivors of human and mouse sepsis that precludes sepsis resolution. This immunometabolic dysregulation is biomarked by ex vivo endotoxin tolerance to increased glycolysis and TNF-α expression. To investigate how tolerance switches to resolution, we adapted our previously documented models associated with acute inflammatory, immune, and metabolic reprogramming that induces endotoxin tolerance as a model of sepsis in human monocytes. We report here that mitochondrial sirtuin 4 (SIRT4 physiologically breaks tolerance and resolves acute inflammation in human monocytes by coordinately reprogramming of metabolism and bioenergetics. We find that increased SIRT4 mRNA and protein expression during immune tolerance counters the increase in pyruvate dehydrogenase kinase 1 (PDK1 and SIRT1 that promote tolerance by switching glucose-dependent support of immune resistance to fatty acid oxidation support of immune tolerance. By decreasing PDK1, pyruvate dehydrogenase complex reactivation rebalances mitochondrial respiration, and by decreasing SIRT1, SIRT4 represses fatty acid oxidation. The precise mechanism for the mitochondrial SIRT4 nuclear feedback is unclear. Our findings are consistent with a new concept in which mitochondrial SIRT4 directs the axis that controls anabolic and catabolic energy sources.

  11. Exercise promotes collateral artery growth mediated by monocytic nitric oxide.

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    Schirmer, Stephan H; Millenaar, Dominic N; Werner, Christian; Schuh, Lisa; Degen, Achim; Bettink, Stephanie I; Lipp, Peter; van Rooijen, Nico; Meyer, Tim; Böhm, Michael; Laufs, Ulrich

    2015-08-01

    Collateral artery growth (arteriogenesis) is an important adaptive response to hampered arterial perfusion. It is unknown whether preventive physical exercise before limb ischemia can improve arteriogenesis and modulate mononuclear cell function. This study aimed at investigating the effects of endurance exercise before arterial occlusion on MNC function and collateral artery growth. After 3 weeks of voluntary treadmill exercise, ligation of the right femoral artery was performed in mice. Hindlimb perfusion immediately after surgery did not differ from sedentary mice. However, previous exercise improved perfusion restoration ≤7 days after femoral artery ligation, also when exercise was stopped at ligation. This was accompanied by an accumulation of peri-collateral macrophages and increased expression of endothelial nitric oxide synthase and inducible nitric oxide synthase (iNOS) in hindlimb collateral and in MNC of blood and spleen. Systemic monocyte and macrophage depletion by liposomal clodronate but not splenectomy attenuated exercise-induced perfusion restoration, collateral artery growth, peri-collateral macrophage accumulation, and upregulation of iNOS. iNOS-deficient mice did not show exercise-induced perfusion restoration. Transplantation of bone marrow-derived MNC from iNOS-deficient mice into wild-type animals inhibited exercise-induced collateral artery growth. In contrast to sedentary controls, thrice weekly aerobic exercise training for 6 months in humans increased peripheral blood MNC iNOS expression. Circulating mononuclear cell-derived inducible nitric oxide is an important mediator of exercise-induced collateral artery growth. © 2015 American Heart Association, Inc.

  12. Alterations in calcium metabolism during human monocyte activation

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    Scully, S.P.

    1984-01-01

    Human peripheral blood monocytes have been prepared from plateletpheresis residues by counterflow centrifugal elutriation in sufficient quantities to enable quantitative studies of cell calcium. Kinetic analysis of 45 Ca exchange data in resting monocytes was compatible with a model of cellular calcium containing three exchangeable calcium pools. These pools are thought to represent a putative ectocellular pool, a putative cytoplasmic chelated pool, and a putative organelle sequestered pool. Exposure of monocytes to the plant lectin Con A at a concentration that maximally simulated superoxide production caused an increase in the size and a doubling in the exchange rate of the putative cytoplasmic pool without a change in the other cellular pools. The cytoplasmic ionized calcium, [Ca]/sub i/, measured with the fluorescent probe, Quin 2 rose from a resting level of 83 nM to 165 mN within 30 sec of exposure to Con A. This increase in cytoplasmic calcium preceded the release of superoxide radicals. Calcium transport and calcium ATPase activities were identified and characterized in plasma membrane vesicles prepared from monocytes. Both activities were strictly dependent on ATP and Mg, had a Km/sub Ca/ in the submicromolar range and were stimulated by calmodulin. Thus, it seems that monocyte calcium is in a dynamic steady state that is a balance between efflux and influx rates, and that the activation of these cells results in the transition to a new steady state. The alteration in [Ca]/sub i/ that accompany the new steady state are essential for superoxide production by human monocytes

  13. Transcript and protein analysis reveals better survival skills of monocyte-derived dendritic cells compared to monocytes during oxidative stress.

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    Ilse Van Brussel

    Full Text Available BACKGROUND: Dendritic cells (DCs, professional antigen-presenting cells with the unique ability to initiate primary T-cell responses, are present in atherosclerotic lesions where they are exposed to oxidative stress that generates cytotoxic reactive oxygen species (ROS. A large body of evidence indicates that cell death is a major modulating factor of atherogenesis. We examined antioxidant defence systems of human monocyte-derived (moDCs and monocytes in response to oxidative stress. METHODS: Oxidative stress was induced by addition of tertiary-butylhydroperoxide (tert-BHP, 30 min. Cellular responses were evaluated using flow cytometry and confocal live cell imaging (both using 5-(and-6-chloromethyl-2,7-dichlorodihydrofluorescein diacetate, CM-H(2DCFDA. Viability was assessed by the neutral red assay. Total RNA was extracted for a PCR profiler array. Five genes were selected for confirmation by Taqman gene expression assays, and by immunoblotting or immunohistochemistry for protein levels. RESULTS: Tert-BHP increased CM-H(2DCFDA fluorescence and caused cell death. Interestingly, all processes occurred more slowly in moDCs than in monocytes. The mRNA profiler array showed more than 2-fold differential expression of 32 oxidative stress-related genes in unstimulated moDCs, including peroxiredoxin-2 (PRDX2, an enzyme reducing hydrogen peroxide and lipid peroxides. PRDX2 upregulation was confirmed by Taqman assays, immunoblotting and immunohistochemistry. Silencing PRDX2 in moDCs by means of siRNA significantly increased CM-DCF fluorescence and cell death upon tert-BHP-stimulation. CONCLUSIONS: Our results indicate that moDCs exhibit higher intracellular antioxidant capacities, making them better equipped to resist oxidative stress than monocytes. Upregulation of PRDX2 is involved in the neutralization of ROS in moDCs. Taken together, this points to better survival skills of DCs in oxidative stress environments, such as atherosclerotic plaques.

  14. Effects of acute exercise on monocyte subpopulations in metabolic syndrome patients.

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    Wonner, Ralph; Wallner, Stefan; Orsó, Evelyn; Schmitz, Gerd

    2016-06-10

    Acute exercise induces numerous changes in peripheral blood, e.g. counts of leukocytes. CD16 pos monocytes, which play a role in the pathogenesis of arteriosclerosis and the metabolic syndrome (MetS), are among the blood cells with the highest fold increase through exercise. So far no studies have investigated the effect of exercise on the blood cell composition of patients with MetS. Blood cell counts, a wide panel of laboratory tests, as well as lipid and protein content of monocytes and granulocytes were determined in healthy subjects, persons with metabolic risk and MetS patients before and after one minute of exercise at 400 W. Leukocyte counts increased significantly in all groups with CD14 pos CD16 pos monocytes showing the highest fold-change. In MetS patients the fold increase was smaller. They had a higher resting level of CD14 pos CD16 pos monocytes and a lower basal ratio of CD16 neg /CD16 pos monocytes. A similar ratio of these cells was induced in control and risk subjects after exercise. However, absolute counts of mobilized pro-inflammatory monocytes did not differ significantly. Furthermore, we detected a decrease in protein content of monocytes in controls, but not in MetS patients. As strenuous exercise is able to mobilize the same amount of pro-inflammatory monocytes in MetS patients as in healthy persons, the elevated basal level of these cells in MetS patients is likely to be caused by enhanced maturation rather than chronic mobilization. The removal of these monocytes from the endothelium might be part of the beneficial effect of exercise on vascular disease. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

  15. Oxidative metabolism in muscle.

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    Ferrari, M; Binzoni, T; Quaresima, V

    1997-01-01

    Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantage...

  16. Death of Monocytes through Oxidative Burst of Macrophages and Neutrophils: Killing in Trans.

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    Viviane Ponath

    Full Text Available Monocytes and their descendants, macrophages, play a key role in the defence against pathogens. They also contribute to the pathogenesis of inflammatory diseases. Therefore, a mechanism maintaining a balance in the monocyte/macrophage population must be postulated. Our previous studies have shown that monocytes are impaired in DNA repair, rendering them vulnerable to genotoxic stress while monocyte-derived macrophages are DNA repair competent and genotoxic stress-resistant. Based on these findings, we hypothesized that monocytes can be selectively killed by reactive oxygen species (ROS produced by activated macrophages. We also wished to know whether monocytes and macrophages are protected against their own ROS produced following activation. To this end, we studied the effect of the ROS burst on DNA integrity, cell death and differentiation potential of monocytes. We show that monocytes, but not macrophages, stimulated for ROS production by phorbol-12-myristate-13-acetate (PMA undergo apoptosis, despite similar levels of initial DNA damage. Following co-cultivation with ROS producing macrophages, monocytes displayed oxidative DNA damage, accumulating DNA single-strand breaks and a high incidence of apoptosis, reducing their ability to give rise to new macrophages. Killing of monocytes by activated macrophages, termed killing in trans, was abolished by ROS scavenging and was also observed in monocytes co-cultivated with ROS producing activated granulocytes. The data revealed that monocytes, which are impaired in the repair of oxidised DNA lesions, are vulnerable to their own ROS and ROS produced by macrophages and granulocytes and support the hypothesis that this is a mechanism regulating the amount of monocytes and macrophages in a ROS-enriched inflammatory environment.

  17. Differential oxidative stress induced by dengue virus in monocytes from human neonates, adult and elderly individuals.

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    Nereida Valero

    Full Text Available Changes in immune response during lifespan of man are well known. These changes involve decreased neonatal and elderly immune response. In addition, it has been shown a relationship between immune and oxidative mechanisms, suggesting that altered immune response could be associated to altered oxidative response. Increased expression of nitric oxide (NO has been documented in dengue and in monocyte cultures infected with different types of dengue virus. However, there is no information about the age-dependent NO oxidative response in humans infected by dengue virus. In this study, monocyte cultures from neonatal, elderly and adult individuals (n = 10 each group were infected with different dengue virus types (DENV- 1 to 4 and oxidative/antioxidative responses and apoptosis were measured at days 1 and 3 of culture. Increased production of NO, lipid peroxidation and enzymatic and nonenzymatic anti-oxidative responses in dengue infected monocyte cultures were observed. However, neonatal and elderly monocytes had lower values of studied parameters when compared to those in adult-derived cultures. Apoptosis was present in infected monocytes with higher values at day 3 of culture. This reduced oxidant/antioxidant response of neonatal and elderly monocytes could be relevant in the pathogenesis of dengue disease.

  18. Protective properties of artichoke (Cynara scolymus) against oxidative stress induced in cultured endothelial cells and monocytes.

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    Zapolska-Downar, Danuta; Zapolski-Downar, Andrzej; Naruszewicz, Marek; Siennicka, Aldona; Krasnodebska, Barbara; Kołdziej, Blanka

    2002-11-01

    It is currently believed that oxidative stress and inflammation play a significant role in atherogenesis. Artichoke extract exhibits hypolipemic properties and contains numerous active substances with antioxidant properties in vitro. We have studied the influence of aqueous and ethanolic extracts from artichoke on intracellular oxidative stress stimulated by inflammatory mediators (TNFalpha and LPS) and ox-LDL in endothelial cells and monocytes. Oxidative stress which reflects the intracellular production of reactive oxygen species (ROS) was followed by measuring the oxidation of 2', 7'-dichlorofluorescin (DCFH) to 2', 7'-dichlorofluorescein (DCF). Agueous and ethanolic extracts from artichoke were found to inhibit basal and stimulated ROS production in endothelial cells and monocytes in dose dependent manner. In endothelial cells, the ethanolic extract (50 microg/ml) reduced ox-LDL-induced intracellular ROS production by 60% (partichoke extracts have marked protective properties against oxidative stress induced by inflammatory mediators and ox-LDL in cultured endothelial cells and monocytes.

  19. Ursolic acid protects monocytes against metabolic stress-induced priming and dysfunction by preventing the induction of Nox4

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    Sarah L. Ullevig

    2014-01-01

    Conclusion: UA protects THP-1 monocytes against dysfunction by suppressing metabolic stress-induced Nox4 expression, thereby preventing the Nox4-dependent dysregulation of redox-sensitive processes, including actin turnover and MAPK-signaling, two key processes that control monocyte migration and adhesion. This study provides a novel mechanism for the anti-inflammatory and athero- and renoprotective properties of UA and suggests that dysfunctional blood monocytes may be primary targets of UA and related compounds.

  20. DMPD: The oxidation of lipoproteins by monocytes-macrophages. Biochemical andbiological mechanisms. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10473535 The oxidation of lipoproteins by monocytes-macrophages. Biochemical andbio.... (.png) (.svg) (.html) (.csml) Show The oxidation of lipoproteins by monocytes-macrophages. Biochemical and...onocytes-macrophages. Biochemical andbiological mechanisms. Authors Chisolm GM 3rd, Hazen SL, Fox PL, Cathca

  1. Consecutive evaluation of graphene oxide and reduced graphene oxide nanoplatelets immunotoxicity on monocytes.

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    Yan, Junyan; Chen, Liliang; Huang, Chih-Ching; Lung, Shih-Chun Candice; Yang, Lingyan; Wang, Wen-Cheng; Lin, Po-Hsiung; Suo, Guangli; Lin, Chia-Hua

    2017-05-01

    The biocompatibilities of graphene-family nanomaterials (GFNs) should be thoroughly evaluated before their application in drug delivery and anticancer therapy. The present study aimed to consecutively assess the immunotoxicity of graphene oxide nanoplatelets (GONPs) and reduced GONPs (rGONPs) on THP-1 cells, a human acute monocytic leukemia cell line. GONPs induced the expression of antioxidative enzymes and inflammatory factors, whereas rGONPs had substantially higher cellular uptake rate, higher levels of NF-κB expression. These distinct toxic mechanisms were observed because the two nanomaterials differ in their oxidation state, which imparts different affinities for the cell membrane. Because GONPs have a higher cell membrane affinity and higher impact on membrane proteins compared with rGONPs, macrophages (THP-1a) derived from GONPs treated THP-1cells showed a severer effect on phagocytosis. By consecutive evaluation the effects of GONPs and rGONPs on THP-1 and THP-1a, we demonstrated that their surface oxidation states may cause GFNs to behave differently and cause different immunotoxic effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Facilitated monocyte-macrophage uptake and tissue distribution of superparmagnetic iron-oxide nanoparticles.

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    Arnaud Beduneau

    Full Text Available BACKGROUND: We posit that the same mononuclear phagocytes (MP that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP and tissue delivery. METHODS: Monocytes and monocyte-derived macrophages (MDM were used as vehicles of superparamagnetic iron oxide (SPIO NP and immunoglobulin (IgG or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was synthesized by covalent linkage and uptake into monocytes and MDM investigated related to size, time, temperature, concentration, and coatings. SPIO and IgG SPIO were infused intravenously into naïve mice. T(2 measures using magnetic resonance imaging (MRI were used to monitor tissue distribution in animals. RESULTS: Oxidation of dextran on the SPIO surface generated reactive aldehyde groups and permitted covalent linkage to amino groups of murine and human IgG and F(ab'(2 fragments and for Alexa Fluor(R 488 hydroxylamine to form a Schiff base. This labile intermediate was immediately reduced with sodium cyanoborohydride in order to stabilize the NP conjugate. Optical density measurements of the oxidized IgG, F(ab'(2, and/or Alexa Fluor(R 488 SPIO demonstrated approximately 50% coupling yield. IgG-SPIO was found stable at 4 degrees C for a period of 1 month during which size and polydispersity index varied little from 175 nm and 200 nm, respectively. In vitro, NP accumulated readily within monocyte and MDM cytoplasm after IgG-SPIO exposure; whereas, the uptake of native SPIO in monocytes and MDM was 10-fold less. No changes in cell viability were noted for the SPIO-containing monocytes and MDM. Cell morphology was not changed as observed by transmission electron microscopy. Compared to unconjugated

  3. Arsenic alters monocyte superoxide anion and nitric oxide production in environmentally exposed children

    International Nuclear Information System (INIS)

    Luna, Ana L.; Acosta-Saavedra, Leonor C.; Lopez-Carrillo, Lizbeth; Conde, Patricia; Vera, Eunice; De Vizcaya-Ruiz, Andrea; Bastida, Mariana; Cebrian, Mariano E.; Calderon-Aranda, Emma S.

    2010-01-01

    Arsenic (As) exposure has been associated with alterations in the immune system, studies in experimental models and adults have shown that these effects involve macrophage function; however, limited information is available on what type of effects could be induced in children. The aim of this study was to evaluate effects of As exposure, through the association of inorganic As (iAs) and its metabolites [monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] with basal levels of nitric oxide (NO ·- ) and superoxide anion (O 2 ·- ), in peripheral blood mononuclear cells (PBMC) and monocytes, and NO ·- and O 2 ·- produced by activated monocytes. Hence, a cross-sectional study was conducted in 87 children (6-10 years old) who had been environmentally exposed to As through drinking water. Levels of urinary As species (iAs, MMA and DMA) were determined by hydride generation atomic absorption spectrometry, total As (tAs) represents the sum of iAs and its species; tAs urine levels ranged from 12.3 to 1411 μg/g creatinine. Using multiple linear regression models, iAs presented a positive and statistical association with basal NO ·- in PBMC (β = 0.0048, p = 0.049) and monocytes (β = 0.0044, p = 0.044), while basal O 2 ·- had a significant positive association with DMA (β = 0.0025, p = 0.046). In activated monocytes, O 2 ·- showed a statistical and positive association with iAs (β = 0.0108, p = 0.023), MMA (β = 0.0066, p = 0.022), DMA (β = 0.0018, p = 0.015), and tAs (β = 0.0013, p = 0.015). We conclude that As exposure in the studied children was positively associated with basal levels of NO ·- and O 2 ·- in PBMC and monocytes, suggesting that As induces oxidative stress in circulating blood cells. Additionally, this study showed a positive association of O 2 ·- production with iAs and its metabolites in stimulated monocytes, supporting previous data that suggests that these cells, and particularly the O 2 ·- activation pathway, are relevant targets

  4. Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein.

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    Li, Zhijuan; Cheng, Jianxin; Wang, Liping

    2015-10-30

    Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuated the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation. Copyright © 2015. Published by Elsevier Inc.

  5. Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein

    International Nuclear Information System (INIS)

    Li, Zhijuan; Cheng, Jianxin; Wang, Liping

    2015-01-01

    Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuated the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation. - Highlights: • Edaravone reduces oxLDL-induced monocyte adhesion to HUVECs. • Edaravone attenuates oxLDL-induced expression of MCP-1, VCAM-1, and ICAM-1. • Edaravone reduces NF-κB transcriptional activity and p65 nuclear translocation.

  6. Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhijuan, E-mail: zjlee038@163.com; Cheng, Jianxin; Wang, Liping

    2015-10-30

    Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuated the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation. - Highlights: • Edaravone reduces oxLDL-induced monocyte adhesion to HUVECs. • Edaravone attenuates oxLDL-induced expression of MCP-1, VCAM-1, and ICAM-1. • Edaravone reduces NF-κB transcriptional activity and p65 nuclear translocation.

  7. Oxidative stress induces monocyte necrosis with enrichment of cell-bound albumin and overexpression of endoplasmic reticulum and mitochondrial chaperones.

    Directory of Open Access Journals (Sweden)

    Haiping Tang

    Full Text Available In the present study, monocytes were treated with 5-azacytidine (azacytidine, gossypol or hydrogen peroxide to induce cell death through oxidative stress. A shift from apoptotic to necrotic cell death occurred when monocytes were treated with 100 µM azacytidine for more than 12 hours. Necrotic monocytes exhibited characteristics, including enrichment of cell-bound albumin and up-regulation of endoplasmic reticulum (ER- and mitochondrial-specific chaperones to protect mitochondrial integrity, which were not observed in other necrotic cells, including HUH-7, A2780, A549 and HOC1a. Our results show that the cell-bound albumin originates in the culture medium rather than from monocyte-derived hepatocytes, and that HSP60 is a potential binding partner of the cell-bound albumin. Proteomic analysis shows that HSP60 and protein disulfide isomerase are the most abundant up-regulated mitochondrial and ER-chaperones, and that both HSP60 and calreticulin are ubiquitinated in necrotic monocytes. In contrast, expression levels of the cytosolic chaperones HSP90 and HSP71 were down-regulated in the azacytidine-treated monocytes, concomitant with an increase in the levels of these chaperones in the cell culture medium. Collectively, our results demonstrates that chaperones from different organelles behave differently in necrotic monocytes, ER- and mitochondrial chaperones being retained and cytosolic and nuclear chaperones being released into the cell culture medium through the ruptured cell membrane. HSP60 may serve as a new target for development of myeloid leukemia treatment.

  8. The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.

    Science.gov (United States)

    Feeney, Eoin R; McAuley, Nuala; O'Halloran, Jane A; Rock, Clare; Low, Justin; Satchell, Claudette S; Lambert, John S; Sheehan, Gerald J; Mallon, Patrick W G

    2013-02-15

    Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA). We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg). HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P ART-Treated and ART-Naive subjects than in HIV-Neg controls. In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.

  9. Interaction between Salmonella typhimurium and phagocytic cells in pigs - Phagocytosis, oxidative burst and killing in polymorphonuclear leukocytes and monocytes

    DEFF Research Database (Denmark)

    Riber, Ulla; Lind, Peter

    1999-01-01

    Interactions between Salmonella typhimurium and peripheral blood leucocytes from healthy, Salmonella-free pigs were investigated in vitro. Both granulocytes and monocytes phagocytized FITC-labelled heat-killed Salmonella bacteria as shown by flow cytometry. Phagocytosis in whole blood and isolated...... with the exhaustion of oxidative burst in non-adherent monocytes were performed by prestimulation with PMA, heat-killed Salmonella or buffer. Prestimulation with PMA led to a strong reduction in oxidative burst induced by living opsonized Salmonella bacteria, whereas prestimulation with heat-killed bacteria gave rise...

  10. Histone deacetylases in monocyte/macrophage development, activation and metabolism: refining HDAC targets for inflammatory and infectious diseases

    OpenAIRE

    Das Gupta, Kaustav; Shakespear, Melanie R; Iyer, Abishek; Fairlie, David P; Sweet, Matthew J

    2016-01-01

    Macrophages have central roles in danger detection, inflammation and host defense, and consequently, these cells are intimately linked to most disease processes. Major advances in our understanding of the development and function of macrophages have recently come to light. For example, it is now clear that tissue-resident macrophages can be derived from either blood monocytes or through local proliferation of phagocytes that are originally seeded during embryonic development. Metabolic state ...

  11. Unsaponifiable fraction isolated from grape (Vitis vinifera L.) seed oil attenuates oxidative and inflammatory responses in human primary monocytes.

    Science.gov (United States)

    Millan-Linares, Maria C; Bermudez, Beatriz; Martin, Maria E; Muñoz, Ernesto; Abia, Rocio; Millan, Francisco; Muriana, Francisco J G; Montserrat-de la Paz, Sergio

    2018-04-25

    Grape (Vitis vinifera L.) seed has well-known potential for production of oil as a byproduct of winemaking and is a rich source of bioactive compounds. Herein, we report that the unsaponifiable fraction (UF) isolated from grape seed oil (GSO) possesses anti-oxidative and anti-inflammatory properties towards human primary monocytes. The UF isolated from GSO was phytochemically characterized by GC-MS and HPLC. Freshly obtained human monocytes were used to analyse the effects of GSOUF (10-100 μg mL-1) on oxidative and inflammatory responses using FACS analysis, RT-qPCR, and ELISA procedures. GSOUF skewed the monocyte plasticity towards the anti-inflammatory non-classical CD14+CD16++ monocytes and reduced the inflammatory competence of LPS-treated human primary monocytes diminishing TNF-α, IL-1β, and IL-6 gene expression and secretion. In addition, GSOUF showed a strong reactive oxygen species (ROS)-scavenging activity, reducing significantly nitrite levels with a significant decrease in Nos2 gene expression. Our results suggest that the UF isolated from GSO has significant potential for the management of inflammatory and oxidative conditions and offer novel benefits derived from the consumption of GSO in the prevention of inflammation-related diseases.

  12. Zinc oxide nanoparticles and monocytes: Impact of size, charge and solubility on activation status

    International Nuclear Information System (INIS)

    Prach, Morag; Stone, Vicki; Proudfoot, Lorna

    2013-01-01

    Zinc oxide (ZnO) particle induced cytotoxicity was dependent on size, charge and solubility, factors which at sublethal concentrations may influence the activation of the human monocytic cell line THP1. ZnO nanoparticles (NP; average diameter 70 nm) were more toxic than the bulk form ( 2+ ion with protein. This association with protein may influence interaction of the ZnO particles and NP with THP1 cells. After 24 h exposure to the ZnO particles and NP at sublethal concentrations there was little effect on immunological markers of inflammation such as HLA DR and CD14, although they may induce a modest increase in the adhesion molecule CD11b. The cytokine TNFα is normally associated with proinflammatory immune responses but was not induced by the ZnO particles and NP. There was also no effect on LPS stimulated TNFα production. These results suggest that ZnO particles and NP do not have a classical proinflammatory effect on THP1 cells. -- Highlights: ► ZnO is cytotoxic to THP-1 monocytes. ► ZnO nanoparticles are more toxic than the bulk form. ► Positive charge enhances ZnO nanoparticle cytotoxicity. ► Sublethal doses of ZnO particles do not induce classical proinflammatory markers.

  13. Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques

    International Nuclear Information System (INIS)

    Jang, Moon Kyoo; Kim, Ji Young; Jeoung, Nam Ho; Kang, Mi Ae; Choi, Myung-Sook; Oh, Goo Taeg; Nam, Kyung Tak; Lee, Won-Ha; Park, Yong Bok

    2004-01-01

    Genes induced or suppressed by oxidized low-density lipoproteins (oxLDL) in human monocytic THP-1 cells were searched using the differential display reverse transcriptase polymerase chain reaction. One of the differentially expressed (up-regulated) cDNA fragments was found to contain sequences corresponding to monocyte chemotactic protein-3 (MCP-3). The stimulatory effect of the oxLDL on the expression of MCP-3 mRNA was both time- and dose-dependent. Treatment with GF109203X and genistein, inhibitors of protein kinase C and tyrosine kinase, respectively, had no effect on the induction of MCP-3 mRNA by oxLDL, while treatment with cycloheximide inhibited the induction. The induction was reproduced by the lipid components in oxLDL such as 9-HODE and 13-HODE, which are known to activate the peroxisome proliferator-activated receptor γ (PPARγ). Introduction of an endogenous PPARγ ligand, 15d-PGJ2, in the culture of THP-1 cells resulted in the induction of MCP-3 gene expression. Furthermore, analyses of human atherosclerotic plaques revealed that the expressional pattern of MCP-3 in the regions of neointimal and necrotic core overlapped with that of PPARγ. These results suggest that oxLDL delivers its signal for MCP-3 expression via PPARγ, which may be further related to the atherogenesis

  14. Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Yuka; Tada-Oikawa, Saeko [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan); Ichihara, Gaku [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya (Japan); Yabata, Masayuki; Izuoka, Kiyora [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan); Suzuki, Masako; Sakai, Kiyoshi [Nagoya City Public Health Research Institute, Nagoya (Japan); Ichihara, Sahoko, E-mail: saho@gene.mie-u.ac.jp [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan)

    2014-07-01

    Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO{sub 2} and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocyte chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO{sub 2} particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation. - Highlights: • Effects of metal oxide nanoparticles on foam cell formation were investigated. • Exposure to ZnO nanoparticles induced migration and adhesion of monocytes. • Exposure to ZnO nanoparticles increased macrophage cholesterol uptake. • Expression of membrane scavenger receptors of modified LDL was also increased. • These effects were not observed after exposure to TiO{sub 2} nanoparticles.

  15. Bystander signaling via oxidative metabolism.

    Science.gov (United States)

    Sawal, Humaira Aziz; Asghar, Kashif; Bureik, Matthias; Jalal, Nasir

    2017-01-01

    The radiation-induced bystander effect (RIBE) is the initiation of biological end points in cells (bystander cells) that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS) act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to pursue this field of science.

  16. Zinc oxide nanoparticles and monocytes: Impact of size, charge and solubility on activation status

    Energy Technology Data Exchange (ETDEWEB)

    Prach, Morag [Edinburgh Napier University, School of Life, Sport and Social Science, Edinburgh (United Kingdom); Stone, Vicki [Heriot-Watt University, School of Life Sciences, Edinburgh (United Kingdom); Proudfoot, Lorna, E-mail: l.proudfoot@napier.ac.uk [Edinburgh Napier University, School of Life, Sport and Social Science, Edinburgh (United Kingdom)

    2013-01-01

    Zinc oxide (ZnO) particle induced cytotoxicity was dependent on size, charge and solubility, factors which at sublethal concentrations may influence the activation of the human monocytic cell line THP1. ZnO nanoparticles (NP; average diameter 70 nm) were more toxic than the bulk form (< 44 μm mesh) and a positive charge enhanced cytotoxicity of the NP despite their relatively high dissolution. A positive charge of the particles has been shown in other studies to have an influence on cell viability. Centrifugal filtration using a cut off of 5 kDa and Zn element analysis by atomic absorption spectroscopy confirmed that exposure of the ZnO particles and NP to 10% foetal bovine serum resulted in a strong association of the Zn{sup 2+} ion with protein. This association with protein may influence interaction of the ZnO particles and NP with THP1 cells. After 24 h exposure to the ZnO particles and NP at sublethal concentrations there was little effect on immunological markers of inflammation such as HLA DR and CD14, although they may induce a modest increase in the adhesion molecule CD11b. The cytokine TNFα is normally associated with proinflammatory immune responses but was not induced by the ZnO particles and NP. There was also no effect on LPS stimulated TNFα production. These results suggest that ZnO particles and NP do not have a classical proinflammatory effect on THP1 cells. -- Highlights: ► ZnO is cytotoxic to THP-1 monocytes. ► ZnO nanoparticles are more toxic than the bulk form. ► Positive charge enhances ZnO nanoparticle cytotoxicity. ► Sublethal doses of ZnO particles do not induce classical proinflammatory markers.

  17. Bystander signaling via oxidative metabolism

    Directory of Open Access Journals (Sweden)

    Sawal HA

    2017-08-01

    Full Text Available Humaira Aziz Sawal,1 Kashif Asghar,2 Matthias Bureik,3 Nasir Jalal4 1Healthcare Biotechnology Department, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 2Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan; 3Health Science Platform, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China; 4Health Science Platform, Department of Molecular and Cellular Pharmacology, Tianjin University, Tianjin, China Abstract: The radiation-induced bystander effect (RIBE is the initiation of biological end points in cells (bystander cells that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to

  18. Nitric oxide and superoxide anion production in monocytes from children exposed to arsenic and lead in region Lagunera, Mexico

    International Nuclear Information System (INIS)

    Pineda-Zavaleta, Ana Patricia; Garcia-Vargas, Gonzalo; Borja-Aburto, Victor H.; Acosta-Saavedra, Leonor C.; Vera Aguilar, Eunice; Gomez-Munoz, Aristides; Cebrian, Mariano E.; Calderon-Aranda, Emma S.

    2004-01-01

    We evaluated in Mexican children environmentally exposed to arsenic and lead monocyte nitric oxide (NO) and superoxide anion production in response to direct activation with interferon-γ (IFN-γ) + lipopolysaccharide (LPS). The integrity of Th1-regulated cellular immune response when monocytes were indirectly activated was also evaluated. Most children lived near a primary lead smelter. Lead and arsenic contamination in soil and dust by far exceeded background levels. As levels in water were between 10 and 30 ppb. Most children (93%) had urinary arsenic (AsU) concentrations above 50 μg/l (range 16.75-465.75) and 65% had lead blood levels (PbB) above 10 μg/dl (range 3.47-49.19). Multivariate analyses showed that NO production in monocytes activated indirectly was negatively associated with both PbB and AsU. Superoxide production in directly activated monocytes was negatively associated with AsU but positively associated with PbB. The models including the interaction term for AsU and PbB suggested the possibility of a negative interaction for NO production and a positive interaction for superoxide. There were indications of differential gender-based associations, NO production in indirectly activated monocytes obtained from girls was negatively associated with AsU but not with PbB. Superoxide production was positively associated with PbB in both directly and indirectly activated monocytes from boys but the latter was negatively associated with AsU. These effects are consistent with immune system abnormalities observed in human populations exposed to Pb or As. Further studies in larger populations are required to characterize As and Pb interactions and the mechanism(s) underlying the observed effects

  19. Nitric oxide and mitochondria in metabolic syndrome

    Science.gov (United States)

    Litvinova, Larisa; Atochin, Dmitriy N.; Fattakhov, Nikolai; Vasilenko, Mariia; Zatolokin, Pavel; Kirienkova, Elena

    2015-01-01

    Metabolic syndrome (MS) is a cluster of metabolic disorders that collectively increase the risk of cardiovascular disease. Nitric oxide (NO) plays a crucial role in the pathogeneses of MS components and is involved in different mitochondrial signaling pathways that control respiration and apoptosis. The present review summarizes the recent information regarding the interrelations of mitochondria and NO in MS. Changes in the activities of different NO synthase isoforms lead to the formation of metabolic disorders and therefore are highlighted here. Reduced endothelial NOS activity and NO bioavailability, as the main factors underlying the endothelial dysfunction that occurs in MS, are discussed in this review in relation to mitochondrial dysfunction. We also focus on potential therapeutic strategies involving NO signaling pathways that can be used to treat patients with metabolic disorders associated with mitochondrial dysfunction. The article may help researchers develop new approaches for the diagnosis, prevention and treatment of MS. PMID:25741283

  20. Histone deacetylases in monocyte/macrophage development, activation and metabolism: refining HDAC targets for inflammatory and infectious diseases.

    Science.gov (United States)

    Das Gupta, Kaustav; Shakespear, Melanie R; Iyer, Abishek; Fairlie, David P; Sweet, Matthew J

    2016-01-01

    Macrophages have central roles in danger detection, inflammation and host defense, and consequently, these cells are intimately linked to most disease processes. Major advances in our understanding of the development and function of macrophages have recently come to light. For example, it is now clear that tissue-resident macrophages can be derived from either blood monocytes or through local proliferation of phagocytes that are originally seeded during embryonic development. Metabolic state has also emerged as a major control point for macrophage activation phenotypes. Herein, we review recent literature linking the histone deacetylase (HDAC) family of enzymes to macrophage development and activation, particularly in relation to these recent developments. There has been considerable interest in potential therapeutic applications for small molecule inhibitors of HDACs (HDACi), not only for cancer, but also for inflammatory and infectious diseases. However, the enormous range of molecular and cellular processes that are controlled by different HDAC enzymes presents a potential stumbling block to clinical development. We therefore present examples of how classical HDACs control macrophage functions, roles of specific HDACs in these processes and approaches for selective targeting of drugs, such as HDACi, to macrophages. Development of selective inhibitors of macrophage-expressed HDACs and/or selective delivery of pan HDACi to macrophages may provide avenues for enhancing efficacy of HDACi in therapeutic applications, while limiting unwanted side effects.

  1. Monocytic leukemias.

    Science.gov (United States)

    Shaw, M T

    1980-05-01

    The monocytic leukemias may be subdivided into acute monocytic leukemia, acute myelomonocytic leukemia, and subacute and chronic myelomonocytic leukemia. The clinical features of acute monocytic and acute myelomonocytic leukemias are similar and are manifestations of bone marrow failure. Gingival hypertrophy and skin infiltration are more frequent in acute monocytic leukemia. Cytomorphologically the blast cells in acute monocytic leukemia may be undifferentiated or differentiated, whereas in the acute myelomonocytic variety there are mixed populations of monocytic and myeloblastic cells. Cytochemical characteristics include strongly positive reactions for nonspecific esterase, inhibited by fluoride. The functional characteristics of acute monocytic and acute myelomonocytic cells resemble those of monocytes and include glass adherence and phagocytoses, the presence of Fc receptors for IgG and C'3, and the production of colony stimulating activity. Subacute and chronic myelomonocytic leukemias are insidious and slowly progressive diseases characterized by anemia and peripheral blood monocytosis. Atypical monocytes called paramyeloid cells are characteristic. The drugs used in the treatment of acute monocytic and acute myelomonocytic leukemias include cytosine arabinoside, the anthracyclines, and VP 16-213. Drug therapy in subacute and chronic myelomonocytic leukemias is not usually indicated, although VP 16-213 has been claimed to be effective.

  2. Lactate: link between glycolytic and oxidative metabolism.

    Science.gov (United States)

    Brooks, George A

    2007-01-01

    Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilised continuously under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of cell-cell shuttles include lactate exchanges (i) between white-glycolytic and red-oxidative fibres within a working muscle bed; (ii) between working skeletal muscle and heart; and (iii) between tissues of net lactate release and gluconeogenesis. Lactate shuttles exist in diverse tissues including in the brain, where a shuttle between astrocytes and neurons is linked to glutamatergic signalling. Because lactate, the product of glycogenolysis and glycolysis, is disposed of by oxidative metabolism, lactate shuttling unites the two major processes of cellular energy transduction. Lactate disposal is mainly through oxidation, especially during exercise when oxidation accounts for 70-75% of removal and gluconeogenesis the remainder. Lactate flux occurs down proton and concentration gradients that are established by the mitochondrial lactate oxidation complex. Marathon running is a power activity requiring high glycolytic and oxidative fluxes; such activities require lactate shuttling. Knowledge of the lactate shuttle is yet to be imparted to the sport.

  3. Influence of nutrition on liver oxidative metabolism.

    Science.gov (United States)

    Jorquera, F; Culebras, J M; González-Gallego, J

    1996-06-01

    The liver plays a major role in the disposition of the majority of drugs. This is due to the presence of several drug-metabolizing enzyme systems, including a group of membrane-bound mixed-function oxidative enzymes, mainly the cytochrome P450 system. Hepatic oxidative capacity can be assessed by changes in antipyrine metabolism. Different drugs and other factors may induce or inhibit the cytochrome P450-dependent system. This effect is important in terms of the efficacy or toxicity of drugs that are substrates for the system. Microsomal oxidation in animals fed with protein-deficient diets is depressed. The mixed-function oxidase activity recovers after a hyperproteic diet or the addition of lipids. Similar findings have been reported in patients with protein-calorie malnutrition, although results in the elderly are conflicting. Different studies have revealed that microsomal oxidation is impaired by total parenteral nutrition and that this effect is absent when changing the caloric source from carbohydrates to a conventional amino acid solution or after lipid addition, especially when administered as medium-chain/long-chain triglyceride mixtures. Peripheral parenteral nutrition appears to increase antipyrine clearance.

  4. Effect of intravenous plasma transfusion on granulocyte and monocyte oxidative and phagocytic activity in dairy calves with failure of passive immunity.

    Science.gov (United States)

    Yang, Victoria C; Rayburn, Maire C; Chigerwe, Munashe

    2017-12-01

    Plasma administration has been recommended in calves older than 48h with failure of passive immunity (FPI) to provide immunity consistent with adequate colostral ingestion. However, the protective serum immunoglobulin G (IgG) concentrations (≥1000mg/dL) of plasma derived IgG only lasts up to 12h. In addition to IgG, maternally derived colostral cells also confer immunity. The objective of the study was to determine the effect of intravenous plasma transfusion on granulocyte and monocyte oxidative and phagocytic activity in calves with FPI. Twenty-seven, one day-old, Jersey calves were assigned into 3 groups. The colostral (CL, N=9) group received 3L of colostrum once by oroesophageal tubing. Two other groups of calves received 1L of colostrum once by oroesophageal tubing and were assigned based on their health status (sick or non-sick) at 4days of age, as the sick-group (SG, N=7) or the non-sick (NG, N=11) groups. At 4days of age, the SG and NG groups were administered plasma intravenously at 30mL/kg. Granulocyte and monocyte oxidative and phagocytic activity was determined by flow cytometry. There was no significant difference in the granulocyte and monocyte oxidative or phagocytic activity among the 3 groups (P>0.05). Plasma administration had no significant effect on the oxidative or phagocytic activity of granulocytes or monocytes. In clinical practice, plasma administration for enhancing oxidative or phagocytic activity of granulocytes or monocytes, alone, might not be justified in calves with FPI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Radiation effects on cultured human monocytes and on monocyte-derived macrophages

    International Nuclear Information System (INIS)

    Buescher, E.S.; Gallin, J.I.

    1984-01-01

    Prior to administration, leukocyte transfusions are commonly irradiated with up to 5,000 R to eliminate lymphocytes and thereby prevent graft-versus-host disease in the recipient. It has been widely believed that phagocytes are resistant to this irradiation. In a recent report, it was noted that phagocyte oxidative metabolism was compromised during preparation of white cells for transfusion. As part of the effort to examine the basis for this inhibition of phagocyte function during white cell preparation, an assessment was made of the effects of irradiation on the long-lived monocytes that have been shown to persist at inflammatory foci posttransfusion. Human monocytes were irradiated for up to 3 min, receiving 2,500-5,000 R. This irradiation damaged human monocytes, significantly decreasing their in vitro survival for the first 3 wk of culture, and growth as assessed by two-dimensional cell size measurements during the first 2 wk of culture. Despite smaller cell size, total cell protein was significantly increased over time in irradiated cultures. Extracellular release of lysozyme and beta-glucuronidase per cell was not affected by irradiation, but extracellular lactate dehydrogenase (LDH) release was significantly increased after irradiation. Irradiated monocytes killed Listeria monocytogenes at a slower rate than the nonirradiated controls. Thus, the data indicate that irradiation in doses used to prevent graft-versus-host disease in leukocyte transfusion recipients has a deleterious effect on in vitro human monocyte survival and function

  6. Elevated Atherosclerosis-Related Gene Expression, Monocyte Activation and Microparticle-Release Are Related to Increased Lipoprotein-Associated Oxidative Stress in Familial Hypercholesterolemia

    DEFF Research Database (Denmark)

    Hjuler Nielsen, Morten; Irvine, Helle; Vedel, Simon

    2015-01-01

    OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate the hypoth......OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate...... in subjects with heterozygous familial hypercholesterolemia (FH), in particular in the presence of Achilles tendon xanthomas (ATX). APPROACH AND RESULTS: We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT) and Achilles tendon (AT......LDL-C-CD36 interaction was increased in FH, especially in ATX+ subjects. Monocyte chemokine receptor CX3CR1 was identified as an independent contributor to IMT. CONCLUSIONS: Our data support that lipoprotein-associated oxidative stress is involved in accelerated atherosclerosis in FH, particularly...

  7. Uptake of cerium oxide nanoparticles and its influence on functions of mouse leukemic monocyte macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiangyan; Wang, Bing; Jiang, Pengfei; Chen, Yiqi; Mao, Zhengwei, E-mail: zwmao@zju.edu.cn; Gao, Changyou [Zhejiang University, MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering (China)

    2015-01-15

    Exposure of the CeO{sub 2} nanoparticles (NPs) causes a public concern on their potential health risk due to their wide applications in the fields of fuel additive, commodities, pharmaceutical, and other industries. In this study, the interactions between two commercial CeO{sub 2} NPs (D-CeO{sub 2} from Degussa and PC-CeO{sub 2} from PlasmaChem) and mouse leukemic monocyte macrophage Raw264.7 cells were investigated to provide a fast and in-depth understanding of the biological influences of the NPs. Both types of the CeO{sub 2} NPs had a negative surface charge around −12 mV and showed a tendency to form aggregates with sizes of 191 ± 5.9 and 60.9 ± 2.8 nm in cell culture environment, respectively. The cellular uptake of the CeO{sub 2} NPs increased along with the increase of feeding dosage and prolongation of the culture time. The PC-CeO{sub 2} NPs had a faster uptake rate and reached higher cellular loading amount at the highest feeding concentration (200 µg/mL). In general, both types of the CeO{sub 2} NPs had rather small cytotoxicity even with a dosage as high as 200 µg/mL. The D-CeO{sub 2} NPs showed a relative stronger cytotoxicity especially at higher concentrations and longer incubation time. The NPs were dispersed in vacuoles (most likely endosomes and lysosomes) and cytoplasm. Although both types of the CeO{sub 2} NPs could suppress the production of reactive oxygen species, they impaired the mitochondria membrane potential to some extent. The cytoskeleton organization was altered and consequently the cell adhesion ability decreased after uptake of both types of the CeO{sub 2} NPs.

  8. Effects of Cigarette Smoke Condensate on Oxidative Stress, Apoptotic Cell Death, and HIV Replication in Human Monocytic Cells.

    Directory of Open Access Journals (Sweden)

    Pss Rao

    Full Text Available While cigarette smoking is prevalent amongst HIV-infected patients, the effects of cigarette smoke constituents in cells of myeloid lineage are poorly known. Recently, we have shown that nicotine induces oxidative stress through cytochrome P450 (CYP 2A6-mediated pathway in U937 monocytic cells. The present study was designed to examine the effect of cigarette smoke condensate (CSC, which contains majority of tobacco constituents, on oxidative stress, cytotoxicity, expression of CYP1A1, and/or HIV-1 replication in HIV-infected (U1 and uninfected U937 cells. The effects of CSC on induction of CYP1 enzymes in HIV-infected primary macrophages were also analyzed. The results showed that the CSC-mediated increase in production of reactive oxygen species (ROS in U937 cells is dose- and time-dependent. Moreover, CSC treatment was found to induce cytotoxicity in U937 cells through the apoptotic pathway via activation of caspase-3. Importantly, pretreatment with vitamin C blocked the CSC-mediated production of ROS and induction of caspase-3 activity. In U1 cells, acute treatment of CSC increased ROS production at 6H (>2-fold and both ROS (>2 fold and HIV-1 replication (>3-fold after chronic treatment. The CSC mediated effects were associated with robust induction in the expression of CYP1A1 mRNA upon acute CSC treatment of U937 and U1 cells (>20-fold, and upon chronic CSC treatment to U1 cells (>30-fold. In addition, the CYP1A1 induction in U937 cells was mediated through the aromatic hydrocarbon receptor pathway. Lastly, CSC, which is known to increase viral replication in primary macrophages, was also found to induce CYP1 enzymes in HIV-infected primary macrophages. While mRNA levels of both CYP1A1 and CYP1B1 were elevated following CSC treatment, only CYP1B1 protein levels were increased in HIV-infected primary macrophages. In conclusion, these results suggest a possible association between oxidative stress, CYP1 expression, and viral replication in

  9. Jab1/Csn5-Thioredoxin Signaling in Relapsed Acute Monocytic Leukemia under Oxidative Stress.

    Science.gov (United States)

    Zhou, Fuling; Pan, Yunbao; Wei, Yongchang; Zhang, Ronghua; Bai, Gaigai; Shen, Qiuju; Meng, Shan; Le, Xiao-Feng; Andreeff, Michael; Claret, Francois X

    2017-08-01

    Purpose: High levels of ROS and ineffective antioxidant systems contribute to oxidative stress, which affects the function of hematopoietic cells in acute myeloid leukemia (AML); however, the mechanisms by which ROS lead to malignant transformation in relapsed AML-M5 are not completely understood. We hypothesized that alterations in intracellular ROS would trigger AML-M5 relapse by activating the intrinsic pathway. Experimental Design: We studied ROS levels and conducted c-Jun activation domain-binding protein-1 ( JAB1/COPS5 ) and thioredoxin ( TRX ) gene expression analyses with blood samples obtained from 60 matched AML-M5 patients at diagnosis and relapse and conducted mechanism studies of Jab1's regulation of Trx in leukemia cell lines. Results: Our data showed that increased production of ROS and a low capacity of antioxidant enzymes were characteristics of AML-M5, both at diagnosis and at relapse. Consistently, increased gene expression levels of TRX and JAB1/COPS5 were associated with low overall survival rates in patients with AML-M5. In addition, stimulating AML-M5 cells with low concentrations of hydrogen peroxide led to increased Jab1 and Trx expression. Consistently, transfection of ectopic Jab1 into leukemia cells increased Trx expression, whereas silencing of Jab1 in leukemia cells reduced Trx expression. Mechanistically, Jab1 interacted with Trx and stabilized Trx protein. Moreover, Jab1 transcriptionally regulated Trx. Furthermore, depletion of Jab1 inhibited leukemia cell growth both in vitro and in vivo Conclusions: We identified a novel Jab1-Trx axis that is a key cellular process in the pathobiologic characteristics of AML-M5. Targeting the ROS/Jab1/Trx pathway could be beneficial in the treatment of AML-M5. Clin Cancer Res; 23(15); 4450-61. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. Skeletal muscle capillarization and oxidative metabolism in healthy smokers

    NARCIS (Netherlands)

    Wüst, Rob C. I.; Jaspers, Richard T.; van der Laarse, Willem J.; Degens, Hans

    2008-01-01

    We investigated whether the lower fatigue resistance in smokers than in nonsmokers is caused by a compromised muscle oxidative metabolism. Using calibrated histochemistry, we found no differences in succinate dehydrogenase (SDH) activity, myoglobin concentration, or capillarization in sections of

  11. Changes in adhesion molecule expression and oxidative burst activity of granulocytes and monocytes during open-heart surgery with cardiopulmonary bypass compared with abdominal surgery

    DEFF Research Database (Denmark)

    Toft, P; Nielsen, C H; Tønnesen, Else Kirstine

    1998-01-01

    Cardiac and major abdominal surgery are associated with granulocytosis in peripheral blood. The purpose of the present study was to describe the granulocyte and monocyte oxidative burst and the expression of adhesion molecules following cardiac surgery with cardiopulmonary bypass and abdominal...... during cardiopulmonary bypass was observed. The percentage of CD11a-positive granulocytes increased from 30% pre-operatively to 75% following cardiopulmonary bypass, while CD44-positive granulocytes increased from 5% to 13%. Despite the extent of the changes, these were not significant. The oxidative...... to an increased per-operative oxidative burst activity, and the induction of adhesion molecules on granulocytes associated with the cardiopulmonary bypass and surgery. In conclusion, open-heart surgery with cardiopulmonary bypass was associated with a rapid and pronounced activation of leukocytes which may play...

  12. Estradiol coupling to human monocyte nitric oxide release is dependent on intracellular calcium transients: evidence for an estrogen surface receptor.

    Science.gov (United States)

    Stefano, G B; Prevot, V; Beauvillain, J C; Fimiani, C; Welters, I; Cadet, P; Breton, C; Pestel, J; Salzet, M; Bilfinger, T V

    1999-10-01

    We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase (cNOS) activity in human peripheral monocytes by acting on an estrogen surface receptor. NO release was measured in real time with an amperometric probe. 17beta-estradiol exposure to monocytes stimulated NO release within seconds in a concentration-dependent manner, whereas 17alpha-estradiol had no effect. 17beta-estradiol conjugated to BSA (E2-BSA) also stimulated NO release, suggesting mediation by a membrane surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized the action of both 17beta-estradiol and E2-BSA, whereas ICI 182,780, a selective inhibitor of the nuclear estrogen receptor, had no effect. We further showed, using a dual emission microfluorometry in a calcium-free medium, that the 17beta-estradiol-stimulated release of monocyte NO was dependent on the initial stimulation of intracellular calcium transients in a tamoxifen-sensitive process. Leeching out the intracellular calcium stores abolished the effect of 17beta-estradiol on NO release. RT-PCR analysis of RNA obtained from the cells revealed a strong estrogen receptor-alpha amplification signal and a weak beta signal. Taken together, a physiological dose of estrogen acutely stimulates NO release from human monocytes via the activation of an estrogen surface receptor that is coupled to increases in intracellular calcium.

  13. Electrochemical Oxidation by Square-Wave Potential Pulses in the Imitation of Oxidative Drug Metabolism

    NARCIS (Netherlands)

    Nouri-Nigjeh, Eslam; Permentier, Hjalmar P.; Bischoff, Rainer; Bruins, Andries P.

    2011-01-01

    Electrochemistry combined with mass spectrometry (EC-MS) is an emerging analytical technique in the imitation of oxidative drug metabolism at the early stages of new drug development. Here, we present the benefits of electrochemical oxidation by square-wave potential pulses for the oxidation of

  14. Protective role of klotho protein on epithelial cells upon co-culture with activated or senescent monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Mytych, Jennifer, E-mail: jennifermytych@gmail.com [Institute of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa (Poland); Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa (Poland); Wos, Izabela; Solek, Przemyslaw; Koziorowski, Marek [Institute of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa (Poland); Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa (Poland)

    2017-01-15

    Monocytes ensure proper functioning and maintenance of epithelial cells, while good condition of monocytes is a key factor of these interactions. Although, it was shown that in some circumstances, a population of altered monocytes may appear, there is no data regarding their effect on epithelial cells. In this study, using direct co-culture model with LPS-activated and Dox-induced senescent THP-1 monocytes, we reported for the first time ROS-induced DNA damage, reduced metabolic activity, proliferation inhibition and cell cycle arrest followed by p16-, p21- and p27-mediated DNA damage response pathways activation, premature senescence and apoptosis induction in HeLa cells. Also, we show that klotho protein possessing anti-aging and anti-inflammatory characteristics reduced cytotoxic and genotoxic events by inhibition of insulin/IGF-IR and downregulation of TRF1 and TRF2 proteins. Therefore, klotho protein could be considered as a protective factor against changes caused by altered monocytes in epithelial cells. - Highlights: • Activated and senescent THP-1 monocytes induced cyto- and genotoxicity in HeLa cells. • Altered monocytes provoked oxidative and nitrosative stress-induced DNA damage. • DNA damage activated DDR pathways and lead to premature senescence and apoptosis. • Klotho reduced ROS/RNS-mediated toxicity through insulin/IGF-IR pathway inhibition. • Klotho protects HeLa cells from cyto- and genotoxicity induced by altered monocytes.

  15. Protective role of klotho protein on epithelial cells upon co-culture with activated or senescent monocytes

    International Nuclear Information System (INIS)

    Mytych, Jennifer; Wos, Izabela; Solek, Przemyslaw; Koziorowski, Marek

    2017-01-01

    Monocytes ensure proper functioning and maintenance of epithelial cells, while good condition of monocytes is a key factor of these interactions. Although, it was shown that in some circumstances, a population of altered monocytes may appear, there is no data regarding their effect on epithelial cells. In this study, using direct co-culture model with LPS-activated and Dox-induced senescent THP-1 monocytes, we reported for the first time ROS-induced DNA damage, reduced metabolic activity, proliferation inhibition and cell cycle arrest followed by p16-, p21- and p27-mediated DNA damage response pathways activation, premature senescence and apoptosis induction in HeLa cells. Also, we show that klotho protein possessing anti-aging and anti-inflammatory characteristics reduced cytotoxic and genotoxic events by inhibition of insulin/IGF-IR and downregulation of TRF1 and TRF2 proteins. Therefore, klotho protein could be considered as a protective factor against changes caused by altered monocytes in epithelial cells. - Highlights: • Activated and senescent THP-1 monocytes induced cyto- and genotoxicity in HeLa cells. • Altered monocytes provoked oxidative and nitrosative stress-induced DNA damage. • DNA damage activated DDR pathways and lead to premature senescence and apoptosis. • Klotho reduced ROS/RNS-mediated toxicity through insulin/IGF-IR pathway inhibition. • Klotho protects HeLa cells from cyto- and genotoxicity induced by altered monocytes.

  16. Oxidative status and lipid profile in metabolic syndrome: gender differences.

    Science.gov (United States)

    Kaya, Aysem; Uzunhasan, Isil; Baskurt, Murat; Ozkan, Alev; Ataoglu, Esra; Okcun, Baris; Yigit, Zerrin

    2010-02-01

    Metabolic syndrome is associated with cardiovascular disease and oxidative stress. The aim of this study was to investigate the differences of novel oxidative stress parameters and lipid profiles in men and women with metabolic syndrome. The study population included 88 patients with metabolic syndrome, consisting of 48 postmenauposal women (group I) and 40 men (group II). Premenauposal women were excluded. Plasma levels of total antioxidant status (TAS) and total oxidative status (TOS) were determined by using the Erel automated measurement method, and oxidative stress index (OSI) was calculated. To perform the calculation, the resulting unit of TAS, mmol Trolox equivalent/L, was converted to micromol equivalent/L and the OSI value was calculated as: OSI = [(TOS, micromol/L)/(TAS, mmol Trolox equivalent/L) x 100]. The Student t-test, Mann-Whitney-U test, and chi-squared test were used for statistical analysis; the Pearson correlation coefficient and Spearman rank test were used for correlation analysis. P women and men had similar properties regarding demographic characteristics and biochemical work up. Group II had significantly lower levels of antioxidant levels of TAS and lower levels of TOS and OSI compared with group I (P = 0.0001, P = 0.0035, and P = 0,0001). Apolipoprotein A (ApoA) levels were significantly higher in group I compared with group II. Our findings indicate that women with metabolic syndrome have a better antioxidant status and higher ApoA levels compared with men. Our findings suggest the existence of a higher oxidative stress index in men with metabolic syndrome. Considering the higher risk of atherosclerosis associated with men, these novel oxidative stress parameters may be valuable in the evaluation of patients with metabolic sydrome.

  17. Oxidative Metabolism Genes Are Not Responsive to Oxidative Stress in Rodent Beta Cell Lines

    Directory of Open Access Journals (Sweden)

    Faer Morrison

    2012-01-01

    Full Text Available Altered expression of oxidative metabolism genes has been described in the skeletal muscle of individuals with type 2 diabetes. Pancreatic beta cells contain low levels of antioxidant enzymes and are particularly susceptible to oxidative stress. In this study, we explored the effect of hyperglycemia-induced oxidative stress on a panel of oxidative metabolism genes in a rodent beta cell line. We exposed INS-1 rodent beta cells to low (5.6 mmol/L, ambient (11 mmol/L, and high (28 mmol/L glucose conditions for 48 hours. Increases in oxidative stress were measured using the fluorescent probe dihydrorhodamine 123. We then measured the expression levels of a panel of 90 oxidative metabolism genes by real-time PCR. Elevated reactive oxygen species (ROS production was evident in INS-1 cells after 48 hours (P<0.05. TLDA analysis revealed a significant (P<0.05 upregulation of 16 of the 90 genes under hyperglycemic conditions, although these expression differences did not reflect differences in ROS. We conclude that although altered glycemia may influence the expression of some oxidative metabolism genes, this effect is probably not mediated by increased ROS production. The alterations to the expression of oxidative metabolism genes previously observed in human diabetic skeletal muscle do not appear to be mirrored in rodent pancreatic beta cells.

  18. The Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia.

    Science.gov (United States)

    Sim, Jingwei; Cowburn, Andrew S; Palazon, Asis; Madhu, Basetti; Tyrakis, Petros A; Macías, David; Bargiela, David M; Pietsch, Sandra; Gralla, Michael; Evans, Colin E; Kittipassorn, Thaksaon; Chey, Yu C J; Branco, Cristina M; Rundqvist, Helene; Peet, Daniel J; Johnson, Randall S

    2018-04-03

    Animals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/vHL pathway to accelerate HIF-mediated metabolic responses to hypoxia. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. The effect of increasing body mass index on cardio-metabolic risk and biomarkers of oxidative stress and inflammation in nascent metabolic syndrome.

    Science.gov (United States)

    Pahwa, Roma; Adams-Huet, Beverley; Jialal, Ishwarlal

    2017-05-01

    The effect of BMI defined obesity on cardio-metabolic features and biomarkers of oxidative stress and inflammation in patients with nascent metabolic Syndrome (MetS) is poorly defined. Hence the aim of this study was to examine the effect of increasing obesity on the cardio metabolic risk profile, pro-oxidant state and pro-inflammatory features in nascent MetS patients without Diabetes or CVD. MetS was diagnosed by ATPIII criteria using waist circumference (WC) as the measure of adiposity. Patients (n=58) were stratified into overweight, obese and extreme obesity groups using BMI cut offs of 25-29.9, 30-39.9kg/m 2 and ≥40kg/m 2 and cardio-metabolic features, circulating and cellular biomarkers of oxidative stress and inflammation were determined and correlated with BMI. None of the main cardio-metabolic features including blood pressure, blood glucose, HDL-cholesterol, triglycerides, HOMA-IR, free fatty acids were increased with increasing BMI. Also none of the biomarkers of oxidative stress (ox-LDL, nitrotyrosine and monocyte superoxide anion release) were increased with increasing BMI. However, significant increase in hsCRP, the soluble TNFR1 and sTNFR2 and leptin, were observed with increasing adiposity. Other inflammatory bio-mediators (IL-1β, IL-6, IL-8, MCP-1, Toll-like receptors 2-4), endotoxin, LBP, sCD14 and HMGB1, adiponectin, and chemerin did not show significant increases with increasing BMI. Leptin, hsCRP, sTNFR1, and sTNFR2 correlated significantly with BMI. In conclusion, capturing the cardio-metabolic cluster of MetS that predisposed to both increased risk of diabetes and CVD, using waist circumference, as one of the 5 diagnostic criteria is sufficient and BMI does not appear to afford any major incremental benefit on the cardio-metabolic risk factors, increased oxidative stress and the majority of both cellular and circulating biomarkers of inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Monocyte chemotactic protein-1, RANTES and macrophage migration inhibitory factor levels in gingival crevicular fluid of metabolic syndrome patients with gingivitis.

    Science.gov (United States)

    Gürkan, Ali; Eren, Gülnihal; Çetinkalp, Şevki; Akçay, Yasemin Delen; Emingil, Gülnur; Atilla, Gül

    2016-09-01

    The aim of the present study was to determine gingival crevicular fluid (GCF) levels of monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted protein (RANTES) and macrophage migration inhibitory factor (MIF) in metabolic syndrome patients with gingivitis. Twenty metabolic syndrome patients with gingivitis (MSG), 20 MetS patients with clinically healthy periodontium (MSH), 20 systemically healthy subjects with gingivitis and 20 subjects who were both systemically and periodontally healthy were included. Periodontal and systemical parameters were recorded. GCF MCP-1, RANTES and MIF levels were assayed by enzyme-linked immunosorbent assay method. MSG and MSH groups had elevated blood pressure, triglyceride, waist circumference and fasting glucose values in comparison to gingivitis and healthy groups (Pgingivitis groups when compared to those of the MSH and healthy groups (Pgingivitis group had higher MCP-1, RANTES and MIF levels compared to the healthy group (P=0.011, P=0.0001, P=0.011 respectively). The RANTES level of MSG group was significantly higher than those of the gingivitis group (P=0.01), but MCP-1 and MIF levels were similar in the MSG and gingivitis groups (P>0.05). Elevated levels of GCF RANTES in MetS patients with gingivitis might associate with the presence of increased gingival inflammation by MetS. Low-grade systemic inflammation associated with MetS and adipose tissue-derived RANTES might lead to altered GCF RANTES levels in the presence of gingival inflammation. Copyright © 2016. Published by Elsevier Ltd.

  1. Sugar alcohols-induced oxidative metabolism in cotton callus culture

    African Journals Online (AJOL)

    Sugar alcohols (mannitol and sorbitol) may cause oxidative damage in plants if used in higher concentration. Our present experiment was undertaken to study physiological and metabolic responses in cotton (Gossypium hirsutum L.) callus against mannitol and sorbitol higher doses. Both markedly declined mean values of ...

  2. Malarial pigment haemozoin, IFN-gamma, TNF-alpha, IL-1beta and LPS do not stimulate expression of inducible nitric oxide synthase and production of nitric oxide in immuno-purified human monocytes

    Directory of Open Access Journals (Sweden)

    Ceretto Monica

    2007-06-01

    Full Text Available Abstract Background Enhanced production of nitric oxide (NO following upmodulation of the inducible isoform of NO synthase (iNOS by haemozoin (HZ, inflammatory cytokines and LPS may provide protection against Plasmodium falciparum malaria by killing hepatic and blood forms of parasites and inhibiting the cytoadherence of parasitized erythrocytes (RBC to endothelial cells. Monocytes and macrophages are considered to contribute importantly to protective upregulation of iNOS and production of NO. Data obtained with murine phagocytes fed with human HZ and synthetic HZ (sHZ indicate that supplemental treatment of those cells with IFN-gamma elicited significant increases in protein and mRNA expression of iNOS and NO production, providing a potential mechanism linking HZ phagocytosis and increased production of NO. Purpose of this study was to analyse the effect of P. falciparum HZ and sHZ supplemental to treatment with IFN-gamma and/or a stimulatory cytokine-LPS mix on iNOS protein and mRNA expression in immuno-purified human monocytes. Methods Adherent immunopurified human monocytes (purity >85%, and murine phagocytic cell lines RAW 264.7, N11 and ANA1 were fed or not with P. falciparum HZ or sHZ and treated or not with IFN-gamma or a stimulatory cytokine-LPS mix. Production of NO was quantified in supernatants, iNOS protein and mRNA expression were measured after immunoprecipitation and Western blotting and quantitative RT-PCT, respectively. Results Phagocytosis of HZ/sHZ by human monocytes did not increase iNOS protein and mRNA expression and NO production either after stimulation by IFN-gamma or the cytokine-LPS mix. By contrast, in HZ/sHZ-laden murine macrophages, identical treatment with IFN-gamma and the cytokine-LPS mix elicited significant increases in protein and mRNA expression of iNOS and NOS metabolites production, in agreement with literature data. Conclusion Results indicate that human monocytes fed or not with HZ/sHZ were constantly

  3. Real-time cytometric assay of nitric oxide and superoxide interaction in peripheral blood monocytes: A no-wash, no-lyse kinetic method.

    Science.gov (United States)

    Balaguer, Susana; Diaz, Laura; Gomes, Angela; Herrera, Guadalupe; O'Connor, José-Enrique; Urios, Amparo; Felipo, Vicente; Montoliu, Carmina

    2017-05-01

    Nitric oxide (NO) and its related reactive nitrogen species (RNS) and reactive oxygen species (ROS) are crucial in monocyte responses against pathogens and also in inflammatory conditions. Central to both processes is the generation of the strong oxidant peroxynitrite (ONOO) by a fast reaction between NO and superoxide anion. ONOO is a biochemical junction for ROS- and RNS cytotoxicity and causes protein nitrosylation. Circulating by-products of protein nitrosylation are early biomarkers of inflammation-based conditions, including minimal hepatic encephalopathy in cirrhotic patients (Montoliu et al., Am J Gastroenterol 2011; 106:1629-1637). In this context, we have designed a novel no-wash, no-lyse real-time flow cytometry assay to detect and follow-up the NO- and superoxide-driven generation of ONOO in peripheral blood monocytes. Whole blood samples were stained with CD45 and CD14 antibodies plus one of a series of fluorescent probes sensitive to RNS, ROS, or glutathione, namely 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, dihydrorhodamine 123, MitoSOX Red, dihydroethidium, and 5-chloromethylfluorescein diacetate. Samples were exposed sequentially to a NO donor and three different superoxide donors, and analyzed in real time by kinetic flow cytometry. Relevant kinetic descriptors, such as the rate of fluorescence change, were calculated from the kinetic plot. The generation of ONOO, which consumes both NO and superoxide, led to a decrease in the intensity of the cellular fluorescence of the probes sensitive to these molecules. This is a fast and simple assay that may be used to monitor the intracellular generation of ONOO in physiological, pathological, and pharmacological contexts. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.

  4. Oxidative Stress and the Homeodynamics of Iron Metabolism

    Science.gov (United States)

    Bresgen, Nikolaus; Eckl, Peter M.

    2015-01-01

    Iron and oxygen share a delicate partnership since both are indispensable for survival, but if the partnership becomes inadequate, this may rapidly terminate life. Virtually all cell components are directly or indirectly affected by cellular iron metabolism, which represents a complex, redox-based machinery that is controlled by, and essential to, metabolic requirements. Under conditions of increased oxidative stress—i.e., enhanced formation of reactive oxygen species (ROS)—however, this machinery may turn into a potential threat, the continued requirement for iron promoting adverse reactions such as the iron/H2O2-based formation of hydroxyl radicals, which exacerbate the initial pro-oxidant condition. This review will discuss the multifaceted homeodynamics of cellular iron management under normal conditions as well as in the context of oxidative stress. PMID:25970586

  5. Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy

    DEFF Research Database (Denmark)

    Iversen, Peter; Mouridsen, Kim; Hansen, Mikkel B

    2014-01-01

    In patients with impaired liver function and hepatic encephalopathy (HE), consistent elevations of blood ammonia concentration suggest a crucial role in the pathogenesis of HE. Ammonia and acetate are metabolized in brain both primarily in astrocytes. Here, we used dynamic [(11)C]acetate PET...... of the brain to measure the contribution of astrocytes to the previously observed reduction of brain oxidative metabolism in patients with liver cirrhosis and HE, compared to patients with cirrhosis without HE, and to healthy subjects. We used a new kinetic model to estimate uptake from blood to astrocytes...

  6. Energy Metabolism during Anaerobic Methane Oxidation in ANME Archaea

    Science.gov (United States)

    McGlynn, Shawn E.

    2017-01-01

    Anaerobic methane oxidation in archaea is often presented to operate via a pathway of “reverse methanogenesis”. However, if the cumulative reactions of a methanogen are run in reverse there is no apparent way to conserve energy. Recent findings suggest that chemiosmotic coupling enzymes known from their use in methylotrophic and acetoclastic methanogens—in addition to unique terminal reductases—biochemically facilitate energy conservation during complete CH4 oxidation to CO2. The apparent enzyme modularity of these organisms highlights how microbes can arrange their energy metabolisms to accommodate diverse chemical potentials in various ecological niches, even in the extreme case of utilizing “reverse” thermodynamic potentials. PMID:28321009

  7. Fat oxidation at rest predicts peak fat oxidation during exercise and metabolic phenotype in overweight men

    DEFF Research Database (Denmark)

    Rosenkilde, M; Nordby, P; Nielsen, L B

    2010-01-01

    OBJECTIVE: To elucidate if fat oxidation at rest predicts peak fat oxidation during exercise and/or metabolic phenotype in moderately overweight, sedentary men. DESIGN: Cross-sectional study.Subjects:We measured respiratory exchange ratio (RER) at rest in 44 moderately overweight, normotensive...... the International Diabetes Federation criteria, we found that there was a lower accumulation of metabolic risk factors in L-RER than in H-RER (1.6 vs 3.5, P=0.028), and no subjects in L-RER and four of eight subjects in H-RER had the metabolic syndrome. Resting RER was positively correlated with plasma...... triglycerides (Pexercise was positively correlated with plasma free fatty acid concentration at rest (Pexercise and a healthy metabolic...

  8. Coordinated balancing of muscle oxidative metabolism through PGC-1{alpha} increases metabolic flexibility and preserves insulin sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Summermatter, Serge [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland); Troxler, Heinz [Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University Children' s Hospital, University of Zurich, Steinwiesstrasse 75, CH-8032 Zurich (Switzerland); Santos, Gesa [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland); Handschin, Christoph, E-mail: christoph.handschin@unibas.ch [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland)

    2011-04-29

    Highlights: {yields} PGC-1{alpha} enhances muscle oxidative capacity. {yields} PGC-1{alpha} promotes concomitantly positive and negative regulators of lipid oxidation. {yields} Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. {yields} Balanced oxidation prevents detrimental acylcarnitine and ROS generation. {yields} Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor {gamma} coactivator 1{alpha} (PGC-1{alpha}) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1{alpha} on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1{alpha} in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1{alpha} induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1{alpha} enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1{alpha} boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1{alpha} coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1{alpha} does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1{alpha} mimic the beneficial effects of endurance training

  9. Coordinated balancing of muscle oxidative metabolism through PGC-1α increases metabolic flexibility and preserves insulin sensitivity

    International Nuclear Information System (INIS)

    Summermatter, Serge; Troxler, Heinz; Santos, Gesa; Handschin, Christoph

    2011-01-01

    Highlights: → PGC-1α enhances muscle oxidative capacity. → PGC-1α promotes concomitantly positive and negative regulators of lipid oxidation. → Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. → Balanced oxidation prevents detrimental acylcarnitine and ROS generation. → Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1α on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1α in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1α induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1α enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1α boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1α coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1α does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1α mimic the beneficial effects of endurance training on muscle metabolism in this context.

  10. Monoterpenol Oxidative Metabolism: Role in Plant Adaptation and Potential Applications

    Science.gov (United States)

    Ilc, Tina; Parage, Claire; Boachon, Benoît; Navrot, Nicolas; Werck-Reichhart, Danièle

    2016-01-01

    Plants use monoterpenols as precursors for the production of functionally and structurally diverse molecules, which are key players in interactions with other organisms such as pollinators, flower visitors, herbivores, fungal, or microbial pathogens. For humans, many of these monoterpenol derivatives are economically important because of their pharmaceutical, nutraceutical, flavor, or fragrance applications. The biosynthesis of these derivatives is to a large extent catalyzed by enzymes from the cytochrome P450 superfamily. Here we review the knowledge on monoterpenol oxidative metabolism in plants with special focus on recent elucidations of oxidation steps leading to diverse linalool and geraniol derivatives. We evaluate the common features between oxidation pathways of these two monoterpenols, such as involvement of the CYP76 family, and highlight the differences. Finally, we discuss the missing steps and other open questions in the biosynthesis of oxygenated monoterpenol derivatives. PMID:27200002

  11. Palmitate and insulin synergistically induce IL-6 expression in human monocytes

    Directory of Open Access Journals (Sweden)

    Lumpkin Charles K

    2010-11-01

    Full Text Available Abstract Background Insulin resistance is associated with a proinflammatory state that promotes the development of complications such as type 2 diabetes mellitus (T2DM and atherosclerosis. The metabolic stimuli that initiate and propagate proinflammatory cytokine production and the cellular origin of proinflammatory cytokines in insulin resistance have not been fully elucidated. Circulating proinflammatory monocytes show signs of enhanced inflammation in obese, insulin resistant subjects and are thus a potential source of proinflammatory cytokine production. The specific, circulating metabolic factors that might stimulate monocyte inflammation in insulin resistant subjects are poorly characterized. We have examined whether saturated nonesterified fatty acids (NEFA and insulin, which increase in concentration with developing insulin resistance, can trigger the production of interleukin (IL-6 and tumor necrosis factor (TNF-α in human monocytes. Methods Messenger RNA and protein levels of the proinflammatory cytokines IL-6 and TNF-α were measured by quantitative real-time PCR (qRT-PCR and Luminex bioassays. Student's t-test was used with a significance level of p Results Esterification of palmitate with coenzyme A (CoA was necessary, while β-oxidation and ceramide biosynthesis were not required, for the induction of IL-6 and TNF-α in THP-1 monocytes. Monocytes incubated with insulin and palmitate together produced more IL-6 mRNA and protein, and more TNF-α protein, compared to monocytes incubated with palmitate alone. Incubation of monocytes with insulin alone did not affect the production of IL-6 or TNF-α. Both PI3K-Akt and MEK/ERK signalling pathways are important for cytokine induction by palmitate. MEK/ERK signalling is necessary for synergistic induction of IL-6 by palmitate and insulin. Conclusions High levels of saturated NEFA, such as palmitate, when combined with hyperinsulinemia, may activate human monocytes to produce

  12. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

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    K. Jayasri

    2016-12-01

    Full Text Available Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS, glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175% was found to be increased, whereas glucose-6-phosphatase (33%, fructose-1, 6-bisphosphatase (42%, and G6PD (5 fold activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors.

  13. Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism

    Science.gov (United States)

    Price, Alex; Pearson, Victoria K.; Schwenzer, Susanne P.; Miot, Jennyfer; Olsson-Francis, Karen

    2018-01-01

    This work considers the hypothetical viability of microbial nitrate-dependent Fe2+ oxidation (NDFO) for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1–3.7 Ga) match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with appropriate

  14. Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism

    Directory of Open Access Journals (Sweden)

    Alex Price

    2018-03-01

    Full Text Available This work considers the hypothetical viability of microbial nitrate-dependent Fe2+ oxidation (NDFO for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1–3.7 Ga match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with

  15. Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism.

    Science.gov (United States)

    Price, Alex; Pearson, Victoria K; Schwenzer, Susanne P; Miot, Jennyfer; Olsson-Francis, Karen

    2018-01-01

    This work considers the hypothetical viability of microbial nitrate-dependent Fe 2+ oxidation (NDFO) for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe 2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe 2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1-3.7 Ga) match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe 2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with appropriate

  16. Metabolic oxidative stress in cancer biology and therapy

    International Nuclear Information System (INIS)

    Spitz, Douglas R.

    2014-01-01

    Cancer cells (relative to normal cells) exhibit increased glycolysis and pentose cycle activity. These metabolic alterations were thought to arise from damage to the respiratory mechanism and cancer cells were thought to compensate for this defect by increasing glycolysis (Science 132:309). In addition to its role in ATP production, glucose metabolism results in the formation of pyruvate and NADPH which both play an integral role in peroxide detoxification (Ann. NY Acad. Sci. 899:349). Recently, cancer cells have been shown to have enhanced susceptibility to glucose deprivation-induced oxidative stress, relative to normal cells, that is mediated by reactive oxygen species (ROS; Biochem.J. 418:29-37). These results support the hypothesis that cancer cells may have a defect in mitochondrial respiration leading to increased steady-state levels of ROS (i.e., O 2 and H 2 O 2 ) and glucose metabolism may be increased to provide reducing equivalents to compensate for this defect. The application of these findings to developing new combined modality cancer therapy protocols will be discussed. (author)

  17. State of dog's metabolism in the remote period after the oxide tritium influence

    International Nuclear Information System (INIS)

    Kalistratova, V.S.; Tishchenko, G.S.; Bortnik, L.A.; Nisimov, P.G.; Romanova, I.B.

    2000-01-01

    Influence of tritium oxide on the metabolism by some indices of lipid metabolism (common lipids, β-lipoproteins, cholesterin), protein metabolism (cholinesterase) and carbohydrate metabolism (blood sugar) was studied. It was established that the introduction into organism of tritium oxide in the quantities, which could form lethal and sublethal doses of internal radiation, provoked the main changes of values of mentioned indices of metabolism. The character of metabolism changes in the remote period allows to judge about the development of sclerosis processes which can be the result of radiation-stipulated acceleration of organism aging [ru

  18. Relationships between inflammation, adiponectin, and oxidative stress in metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Shu-Ju Chen

    Full Text Available Metabolic syndrome (MS represents a cluster of physiological and anthropometric abnormalities. The purpose of this study was to investigate the relationships between the levels of inflammation, adiponectin, and oxidative stress in subjects with MS. The inclusion criteria for MS, according to the Taiwan Bureau of Health Promotion, Department of Health, were applied to the case group (n = 72. The control group (n = 105 comprised healthy individuals with normal blood biochemical values. The levels of inflammatory markers [high sensitivity C-reactive protein (hs-CRP and interleukin-6 (IL-6, adiponectin, an oxidative stress marker (malondialdehyde, and antioxidant enzymes activities [catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GPx] were measured. Subjects with MS had significantly higher concentrations of inflammatory markers and lower adiponectin level, and lower antioxidant enzymes activities than the control subjects. The levels of inflammatory markers and adiponectin were significantly correlated with the components of MS. The level of hs-CRP was significantly correlated with the oxidative stress marker. The IL-6 level was significantly correlated with the SOD and GPx activities, and the adiponectin level was significantly correlated with the GPx activity. A higher level of hs-CRP (≥1.00 mg/L, or IL-6 (≥1.50 pg/mL or a lower level of adiponectin (<7.90 µg/mL were associated with a significantly greater risk of MS. In conclusion, subjects suffering from MS may have a higher inflammation status and a higher level of oxidative stress. A higher inflammation status was significantly correlated with decreases in the levels of antioxidant enzymes and adiponectin and an increase in the risk of MS.

  19. Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Vemuri, Goutham; Eiteman, M.A; McEwen, J.E

    2007-01-01

    effect is due to limited respiratory capacity or is caused by glucose-mediated repression of respiration. When respiration in S. cerevisiae was increased by introducing a heterologous alternative oxidase, we observed reduced aerobic ethanol formation. In contrast, increasing nonrespiratory NADH oxidation...... Crabtree effect.’’ The yeast Saccharomyces cerevisiae has served as an important model organism for studying the Crabtree effect. When subjected to increasing glycolytic fluxes under aerobic conditions, there is a threshold value of the glucose uptake rate at which the metabolism shifts from purely...... respiratory to mixed respiratory and fermentative. It is well known that glucose repression of respiratory pathways occurs at high glycolytic fluxes, resulting in a decrease in respiratory capacity. Despite many years of detailed studies on this subject, it is not known whether the onset of the Crabtree...

  20. Assessment of oxidative metabolism in Brown Fat using PET imaging

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    Otto eMuzik

    2012-02-01

    Full Text Available Objective: Although it has been believed that brown adipose tissue (BAT depots disappear shortly after the perinatal period in humans, PET imaging using the glucose analog FDG has shown unequivocally the existence of functional BAT in humans. The objective of this study was to determine, using dynamic oxygen-15 (15O PET imaging, to what extent BAT thermogenesis is activated in adults during cold stress and to establish the relationship between BAT oxidative metabolism and FDG tracer uptake.Methods: Fourteen adult normal subjects (9F/5M, 30+7 years underwent triple oxygen scans (H215O, C15O, 15O2 as well as indirect calorimetric measurements at rest and following exposure to mild cold (60F. Subjects were divided into two groups (BAT+ and BAT- based on the presence or absence of FDG tracer uptake (SUV > 2 in supraclavicular BAT. Blood flow (BF and oxygen extraction fraction (OEF was calculated from dynamic PET scans at the location of BAT, muscle and white adipose tissue (WAT. The metabolic rate of oxygen (MRO2 in BAT was determined and used to calculate the contribution of activated BAT to daily energy expenditure (DEE.Results: The median mass of activated BAT in the BAT+ group (5F, 31+8yrs was 52.4 g (14-68g and was 1.7 g (0-6.3g in the BAT- group (5M/4F, 29+6yrs. SUV values were significantly higher in the BAT+ as compared to the BAT- group (7.4+3.7 vs 1.9+0.9; p=0.03. BF values in BAT were significantly higher in the BAT+ as compared to the BAT- group (13.1+4.4 vs 5.7+1.1 ml/100g/min, p=0.03, but were similar in WAT (4.1+1.6 vs 4.2+1.8 ml/100g/min and muscle (3.7+0.8 vs 3.3+1.2 ml/100g/min. Calculated MRO2 values in BAT increased from 0.95+0.74 to 1.62+0.82 ml/100g/min in the BAT+ group and were significantly higher than those determined in the BAT- group (0.43+0.27 vs 0.56+0.24; p=0.67. The DEE associated with BAT oxidative metabolism was highly variable in the BAT+ group, with an average of 5.5+6.4 kcal/day (range 0.57–15.3 kcal/day.

  1. Biochemical and ultrastructural analysis of β-VLDL and AC-LDL metabolism by pigeon monocyte-derived macrophages in culture

    International Nuclear Information System (INIS)

    Henson, D.A.

    1987-01-01

    It is proposed that monocyte-derived foam cells in atherosclerotic lesions of White Carneau pigeons become lipid-filled through the uptake of lipoproteins including β-migrating very low density lipoproteins (β-VLDL) and acetylated low density lipoproteins (Ac-LDL). Using iodinated forms of the above lipoproteins, specific and saturable receptors for both β-VLDL and Ac-LDL were detected on the surface of White Carneau pigeon monocyte-derived macrophages in culture. Competition studies demonstrated the high degree of binding specificity for 125 I-Ac-LDL. Likewise, binding of 125 I-β-VLDL to its receptor was significantly inhibited by excess β-VLDL, however LDL from both hyper- and normocholesterolemic pigeons were also recognized by the receptor. Upon binding of β-VLDL and Ac-LDL to their respective receptors, the lipoproteins were rapidly internalized and delivered to intracellular sites of degradation. As measured by the amount of 14 C-oleate incorporated into cholesteryl 14 C-oleate, the cholesterole liberated from the degradation of both β-VLDL and Ac-LDL stimulated cholesteryl ester synthesis in the pigeon cells. Using lipoproteins conjugated to colloidal gold of visualization with transmission electron microscopy, a major difference in the binding and uptake properties of β-VLDL-Gold and Ac-LDL-Gold was documented

  2. Expression of adhesion molecules, monocyte interactions and oxidative stress in human endothelial cells exposed to wood smoke and diesel exhaust particulate matter

    DEFF Research Database (Denmark)

    Forchhammer, Lykke; Loft, Steffen; Roursgaard, Martin

    2012-01-01

    Toxicological effects of wood smoke particles are less investigated than traffic-related combustion particles. We investigated the effect of wood smoke particles, generated by smouldering combustion conditions, on human umbilical endothelial cells (HUVECs) co-cultured with or without monocytic TH...

  3. Effects of Graphene Oxide and Oxidized Carbon Nanotubes on the Cellular Division, Microstructure, Uptake, Oxidative Stress, and Metabolic Profiles.

    Science.gov (United States)

    Hu, Xiangang; Ouyang, Shaohu; Mu, Li; An, Jing; Zhou, Qixing

    2015-09-15

    Nanomaterial oxides are common formations of nanomaterials in the natural environment. Herein, the nanotoxicology of typical graphene oxide (GO) and carboxyl single-walled carbon nanotubes (C-SWCNT) was compared. The results showed that cell division of Chlorella vulgaris was promoted at 24 h and then inhibited at 96 h after nanomaterial exposure. At 96 h, GO and C-SWCNT inhibited the rates of cell division by 0.08-15% and 0.8-28.3%, respectively. Both GO and C-SWCNT covered the cell surface, but the uptake percentage of C-SWCNT was 2-fold higher than that of GO. C-SWCNT induced stronger plasmolysis and mitochondrial membrane potential loss and decreased the cell viability to a greater extent than GO. Moreover, C-SWCNT-exposed cells exhibited more starch grains and lysosome formation and higher reactive oxygen species (ROS) levels than GO-exposed cells. Metabolomics analysis revealed significant differences in the metabolic profiles among the control, C-SWCNT and GO groups. The metabolisms of alkanes, lysine, octadecadienoic acid and valine was associated with ROS and could be considered as new biomarkers of ROS. The nanotoxicological mechanisms involved the inhibition of fatty acid, amino acid and small molecule acid metabolisms. These findings provide new insights into the effects of GO and C-SWCNT on cellular responses.

  4. Role of nitric oxide in cellular iron metabolism.

    Science.gov (United States)

    Kim, Sangwon; Ponka, Prem

    2003-03-01

    Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) which are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO*, a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO+ (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO+-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

  5. Quantitative combination of natural anti-oxidants prevents metabolic syndrome by reducing oxidative stress.

    Science.gov (United States)

    Gao, Mingjing; Zhao, Zhen; Lv, Pengyu; Li, YuFang; Gao, Juntao; Zhang, Michael; Zhao, Baolu

    2015-12-01

    Insulin resistance and abdominal obesity are present in the majority of people with the metabolic syndrome. Antioxidant therapy might be a useful strategy for type 2 diabetes and other insulin-resistant states. The combination of vitamin C (Vc) and vitamin E has synthetic scavenging effect on free radicals and inhibition effect on lipid peroxidation. However, there are few studies about how to define the best combination of more than three anti-oxidants as it is difficult or impossible to test the anti-oxidant effect of the combination of every concentration of each ingredient experimentally. Here we present a math model, which is based on the classical Hill equation to determine the best combination, called Fixed Dose Combination (FDC), of several natural anti-oxidants, including Vc, green tea polyphenols (GTP) and grape seed extract proanthocyanidin (GSEP). Then we investigated the effects of FDC on oxidative stress, blood glucose and serum lipid levels in cultured 3T3-L1 adipocytes, high fat diet (HFD)-fed rats which serve as obesity model, and KK-ay mice as diabetic model. The level of serum malondialdehyde (MDA) in the treated rats was studied and Hematoxylin-Eosin (HE) staining or Oil red slices of liver and adipose tissue in the rats were examined as well. FDC shows excellent antioxidant and anti-glycation activity by attenuating lipid peroxidation. FDC determined in this investigation can become a potential solution to reduce obesity, to improve insulin sensitivity and be beneficial for the treatment of fat and diabetic patients. It is the first time to use the math model to determine the best ratio of three anti-oxidants, which can save much more time and chemical materials than traditional experimental method. This quantitative method represents a potentially new and useful strategy to screen all possible combinations of many natural anti-oxidants, therefore may help develop novel therapeutics with the potential to ameliorate the worldwide metabolic

  6. In vivo imaging of monocyte trafficking with 18F-fluorodeoxyglucose labeled monocytes

    International Nuclear Information System (INIS)

    Paik, Jin Young; Lee, Kyung Han; Han, Yu Mi; Choe, Yearn Seong; Kim, Byung Tae

    2000-01-01

    Since the ability to monitor in vivo monocyte trafficking would contribute to our understanding of the pathophysiology of various inflammatory disorders, we investigated the feasibility of labeling human monocytes with 18 F-FDG. Human monocytes were separated by Ficoll/Hypaque gradient and purity was assessed by flow cytometry. The influence of insulin and/or glucose on labeling efficiency was evaluated. Cell viability and activation was measured with trypan blue exclusion and hydrogen peroxide assays, respectively. Label stability was measured for up to 18 hr, and the effect of insulin pre-incubation on FDG washout was investigated. PET images were acquired in SD rats at various time points after injection of FDG labeled monocytes. Monocytes were >85% pure, and labeling efficiency was 35% for 1x106 cells after 40 min incubation with 2 mCi 18 F-FDG without insulin. Pre-incubation with 10∼100 nM insulin significantly increased FDG uptake which reached 400% of baseline levels, whereas presence of glucose or serum decreased FDG uptake. Labeled cells were >90% viable for up to 22 hr, and the labeling process did appear to significantly activate cells, Washout studies however, demonstrated gradual washout of the FDG from monocytes after initial uptake PET images of FDG labeled monocytes in SD rats showed consistent findings. Utilizing insulin effects on cellular glucose metabolism may be a feasible way of labeling monocytes with 18 F-FDG for PET imaging. However, gradual washout of FDG after initial uptake poses as a potential problem which needs to be addressed before practical application

  7. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for molecules associated with metabolism, signaling and regulation in central nervous system mixed glial cell cultures

    Directory of Open Access Journals (Sweden)

    Studzinski Diane

    2009-01-01

    Full Text Available Abstract Background Cytokines secreted by immune cells and activated glia play central roles in both the pathogenesis of and protection from damage to the central nervous system (CNS in multiple sclerosis (MS. Methods We have used gene array analysis to identify the initial direct effects of cytokines on CNS glia by comparing changes in early gene expression in CNS glial cultures treated for 6 hours with cytokines typical of those secreted by Th1 and Th2 lymphocytes and monocyte/macrophages (M/M. Results In two previous papers, we summarized effects of these cytokines on immune-related molecules, and on neural and glial related proteins, including neurotrophins, growth factors and structural proteins. In this paper, we present the effects of the cytokines on molecules involved in metabolism, signaling and regulatory mechanisms in CNS glia. Many of the changes in gene expression were similar to those seen in ischemic preconditioning and in early inflammatory lesions in experimental autoimmune encephalomyelitis (EAE, related to ion homeostasis, mitochondrial function, neurotransmission, vitamin D metabolism and a variety of transcription factors and signaling pathways. Among the most prominent changes, all three cytokine mixtures markedly downregulated the dopamine D3 receptor, while Th1 and Th2 cytokines downregulated neuropeptide Y receptor 5. An unexpected finding was the large number of changes related to lipid metabolism, including several suggesting a switch from diacylglycerol to phosphatidyl inositol mediated signaling pathways. Using QRT-PCR we validated the results for regulation of genes for iNOS, arginase and P glycoprotein/multi-drug resistance protein 1 (MDR1 seen at 6 hours with microarray. Conclusion Each of the three cytokine mixtures differentially regulated gene expression related to metabolism and signaling that may play roles in the pathogenesis of MS, most notably with regard to mitochondrial function and neurotransmitter

  8. Matrix metalloproteinase-2 and -9 are induced differently by metal nanoparticles in human monocytes: The role of oxidative stress and protein tyrosine kinase activation

    International Nuclear Information System (INIS)

    Wan Rong; Mo Yiqun; Zhang Xing; Chien Sufan; Tollerud, David J.; Zhang Qunwei

    2008-01-01

    Recently, many studies have shown that nanoparticles can translocate from the lungs to the circulatory system. As a particulate foreign body, nanoparticles could induce host responses such as reactive oxygen species (ROS) generation, inflammatory cytokine and matrix metalloproteinase (MMP) release which play a major role in tissue destruction and remodeling. However, the direct effects of nanoparticles on leukocytes, especially monocytes, are still unclear. The objective of the present study was to compare the ability of Nano-Co and Nano-TiO 2 to cause alteration of transcription and activity of MMPs and to explore possible mechanisms. We hypothesized that non-toxic doses of some transition metal nanoparticles stimulate an imbalance of MMP/TIMP that cause MMP production that may contribute to their health effects. To test this hypothesis, U937 cells were treated with Nano-Co and Nano-TiO 2 and cytotoxic effects and ROS generation were measured. The alteration of MMP-2 and MMP-9 expression and activity of MMP-2 and MMP-9 after exposure to these metal nanoparticles were subsequently determined. To investigate the potential signaling pathways involved in the Nano-Co-induced MMP activation, the ROS scavengers or inhibitors, AP-1 inhibitor, and protein tyrosine kinase (PTK) inhibitors were also used to pre-treat U937 cells. Our results demonstrated that exposure of U937 cells to Nano-Co, but not to Nano-TiO 2 , at a dose that does not cause cytotoxicity, resulted in ROS generation and up-regulation of MMP-2 and MMP-9 mRNA expression .. Our results also showed dose- and time-related increases in pro-MMP-2 and pro-MMP-9 gelatinolytic activities in conditioned media after exposure of U937 cells to Nano-Co, but not to Nano-TiO 2 . Nano-Co-induced pro-MMP-2 and pro-MMP-9 activity increases were inhibited by pre-treatment with ROS scavengers or inhibitors. We also demonstrated dose- and time-related decreases in tissue inhibitors of metalloproteinases 2 (TIMP-2) in U937 cells

  9. Microbiological Diversity Demonstrates the Potential which Collaboratively Metabolize Nitrogen Oxides ( NOx) under Smog Environmental Stress

    Science.gov (United States)

    Chen, X. Z.; Zhao, X. H.; Chen, X. P.

    2018-03-01

    Recently, smoggy weather has become a daily in large part of China because of rapidly economic growth and accelerative urbanization. Stressed on the smoggy situation and economic growth, the green and environment-friendly technology is necessary to reduce or eliminate the smog and promote the sustainable development of economy. Previous studies had confirmed that nitrogen oxides ( NOx ) is one of crucial factors which forms smog. Microorganisms have the advantages of quickly growth and reproduction and metabolic diversity which can collaboratively Metabolize various NOx. This study will design a kind of bacteria & algae cultivation system which can metabolize collaboratively nitrogen oxides in air and intervene in the local nitrogen cycle. Furthermore, the nitrogen oxides can be transformed into nitrogen gas or assembled in protein in microorganism cell by regulating the microorganism types and quantities and metabolic pathways in the system. Finally, the smog will be alleviated or eliminated because of reduction of nitrogen oxides emission. This study will produce the green developmental methodology.

  10. Increased oxidative stress and its relation with collagen metabolism in knee osteoarthritis.

    Science.gov (United States)

    Altindag, Ozlem; Erel, Ozcan; Aksoy, Nurten; Selek, Sahabettin; Celik, Hakim; Karaoglanoglu, Mustafa

    2007-02-01

    The purpose of this study was to determine serum oxidative/antioxidative status in patients with knee osteoarthritis and its relation with prolidase activity, which plays an important role in collagen metabolism. Serum antioxidative status was evaluated by measuring total antioxidant capacity (TAC), thiol level and catalase enzyme activity in patients with osteoarthritis and in healthy controls. Serum oxidative status was evaluated by measuring total peroxide (TP) and lipid hydroperoxide. Oxidative stress index (OSI) was calculated. Prolidase enzyme activity was measured to investigate the collagen metabolism. Serum TAC, thiol level, catalase activity and prolidase activity were significantly lower in patients than in controls (P antioxidant parameters decreased in patients with osteoarthritis; therefore, these patients may be exposed to a potent oxidative stress. Decreased collagen metabolism may be related with oxidative stress, which has a role in the ethiopathogenesis and/or in the progression of the disease.

  11. Metabolic and oxidative stress markers in Wistar rats after 2?months on a high-fat diet

    OpenAIRE

    Auberval, Nathalie; Dal, St?phanie; Bietiger, William; Pinget, Michel; Jeandidier, Nathalie; Maillard-Pedracini, Elisa; Schini-Kerth, Val?rie; Sigrist, S?verine

    2014-01-01

    Background Metabolic syndrome is associated with an increased risk of cardiovascular and hepatic complications. Oxidative stress in metabolic tissues has emerged as a universal feature of metabolic syndrome and its co-morbidities. We aimed to develop a rapidly and easily induced model of metabolic syndrome in rats to evaluate its impact on plasma and tissue oxidative stress. Materials and methods Metabolic syndrome was induced in rats using a high-fat diet (HFD), and these rats were compared ...

  12. Monocyte functions in diabetes mellitus

    DEFF Research Database (Denmark)

    Geisler, C; Almdal, T; Bennedsen, J

    1982-01-01

    The aim of this study was to investigate the functions of monocytes obtained from 14 patients with diabetes mellitus (DM) compared with those of monocytes from healthy individuals. It was found that the total number of circulating monocytes in the 14 diabetic patients was lower than that from...... for the elucidation of concomitant infections in diabetic patients are discussed....

  13. The Association between Oxidative Stress and Metabolic Syndrome in Adults

    OpenAIRE

    Chung, So-Won; Kang, Sung-Goo; Rho, Jun-Seung; Kim, Ha-Na; Song, In-Sun; Lee, Yun-Ah; Heo, Soo-Jeong; Song, Sang-Wook

    2013-01-01

    Background In this Study, we investigated the effects of lifestyle and metabolic syndrome on free oxygen radical levels in men and women in Korea. Methods A total of 254 adults were included in this study from February 2011 to June 2012 at a health promotion center. Information of the lifestyles and presence of metabolic syndrome factors was obtained. Biochemical markers were measured and free oxygen radicals test (FORT) was performed on the blood. Results Of the 254 subjects, 86 (33.9%) had ...

  14. Cerebral Metabolic Changes Related to Oxidative Metabolism in a Model of Bacterial Meningitis Induced by Lipopolysaccharide

    DEFF Research Database (Denmark)

    Munk, Michael; Rom Poulsen, Frantz; Larsen, Lykke

    2018-01-01

    BACKGROUND: Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible...... with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis. METHODS: Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral...... dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO2, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed...

  15. Transfecting Human Monocytes with RNA.

    Science.gov (United States)

    Dannull, Jens; Nair, Smita K

    2016-01-01

    Targeting monocytes as a delivery system for drugs or nucleic acids, and thereby harnessing their natural tissue-infiltrating capacity, has become an area of intense investigation in both basic and clinical research. Herein we describe an efficient method to deliver mRNA (messenger RNA) or siRNA (small interfering RNA) into human monocytes by electroporation. This method can be applied in the laboratory to monocytes isolated via magnetic bead-based techniques, or in a clinical setting using monocytes that were collected via counterflow centrifugation elutriation using the Elutra(®) Cell Separation System. We further demonstrate that electroporation of monocytes with RNA represents a robust and highly relevant approach to modify monocytes for cell-based therapies. Last, the procedure described can readily be adapted to monocytes from different species, hence facilitating research in animal models.

  16. Electrocatalytic oxidation of hydrogen peroxide on a platinum electrode in the imitation of oxidative drug metabolism of lidocaine

    NARCIS (Netherlands)

    Nouri-Nigjeh, Eslam; Bruins, Andries P.; Bischoff, Rainer; Permentier, Hjalmar P.

    2012-01-01

    Electrochemistry in combination with mass spectrometry has shown promise as a versatile technique not only in the analytical assessment of oxidative drug metabolism, but also for small-scale synthesis of drug metabolites. However, electrochemistry is generally limited to reactions initiated by

  17. Arsenic triggers the nitric oxide (NO) and S-nitrosoglutathione (GSNO) metabolism in Arabidopsis

    International Nuclear Information System (INIS)

    Leterrier, Marina; Airaki, Morad; Palma, José M.; Chaki, Mounira; Barroso, Juan B.; Corpas, Francisco J.

    2012-01-01

    Environmental contamination by arsenic constitutes a problem in many countries, and its accumulation in food crops may pose health complications for humans. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved at various levels in the mechanism of responding to environmental stress in higher plants. Using Arabidopsis seedlings exposed to different arsenate concentrations, physiological and biochemical parameters were analyzed to determine the status of ROS and RNS metabolisms. Arsenate provoked a significant reduction in growth parameters and an increase in lipid oxidation. These changes were accompanied by an alteration in antioxidative enzymes and the nitric oxide (NO) metabolism, with a significant increase in NO content, S-nitrosoglutathione reductase (GSNOR) activity and protein tyrosine nitration as well as a concomitant reduction in glutathione and S-nitrosoglutathione (GSNO) content. Our results indicate that 500 μM arsenate (AsV) causes nitro-oxidative stress in Arabidopsis, being the glutathione reductase and the GSNOR activities clearly affected. - Highlights: ► In Arabidopsis, arsenate provokes damages in the membrane integrity of root cells. ► As induces an oxidative stress according to an increase in lipid oxidation. ► NO content and protein tyrosine nitration increases under arsenate stress. ► Arsenate provokes a reduction of GSH, GSSG and GSNO content. ► Arsenate induces a nitro-oxidative stress in Arabidopsis. - Arsenic stress affects nitric oxide (NO) and glutathione (GSH) metabolism which provokes a nitro-oxidative stress.

  18. Electrochemistry in the mimicry of oxidative drug metabolism by cytochrome P450s.

    Science.gov (United States)

    Nouri-Nigjeh, Eslam; Bischoff, Rainer; Bruins, Andries P; Permentier, Hjalmar P

    2011-05-01

    Prediction of oxidative drug metabolism at the early stages of drug discovery and development requires fast and accurate analytical techniques to mimic the in vivo oxidation reactions by cytochrome P450s (CYP). Direct electrochemical oxidation combined with mass spectrometry, although limited to the oxidation reactions initiated by charge transfer, has shown promise in the mimicry of certain CYP-mediated metabolic reactions. The electrochemical approach may further be utilized in an automated manner in microfluidics devices facilitating fast screening of oxidative drug metabolism. A wide range of in vivo oxidation reactions, particularly those initiated by hydrogen atom transfer, can be imitated through the electrochemically-assisted Fenton reaction. This reaction is based on O-O bond activation in hydrogen peroxide and oxidation by hydroxyl radicals, wherein electrochemistry is used for the reduction of molecular oxygen to hydrogen peroxide, as well as the reduction of Fe(3+) to Fe(2+). Metalloporphyrins, as surrogates for the prosthetic group in CYP, utilizing metallo-oxo reactive species, can also be used in combination with electrochemistry. Electrochemical reduction of metalloporphyrins in solution or immobilized on the electrode surface activates molecular oxygen in a manner analogous to the catalytical cycle of CYP and different metalloporphyrins can mimic selective oxidation reactions. Chemoselective, stereoselective, and regioselective oxidation reactions may be mimicked using electrodes that have been modified with immobilized enzymes, especially CYP itself. This review summarizes the recent attempts in utilizing electrochemistry as a versatile analytical and preparative technique in the mimicry of oxidative drug metabolism by CYP. © 2011 Bentham Science Publishers Ltd.

  19. Monocyte transferrin-iron uptake in hereditary hemochromatosis

    International Nuclear Information System (INIS)

    Sizemore, D.J.; Bassett, M.L.

    1984-01-01

    Transferrin-iron uptake by peripheral blood monocytes was studied in vitro to test the hypothesis that the relative paucity of mononuclear phagocyte iron loading in hereditary hemochromatosis results from a defect in uptake of iron from transferrin. Monocytes from nine control subjects and 17 patients with hemochromatosis were cultured in the presence of 59Fe-labelled human transferrin. There was no difference in 59Fe uptake between monocytes from control subjects and monocytes from patients with hemochromatosis who had been treated by phlebotomy and who had normal body iron stores. However, 59Fe uptake by monocytes from iron-loaded patients with hemochromatosis was significantly reduced compared with either control subjects or treated hemochromatosis patients. It is likely that this was a secondary effect of iron loading since iron uptake by monocytes from treated hemochromatosis patients was normal. Assuming that monocytes in culture reflect mononuclear phagocyte iron metabolism in vivo, this study suggests that the relative paucity of mononuclear phagocyte iron loading in hemochromatosis is not related to an abnormality in transferrin-iron uptake by these cells

  20. Electrocatalytic oxidation of hydrogen peroxide on a platinum electrode in the imitation of oxidative drug metabolism of lidocaine.

    Science.gov (United States)

    Nouri-Nigjeh, Eslam; Bruins, Andries P; Bischoff, Rainer; Permentier, Hjalmar P

    2012-10-21

    Electrochemistry in combination with mass spectrometry has shown promise as a versatile technique not only in the analytical assessment of oxidative drug metabolism, but also for small-scale synthesis of drug metabolites. However, electrochemistry is generally limited to reactions initiated by direct electron transfer. In the case of substituted-aromatic compounds, oxidation proceeds through a Wheland-type intermediate where resonance stabilization of the positive charge determines the regioselectivity of the anodic substitution reaction, and hence limits the extent of generating drug metabolites in comparison with in vivo oxygen insertion reactions. In this study, we show that the electrocatalytic oxidation of hydrogen peroxide on a platinum electrode generates reactive oxygen species, presumably surface-bound platinum-oxo species, which are capable of oxygen insertion reactions in analogy to oxo-ferryl radical cations in the active site of Cytochrome P450. Electrochemical oxidation of lidocaine at constant potential in the presence of hydrogen peroxide produces both 3- and 4-hydroxylidocaine, suggesting reaction via an arene oxide rather than a Wheland-type intermediate. No benzylic hydroxylation was observed, thus freely diffusing radicals do not appear to be present. The results of the present study extend the possibilities of electrochemical imitation of oxidative drug metabolism to oxygen insertion reactions.

  1. Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Rehrer, N J; Pilegaard, H

    2007-01-01

    AIM: Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. METHODS: Data were...... exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes....

  2. Nitrogen metabolism and kinetics of ammonia-oxidizing archaea.

    Science.gov (United States)

    Martens-Habbena, Willm; Stahl, David A

    2011-01-01

    The discovery of ammonia-oxidizing mesophilic and thermophilic Group I archaea changed the century-old paradigm that aerobic ammonia oxidation is solely mediated by two small clades of Beta- and Gammaproteobacteria. Group I archaea are extremely diverse and ubiquitous in marine and terrestrial environments, accounting for 20-30% of the microbial plankton in the global oceans. Recent studies indicated that many of these organisms carry putative ammonia monooxygenase genes and are more abundant than ammonia-oxidizing bacteria in most natural environments suggesting a potentially significant role in the nitrogen cycle. The isolation of Nitrosopumilus maritimus strain SCM1 provided the first direct evidence that Group I archaea indeed gain energy from ammonia oxidation. To characterize the physiology of this archaeal nitrifier, we developed a respirometry setup particularly suited for activity measurements in dilute microbial cultures with extremely low oxygen uptake rates. Here, we describe the setup and review the kinetic experiments conducted with N. maritimus and other nitrifying microorganisms. These experiments demonstrated that N. maritimus is adapted to grow on ammonia concentrations found in oligotrophic open ocean environments, far below the survival threshold of ammonia-oxidizing bacteria. The described setup and experimental procedures should facilitate physiological studies on other nitrifying archaea and oligotrophic microorganisms in general. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

    Science.gov (United States)

    Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Renée; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle; Beauséjour, Christian; Stroncek, David; Le Deist, Françoise; Haddad, Elie

    2016-01-01

    Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation. PMID:27070086

  4. Abcc9 is required for the transition to oxidative metabolism in the newborn heart.

    Science.gov (United States)

    Fahrenbach, John P; Stoller, Douglas; Kim, Gene; Aggarwal, Nitin; Yerokun, Babatunde; Earley, Judy U; Hadhazy, Michele; Shi, Nian-Qing; Makielski, Jonathan C; McNally, Elizabeth M

    2014-07-01

    The newborn heart adapts to postnatal life by shifting from a fetal glycolytic metabolism to a mitochondrial oxidative metabolism. Abcc9, an ATP-binding cassette family member, increases expression concomitant with this metabolic shift. Abcc9 encodes a membrane-associated receptor that partners with a potassium channel to become the major potassium-sensitive ATP channel in the heart. Abcc9 also encodes a smaller protein enriched in the mitochondria. We now deleted exon 5 of Abcc9 to ablate expression of both plasma membrane and mitochondria-associated Abcc9-encoded proteins, and found that the myocardium failed to acquire normal mature metabolism, resulting in neonatal cardiomyopathy. Unlike wild-type neonatal cardiomyocytes, mitochondria from Ex5 cardiomyocytes were unresponsive to the KATP agonist diazoxide, consistent with loss of KATP activity. When exposed to hydrogen peroxide to induce cell stress, Ex5 neonatal cardiomyocytes displayed a rapid collapse of mitochondria membrane potential, distinct from wild-type cardiomyocytes. Ex5 cardiomyocytes had reduced fatty acid oxidation, reduced oxygen consumption and reserve. Morphologically, Ex5 cardiac mitochondria exhibited an immature pattern with reduced cross-sectional area and intermitochondrial contacts. In the absence of Abcc9, the newborn heart fails to transition normally from fetal to mature myocardial metabolism.-Fahrenbach, J. P., Stoller, D., Kim, G., Aggarwal, N., Yerokun, B., Earley, J. U., Hadhazy, M., Shi, N.-Q., Makielski, J. C., McNally, E. M. Abcc9 is required for the transition to oxidative metabolism in the newborn heart. © FASEB.

  5. MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women.

    Science.gov (United States)

    Diamanti-Kandarakis, Evanthia; Papalou, Olga; Kandaraki, Eleni A; Kassi, Georgia

    2017-02-01

    Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders. © 2017 European Society of Endocrinology.

  6. Recurrent antecedent hypoglycemia alters neuronal oxidative metabolism in vivo.

    Science.gov (United States)

    Jiang, Lihong; Herzog, Raimund I; Mason, Graeme F; de Graaf, Robin A; Rothman, Douglas L; Sherwin, Robert S; Behar, Kevin L

    2009-06-01

    The objective of this study was to characterize the changes in brain metabolism caused by antecedent recurrent hypoglycemia under euglycemic and hypoglycemic conditions in a rat model and to test the hypothesis that recurrent hypoglycemia changes the brain's capacity to utilize different energy substrates. Rats exposed to recurrent insulin-induced hypoglycemia for 3 days (3dRH rats) and untreated controls were subject to the following protocols: [2-(13)C]acetate infusion under euglycemic conditions (n = 8), [1-(13)C]glucose and unlabeled acetate coinfusion under euglycemic conditions (n = 8), and [2-(13)C]acetate infusion during a hyperinsulinemic-hypoglycemic clamp (n = 8). In vivo nuclear magnetic resonance spectroscopy was used to monitor the rise of(13)C-labeling in brain metabolites for the calculation of brain metabolic fluxes using a neuron-astrocyte model. At euglycemia, antecedent recurrent hypoglycemia increased whole-brain glucose metabolism by 43 +/- 4% (P glucose utilization in neurons. Although acetate metabolism remained the same, control and 3dRH animals showed a distinctly different response to acute hypoglycemia: controls decreased pyruvate dehydrogenase (PDH) flux in astrocytes by 64 +/- 20% (P = 0.01), whereas it increased by 37 +/- 3% in neurons (P = 0.01). The 3dRH animals decreased PDH flux in both compartments (-75 +/- 20% in astrocytes, P neurons, P = 0.005). Thus, acute hypoglycemia reduced total brain tricarboxylic acid cycle activity in 3dRH animals (-37 +/- 4%, P = 0.001), but not in controls. Our findings suggest that after antecedent hypoglycemia, glucose utilization is increased at euglycemia and decreased after acute hypoglycemia, which was not the case in controls. These findings may help to identify better methods of preserving brain function and reducing injury during acute hypoglycemia.

  7. Oxidative stress among subjects with metabolic syndrome in Sokoto ...

    African Journals Online (AJOL)

    2015-08-20

    Aug 20, 2015 ... Background: Oxidative stress is known to play a role in the ... others to remix, tweak, and build upon the work non-commercially, as long as the ..... Report of the National Heart, Lung, and Blood Institute/American Heart.

  8. Arginine, citrulline and nitric oxide metabolism in sepsis

    Science.gov (United States)

    Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

  9. Microbiota-dependent metabolite and cardiovascular disease marker trimethylamine-N-oxide (TMAO) is associated with monocyte activation but not platelet function in untreated HIV infection

    DEFF Research Database (Denmark)

    Haissman, Judith M; Haugaard, Anna K; Ostrowski, Sisse R

    2017-01-01

    and combination anti-retroviral therapy (cART) HIV infection. METHODS: TMAO and the pre-cursors betaine, choline, and carnitine were quantified by mass-spectrometry in plasma samples from a previously established cross-sectional cohort of 50 untreated and 50 cART treated HIV-infected individuals. Whole...... agonists, or with overall hypo- or hyperreactivity in untreated or treated HIV-infected individuals. In contrast, sCD14 a marker of both monocyte activation and microbial translocation was independently associated with TMAO in untreated HIV-infection (R = 0.381, P = 0.008). Lower levels of carnitine [32.......2 (28.4-36.8) vs. 38.2 (33.6-42.0), P = 0.001] and betaine [33.1 (27.3-43.4) vs.37.4 (31.5-48.7, P = 0.02], but similar TMAO levels [3.8 (2.3-6.1), vs. 2.9 μM (1.9-4.8) P = 0.15] were found in cART treated compared to untreated HIV-infected individuals, resulting in higher ratios of TMAO/carnitine [0...

  10. A RAPID THIN-LAYER CHROMATOGRAPHIC PROCEDURE TO IDENTIFY POOR AND EXTENSIVE OXIDATIVE DRUG METABOLIZERS IN MAN USING DEXTROMETHORPHAN

    NARCIS (Netherlands)

    DEZEEUW, RA; EIKEMA, D; FRANKE, JP; JONKMAN, JHG

    A rapid TLC method is presented to distinguish poor oxidative drug metabolizers from extensive oxidative drug metabolizers. Dextromethorphan (1) is used as test probe because it is safe, well characterized, generally available and easy to measure. The method is based on the extraction of 1 and its

  11. Transcriptome analysis of monocyte-HIV interactions

    Directory of Open Access Journals (Sweden)

    Tran Huyen

    2010-06-01

    Full Text Available Abstract Background During HIV infection and/or antiretroviral therapy (ART, monocytes and macrophages exhibit a wide range of dysfunctions which contribute significantly to HIV pathogenesis and therapy-associated complications. Nevertheless, the molecular components which contribute to these dysfunctions remain elusive. We therefore applied a parallel approach of genome-wide microarray analysis and focused gene expression profiling on monocytes from patients in different stages of HIV infection and/or ART to further characterise these dysfunctions. Results Processes involved in apoptosis, cell cycle, lipid metabolism, proteasome function, protein trafficking and transcriptional regulation were identified as areas of monocyte dysfunction during HIV infection. Individual genes potentially contributing to these monocyte dysfunctions included several novel factors. One of these is the adipocytokine NAMPT/visfatin, which we show to be capable of inhibiting HIV at an early step in its life cycle. Roughly half of all genes identified were restored to control levels under ART, while the others represented a persistent dysregulation. Additionally, several candidate biomarkers (in particular CCL1 and CYP2C19 for the development of the abacavir hypersensitivity reaction were suggested. Conclusions Previously described areas of monocyte dysfunction during HIV infection were confirmed, and novel themes were identified. Furthermore, individual genes associated with these dysfunctions and with ART-associated disorders were pinpointed. These genes form a useful basis for further functional studies concerning the contribution of monocytes/macrophages to HIV pathogenesis. One such gene, NAMPT/visfatin, represents a possible novel restriction factor for HIV. Background Both macrophages and T lymphocyte subsets express the CD4 receptor and either the CXCR4 and/or the CCR5 coreceptor which confer susceptibility to infection with the Human Immunodeficiency Virus

  12. Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise

    2015-01-01

    Aging is associated with oxidative stress-generated damage to DNA and this could be related to metabolic disturbances. This study investigated the association between levels of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs) and metabolic risk factors in 1,019 subjects, aged...... 18-93 years. DNA damage was analyzed as strand breaks by the comet assay and levels of formamidopyrimidine (FPG-) and human 8-oxoguanine DNA glycosylase 1 (hOGG1)-sensitive sites There was an association between age and levels of FPG-sensitive sites for women, but not for men. The same tendency......, cholesterol and glycosylated hemoglobin (HbA1c). In the group of men, there were significant positive associations between alcohol intake, HbA1c and FPG-sensitive sites in multivariate analysis. The levels of metabolic risk factors were positively associated with age, yet only few subjects fulfilled all...

  13. Changes in oxidative properties of Kalanchoe blossfeldiana leaf mitochondria during development of Crassulacean acid metabolism.

    Science.gov (United States)

    Rustin, P; Queiroz-Claret, C

    1985-06-01

    Kalanchoe blossfeldiana plants grown under long days (16 h light) exhibit a C3-type photosynthetic metabolism. Switching to short days (9 h light) leads to a gradual development of Crassulacean acid metabolism (CAM). Under the latter conditions, dark CO2 fixation produces large amounts of malate. During the first hours of the day, malate is rapidly decarboxylated into pyruvate through the action of a cytosolic NADP(+)-or a mitochondrial NAD(+)-dependent malic enzyme. Mitochondria were isolated from leaves of plants grown under long days or after treatment by an increasing number of short days. Tricarboxylic acid cycle intermediates as well as exogenous NADH and NADPH were readily oxidized by mitochondria isolated from the two types of plants. Glycine, known to be oxidized by C3-plant mitochondria, was still oxidized after CAM establishment. The experiments showed a marked parallelism in the increase of CAM level and the increase in substrate-oxidation capacity of the isolated mitochondria, particularly the capacity to oxidize malate in the presence of cyanide. These simultaneous variations in CAM level and in mitochondrial properties indicate that the mitochondrial NAD(+)-malic enzyme could account at least for a part of the oxidation of malate. The studies of whole-leaf respiration establish that mitochondria are implicated in malate degradation in vivo. Moreover, an increase in cyanide resistance of the leaf respiration has been observed during the first daylight hours, when malate was oxidized to pyruvate by cytosolic and mitochondrial malic enzymes.

  14. The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

    Science.gov (United States)

    Hutcheson, Rebecca; Rocic, Petra

    2012-01-01

    The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD) in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs), and angiotensin II converting enzyme (ACE) inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome. PMID:22829804

  15. The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

    Directory of Open Access Journals (Sweden)

    Rebecca Hutcheson

    2012-01-01

    Full Text Available The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs, and angiotensin II converting enzyme (ACE inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome.

  16. Urinary F2-Isoprostanes and Metabolic Markers of Fat Oxidation

    Directory of Open Access Journals (Sweden)

    Dora Il’yasova

    2015-01-01

    Full Text Available Metabolomic studies of increased fat oxidation showed increase in circulating acylcarnitines C2, C8, C10, and C12 and decrease in C3, C4, and C5. We hypothesize that urinary F2-isoprostanes reflect intensity of fatty acid oxidation and are associated with circulating C2, C8, C10, and C12 directly and with C3, C4, and C5 inversely. Four urinary F2-isoprostane isomers and serum acylcarnitines are quantified using LC-MS/MS within the Insulin Resistance Atherosclerosis Study nondiabetic cohort (n = 682. Cross-sectional associations between fasting urinary F2-isoprostanes (summarized as a composite index and the selected acylcarnitines are examined using generalized linear models. F2-isoprostane index is associated with C2 and C12 directly and with C5 inversely: the adjusted beta coefficients are 0.109, 0.072, and −0.094, respectively (P < 0.05. For these acylcarnitines and for F2-isoprostanes, the adjusted odds ratios (ORs of incident diabetes are calculated from logistic regression models: the ORs (95% CI are 0.77 (0.60–0.97, 0.79 (0.62–1.01, 1.18 (0.92–1.53, and 0.51 (0.35–0.76 for C2, C12, C5, and F2-isoprostanes, respectively. The direction of the associations between urinary F2-isoprostanes and three acylcarnitines (C2, C5, and C12 supports our hypothesis. The inverse associations of C2 and C12 and with incident diabetes are consistent with the suggested protective role of efficient fat oxidation.

  17. Metabolic consequences of decreased nitric oxide synthesis in the hearth

    International Nuclear Information System (INIS)

    Pechanova, O.; Bernatova, I.; Pelouch, V.

    1998-01-01

    The aim of the present study was to determine long-term effect of NO-synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) on concentrations of cyclic nucleotides, nucleic acids and of collagenous proteins in the left ventricle. Male Wistar rats were investigated. NO-synthase activity in the homogenates of left ventricle was determined by measuring the formation of 3 H]-L-citrulline from [ 3 H]-L-arginine. Cyclic GMP and cAMP concentrations were determined by using radioimmunoassay procedures and commercial cGMP and cAMP 125 I scintillation proximity assay systems.Significantly more remarkable decrease of NO-synthase activity was recorded in the group with higher dose (40 mg/kg/day) of L-NAME. The changes in metabolic parameters corresponded well with the dose-depend decrease of NO-synthase activity. (authors)

  18. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism.

    Science.gov (United States)

    Lee, Jieun; Wolfgang, Michael J

    2012-10-25

    Carnitine Palmitoyltransferase-1c (CPT1c) is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT) and CPT1c knockout (KO) mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

  19. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism

    Directory of Open Access Journals (Sweden)

    Lee Jieun

    2012-10-01

    Full Text Available Abstract Background Carnitine Palmitoyltransferase-1c (CPT1c is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. Results In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT and CPT1c knockout (KO mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Conclusions Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

  20. Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism

    Science.gov (United States)

    Melnyk, Stepan; Fuchs, George J.; Schulz, Eldon; Lopez, Maya; Kahler, Stephen G.; Fussell, Jill J.; Bellando, Jayne; Pavliv, Oleksandra; Rose, Shannon; Seidel, Lisa; Gaylor, David W.

    2012-01-01

    Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected siblings differed significantly from case siblings but not from controls. Oxidative protein/DNA damage and DNA hypomethylation (epigenetic alteration) were found in autistic children but not paired siblings or controls. These data indicate that the deficit in antioxidant and methylation capacity is specific for autism and may promote cellular damage and altered epigenetic gene expression. Further, these results suggest a plausible mechanism by which pro-oxidant environmental stressors may modulate genetic predisposition to autism. PMID:21519954

  1. 14C-carbaril metabolism in soils modified by organic matter oxidation and addition of glucose

    International Nuclear Information System (INIS)

    Hirata, R.; Ruegg, E.F.

    1984-01-01

    Carbaril behaviour is studied in samples of Brunizen and Dark Red Latosol soils from Parana, using radiometric techniques, with the objective of determining the role of oxidation fo its organic components, and enrichment with glucose, in the metabolism of the insecticide. Lots of autoclaved soils, oxidized and with no previous treatment, with and without glucose addition, are incubated with 14 C-carbaril and analysed during eight weeks. Its was noted that, as a result of oxidation both soils showed a marked improvement in the metabolism of the agrochemical while addition of glucose exerted litlle influence on the degrading processes. Three metabolites were detected with R sub(f) 0.23, 0.40 and 0.70. (Author) [pt

  2. Changes in adhesion molecule expression and oxidative burst activity of granulocytes and monocytes during open-heart surgery with cardiopulmonary bypass compared with abdominal surgery

    DEFF Research Database (Denmark)

    Toft, P; Nielsen, C H; Tønnesen, E

    1998-01-01

    surgery. The ability to respond with an oxidative burst was measured by means of flow cytometry using 123-dihydrorhodamine. The adhesion molecules CD11a/CD18, CD11c/CD18, CD44 were measured using monoclonal antibodies. Blood samples from eight patients undergoing open-heart surgery were taken before...... to an increased per-operative oxidative burst activity, and the induction of adhesion molecules on granulocytes associated with the cardiopulmonary bypass and surgery. In conclusion, open-heart surgery with cardiopulmonary bypass was associated with a rapid and pronounced activation of leukocytes which may play...

  3. Erectile dysfunction and diabetes: Association with the impairment of lipid metabolism and oxidative stress.

    Science.gov (United States)

    Belba, Arben; Cortelazzo, Alessio; Andrea, Giansanti; Durante, Jacopo; Nigi, Laura; Dotta, Francesco; Timperio, Anna Maria; Zolla, Lello; Leoncini, Roberto; Guerranti, Roberto; Ponchietti, Roberto

    2016-01-01

    To test the hypothesis that exists an association of non-diabetic and diabetic patients suffering from erectile dysfunction (ED) with lipid metabolism and oxidative stress. Clinical and laboratory characteristics in non-diabetic (n = 30, middle age range: 41–55.5 years; n = 25, old age range: 55.5–73), diabetic ED patients (n = 30, age range: 55.5–75 years) and diabetic patients (n = 25, age range: 56–73.25), were investigated. Proteomic analysis was performed to identify differentially expressed plasma proteins and to evaluate their oxidative posttranslational modifications. A decreased level of high-density lipoproteins in all ED patients (P < 0.001, C.I. 0.046–0.10), was detected by routine laboratory tests. Proteomic analysis showed a significant decreased expression (P < 0.05) of 5 apolipoproteins (i.e. apolipoprotein H, apolipoprotein A4, apolipoprotein J, apolipoprotein E and apolipoprotein A1) and zinc-alpha-2-glycoprotein, 50% of which are more oxidized proteins. Exclusively for diabetic ED patients, oxidative posttranslational modifications for prealbumin, serum albumin, serum transferrin and haptoglobin markedly increased. Showing evidence for decreased expression of apolipoproteins in ED and the remarkable enhancement of oxidative posttranslational modifications in diabetes-associated ED, considering type 2 diabetes mellitus and age as independent risk factors involved in the ED pathogenesis, lipid metabolism and oxidative stress appear to exert a complex interplay in the disease.

  4. In Vitro experimental model of trained innate immunity in human primary monocytes

    DEFF Research Database (Denmark)

    Bekkering, S.; Blok, B. A.; Joosten, Leo A B

    2016-01-01

    experimental protocol of monocyte training using three of the most commonly used training stimuli from the literature: β-glucan, the bacillus Calmette-Guérin (BCG) vaccine, and oxidized low-density lipoprotein (ox-LDL). We investigated and optimized a protocol of monocyte trained immunity induced by an initial....... All Rights Reserved....

  5. Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility

    International Nuclear Information System (INIS)

    Aw, Tak Yee

    2005-01-01

    The intestine is a primary site of nutrient absorption and a critical defense barrier against dietary-derived mutagens, carcinogens, and oxidants. Accumulation of oxidants like peroxidized lipids in the gut lumen can contribute to impairment of mucosal metabolic pathways, enterocyte dysfunction independent of cell injury, and development of gut pathologies, such as inflammation and cancer. Despite this recognition, we know little of the pathways of intestinal transport, metabolism, and luminal disposition of dietary peroxides in vivo or of the underlying mechanisms of lipid peroxide-induced genesis of intestinal disease processes. This chapter summarizes our current understanding of the determinants of intestinal absorption and metabolism of peroxidized lipids. I will review experimental evidence from our laboratory and others (Table 1) supporting the pivotal role that glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play in mucosal transport and metabolism of lipid hydroperoxides and how reductant availability can be compromised under chronic stress such as hypoxia, and the influence of GSH on oxidative susceptibility, and redox contribution to genesis of gut disorders. The discussion is pertinent to understanding dietary lipid peroxides and GSH redox balance in intestinal physiology and pathophysiology and the significance of luminal GSH in preserving the integrity of the intestinal epithelium

  6. Oxidative Stress and Metabolic Syndrome: Cause or Consequence of Alzheimer's Disease?

    Directory of Open Access Journals (Sweden)

    Diana Luque-Contreras

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is a major neurodegenerative disease affecting the elderly. Clinically, it is characterized by a progressive loss of memory and cognitive function. Neuropathologically, it is characterized by the presence of extracellular β-amyloid (Aβ deposited as neuritic plaques (NP and neurofibrillary tangles (NFT made of abnormal and hyperphosphorylated tau protein. These lesions are capable of generating the neuronal damage that leads to cell death and cognitive failure through the generation of reactive oxygen species (ROS. Evidence indicates the critical role of Aβ metabolism in prompting the oxidative stress observed in AD patients. However, it has also been proposed that oxidative damage precedes the onset of clinical and pathological AD symptoms, including amyloid-β deposition, neurofibrillary tangle formation, vascular malfunction, metabolic syndrome, and cognitive decline. This paper provides a brief description of the three main proteins associated with the development of the disease (Aβ, tau, and ApoE and describes their role in the generation of oxidative stress. Finally, we describe the mitochondrial alterations that are generated by Aβ and examine the relationship of vascular damage which is a potential prognostic tool of metabolic syndrome. In addition, new therapeutic approaches targeting ROS sources and metabolic support were reported.

  7. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    Directory of Open Access Journals (Sweden)

    Carles Lerin

    2016-10-01

    Full Text Available Objective: Plasma levels of branched-chain amino acids (BCAA are consistently elevated in obesity and type 2 diabetes (T2D and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. Methods: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28. We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Results: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D. Keywords: Insulin sensitivity, BCAA, Fatty acid oxidation, TCA cycle

  8. Noninvasive assessment of canine myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography

    International Nuclear Information System (INIS)

    Brown, M.A.; Myears, D.W.; Bergmann, S.R.

    1988-01-01

    Noninvasive quantification of regional myocardial metabolism would be highly desirable to evaluate pathogenetic mechanisms of heart disease and their response to therapy. It was previously demonstrated that the metabolism of radiolabeled acetate, a readily utilized myocardial substrate predominantly metabolized to carbon dioxide (CO2) by way of the tricarboxylic acid cycle, provides a good index of oxidative metabolism in isolated perfused rabbit hearts because of tight coupling between the tricarboxylic acid cycle and oxidative phosphorylation. In the present study, in a prelude to human studies, the relation between myocardial clearance of carbon-11 (11C)-labeled acetate and myocardial oxygen consumption was characterized in eight intact dogs using positron emission tomography. Anesthetized dogs were studied during baseline conditions and again during either high or low work states induced pharmacologically. High myocardial extraction and rapid blood clearance of tracer yielded myocardial images of excellent quality. The turnover (clearance) of 11C radioactivity from the myocardium was biexponential with the mean half-time of the dominant rapid phase averaging 5.4 +/- 2.2, 2.8 +/- 1.3 and 11.1 +/- 1.3 min in control, high and low work load studies, respectively. No significant difference was found between the rate of clearance of 11C radioactivity from the myocardium measured noninvasively with positron emission tomography and the myocardial efflux of 11CO2 measured directly from the coronary sinus. The rate of clearance of the 11C radioactivity from the heart correlated closely with myocardial oxygen consumption (r = 0.90, p less than 0.001) as well as with the rate-pressure product (r = 0.95, p less than 0.001). Hence, the rate of oxidation of 11C-acetate can be determined noninvasively with positron emission tomography, providing a quantitative index of oxidative metabolism under diverse conditions

  9. Oral absorption and oxidative metabolism of atrazine in rats evaluated by physiological modeling approaches

    International Nuclear Information System (INIS)

    McMullin, Tami S.; Hanneman, William H.; Cranmer, Brian K.; Tessari, John D.; Andersen, Melvin E.

    2007-01-01

    Atrazine (ATRA) is metabolized by cytochrome P450s to the chlorinated metabolites, 2-chloro-4-ethylamino-6-amino-1,3,5-triazine (ETHYL), 2-chloro-4-amino-6-isopropylamino-1, 3, 5-triazine (ISO), and diaminochlorotriazine (DACT). Here, we develop a set of physiologically based pharmacokinetic (PBPK) models that describe the influence of oral absorption and oxidative metabolism on the blood time course curves of individual chlorotriazines (Cl-TRIs) in rat after oral dosing of ATRA. These models first incorporated in vitro metabolic parameters to describe time course plasma concentrations of DACT, ETHYL, and ISO after dosing with each compound. Parameters from each individual model were linked together into a final composite model in order to describe the time course of all 4 Cl-TRIs after ATRA dosing. Oral administration of ISO, ETHYL and ATRA produced double peaks of the compounds in plasma time courses that were described by multiple absorption phases from gut. An adequate description of the uptake and bioavailability of absorbed ATRA also required inclusion of additional oxidative metabolic clearance of ATRA to the mono-dealkylated metabolites occurring in GI a tract compartment. These complex processes regulating tissue dosimetry of atrazine and its chlorinated metabolites likely reflect limited compound solubility in the gut from dosing with an emulsion, and sequential absorption and metabolism along the GI tract at these high oral doses

  10. Calcium Co-regulates Oxidative Metabolism and ATP Synthase-dependent Respiration in Pancreatic Beta Cells

    Science.gov (United States)

    De Marchi, Umberto; Thevenet, Jonathan; Hermant, Aurelie; Dioum, Elhadji; Wiederkehr, Andreas

    2014-01-01

    Mitochondrial energy metabolism is essential for glucose-induced calcium signaling and, therefore, insulin granule exocytosis in pancreatic beta cells. Calcium signals are sensed by mitochondria acting in concert with mitochondrial substrates for the full activation of the organelle. Here we have studied glucose-induced calcium signaling and energy metabolism in INS-1E insulinoma cells and human islet beta cells. In insulin secreting cells a surprisingly large fraction of total respiration under resting conditions is ATP synthase-independent. We observe that ATP synthase-dependent respiration is markedly increased after glucose stimulation. Glucose also causes a very rapid elevation of oxidative metabolism as was followed by NAD(P)H autofluorescence. However, neither the rate of the glucose-induced increase nor the new steady-state NAD(P)H levels are significantly affected by calcium. Our findings challenge the current view, which has focused mainly on calcium-sensitive dehydrogenases as the target for the activation of mitochondrial energy metabolism. We propose a model of tight calcium-dependent regulation of oxidative metabolism and ATP synthase-dependent respiration in beta cell mitochondria. Coordinated activation of matrix dehydrogenases and respiratory chain activity by calcium allows the respiratory rate to change severalfold with only small or no alterations of the NAD(P)H/NAD(P)+ ratio. PMID:24554722

  11. Unveiling the oxidative metabolism of Achatina fulica (Mollusca: Gastropoda) experimentally infected to Angiostrongylus cantonensis (Nematoda: Metastrongylidae).

    Science.gov (United States)

    Tunholi-Alves, Vinícius Menezes; Tunholi, Victor Menezes; Garcia, Juberlan; Mota, Esther Maria; Castro, Rosane Nora; Pontes, Emerson Guedes; Pinheiro, Jairo

    2018-06-01

    For the first time, alterations in the oxidative metabolism of Achatina fulica experimentally infected with different parasite loads of Angiostrongylus cantonensis were determined. For this, the hemolymph activities of lactate dehydrogenase (LDH) and hexokinase and the glucose concentrations in the hemolymph, as well as the polysaccharide reserves in the digestive gland and cephalopedal mass, were assessed. Additionally, the contents of some carboxylic acids in the hemolymph of infected and uninfected snails were determined by high-performance liquid chromatography (HPLC), permitting a better understanding of the alterations related to the host's oxidative metabolism. As the main results, activation of oxidative pathways, such as the glycolytic pathway, was demonstrated in response to the increase in the activity of hexokinase. This tendency was confirmed by the decrease in the contents of glucose in the hemolymph of parasitized snails, indicating that the infection by A. cantonensis alters the host's metabolism, and that these changes are strongly influenced by the parasite load. This metabolic scenario was accompanied by activation of the anaerobic fermentative metabolism, indicated not only by an increase in the activity of (LDH), but also by a reduction of the content of pyruvic acid and accumulation of lactic acid in the hemolymph of parasitized snails. In this circumstance, maintenance of the host's redox balance occurs through activation of the fermentative pathways, and LDH plays a central role in this process. Together, the results indicate that A. cantonensis infection induces activation of the anaerobic metabolism of A. fulica, characterized not only by the accumulation of lactic acid, but also by a reduction in the pyruvic acid and oxalic acid contents in the hemolymph of the infected snails.

  12. Oxidative metabolism of 5-o-caffeoylquinic acid (chlorogenic acid), a bioactive natural product, by metalloporphyrin and rat liver mitochondria.

    Science.gov (United States)

    dos Santos, Michel D; Martins, Patrícia R; dos Santos, Pierre A; Bortocan, Renato; Iamamoto, Y; Lopes, Norberto P

    2005-09-01

    Synthetic metalloporphyrins, in the presence of monooxygen donors, are known to mimic the various reactions of cytochrome P450 enzymes systems in the oxidation and oxygenation of various drugs and biologically active compounds. This paper reports an HPLC-MS-MS investigation of chlorogenic acid (CGA) oxidation by iodosylbenzene using iron(III) tetraphenylporphyrin chloride as catalyst. The oxidation products have been detected by sequential MS analyses. In addition, CGA was submitted to an in vitro metabolism assay employing isolated rat liver mitochondria. The single oxidized product obtained from mitochondrial metabolism corresponds to the major product formed by the metalloporphyrin-catalyzed reaction. These results indicate that biomimetic oxidation reactions, in addition to in vitro metabolism assays employing isolated organs/organelles, could replace some in vivo metabolism studies, thus minimizing the problems related to the use of a large number of living animals in experimental research.

  13. Vascular affection in relation to oxidative DNA damage in metabolic syndrome.

    Science.gov (United States)

    Abd El Aziz, Rokayaa; Fawzy, Mary Wadie; Khalil, Noha; Abdel Atty, Sahar; Sabra, Zainab

    2018-02-01

    Obesity has become an important issue affecting both males and females. Obesity is now regarded as an independent risk factor for atherosclerosis-related diseases. Metabolic syndrome is associated with increased risk for development of cardiovascular disease. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine concentration has been used to express oxidation status. Twenty-seven obese patients with metabolic syndrome, 25 obese patients without metabolic syndrome and 31 healthy subjects were included in our study. They were subjected to full history and clinical examination; fasting blood sugar (FBS), 2 hour post prandial blood sugar (2HPP), lipid profile, urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and carotid duplex, A/B index and tibial diameters were all assessed. There was a statistically significant difference ( p = 0.027) in diameter of the right anterior tibial artery among the studied groups, with decreased diameter of the right anterior tibial artery in obese patients with metabolic syndrome compared to those without metabolic syndrome; the ankle brachial index revealed a lower index in obese patients with metabolic syndrome compared to those without metabolic syndrome. There was a statistically insignificant difference ( p = 0.668) in the 8-oxodG in the studied groups. In obese patients with metabolic syndrome there was a positive correlation between 8-oxodG and total cholesterol and LDL. Urinary 8-oxodG is correlated to total cholesterol and LDL in obese patients with metabolic syndrome; signifying its role in the mechanism of dyslipidemia in those patients. Our study highlights the importance of anterior tibial artery diameter measurement and ankle brachial index as an early marker of atherosclerosis, and how it may be an earlier marker than carotid intima-media thickness.

  14. Astrocyte oxidative metabolism and metabolite trafficking after fluid percussion brain injury in adult rats.

    Science.gov (United States)

    Bartnik-Olson, Brenda L; Oyoyo, Udochukwu; Hovda, David A; Sutton, Richard L

    2010-12-01

    Despite various lines of evidence pointing to the compartmentation of metabolism within the brain, few studies have reported the effect of a traumatic brain injury (TBI) on neuronal and astrocyte compartments and/or metabolic trafficking between these cells. In this study we used ex vivo ¹³C NMR spectroscopy following an infusion of [1-¹³C] glucose and [1,2-¹³C₂] acetate to study oxidative metabolism in neurons and astrocytes of sham-operated and fluid percussion brain injured (FPI) rats at 1, 5, and 14 days post-surgery. FPI resulted in a decrease in the ¹³C glucose enrichment of glutamate in neurons in the injured hemisphere at day 1. In contrast, enrichment of glutamine in astrocytes from acetate was not significantly decreased at day 1. At day 5 the ¹³C enrichment of glutamate and glutamine from glucose in the injured hemisphere of FPI rats did not differ from sham levels, but glutamine derived from acetate metabolism in astrocytes was significantly increased. The ¹³C glucose enrichment of the C3 position of glutamate (C3) in neurons was significantly decreased ipsilateral to FPI at day 14, whereas the enrichment of glutamine in astrocytes had returned to sham levels at this time point. These findings indicate that the oxidative metabolism of glucose is reduced to a greater extent in neurons compared to astrocytes following a FPI. The increased utilization of acetate to synthesize glutamine, and the acetate enrichment of glutamate via the glutamate-glutamine cycle, suggests an integral protective role for astrocytes in maintaining metabolic function following TBI-induced impairments in glucose metabolism.

  15. Interrelationships between mitochondrial fusion, energy metabolism and oxidative stress during development in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kayo [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Hartman, Philip S. [Biology Department, Texas Christian University, Fort Worth, TX 76129 (United States); Ishii, Takamasa [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Suda, Hitoshi [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Akatsuka, Akira [Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Shoyama, Tetsuji [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Miyazawa, Masaki [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Ishii, Naoaki, E-mail: nishii@is.icc.u-tokai.ac.jp [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan)

    2011-01-21

    Research highlights: {yields} Growth and development of a fzo-1 mutant defective in the fusion process of mitochondria was delayed relative to the wild type of Caenorhabditis elegans. {yields} Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. {yields} fzo-1 animals had significantly lower metabolism than did N2 and mev-1 overproducing superoxide from mitochondrial electron transport complex II. {yields} Mitochondrial fusion can profoundly affect energy metabolism and development. -- Abstract: Mitochondria are known to be dynamic structures with the energetically and enzymatically mediated processes of fusion and fission responsible for maintaining a constant flux. Mitochondria also play a role of reactive oxygen species production as a byproduct of energy metabolism. In the current study, interrelationships between mitochondrial fusion, energy metabolism and oxidative stress on development were explored using a fzo-1 mutant defective in the fusion process and a mev-1 mutant overproducing superoxide from mitochondrial electron transport complex II of Caenorhabditis elegans. While growth and development of both single mutants was slightly delayed relative to the wild type, the fzo-1;mev-1 double mutant experienced considerable delay. Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. fzo-1 animals had significantly lower metabolism than did N2 and mev-1. These data indicate that mitochondrial fusion can profoundly affect energy metabolism and development.

  16. Role of NAD, Oxidative Stress, and Tryptophan Metabolism in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Musthafa Mohamed Essa

    2013-01-01

    Full Text Available Autism spectrum disorder (ASD is a pervasive neuro-developmental disorder characterized by impaired social interaction, reduced/absent verbal and non-verbal communication, and repetitive behavior during early childhood. The etiology of this developmental disorder is poorly understood, and no biomarkers have been identified. Identification of novel biochemical markers related to autism would be advantageous for earlier clinical diagnosis and intervention. Studies suggest that oxidative stress-induced mechanisms and reduced antioxidant defense, mitochondrial dysfunction, and impaired energy metabolism (NAD + , NADH, ATP, pyruvate, and lactate, are major causes of ASD. This review provides renewed insight regarding current autism research related to oxidative stress, mitochondrial dysfunction, and altered tryptophan metabolism in ASD.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Metabolic and oxidative stress markers in Wistar rats after 2 months on a high-fat diet.

    Science.gov (United States)

    Auberval, Nathalie; Dal, Stéphanie; Bietiger, William; Pinget, Michel; Jeandidier, Nathalie; Maillard-Pedracini, Elisa; Schini-Kerth, Valérie; Sigrist, Séverine

    2014-01-01

    Metabolic syndrome is associated with an increased risk of cardiovascular and hepatic complications. Oxidative stress in metabolic tissues has emerged as a universal feature of metabolic syndrome and its co-morbidities. We aimed to develop a rapidly and easily induced model of metabolic syndrome in rats to evaluate its impact on plasma and tissue oxidative stress. Metabolic syndrome was induced in rats using a high-fat diet (HFD), and these rats were compared to rats fed a normal diet (ND) for 2 months. Metabolic control was determined by measuring body weight, blood glucose, triglycerides, lipid peroxidation and protein carbonylation in plasma. Insulinemia was evaluated through the measure of C-peptide. Histological analysis was performed on the pancreas, liver and blood vessels. After 2 months, the HFD induced an increase in body weight, insulin and triglycerides. Liver steatosis was also observed in the HFD group, which was associated with an increase in glycogen storage. In the pancreas, the HFD induced islet hyperplasia. Tissue oxidative stress was also increased in the liver, pancreas and blood vessels, but plasma oxidative stress remained unchanged. This paper reports the development of a fast and easy model of rat metabolic syndrome associated with tissue oxidative stress. This model may be a good tool for the biological validation of drugs or antioxidants to limit or prevent the complications of metabolic syndrome.

  19. Unchanged cerebral blood flow and oxidative metabolism after acclimatization to high altitude

    DEFF Research Database (Denmark)

    Møller, Kirsten; Paulson, Olaf B; Hornbein, Thomas F.

    2002-01-01

    The authors investigated the effect of acclimatization to high altitude on cerebral blood flow and oxidative metabolism at rest and during exercise. Nine healthy, native sea-level residents were studied 3 weeks after arrival at Chacaltaya, Bolivia (5,260 m) and after reacclimatization to sea level....... At high altitude at rest, arterial carbon dioxide tension, oxygen saturation, and oxygen tension were significantly reduced, and arterial oxygen content was increased because of an increase in hemoglobin concentration. Global cerebral blood flow was similar in the four conditions. Cerebral oxygen delivery...... and cerebral metabolic rates of oxygen and glucose also remained unchanged, whereas cerebral metabolic rates of lactate increased slightly but nonsignificantly at high altitude during exercise compared with high altitude at rest. Reaction time was unchanged. The data indicate that cerebral blood flow...

  20. The role of oxidative stress on the pathophysiology of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Fabiane Valentini Francisqueti

    Full Text Available Summary Metabolic syndrome (MetS has a high prevalence around the world. Considering the components used to classify MetS, it is clear that it is closely related to obesity. These two conditions begin with an increase in abdominal adipose tissue, which is metabolically more active, containing a greater amount of resident macrophages compared to other fat deposits. Abdominal adiposity promotes inflammation and oxidative stress, which are precursors of various complications involving MetS components, namely insulin resistance, hypertension and hyperlipidemia. One way to block the effects of oxidative stress would be through the antioxidant defense system, which offsets the excess free radicals. It is known that individuals with metabolic syndrome and obesity have high consumption of fats and sugars originated from processed foods containing high levels of sodium as well as low intake of fruits and vegetables, thus maintaining a state of oxidative stress, that can speed up the onset of MetS. Healthy eating habits could prevent or delay MetS by adding antioxidant-rich foods into the diet.

  1. Fasting ameliorates metabolism, immunity, and oxidative stress in carbon tetrachloride-intoxicated rats.

    Science.gov (United States)

    Sadek, Km; Saleh, Ea

    2014-12-01

    Fasting has been recently discovered to improve overall health, but its beneficial effects in the presence of hepatic insufficiency have not been proven. The influence of fasting on the metabolism, immunological aspects, and oxidative stress of 40 male carbon tetrachloride (CCl4)-intoxicated Wistar rats was investigated in the present study. The rats were divided into four groups, including a placebo group, CCl4-intoxicated rats, which were injected subcutaneously with 1.0 ml/kg of CCl4 solution, a fasting group, which was fasted 12 h/day for 30 days, and a fourth group, which was injected with CCl4 and fasted. The metabolism, immunity, and oxidative stress improved in CCl4-intoxicated rats fasted for 12 h/day for 30 days, as evidenced in significant increase (p fasting improved metabolism, immunity, and oxidative stress in CCl4-intoxicated rats. Thus, fasting during Ramadan is safe for patients with hepatic disorders, as the prophet Mohammed (S) said "Keep the fast, keep your health". © The Author(s) 2014.

  2. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.

    Science.gov (United States)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner; Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M; De Sousa-Coelho, Ana Luisa; Daher, Grace; Manoli, Irini; Sysol, Justin R; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J; Beebe, Kirk; Gall, Walt; Venditti, Charles P; Patti, Mary-Elizabeth

    2016-10-01

    Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

  3. Calorie restriction hysteretically primes aging Saccharomyces cerevisiae toward more effective oxidative metabolism.

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    Erich B Tahara

    Full Text Available Calorie restriction (CR is an intervention known to extend the lifespan of a wide variety of organisms. In S. cerevisiae, chronological lifespan is prolonged by decreasing glucose availability in the culture media, a model for CR. The mechanism has been proposed to involve an increase in the oxidative (versus fermentative metabolism of glucose. Here, we measured wild-type and respiratory incompetent (ρ(0 S. cerevisiae biomass formation, pH, oxygen and glucose consumption, and the evolution of ethanol, glycerol, acetate, pyruvate and succinate levels during the course of 28 days of chronological aging, aiming to identify metabolic changes responsible for the effects of CR. The concomitant and quantitative measurements allowed for calculations of conversion factors between different pairs of substrates and products, maximum specific substrate consumption and product formation rates and maximum specific growth rates. Interestingly, we found that the limitation of glucose availability in CR S. cerevisiae cultures hysteretically increases oxygen consumption rates many hours after the complete exhaustion of glucose from the media. Surprisingly, glucose-to-ethanol conversion and cellular growth supported by glucose were not quantitatively altered by CR. Instead, we found that CR primed the cells for earlier, faster and more efficient metabolism of respiratory substrates, especially ethanol. Since lifespan-enhancing effects of CR are absent in respiratory incompetent ρ(0 cells, we propose that the hysteretic effect of glucose limitation on oxidative metabolism is central toward chronological lifespan extension by CR in this yeast.

  4. Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons

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    Anne Abot

    2018-04-01

    Full Text Available Objective: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. Methods: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut–brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism were assessed. Results: We show that galanin, a neuropeptide expressed in the small intestine, decreases duodenal contraction by stimulating nitric oxide release from enteric neurons. This is associated with modification of hypothalamic nitric oxide release that favors glucose uptake in metabolic tissues such as skeletal muscle, liver, and adipose tissue. Oral chronic gavage with galanin in diabetic mice increases insulin sensitivity, which is associated with an improvement of several metabolic parameters such as glucose tolerance, fasting blood glucose, and insulin. Conclusion: Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D. Keywords: Galanin, Enteric nervous system, Diabetes

  5. Increasing NAD Synthesis in Muscle via Nicotinamide Phosphoribosyltransferase Is Not Sufficient to Promote Oxidative Metabolism*

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    Frederick, David W.; Davis, James G.; Dávila, Antonio; Agarwal, Beamon; Michan, Shaday; Puchowicz, Michelle A.; Nakamaru-Ogiso, Eiko; Baur, Joseph A.

    2015-01-01

    The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle. PMID:25411251

  6. A novel strategy involved in [corrected] anti-oxidative defense: the conversion of NADH into NADPH by a metabolic network.

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    Ranji Singh

    Full Text Available The reduced nicotinamide adenine dinucleotide phosphate (NADPH is pivotal to the cellular anti-oxidative defence strategies in most organisms. Although its production mediated by different enzyme systems has been relatively well-studied, metabolic networks dedicated to the biogenesis of NADPH have not been fully characterized. In this report, a metabolic pathway that promotes the conversion of reduced nicotinamide adenine dinucleotide (NADH, a pro-oxidant into NADPH has been uncovered in Pseudomonas fluorescens exposed to oxidative stress. Enzymes such as pyruvate carboxylase (PC, malic enzyme (ME, malate dehydrogenase (MDH, malate synthase (MS, and isocitrate lyase (ICL that are involved in disparate metabolic modules, converged to create a metabolic network aimed at the transformation of NADH into NADPH. The downregulation of phosphoenol carboxykinase (PEPCK and the upregulation of pyruvate kinase (PK ensured that this metabolic cycle fixed NADH into NADPH to combat the oxidative stress triggered by the menadione insult. This is the first demonstration of a metabolic network invoked to generate NADPH from NADH, a process that may be very effective in combating oxidative stress as the increase of an anti-oxidant is coupled to the decrease of a pro-oxidant.

  7. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism

    DEFF Research Database (Denmark)

    Mourtzakis, M.; Graham, T.E.; Gonzalez-Alonso, J.

    2008-01-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate...... declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70......% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (Pglutamate infusion. Peak...

  8. Citrus Polyphenol Hesperidin Stimulates Production of Nitric Oxide in Endothelial Cells while Improving Endothelial Function and Reducing Inflammatory Markers in Patients with Metabolic Syndrome

    Science.gov (United States)

    Rizza, Stefano; Muniyappa, Ranganath; Iantorno, Micaela; Kim, Jeong-a; Chen, Hui; Pullikotil, Philomena; Senese, Nicoletta; Tesauro, Manfredi; Lauro, Davide; Cardillo, Carmine

    2011-01-01

    Context: Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. Objective: We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. Design, Setting, and Interventions: Cellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24). Main Outcome Measure: We measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods. Results: Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H2O2. Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 ± 1.19 vs. 7.78 ± 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin). Conclusions: Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption. PMID:21346065

  9. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    Science.gov (United States)

    Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

    2016-01-01

    Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

  10. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

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    Elena Lima-Cabello

    2016-01-01

    Full Text Available Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

  11. Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved?

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    Thalia M. T. Avelar

    2015-08-01

    Full Text Available ABSTRACTMetabolic syndrome (MS is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD, catalase (CAT and gluthatione peroxidase (GPx. The high-density lipoprotein cholesterol (HDL-c is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1 activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

  12. Role of ring oxidation in the metabolic activation of 1-nitropyrene.

    Science.gov (United States)

    Beland, F A

    1991-12-01

    Nitrated polycyclic aromatic hydrocarbons are wide-spread environmental pollutants that have been detected in photocopier toners, airborne particulates, coal fly ash, and diesel engine exhaust emissions. 1-Nitropyrene, a representative nitropolycyclic aromatic hydrocarbon present in diesel particulates, is a mutagen in Salmonella typhimurium and a tumorigen in laboratory animals. The activation of 1-nitropyrene to a bacterial mutagen has been attributed to nitroreduction; however, the metabolic pathways involved in its metabolism to a tumorigen are not known, but may involve nitroreduction, ring oxidation, or a combination of the two. In these experiments, we examined the importance of ring oxidation in the activation of 1-nitropyrene (99.85 to 99.98 percent 1-nitropyrene, 0.15 to 0.02 percent 1,3-, 1,6-, and 1,8-dinitropyrene by mass spectral analyses) to a mammalian-cell mutagen and carcinogen. Chinese hamster ovary cells were used to assess the mutagenicity of ring-oxidized 1-nitropyrene metabolites. In the absence of a rat liver 9,000 x g supernatant, 6-hydroxy-1-nitropyrene, 1-nitropyrene-9,10-oxide, and pyrene-4,5-oxide were the most mutagenic compounds tested. 3-Hydroxy-1-nitropyrene, 8-hydroxy-1-nitropyrene, and 1-nitropyrene-4,5-oxide were weaker mutagens, whereas pyrene and 1-nitropyrene were essentially nonmutagenic. The order of mutagenic potency with S9 was: 1-nitropyrene-4,5-oxide greater than 6-hydroxy-1-nitropyrene approximately 1-nitropyrene-9,10-oxide greater than 1-nitropyrene approximately 3-hydroxy-1-nitropyrene approximately 8-hydroxy-1-nitropyrene greater than pyrene approximately pyrene-4,5-oxide, with the last two compounds being nearly nonmutagenic. The epoxide hydrase inhibitor 1,2-epoxy-3,3,3-trichloropropane increased the mutation frequency fivefold. In addition, guinea pig liver microsomes and Aroclor-induced rat liver microsomes, which increased the formation of 1-nitropyrene-4,5-oxide and 1-nitropyrene-9,10-oxide, increased the

  13. Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals.

    Science.gov (United States)

    Bañuls, C; Rovira-Llopis, S; Lopez-Domenech, S; Diaz-Morales, N; Blas-Garcia, A; Veses, S; Morillas, C; Victor, V M; Rocha, M; Hernandez-Mijares, A

    2017-10-01

    Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO) and 31 had type 2 diabetes (MADO). We assessed metabolic parameters, proinflammatory cytokines (TNFα and IL-6), mitochondrial and total reactive oxygen species (ROS) production, glutathione levels, antioxidant enzymes activity, total antioxidant status, mitochondrial membrane potential and ER stress marker expression levels (glucose-regulated protein (GRP78), spliced X-box binding protein 1 (XBP1), P-subunit 1 alpha (P-eIF2α) and activating transcription factor 6 (ATF6). The MAO and MADO groups showed higher blood pressure, atherogenic dyslipidemia, insulin resistance and inflammatory profile than that of MHO subjects. Total and mitochondrial ROS production was enhanced in MAO and MADO patients, and mitochondrial membrane potential and catalase activity differed significantly between the MADO and MHO groups. In addition, decreases in glutathione levels and superoxide dismutase activity were observed in the MADO vs MAO and MHO groups. GRP78 and CHOP protein and gene expression were higher in the MAO and MADO groups with respect to MHO subjects, and sXBP1 gene expression was associated with the presence of diabetes. Furthermore, MAO patients exhibited higher levels of ATF6 than their MHO counterparts. Waist circumference was positively correlated with ATF6 and GRP78, and A1c was positively correlated with P-Eif2α. Interestingly, CHOP was positively correlated with TNFα and total ROS production and GRP78 was negatively correlated with glutathione levels. Our findings support the

  14. CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48.

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    Holm, Niels Bjerre; Nielsen, Line Marie; Linnet, Kristian

    2015-09-01

    Synthetic cannabinoid designer drugs have emerged as drugs of abuse during the last decade, and acute intoxication cases are documented in the scientific literature. Synthetic cannabinoids are extensively metabolized, but our knowledge of the involved enzymes is limited. Here, we investigated the metabolism of N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), a compound identified in herbal blends from 2012 and onwards. We screened for metabolite formation using a panel of nine recombinant cytochrome P450 (CYP) enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4) and compared the formed metabolites to human liver microsomal (HLM) incubations with specific inhibitors against CYP2D6, 2C19, and 3A4, respectively. The data reported here demonstrate CYP3A4 to be the major CYP enzyme responsible for the oxidative metabolism of AKB-48, preferentially performing the oxidation on the adamantyl moiety. Genetic polymorphisms are likely not important with regard to toxicity given the major involvement of CYP3A4. Adverse drug-drug interactions (DDIs) could potentially occur in cases with co-intake of strong CYP3A4 inhibitors, e.g., HIV antivirals and azole antifungal agents.

  15. Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle.

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    Sofi G Julien

    2017-02-01

    Full Text Available Obesity develops when caloric intake exceeds metabolic needs. Promoting energy expenditure represents an attractive approach in the prevention of this fast-spreading epidemic. Here, we report a novel pharmacological strategy in which a natural compound, narciclasine (ncls, attenuates diet-induced obesity (DIO in mice by promoting energy expenditure. Moreover, ncls promotes fat clearance from peripheral metabolic tissues, improves blood metabolic parameters in DIO mice, and protects these mice from the loss of voluntary physical activity. Further investigation suggested that ncls achieves these beneficial effects by promoting a shift from glycolytic to oxidative muscle fibers in the DIO mice thereby enhancing mitochondrial respiration and fatty acid oxidation (FAO in the skeletal muscle. Moreover, ncls strongly activates AMPK signaling specifically in the skeletal muscle. The beneficial effects of ncls treatment in fat clearance and AMPK activation were faithfully reproduced in vitro in cultured murine and human primary myotubes. Mechanistically, ncls increases cellular cAMP concentration and ADP/ATP ratio, which further lead to the activation of AMPK signaling. Blocking AMPK signaling through a specific inhibitor significantly reduces FAO in myotubes. Finally, ncls also enhances mitochondrial membrane potential and reduces the formation of reactive oxygen species in cultured myotubes.

  16. Ordovas-Oxidized LDL is associated with metabolic syndrome traits independently of central obesity and insulin resistance

    Science.gov (United States)

    This study assesses whether oxidative stress, using oxidized LDL (ox-LDL) as a proxy, is associated with metabolic syndrome (MS), whether ox-LDL mediates the association between central obesity and MS, and whether insulin resistance mediates the association between ox-LDL and MS. We examined baselin...

  17. The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism.

    Science.gov (United States)

    Cisternas, Pedro; Silva-Alvarez, Carmen; Martínez, Fernando; Fernandez, Emilio; Ferrada, Luciano; Oyarce, Karina; Salazar, Katterine; Bolaños, Juan P; Nualart, Francisco

    2014-05-01

    Vitamin C is an essential factor for neuronal function and survival, existing in two redox states, ascorbic acid (AA), and its oxidized form, dehydroascorbic acid (DHA). Here, we show uptake of both AA and DHA by primary cultures of rat brain cortical neurons. Moreover, we show that most intracellular AA was rapidly oxidized to DHA. Intracellular DHA induced a rapid and dramatic decrease in reduced glutathione that was immediately followed by a spontaneous recovery. This transient decrease in glutathione oxidation was preceded by an increase in the rate of glucose oxidation through the pentose phosphate pathway (PPP), and a concomitant decrease in glucose oxidation through glycolysis. DHA stimulated the activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the PPP. Furthermore, we found that DHA stimulated the rate of lactate uptake by neurons in a time- and dose-dependent manner. Thus, DHA is a novel modulator of neuronal energy metabolism by facilitating the utilization of glucose through the PPP for antioxidant purposes. © 2014 International Society for Neurochemistry.

  18. Effects of long-term football training on the expression profile of genes involved in muscle oxidative metabolism

    DEFF Research Database (Denmark)

    Alfieri, A; Martone, D; Randers, Morten Bredsgaard

    2015-01-01

    and a muscle biopsy from the vastus lateralis were collected at T0 (pre intervention) and at T1 (post intervention). Gene expression was measured by RTqPCR on RNA extracted from muscle biopsies. The expression levels of the genes principally involved in energy metabolism (PPARγ, adiponectin, AMPKα1/α2, TFAM...... to improve the expression of muscle molecular biomarkers that are correlated to oxidative metabolism in healthy males....... are directly or indirectly involved in the glucose and lipid oxidative metabolism. Multiple linear regression analysis revealed that fat percentage was independently associated with NAMPT, PPARγ and adiponectin expression. In conclusion, long-term recreational football training could be a useful tool...

  19. Metatranscriptomic and metagenomic description of the bacterial nitrogen metabolism in waste water wet oxidation effluents

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    Julien Crovadore

    2017-10-01

    Full Text Available Anaerobic digestion is a common method for reducing the amount of sludge solids in used waters and enabling biogas production. The wet oxidation process (WOX improves anaerobic digestion by converting carbon into methane through oxidation of organic compounds. WOX produces effluents rich in ammonia, which must be removed to maintain the activity of methanogens. Ammonia removal from WOX could be biologically operated by aerobic granules. To this end, granulation experiments were conducted in 2 bioreactors containing an activated sludge (AS. For the first time, the dynamics of the microbial community structure and the expression levels of 7 enzymes of the nitrogen metabolism in such active microbial communities were followed in regard to time by metagenomics and metatranscriptomics. It was shown that bacterial communities adapt to the wet oxidation effluent by increasing the expression level of the nitrogen metabolism, suggesting that these biological activities could be a less costly alternative for the elimination of ammonia, resulting in a reduction of the use of chemicals and energy consumption in sewage plants. This study reached a strong sequencing depth (from 4.4 to 7.6 Gb and enlightened a yet unknown diversity of the microorganisms involved in the nitrogen pathway. Moreover, this approach revealed the abundance and expression levels of specialised enzymes involved in nitrification, denitrification, ammonification, dissimilatory nitrate reduction to ammonium (DNRA and nitrogen fixation processes in AS. Keywords: Applied sciences, Biological sciences, Environmental science, Genetics, Microbiology

  20. Hormonal enhancement of insecticide efficacy in Tribolium castaneum: oxidative stress and metabolic aspects.

    Science.gov (United States)

    Plavšin, Ivana; Stašková, Tereza; Šerý, Michal; Smýkal, Vlastimil; Hackenberger, Branimir K; Kodrík, Dalibor

    2015-04-01

    Insect anti-stress responses, including those induced by insecticides, are controlled by adipokinetic hormones (AKHs). We examined the physiological consequences of Pyrap-AKH application on Tribolium castaneum adults (AKH-normal and AKH-deficient prepared by the RNAi technique) treated by two insecticides, pirimiphos-methyl and deltamethrin. Co-application of pirimiphos-methyl and/or deltamethrin with AKH significantly increased beetle mortality compared with application of the insecticides alone. This co-treatment was accompanied by substantial stimulation of general metabolism, as monitored by carbon dioxide production. Further, the insecticide treatment alone affected some basic markers of oxidative stress: it lowered total antioxidative capacity as well as the activity of superoxide dismutase in the beetle body; in addition, it enhanced the activity of catalase and glutathione-S-transferase. However, these discrepancies in oxidative stress markers were eliminated/reduced by co-application with Pyrap-AKH. We suggest that the elevation of metabolism, which is probably accompanied with faster turnover of toxins, might be responsible for the higher mortality that results after AKH and insecticide co-application. Changes in oxidative stress markers are probably not included in the mechanisms responsible for increased mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation.

    Science.gov (United States)

    Zheng, Xinde; Boyer, Leah; Jin, Mingji; Mertens, Jerome; Kim, Yongsung; Ma, Li; Ma, Li; Hamm, Michael; Gage, Fred H; Hunter, Tony

    2016-06-10

    How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size.

  2. Palmitate-induced inflammatory pathways in human adipose microvascular endothelial cells promote monocyte adhesion and impair insulin transcytosis.

    Science.gov (United States)

    Pillon, Nicolas J; Azizi, Paymon M; Li, Yujin E; Liu, Jun; Wang, Changsen; Chan, Kenny L; Hopperton, Kathryn E; Bazinet, Richard P; Heit, Bryan; Bilan, Philip J; Lee, Warren L; Klip, Amira

    2015-07-01

    Obesity is associated with inflammation and immune cell recruitment to adipose tissue, muscle and intima of atherosclerotic blood vessels. Obesity and hyperlipidemia are also associated with tissue insulin resistance and can compromise insulin delivery to muscle. The muscle/fat microvascular endothelium mediates insulin delivery and facilitates monocyte transmigration, yet its contribution to the consequences of hyperlipidemia is poorly understood. Using primary endothelial cells from human adipose tissue microvasculature (HAMEC), we investigated the effects of physiological levels of fatty acids on endothelial inflammation and function. Expression of cytokines and adhesion molecules was measured by RT-qPCR. Signaling pathways were evaluated by pharmacological manipulation and immunoblotting. Surface expression of adhesion molecules was determined by immunohistochemistry. THP1 monocyte interaction with HAMEC was measured by cell adhesion and migration across transwells. Insulin transcytosis was measured by total internal reflection fluorescence microscopy. Palmitate, but not palmitoleate, elevated the expression of IL-6, IL-8, TLR2 (Toll-like receptor 2), and intercellular adhesion molecule 1 (ICAM-1). HAMEC had markedly low fatty acid uptake and oxidation, and CD36 inhibition did not reverse the palmitate-induced expression of adhesion molecules, suggesting that inflammation did not arise from palmitate uptake/metabolism. Instead, inhibition of TLR4 to NF-κB signaling blunted palmitate-induced ICAM-1 expression. Importantly, palmitate-induced surface expression of ICAM-1 promoted monocyte binding and transmigration. Conversely, palmitate reduced insulin transcytosis, an effect reversed by TLR4 inhibition. In summary, palmitate activates inflammatory pathways in primary microvascular endothelial cells, impairing insulin transport and increasing monocyte transmigration. This behavior may contribute in vivo to reduced tissue insulin action and enhanced tissue

  3. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men

    DEFF Research Database (Denmark)

    van der Beek, Christina M; Canfora, Emanuel E; Lenaerts, Kaatje

    2016-01-01

    , circulating hormones or inflammatory markers. In conclusion distal colonic acetate infusions affected whole-body substrate metabolism, with a pronounced increase in fasting fat oxidation and plasma PYY. Modulating colonic acetate may be a nutritional target to treat or prevent metabolic disorders.......Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men...... in the colon for three consecutive test days, enabling colonic acetate (100 or 180 mmol/l) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were...

  4. Methylglyoxal-bis-guanylhydrazone inhibits osteopontin expression and differentiation in cultured human monocytes.

    Science.gov (United States)

    Jin, Xia; Xu, Hua; McGrath, Michael S

    2018-01-01

    Monocyte activation and polarization play essential roles in many chronic inflammatory diseases. An imbalance of M1 and M2 macrophage activation (pro-inflammatory and alternatively activated, respectively) is believed to be a key aspect in the etiology of these diseases, thus a therapeutic approach that regulates macrophage activation could be of broad clinical relevance. Methylglyoxal-bis-guanylhydrazone (MGBG), a regulator of polyamine metabolism, has recently been shown to be concentrated in monocytes and macrophages, and interfere with HIV integration into the DNA of these cells in vitro. RNA expression analysis of monocytes from HIV+ and control donors with or without MGBG treatment revealed the only gene to be consistently down regulated by MGBG to be osteopontin (OPN). The elevated expression of this pro-inflammatory cytokine and monocyte chemoattractant is associated with various chronic inflammatory diseases. We demonstrate that MGBG is a potent inhibitor of secreted OPN (sOPN) in cultured monocytes with 50% inhibition achieved at 0.1 μM of the drug. Furthermore, inhibition of OPN RNA transcription in monocyte cultures occurs at similar concentrations of the drug. During differentiation of monocytes into macrophages in vitro, monocytes express cell surface CD16 and the cells undergo limited DNA synthesis as measured by uptake of BrdU. MGBG inhibited both activities at similar doses to those regulating OPN expression. In addition, monocyte treatment with MGBG inhibited differentiation into both M1 and M2 classes of macrophages at non-toxic doses. The inhibition of differentiation and anti-OPN effects of MGBG were specific for monocytes in that differentiated macrophages were nearly resistant to MGBG activities. Thus MGBG may have potential therapeutic utility in reducing or normalizing OPN levels and regulating monocyte activation in diseases that involve chronic inflammation.

  5. Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways

    Directory of Open Access Journals (Sweden)

    Javed K. Manesia

    2015-11-01

    Full Text Available Hematopoietic stem cells (HSCs in the fetal liver (FL unlike adult bone marrow (BM proliferate extensively, posing different metabolic demands. However, metabolic pathways responsible for the production of energy and cellular building blocks in FL HSCs have not been described. Here, we report that FL HSCs use oxygen dependent energy generating pathways significantly more than their BM counterparts. RNA-Seq analysis of E14.5 FL versus BM derived HSCs identified increased expression levels of genes involved in oxidative phosphorylation (OxPhos and the citric acid cycle (TCA. We demonstrated that FL HSCs contain more mitochondria than BM HSCs, which resulted in increased levels of oxygen consumption and reactive oxygen species (ROS production. Higher levels of DNA repair and antioxidant pathway gene expression may prevent ROS-mediated (genotoxicity in FL HSCs. Thus, we here for the first time highlight the underestimated importance of oxygen dependent pathways for generating energy and building blocks in FL HSCs.

  6. Effects of nitrous oxide on cerebral haemodynamics and metabolism during isoflurane anaesthesia in man

    International Nuclear Information System (INIS)

    Algotsson, L.; Messeter, K.; Rosen, I.; Holmin. T.

    1992-01-01

    Seven normoventilated and five hyperventilated healthy adults undergoing cholecystectomy and anaesthetized with methohexitone, fentanyl and pancuronium were studied with measurement of cerebral blood flow (CBF), cereal metabolic rate of oxygen (CMRo 2 ), and quantified electroencephalography (EEG) under two sets of conditions: 1) 1.7% end-tidal concentration of isoflurane in air/oxygen: 2) 0.85% end-tidal concentration of isoflurane in nitrous oxide (N 2 O)/oxygen. The object was to study the effects of N 2 O during isoflurane anaesthesia on cerebral circulation, metabolism and neuroelectric activity. N 2 O in the anaesthetic gas mixture caused a 43% (P 2 was not significantly altered by N 2 O. EEG demonstrated an activated pattern with decreased low frequency activity and increased high frequency activity. The results confirm that N 2 O is a potent cerebral vasodilator in man, although the mechanisms underlying the effects on CBF are still unclear. (au)

  7. An unknown oxidative metabolism substantially contributes to soil CO2 emissions

    Directory of Open Access Journals (Sweden)

    T. Shahzad

    2013-02-01

    Full Text Available The respiratory release of CO2 from soils is a major determinant of the global carbon cycle. It is traditionally considered that this respiration is an intracellular metabolism consisting of complex biochemical reactions carried out by numerous enzymes and co-factors. Here we show that the endoenzymes released from dead organisms are stabilised in soils and have access to suitable substrates and co-factors to permit function. These enzymes reconstitute an extracellular oxidative metabolism (EXOMET that may substantially contribute to soil respiration (16 to 48% of CO2 released from soils in the present study. EXOMET and respiration from living organisms should be considered separately when studying effects of environmental factors on the C cycle because EXOMET shows specific properties such as resistance to high temperature and toxic compounds.

  8. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

    Science.gov (United States)

    Azzam, Edouard I.; Jay-Gerin, Jean-Paul; Pain, Debkumar

    2013-01-01

    Cellular exposure to ionizing radiation leads to oxidizing events that alter atomic structure through direct interactions of radiation with target macromolecules or via products of water radiolysis. Further, the oxidative damage may spread from the targeted to neighboring, non-targeted bystander cells through redox-modulated intercellular communication mechanisms. To cope with the induced stress and the changes in the redox environment, organisms elicit transient responses at the molecular, cellular and tissue levels to counteract toxic effects of radiation. Metabolic pathways are induced during and shortly after the exposure. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Physiological levels of reactive oxygen and nitrogen species play critical roles in many cellular functions. In irradiated cells, levels of these reactive species may be increased due to perturbations in oxidative metabolism and chronic inflammatory responses, thereby contributing to the long-term effects of exposure to ionizing radiation on genomic stability. Here, in addition to immediate biological effects of water radiolysis on DNA damage, we also discuss the role of mitochondria in the delayed outcomes of ionization radiation. Defects in mitochondrial functions lead to accelerated aging and numerous pathological conditions. Different types of radiation vary in their linear energy transfer (LET) properties, and we discuss their effects on various aspects of mitochondrial physiology. These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes. PMID:22182453

  9. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  10. Positron emission tomography with [11C]-acetate for evaluation of myocardial oxidative metabolism. Clinical use

    International Nuclear Information System (INIS)

    Litvinova, I.S.; Litvinov, M.M.; Rozhkova, G.G.; Leont'eva, I.V.; Sebeleva, I.A.; Tumanyan, M.R.; Koledinskij, D.G.; Sukhorukov, V.S.

    2001-01-01

    The diagnostic potentials of positron emission tomography (PET) with [ 11 C]-acetate as applied to mitochondrial disorders in children with cardiomyopathies (CMP) are evaluated. PET examinations are performed in 17 patients of the mean age of 7.5 ± 3.1 years with CMP. A dynamic study with [ 11 C]-acetate is conducted to evaluate the Krebs cycle activity. The experiments have indicated to a fewer accumulation of [ 11 C]-acetate and to its slower clearance in the ischemic zone as compared with the normal myocardium. The Krebs cycle activity has been reduced. By means of PET with [ 11 C]-acetate the oxidation rate constant of the Krebs cycle and the [ 11 C]-acetate-activity clearance half-time can be quantified. This makes possible to assess the extent of oxidative metabolism malfunction, including the case of perfusion reduction [ru

  11. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism.

    Science.gov (United States)

    Mourtzakis, M; Graham, T E; González-Alonso, J; Saltin, B

    2008-08-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (PTCA cycle intermediates. In the UT thigh, peak exercise (vs. rest) induced an increase in fumarate (0.33+/-0.07 vs. 0.02+/-0.01 mmol/kg dry wt (dw), PTCA cycle, glutamate and TCA cycle intermediates do not directly affect VO2peak in either trained or untrained muscle.

  12. High basal metabolic rate does not elevate oxidative stress during reproduction in laboratory mice.

    Science.gov (United States)

    Brzęk, Paweł; Książek, Aneta; Ołdakowski, Łukasz; Konarzewski, Marek

    2014-05-01

    Increased oxidative stress (OS) has been suggested as a physiological cost of reproduction. However, previous studies reported ambiguous results, with some even showing a reduction of oxidative damage during reproduction. We tested whether the link between reproduction and OS is mediated by basal metabolic rate (BMR), which has been hypothesized to affect both the rate of radical oxygen species production and antioxidative capacity. We studied the effect of reproduction on OS in females of laboratory mice divergently selected for high (H-BMR) and low (L-BMR) BMR, previously shown to differ with respect to parental investment. Non-reproducing L-BMR females showed higher oxidative damage to lipids (quantified as the level of malondialdehyde in internal organ tissues) and DNA (quantified as the level of 8-oxodG in blood serum) than H-BMR females. Reproduction did not affect oxidative damage to lipids in either line; however, it reduced damage to DNA in L-BMR females. Reproduction increased catalase activity in liver (significantly stronger in L-BMR females) and decreased it in kidneys. We conclude that the effect of reproduction on OS depends on the initial variation in BMR and varies between studied internal organs and markers of OS.

  13. Nitric oxide metabolism and indole acetic acid biosynthesis cross-talk in Azospirillum brasilense SM.

    Science.gov (United States)

    Koul, Vatsala; Tripathi, Chandrakant; Adholeya, Alok; Kochar, Mandira

    2015-04-01

    Production of nitric oxide (NO) and the presence of NO metabolism genes, nitrous oxide reductase (nosZ), nitrous oxide reductase regulator (nosR) and nitric oxide reductase (norB) were identified in the plant-associated bacterium (PAB) Azospirillum brasilense SM. NO presence was confirmed in all overexpressing strains, while improvement in the plant growth response of these strains was mediated by increased NO and indole-3-acetic acid (IAA) levels in the strains. Electron microscopy showed random distribution to biofilm, with surface colonization of pleiomorphic Azospirilla. Quantitative IAA estimation highlighted a crucial role of nosR and norBC in regulating IAA biosynthesis. The NO quencher and donor reduced/blocked IAA biosynthesis by all strains, indicating their common regulatory role in IAA biosynthesis. Tryptophan (Trp) and l-Arginine (Arg) showed higher expression of NO genes tested, while in the case of ipdC, only Trp and IAA increased expression, while Arg had no significant effect. The highest nosR expression in SMnosR in the presence of IAA and Trp, along with its 2-fold IAA level, confirmed the relationship of nosR overexpression with Trp in increasing IAA. These results indicate a strong correlation between IAA and NO in A. brasilense SM and suggest the existence of cross-talk or shared signaling mechanisms in these two growth regulators. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  14. Simulation of the oxidative metabolism of diclofenac by electrochemistry/(liquid chromatography/)mass spectrometry.

    Science.gov (United States)

    Faber, Helene; Melles, Daniel; Brauckmann, Christine; Wehe, Christoph Alexander; Wentker, Kristina; Karst, Uwe

    2012-04-01

    Diclofenac is a frequently prescribed drug for rheumatic diseases and muscle pain. In rare cases, it may be associated with a severe hepatotoxicity. In literature, it is discussed whether this toxicity is related to the oxidative phase I metabolism, resulting in electrophilic quinone imines, which can subsequently react with nucleophiles present in the liver in form of glutathione or proteins. In this work, electrochemistry coupled to mass spectrometry is used as a tool for the simulation of the oxidative pathway of diclofenac. Using this purely instrumental approach, diclofenac was oxidized in a thin layer cell equipped with a boron doped diamond working electrode. Sum formulae of generated oxidation products were calculated based on accurate mass measurements with deviations below 2 ppm. Quinone imines from diclofenac were detected using this approach. It could be shown for the first time that these quinone imines do not react with glutathione exclusively but also with larger molecules such as the model protein β-lactoglobulin A. A tryptic digest of the generated drug-protein adduct confirms that the protein is modified at the only free thiol-containing peptide. This simple and purely instrumental set-up offers the possibility of generating reactive metabolites of diclofenac and to assess their reactivity rapidly and easily.

  15. Cytochrome P450s: mechanisms and biological implications in drug metabolism and its interaction with oxidative stress.

    Science.gov (United States)

    Bhattacharyya, Sudip; Sinha, Krishnendu; Sil, Parames C

    2014-01-01

    Cytochrome monooxygenases P450 enzymes (CYPs) are terminal oxidases, belonging to the multi-gene family of heme-thiolate enzymes and located in multiple sites of ER, cytosol and mitochondria. CYPs act as catalysts in drugs metabolism. This review highlights the mitochondrial and microsomal CYPs metabolic functions, CYPs mediated ROS generation and its feedback, bioactivation of drugs and related hypersensitivity, metabolic disposition as well as the therapeutic approaches. CYPs mediated drugs bioactivation may trigger oxidative stress and cause pathophysiology. Almost all drugs show some adverse reactions at high doses or accidental overdoses. Drugs lead to hypersensitivity reactions while metabolic predisposition to drug hypersensitivity exaggerates it. Mostly different intermediate bioactive products of CYPs mediated drug metabolism is the principal issue in this respect. On the other hand, CYPs are the main source of ROS. Their generation and feedback are of major concern of this review. Besides drug metabolism, CYPs also contribute significantly to carcinogen metabolism. Ultimately other enzymes in drug metabolism and antioxidant therapy are indispensible. Importance of this field: In a global sense, understanding of exact mechanism can facilitate pharmaceutical industries' challenge of developing drugs without toxicity. Ultimate message: This review would accentuate the recent advances in molecular mechanism of CYPs mediated drug metabolism and complex cross-talks between various restorative novel strategies evolved by CYPs to sustain the redox balance and limit the source of oxidative stress.

  16. The radioactive labeling of monocytes

    International Nuclear Information System (INIS)

    Ensing, G.J.

    1985-01-01

    With the aim of studying a possible relationship between circulating monocytes and Sternberg-Reed cells investigations were started on the specific labeling of monocytes. In this thesis the literature on the pertinent data has been reviewed and a series of experiments on the monocyte labeling procedure has been described. The principles of cell labeling with radioactive compounds were discussed. 1. Total separation of the particular cell population to be labeled and subsequent labeling with a non-specific radiopharmaceutical. 2. Specific cell labeling in a mixture of cell types based on a well defined affinity of the cell under study for the radiopharmaceutical used. Next the radionuclides that can be used for cell labeling purposes were discussed with special attention for 111 In and its chelates. The principles of radiodosimetry were also discussed shortly. This section was focussed on the radiation dose the labeled cells receive because of the intracellular localized radioactivity. The radiation burden is high in comparison to amounts of radiation known to affect cell viability. A newly developed method for labeling monocytes specifically by phagocytosis of 111 In-Fe-colloid without apparent loss of cells was described in detail. (Auth.)

  17. The Impact of Rapid Weight Loss on Oxidative Stress Markers and the Expression of the Metabolic Syndrome in Obese Individuals

    Directory of Open Access Journals (Sweden)

    Eva Tumova

    2013-01-01

    Full Text Available Objective. Obesity is linked with a state of increased oxidative stress, which plays an important role in the etiology of atherosclerosis and type 2 diabetes mellitus. The aim of our study was to evaluate the effect of rapid weight loss on oxidative stress markers in obese individuals with metabolic syndrome (MetS. Design and Methods. We measured oxidative stress markers in 40 obese subjects with metabolic syndrome (MetS+, 40 obese subjects without metabolic syndrome (MetS−, and 20 lean controls (LC at baseline and after three months of very low caloric diet. Results. Oxidized low density lipoprotein (ox-LDL levels decreased by 12% in MetS+ subjects, associated with a reduction in total cholesterol (TC, even after adjustment for age and sex. Lipoprotein associated phospholipase A2 (Lp-PLA2 activity decreased by 4.7% in MetS+ subjects, associated with a drop in LDL-cholesterol (LDL-C, TC, and insulin levels. Multivariate logistic regression analysis showed that a model including ox-LDL, LpPLA2 activity, and myeloperoxidase (MPO improved prediction of MetS status among obese individuals compared to each oxidative stress marker alone. Conclusions. Oxidative stress markers were predictive of MetS in obese subjects, suggesting a higher oxidative stress. Rapid weight loss resulted in a decline in oxidative stress markers, especially in MetS+ patients.

  18. Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro.

    Science.gov (United States)

    Wang, Xu; Wu, Qinghua; Liu, Aimei; Anadón, Arturo; Rodríguez, José-Luis; Martínez-Larrañaga, María-Rosa; Yuan, Zonghui; Martínez, María-Aránzazu

    2017-11-01

    Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.

  19. Metabolic syndrome enhances endoplasmic reticulum, oxidative stress and leukocyte-endothelium interactions in PCOS.

    Science.gov (United States)

    Bañuls, Celia; Rovira-Llopis, Susana; Martinez de Marañon, Aranzazu; Veses, Silvia; Jover, Ana; Gomez, Marcelino; Rocha, Milagros; Hernandez-Mijares, Antonio; Victor, Victor M

    2017-06-01

    Polycystic ovary syndrome (PCOS) is associated with insulin resistance, which can lead to metabolic syndrome (MetS). Oxidative stress and leukocyte-endothelium interactions are related to PCOS. Our aim was to evaluate whether the presence of MetS in PCOS patients can influence endoplasmic reticulum (ER) and oxidative stress and leukocyte-endothelium interactions. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 148 PCOS women (116 without/32 with MetS) and 112 control subjects (87 without / 25 with MetS). Metabolic parameters, reactive oxygen species (ROS) production, ER stress markers (GRP78, sXBP1, ATF6), leukocyte-endothelium interactions, adhesion molecules (VCAM-1, ICAM-1, E-Selectin), TNF-α and IL-6 were determined. Total ROS, inflammatory parameters and adhesion molecules were enhanced in the presence of MetS (pPCOS+MetS group showed higher levels of IL-6 and ICAM-1 than controls (pPCOS and PCOS+MetS groups vs their respective controls (pPCOS groups (pPCOS+MetS patients exhibited higher GRP78 and ATF6 levels than controls and PCOS patients without MetS (pPCOS women, HOMA-IR was positively correlated with ICAM-1 (r=0.501; pPCOS, all of which are related to vascular complications. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

    Science.gov (United States)

    Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

    2014-07-01

    The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Dyslipidemic Diet-Induced Monocyte “Priming” and Dysfunction in Non-Human Primates Is Triggered by Elevated Plasma Cholesterol and Accompanied by Altered Histone Acetylation

    Directory of Open Access Journals (Sweden)

    John D. Short

    2017-08-01

    Full Text Available Monocytes and the recruitment of monocyte-derived macrophages into sites of inflammation play a key role in atherogenesis and other chronic inflammatory diseases linked to cardiometabolic syndrome and obesity. Previous studies from our group have shown that metabolic stress promotes monocyte priming, i.e., enhanced adhesion and accelerated chemotaxis of monocytes in response to chemokines, both in vitro and in dyslipidemic LDLR−/− mice. We also showed that metabolic stress-induced monocyte dysfunction is, at least to a large extent caused by the S-glutathionylation, inactivation, and subsequent degradation of mitogen-activated protein kinase phosphatase 1. Here, we analyzed the effects of a Western-style, dyslipidemic diet (DD, which was composed of high levels of saturated fat, cholesterol, and simple sugars, on monocyte (dysfunction in non-human primates (NHPs. We found that similar to mice, a DD enhances monocyte chemotaxis in NHP within 4 weeks, occurring concordantly with the onset of hypercholesterolemia but prior to changes in triglycerides, blood glucose, monocytosis, or changes in monocyte subset composition. In addition, we identified transitory decreases in the acetylation of histone H3 at the lysine residues 18 and 23 in metabolically primed monocytes, and we found that monocyte priming was correlated with the acetylation of histone H3 at lysine 27 after an 8-week DD regimen. Our data show that metabolic stress promotes monocyte priming and hyper-chemotactic responses in NHP. The histone modifications accompanying monocyte priming in primates suggest a reprogramming of the epigenetic landscape, which may lead to dysregulated responses and functionalities in macrophages derived from primed monocytes that are recruited to sites of inflammation.

  2. Measurement of the unfolded protein response (UPR) in monocytes.

    LENUS (Irish Health Repository)

    Carroll, Tomás P

    2011-01-01

    In mammalian cells, the primary function of the endoplasmic reticulum (ER) is to synthesize and assemble membrane and secreted proteins. As the main site of protein folding and posttranslational modification in the cell, the ER operates a highly conserved quality control system to ensure only correctly assembled proteins exit the ER and misfolded and unfolded proteins are retained for disposal. Any disruption in the equilibrium of the ER engages a multifaceted intracellular signaling pathway termed the unfolded protein response (UPR) to restore normal conditions in the cell. A variety of pathological conditions can induce activation of the UPR, including neurodegenerative disorders such as Parkinson\\'s disease, metabolic disorders such as atherosclerosis, and conformational disorders such as cystic fibrosis. Conformational disorders are characterized by mutations that modify the final structure of a protein and any cells that express abnormal protein risk functional impairment. The monocyte is an important and long-lived immune cell and acts as a key immunological orchestrator, dictating the intensity and duration of the host immune response. Monocytes expressing misfolded or unfolded protein may exhibit UPR activation and this can compromise the host immune system. Here, we describe in detail methods and protocols for the examination of UPR activation in peripheral blood monocytes. This guide should provide new investigators to the field with a broad understanding of the tools required to investigate the UPR in the monocyte.

  3. Measurement of the unfolded protein response (UPR) in monocytes.

    LENUS (Irish Health Repository)

    Carroll, Tomas P

    2012-02-01

    In mammalian cells, the primary function of the endoplasmic reticulum (ER) is to synthesize and assemble membrane and secreted proteins. As the main site of protein folding and posttranslational modification in the cell, the ER operates a highly conserved quality control system to ensure only correctly assembled proteins exit the ER and misfolded and unfolded proteins are retained for disposal. Any disruption in the equilibrium of the ER engages a multifaceted intracellular signaling pathway termed the unfolded protein response (UPR) to restore normal conditions in the cell. A variety of pathological conditions can induce activation of the UPR, including neurodegenerative disorders such as Parkinson\\'s disease, metabolic disorders such as atherosclerosis, and conformational disorders such as cystic fibrosis. Conformational disorders are characterized by mutations that modify the final structure of a protein and any cells that express abnormal protein risk functional impairment. The monocyte is an important and long-lived immune cell and acts as a key immunological orchestrator, dictating the intensity and duration of the host immune response. Monocytes expressing misfolded or unfolded protein may exhibit UPR activation and this can compromise the host immune system. Here, we describe in detail methods and protocols for the examination of UPR activation in peripheral blood monocytes. This guide should provide new investigators to the field with a broad understanding of the tools required to investigate the UPR in the monocyte.

  4. Metabolic engineering of β-oxidation in Penicillium chrysogenum for improved semi-synthetic cephalosporin biosynthesis.

    Science.gov (United States)

    Veiga, Tânia; Gombert, Andreas K; Landes, Nils; Verhoeven, Maarten D; Kiel, Jan A K W; Krikken, Arjen M; Nijland, Jeroen G; Touw, Hesselien; Luttik, Marijke A H; van der Toorn, John C; Driessen, Arnold J M; Bovenberg, Roel A L; van den Berg, Marco A; van der Klei, Ida J; Pronk, Jack T; Daran, Jean-Marc

    2012-07-01

    Industrial production of semi-synthetic cephalosporins by Penicillium chrysogenum requires supplementation of the growth media with the side-chain precursor adipic acid. In glucose-limited chemostat cultures of P. chrysogenum, up to 88% of the consumed adipic acid was not recovered in cephalosporin-related products, but used as an additional carbon and energy source for growth. This low efficiency of side-chain precursor incorporation provides an economic incentive for studying and engineering the metabolism of adipic acid in P. chrysogenum. Chemostat-based transcriptome analysis in the presence and absence of adipic acid confirmed that adipic acid metabolism in this fungus occurs via β-oxidation. A set of 52 adipate-responsive genes included six putative genes for acyl-CoA oxidases and dehydrogenases, enzymes responsible for the first step of β-oxidation. Subcellular localization of the differentially expressed acyl-CoA oxidases and dehydrogenases revealed that the oxidases were exclusively targeted to peroxisomes, while the dehydrogenases were found either in peroxisomes or in mitochondria. Deletion of the genes encoding the peroxisomal acyl-CoA oxidase Pc20g01800 and the mitochondrial acyl-CoA dehydrogenase Pc20g07920 resulted in a 1.6- and 3.7-fold increase in the production of the semi-synthetic cephalosporin intermediate adipoyl-6-APA, respectively. The deletion strains also showed reduced adipate consumption compared to the reference strain, indicating that engineering of the first step of β-oxidation successfully redirected a larger fraction of adipic acid towards cephalosporin biosynthesis. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. A role for PPARα in the regulation of arginine metabolism and nitric oxide synthesis.

    Science.gov (United States)

    Guelzim, Najoua; Mariotti, François; Martin, Pascal G P; Lasserre, Frédéric; Pineau, Thierry; Hermier, Dominique

    2011-10-01

    The pleiotropic effects of PPARα may include the regulation of amino acid metabolism. Nitric oxide (NO) is a key player in vascular homeostasis. NO synthesis may be jeopardized by a differential channeling of arginine toward urea (via arginase) versus NO (via NO synthase, NOS). This was studied in wild-type (WT) and PPARα-null (KO) mice fed diets containing either saturated fatty acids (COCO diet) or 18:3 n-3 (LIN diet). Metabolic markers of arginine metabolism were assayed in urine and plasma. mRNA levels of arginases and NOS were determined in liver. Whole-body NO synthesis and the conversion of systemic arginine into urea were assessed by using (15)N(2)-guanido-arginine and measuring urinary (15)NO(3) and [(15)N]-urea. PPARα deficiency resulted in a markedly lower whole-body NO synthesis, whereas the conversion of systemic arginine into urea remained unaffected. PPARα deficiency also increased plasma arginine and decreased citrulline concentration in plasma. These changes could not be ascribed to a direct effect on hepatic target genes, since NOS mRNA levels were unaffected, and arginase mRNA levels decreased in KO mice. Despite the low level in the diet, the nature of the fatty acids modulated some effects of PPARα deficiency, including plasma arginine and urea, which increased more in KO mice fed the LIN diet than in those fed the COCO diet. In conclusion, PPARα is largely involved in normal whole-body NO synthesis. This warrants further study on the potential of PPARα activation to maintain NO synthesis in the initiation of the metabolic syndrome.

  6. ER-tethered Transcription Factor CREBH Regulates Hepatic Lipogenesis, Fatty Acid Oxidation, and Lipolysis upon Metabolic Stress

    OpenAIRE

    Zhang, Chunbin; Wang, Guohui; Zheng, Ze; Maddipati, Krishna Rao; Zhang, Xuebao; Dyson, Gregory; Williams, Paul; Duncan, Stephen A.; Kaufman, Randal J.; Zhang, Kezhong

    2012-01-01

    CREBH is a liver-specific transcription factor that is localized in the endoplasmic reticulum (ER) membrane. Our previous work demonstrated that CREBH is activated by ER stress or inflammatory stimuli to induce an acute-phase hepatic inflammation. Here we demonstrate that CREBH is a key metabolic regulator of hepatic lipogenesis, fatty acid (FA) oxidation, and lipolysis under metabolic stress. Saturated FA, insulin signals, or an atherogenic high-fat diet can induce CREBH activation in the li...

  7. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  8. Hibiscus sabdariffa calyx palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in fructose-induced metabolic syndrome rats.

    Science.gov (United States)

    Ajiboye, Taofeek O; Raji, Hikmat O; Adeleye, Abdulwasiu O; Adigun, Nurudeen S; Giwa, Oluwayemisi B; Ojewuyi, Oluwayemisi B; Oladiji, Adenike T

    2016-03-30

    The effect of Hibiscus sabdariffa calyx extract was evaluated in high-fructose-induced metabolic syndrome rats. Insulin resistance, hyperglycemia, dyslipidemia and oxidative rout were induced in rats using high-fructose diet. High-fructose diet-fed rats were administered 100 and 200 mg kg(-1) body weight of H. sabdariffa extract for 3 weeks, starting from week 7 of high-fructose diet treatment. High-fructose diet significantly (P Hibiscus extract. Overall, aqueous extract of H. sabdariffa palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in high-fructose-induced metabolic syndrome rats. © 2015 Society of Chemical Industry.

  9. Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

    DEFF Research Database (Denmark)

    Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio

    2015-01-01

    of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further...... and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels...

  10. Oxidative Inactivation of Liver Mitochondria in High Fructose Diet-Induced Metabolic Syndrome in Rats: Effect of Glycyrrhizin Treatment.

    Science.gov (United States)

    Sil, Rajarshi; Chakraborti, Abhay Sankar

    2016-09-01

    Metabolic syndrome is a serious health problem in the present world. Glycyrrhizin, a triterpenoid saponin of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate the primary complications and hepatocellular damage in rats with the syndrome. In this study, we have explored metabolic syndrome-induced changes in liver mitochondrial function and effect of glycyrrhizin against the changes. Metabolic syndrome was induced in rats by high fructose (60%) diet for 6 weeks. The rats were then treated with glycyrrhizin (50 mg/kg body weight) by single intra-peritoneal injection. After 2 weeks of the treatment, the rats were sacrificed to collect liver tissue. Elevated mitochondrial ROS, lipid peroxidation and protein carbonyl, and decreased reduced glutathione content indicated oxidative stress in metabolic syndrome. Loss of mitochondrial inner membrane cardiolipin was observed. Mitochondrial complex I activity did not change but complex IV activity decreased significantly. Mitochondrial MTT reduction ability, membrane potential, phosphate utilisation and oxygen consumption decreased in metabolic syndrome. Reduced mitochondrial aconitase activity and increased aconitase carbonyl content suggested oxidative damage of the enzyme. Elevated Fe(2+) ion level in mitochondria might be associated with increased ROS generation in metabolic syndrome. Glycyrrhizin effectively attenuated mitochondrial oxidative stress and aconitase degradation, and improved electron transport chain activity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    International Nuclear Information System (INIS)

    Defo, Michel A.; Bernatchez, Louis; Campbell, Peter G.C.; Couture, Patrice

    2014-01-01

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  12. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    Energy Technology Data Exchange (ETDEWEB)

    Defo, Michel A. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Bernatchez, Louis [Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, Québec G1V 0A6 (Canada); Campbell, Peter G.C. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Couture, Patrice, E-mail: patrice.couture@ete.inrs.ca [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada)

    2014-09-15

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  13. Exposure to lead in water and cysteine non-oxidative metabolism in Pelophylax ridibundus tissues

    International Nuclear Information System (INIS)

    Kaczor, Marta; Sura, Piotr; Bronowicka-Adamska, Patrycja; Wróbel, Maria

    2013-01-01

    Chronic, low-level exposure to metals is an increasing global problem. Lead is an environmentally persistent toxin that causes many lead-related pathologies, directly affects tissues and cellular components or exerts an effect of the generation of reactive oxygen species causing a diminished level of available sulfhydryl antioxidant reserves. Cysteine is one of substrates in the synthesis of glutathione – the most important cellular antioxidant, and it may also undergo non-oxidative desulfuration that produces compounds containing sulfane sulfur atoms. The aim of the experiment was to examine changes of the non-oxidative metabolism of cysteine and the levels of cysteine and glutathione in the kidneys, heart, brain, liver and muscle of Marsh frogs (Pelophylax ridibundus) exposed to 28 mg/L Pb(NO 3 ) 2 for 10 days. The activities of sulfurtransferases, enzymes related to the sulfane sulfur metabolism – 3-mercaptopyruvate sulfurtransfearse, γ-cystathionase and rhodanese – were detected in tissue homogenates. The activity of sulfurtransferases was much higher in the kidneys of frogs exposed to lead in comparison to control frogs, not exposed to lead. The level of sulfane sulfur remained unchanged. Similarly, the total level of cysteine did not change significantly. The total levels of glutathione and the cysteine/cystine and GSH/GSSG ratios were elevated. Thus, it seems that the exposure to lead intensified the metabolism of sulfane sulfur and glutathione synthesis in the kidneys. The results presented in this work not only confirm the participation of GSH in the detoxification of lead ions and/or products appearing in response to their presence, such as reactive oxygen species, but also indicate the involvement of sulfane sulfur and rhodanese in this process (e.g. brain). As long as the expression of enzymatic proteins (rhodanese, MPST and CST) is not examined, no answer will be provided to the question whether changes in their activity are due to differences

  14. Exposure to lead in water and cysteine non-oxidative metabolism in Pelophylax ridibundus tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kaczor, Marta [Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Sura, Piotr [Department of Human Developmental Biology, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Bronowicka-Adamska, Patrycja [Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Wrobel, Maria, E-mail: mbwrobel@cyf-kr.edu.pl [Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland)

    2013-02-15

    Chronic, low-level exposure to metals is an increasing global problem. Lead is an environmentally persistent toxin that causes many lead-related pathologies, directly affects tissues and cellular components or exerts an effect of the generation of reactive oxygen species causing a diminished level of available sulfhydryl antioxidant reserves. Cysteine is one of substrates in the synthesis of glutathione - the most important cellular antioxidant, and it may also undergo non-oxidative desulfuration that produces compounds containing sulfane sulfur atoms. The aim of the experiment was to examine changes of the non-oxidative metabolism of cysteine and the levels of cysteine and glutathione in the kidneys, heart, brain, liver and muscle of Marsh frogs (Pelophylax ridibundus) exposed to 28 mg/L Pb(NO{sub 3}){sub 2} for 10 days. The activities of sulfurtransferases, enzymes related to the sulfane sulfur metabolism - 3-mercaptopyruvate sulfurtransfearse, {gamma}-cystathionase and rhodanese - were detected in tissue homogenates. The activity of sulfurtransferases was much higher in the kidneys of frogs exposed to lead in comparison to control frogs, not exposed to lead. The level of sulfane sulfur remained unchanged. Similarly, the total level of cysteine did not change significantly. The total levels of glutathione and the cysteine/cystine and GSH/GSSG ratios were elevated. Thus, it seems that the exposure to lead intensified the metabolism of sulfane sulfur and glutathione synthesis in the kidneys. The results presented in this work not only confirm the participation of GSH in the detoxification of lead ions and/or products appearing in response to their presence, such as reactive oxygen species, but also indicate the involvement of sulfane sulfur and rhodanese in this process (e.g. brain). As long as the expression of enzymatic proteins (rhodanese, MPST and CST) is not examined, no answer will be provided to the question whether changes in their activity are due to

  15. Anesthesia with halothane and nitrous oxide alters protein and amino acid metabolism in dogs

    International Nuclear Information System (INIS)

    Horber, F.F.; Krayer, S.; Rehder, K.; Haymond, M.W.

    1988-01-01

    General anesthesia in combination with surgery is known to result in negative nitrogen balance. To determine whether general anesthesia without concomitant surgery decreases whole body protein synthesis and/or increases whole body protein breakdown, two groups of dogs were studied: Group 1 (n = 6) in the conscious state and Group 2 (n = 8) during general anesthesia employing halothane (1.5 MAC) in 50% nitrous oxide and oxygen. Changes in protein metabolism were estimated by isotope dilution techniques employing simultaneous infusions of [4,53H]leucine and alpha-[1-14C]-ketoisocaproate (KIC). Total leucine carbon flux was unchanged or slightly increased in the anesthetized animals when compared to the conscious controls, indicating only a slight increase in the rate of proteolysis. However, leucine oxidation was increased (P less than 0.001) by more than 80% in the anesthetized animals when compared with their conscious controls, whereas whole body nonoxidative leucine disappearance, an indicator of whole body protein synthesis, was decreased. The ratio of leucine oxidation to the nonoxidative rate of leucine disappearance, which provides an index of the catabolism of at least one essential amino acid in the postabsorptive state, was more than twofold increased (P less than 0.001) in the anesthetized animals regardless of the tracer employed. These studies suggest that the administration of anesthesia alone, without concomitant surgery, is associated with a decreased rate of whole body protein synthesis and increased leucine oxidation, resulting in increased leucine and protein catabolism, which may be underlying or initiating some of the protein wasting known to occur in patients undergoing surgery

  16. Dissimilatory metabolism of nitrogen oxides in bacteria: comparative reconstruction of transcriptional networks.

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available Bacterial response to nitric oxide (NO is of major importance since NO is an obligatory intermediate of the nitrogen cycle. Transcriptional regulation of the dissimilatory nitric oxides metabolism in bacteria is diverse and involves FNR-like transcription factors HcpR, DNR, and NnrR; two-component systems NarXL and NarQP; NO-responsive activator NorR; and nitrite-sensitive repressor NsrR. Using comparative genomics approaches, we predict DNA-binding motifs for these transcriptional factors and describe corresponding regulons in available bacterial genomes. Within the FNR family of regulators, we observed a correlation of two specificity-determining amino acids and contacting bases in corresponding DNA recognition motif. Highly conserved regulon HcpR for the hybrid cluster protein and some other redox enzymes is present in diverse anaerobic bacteria, including Clostridia, Thermotogales, and delta-proteobacteria. NnrR and DNR control denitrification in alpha- and beta-proteobacteria, respectively. Sigma-54-dependent NorR regulon found in some gamma- and beta-proteobacteria contains various enzymes involved in the NO detoxification. Repressor NsrR, which was previously known to control only nitrite reductase operon in Nitrosomonas spp., appears to be the master regulator of the nitric oxides' metabolism, not only in most gamma- and beta-proteobacteria (including well-studied species such as Escherichia coli, but also in Gram-positive Bacillus and Streptomyces species. Positional analysis and comparison of regulatory regions of NO detoxification genes allows us to propose the candidate NsrR-binding motif. The most conserved member of the predicted NsrR regulon is the NO-detoxifying flavohemoglobin Hmp. In enterobacteria, the regulon also includes two nitrite-responsive loci, nipAB (hcp-hcr and nipC (dnrN, thus confirming the identity of the effector, i.e. nitrite. The proposed NsrR regulons in Neisseria and some other species are extended to include

  17. Dissimilatory Metabolism of Nitrogen Oxides in Bacteria:Comparative Reconstruction of Transcriptional Networks

    Energy Technology Data Exchange (ETDEWEB)

    Rodionov, Dmitry A.; Dubchak, Inna L.; Arkin, Adam P.; Alm, EricJ.; Gelfand, Mikhail S.

    2005-09-01

    Bacterial response to nitric oxide (NO) is of major importance since NO is an obligatory intermediate of the nitrogen cycle. Transcriptional regulation of the dissimilatory nitric oxides metabolism in bacteria is diverse and involves FNR-like transcription factors HcpR, DNR and NnrR, two-component systems NarXL and NarQP, NO-responsive activator NorR, and nitrite sensitive repressor NsrR. Using comparative genomics approaches we predict DNA-binding signals for these transcriptional factors and describe corresponding regulons in available bacterial genomes. Within the FNR family of regulators, we observed a correlation of two specificity-determining amino acids and contacting bases in corresponding DNA signal. Highly conserved regulon HcpR for the hybrid cluster protein and some other redox enzymes is present in diverse anaerobic bacteria including Clostridia, Thermotogales and delta-proteobacteria. NnrR and DNR control denitrification in alpha- and beta-proteobacteria, respectively. Sigma-54-dependent NorR regulon found in some gamma- and beta-proteobacteria contains various enzymes involved in the NO detoxification. Repressor NsrR, which was previously known to control only nitrite reductase operon in Nitrosomonas spp., appears to be the master regulator of the nitric oxides metabolism not only in most gamma- and beta-proteobacteria (including well-studied species like Escherichia coli), but also in Gram-positive Bacillus and Streptomyces species. Positional analysis and comparison of regulatory regions of NO detoxification genes allows us to propose the candidate NsrR-binding signal. The most conserved member of the predicted NsrR regulon is the NO-detoxifying flavohemoglobin Hmp. In enterobacteria, the regulon includes also two nitrite-responsive loci, nipAB (hcp-hcr) and nipC(dnrN), thus confirming the identity of the effector, i.e., nitrite. The proposed NsrR regulons in Neisseria and some other species are extended to include denitrification genes. As the

  18. ROLE OF POTASSIUM IN THE OXIDATIVE METABOLISM OF MICROCOCCUS SODONENSIS1

    Science.gov (United States)

    Perry, Jerome J.; Evans, James B.

    1961-01-01

    Perry, Jerome J. (The University of Chicago, Chicago, Ill.), and James B. Evans. Role of potassium in the oxidative metabolism of Micrococcus sodonensis. J. Bacteriol. 82:551–555. 1961.—An absolute potassium requirement has been established for the growth of Micrococcus sodonensis with lactate or pyruvate as substrate. Potassium at 0.67 × 10−2m concentration was necessary for maximal growth. Resting cell and cell-free preparations from cells grown on minimal levels of potassium were stimulated by potassium but, due to residual or bound cation, did not show an absolute requirement. Rubidium and cesium replaced potassium in these cells although cesium is much less effective. PMID:14485577

  19. Regulation of egg quality and lipids metabolism by Zinc Oxide Nanoparticles.

    Science.gov (United States)

    Zhao, Yong; Li, Lan; Zhang, Peng-Fei; Liu, Xin-Qi; Zhang, Wei-Dong; Ding, Zhao-Peng; Wang, Shi-Wen; Shen, Wei; Min, Ling-Jiang; Hao, Zhi-Hui

    2016-04-01

    This investigation was designed to explore the effects of Zinc Oxide Nanoparticles (ZnO NP) on egg quality and the mechanism of decreasing of yolk lipids. Different concentration of ZnO NP and ZnSO4 were used to treat hens for 24 weeks. The body weight and egg laying frequency were recorded and analyzed. Albumen height, Haugh unit, and yolk color score were analyzed by an Egg Multi Tester. Breaking strength was determined by an Egg Force Reader. Egg shell thickness was measured using an Egg Shell Thickness Gouge. Shell color was detected by a spectrophotometer. Egg shape index was measured by Egg Form Coefficient Measuring Instrument. Albumen and yolk protein was determined by the Kjeldahl method. Amino acids were determined by an amino acids analyzer. Trace elements Zn, Fe, Cu, and P (mg/kg wet mass) were determined in digested solutions using Inductively Coupled Plasma-Optical Emission Spectrometry. TC and TG were measured using commercial analytical kits. Yolk triglyceride, total cholesterol, pancreatic lipase, and phospholipids were determined by appropriate kits. β-carotene was determined by spectrophotometry. Lipid metabolism was also investigated with liver, plasma, and ovary samples. ZnO NP did not change the body weight of hens during the treatment period. ZnO NP slowed down egg laying frequency at the beginning of egg laying period but not at later time. ZnO NP did not affect egg protein or water contents, slightly decreased egg physical parameters (12 to 30%) and trace elements (20 to 35%) after 24 weeks treatment. However, yolk lipids content were significantly decreased by ZnO NP (20 to 35%). The mechanism of Zinc oxide nanoparticles decreasing yolk lipids was that they decreased the synthesis of lipids and increased lipid digestion. These data suggested ZnO NP affected egg quality and specifically regulated lipids metabolism in hens through altering the function of hen's ovary and liver. © 2016 Poultry Science Association Inc.

  20. Imitation of phase I oxidative metabolism of anabolic steroids by titanium dioxide photocatalysis.

    Science.gov (United States)

    Ruokolainen, Miina; Valkonen, Minna; Sikanen, Tiina; Kotiaho, Tapio; Kostiainen, Risto

    2014-12-18

    The aim of this study was to investigate the feasibility of titanium dioxide (TiO2) photocatalysis for oxidation of anabolic steroids and for imitation of their phase I metabolism. The photocatalytic reaction products of five anabolic steroids were compared to their phase I in vitro metabolites produced by human liver microsomes (HLM). The same main reaction types - hydroxylation, dehydrogenation and combination of these two - were observed both in TiO2 photocatalysis and in microsomal incubations. Several isomers of each product type were formed in both systems. Based on the same mass, retention time and similarity of the product ion spectra, many of the products observed in HLM reactions were also formed in TiO2 photocatalytic reactions. However, products characteristic to only either one of the systems were also formed. In conclusion, TiO2 photocatalysis is a rapid, simple and inexpensive method for imitation of phase I metabolism of anabolic steroids and production of metabolite standards. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Effects of nitrous oxide on cerebral haemodynamics and metabolism during isoflurane anaesthesia in man

    Energy Technology Data Exchange (ETDEWEB)

    Algotsson, L.; Messeter, K. (Department of Anaesthesiology, University Hospital, Lund (Sweden)); Rosen, I. (Department of Clinical Neurophysiology, University Hospital, Lund (Sweden)); Holmin, T. (Department of Surgery, University Hospital, Lund (Sweden))

    1992-01-01

    Seven normoventilated and five hyperventilated healthy adults undergoing cholecystectomy and anaesthetized with methohexitone, fentanyl and pancuronium were studied with measurement of cerebral blood flow (CBF), cereal metabolic rate of oxygen (CMRo[sub 2]), and quantified electroencephalography (EEG) under two sets of conditions: (1) 1.7% end-tidal concentration of isoflurane in air/oxygen: (2) 0.85% end-tidal concentration of isoflurane in nitrous oxide (N[sub 2]O)/oxygen. The object was to study the effects of N[sub 2]O during isoflurane anaesthesia on cerebral circulation, metabolism and neuroelectric activity. N[sub 2]O in the anaesthetic gas mixture caused a 43% (P<0.05) increase in CBF during normocarbic conditions but no significant change during hypocapnia. CMRo[sub 2] was not significantly altered by N[sub 2]O. EEG demonstrated an activated pattern with decreased low frequency activity and increased high frequency activity. The results confirm that N[sub 2]O is a potent cerebral vasodilator in man, although the mechanisms underlying the effects on CBF are still unclear. (au).

  2. Mammalian Tissue Response to Low Dose Ionizing Radiation: The Role of Oxidative Metabolism and Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Azzam, Edouard I

    2013-01-16

    The objective of the project was to elucidate the mechanisms underlying the biological effects of low dose/low dose rate ionizing radiation in organs/tissues of irradiated mice that differ in their susceptibility to ionizing radiation, and in human cells grown under conditions that mimic the natural in vivo environment. The focus was on the effects of sparsely ionizing cesium-137 gamma rays and the role of oxidative metabolism and intercellular communication in these effects. Four Specific Aims were proposed. The integrated outcome of the experiments performed to investigate these aims has been significant towards developing a scientific basis to more accurately estimate human health risks from exposures to low doses ionizing radiation. By understanding the biochemical and molecular changes induced by low dose radiation, several novel markers associated with mitochondrial functions were identified, which has opened new avenues to investigate metabolic processes that may be affected by such exposure. In particular, a sensitive biomarker that is differentially modulated by low and high dose gamma rays was discovered.

  3. Oxidative Stress and Metabolic Perturbations in Wooden Breast Disorder in Chickens.

    Directory of Open Access Journals (Sweden)

    Behnam Abasht

    Full Text Available This study was conducted to characterize metabolic features of the breast muscle (pectoralis major in chickens affected with the Wooden Breast myopathy. Live birds from two purebred chicken lines and one crossbred commercial broiler population were clinically examined by manual palpation of the breast muscle (pectoralis major at 47-48 days of age. Metabolite abundance was determined by gas chromatography/mass spectrometry (GC/MS and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS using breast muscle tissue samples from 16 affected and 16 unaffected chickens. Muscle glycogen content was also quantified in breast muscle tissue samples from affected and unaffected chickens. In total, levels of 140 biochemicals were significantly different (FDR1.3 or <0.77 between affected and unaffected chickens. Glycogen content measurements were considerably lower (1.7-fold in samples taken from Wooden Breast affected birds when compared with samples from unaffected birds. Affected tissues exhibited biomarkers related to increased oxidative stress, elevated protein levels, muscle degradation, and altered glucose utilization. Affected muscle also showed elevated levels of hypoxanthine, xanthine, and urate molecules, the generation of which can contribute to altered redox homeostasis. In conclusion, our findings show that Wooden Breast affected tissues possess a unique metabolic signature. This unique profile may identify candidate biomarkers for diagnostic utilization and provide mechanistic insight into altered biochemical processes contributing to tissue hardening associated with the Wooden Breast myopathy in commercial chickens.

  4. Synergistic effects between catalase inhibitors and modulators of nitric oxide metabolism on tumor cell apoptosis.

    Science.gov (United States)

    Scheit, Katrin; Bauer, Georg

    2014-10-01

    Inhibitors of catalase (such as ascorbate, methyldopa, salicylic acid and neutralizing antibodies) synergize with modulators of nitric oxide (NO) metabolism (such as arginine, arginase inhibitor, NO synthase-inducing interferons and NO dioxygenase inhibitors) in the singlet oxygen-mediated inactivation of tumor cell protective catalase. This is followed by reactive oxygen species (ROS)-dependent apoptosis induction. TGF-beta, NADPH oxidase-1, NO synthase, dual oxidase-1 and caspase-9 are characterized as essential catalysts in this process. The FAS receptor and caspase-8 are required for amplification of ROS signaling triggered by individual compounds, but are dispensable when the synergistic effect is established. Our findings explain the antitumor effects of catalase inhibitors and of compounds that target NO metabolism, as well as their synergy. These data may have an impact on epidemiological studies related to secondary plant compounds and open new perspectives for the establishment of novel antitumor drugs and for the improvement of established chemotherapeutics. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Asiatic Acid Alleviates Hemodynamic and Metabolic Alterations via Restoring eNOS/iNOS Expression, Oxidative Stress, and Inflammation in Diet-Induced Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Poungrat Pakdeechote

    2014-01-01

    Full Text Available Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS induced by a high-carbohydrate, high-fat (HCHF diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α levels (p < 0.05. Plasma nitrate and nitrite (NOx were markedly high with upregulation of inducible nitric oxide synthase (iNOS expression, but dowregulation of endothelial nitric oxide synthase (eNOS expression (p < 0.05. Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p < 0.05. In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

  6. Sex steroids do not affect muscle weight, oxidative metabolism or cytosolic androgen reception binding of functionally overloaded rat Plantaris muscles

    Science.gov (United States)

    Max, S. R.; Rance, N.

    1983-01-01

    The effects of sex steroids on muscle weight and oxidative capacity of rat planaris muscles subjected to functional overload by removal of synergistic muscles were investigated. Ten weeks after bilateral synergist removal, plantaris muscles were significantly hypertrophic compared with unoperated controls. After this period, the ability of the muscles to oxide three substrates of oxidative metabolism was assessed. Experimental procedures are discussed and results are presented herein. Results suggest a lack of beneficial effect of sex hormone status on the process of hypertrophy and on biochemical changes in overloaded muscle. Such findings are not consistent with the idea of synergistic effects of sex steroids and muscle usage.

  7. Peroxisomal β-oxidation regulates whole body metabolism, inflammatory vigor, and pathogenesis of nonalcoholic fatty liver disease

    Science.gov (United States)

    Moreno-Fernandez, Maria E.; Giles, Daniel A.; Stankiewicz, Traci E.; Sheridan, Rachel; Karns, Rebekah; Cappelletti, Monica; Lampe, Kristin; Mukherjee, Rajib; Sina, Christian; Sallese, Anthony; Bridges, James P.; Hogan, Simon P.; Aronow, Bruce J.; Hoebe, Kasper

    2018-01-01

    Nonalcoholic fatty liver disease (NAFLD), a metabolic predisposition for development of hepatocellular carcinoma (HCC), represents a disease spectrum ranging from steatosis to steatohepatitis to cirrhosis. Acox1, a rate-limiting enzyme in peroxisomal fatty acid β-oxidation, regulates metabolism, spontaneous hepatic steatosis, and hepatocellular damage over time. However, it is unknown whether Acox1 modulates inflammation relevant to NAFLD pathogenesis or if Acox1-associated metabolic and inflammatory derangements uncover and accelerate potential for NAFLD progression. Here, we show that mice with a point mutation in Acox1 (Acox1Lampe1) exhibited altered cellular metabolism, modified T cell polarization, and exacerbated immune cell inflammatory potential. Further, in context of a brief obesogenic diet stress, NAFLD progression associated with Acox1 mutation resulted in significantly accelerated and exacerbated hepatocellular damage via induction of profound histological changes in hepatocytes, hepatic inflammation, and robust upregulation of gene expression associated with HCC development. Collectively, these data demonstrate that β-oxidation links metabolism and immune responsiveness and that a better understanding of peroxisomal β-oxidation may allow for discovery of mechanisms central for NAFLD progression. PMID:29563328

  8. Heterogeneity of Bovine Peripheral Blood Monocytes

    Directory of Open Access Journals (Sweden)

    Jamal Hussen

    2017-12-01

    Full Text Available Peripheral blood monocytes of several species can be divided into different subpopulations with distinct phenotypic and functional properties. Herein, we aim at reviewing published work regarding the heterogeneity of the recently characterized bovine monocyte subsets. As the heterogeneity of human blood monocytes was widely studied and reviewed, this work focuses on comparing bovine monocyte subsets with their human counterparts regarding their phenotype, adhesion and migration properties, inflammatory and antimicrobial functions, and their ability to interact with neutrophilic granulocytes. In addition, the differentiation of monocyte subsets into functionally polarized macrophages is discussed. Regarding phenotype and distribution in blood, bovine monocyte subsets share similarities with their human counterparts. However, many functional differences exist between monocyte subsets from the two species. In contrast to their pro-inflammatory functions in human, bovine non-classical monocytes show the lowest phagocytosis and reactive oxygen species generation capacity, an absent ability to produce the pro-inflammatory cytokine IL-1β after inflammasome activation, and do not have a role in the early recruitment of neutrophils into inflamed tissues. Classical and intermediate monocytes of both species also differ in their response toward major monocyte-attracting chemokines (CCL2 and CCL5 and neutrophil degranulation products (DGP in vitro. Such differences between homologous monocyte subsets also extend to the development of monocyte-derived macrophages under the influence of chemokines like CCL5 and neutrophil DGP. Whereas the latter induce the differentiation of M1-polarized macrophages in human, bovine monocyte-derived macrophages develop a mixed M1/M2 macrophage phenotype. Although only a few bovine clinical trials analyzed the correlation between changes in monocyte composition and disease, they suggest that functional differences between

  9. Association of Inflammatory and Oxidative Stress Markers with Metabolic Syndrome in Asian Indians in India

    Directory of Open Access Journals (Sweden)

    Veena S. Rao

    2011-01-01

    Full Text Available Metabolic syndrome (MetS is a primary risk factor for cardiovascular disease and is associated with a proinflammatory state. Here, we assessed the contribution of inflammatory and oxidative stress markers towards prediction of MetS. A total of 2316 individuals were recruited in Phase I of the Indian Atherosclerosis Research Study (IARS. Modified ATPIII guidelines were used for classification of subjects with MetS. Among the inflammatory and oxidative stress markers studied, levels of hsCRP (P<.0001, Neopterin (P=.036, and oxLDL (P<.0001 were significantly higher among subjects with MetS. Among the markers we tested, oxLDL stood out as a robust predictor of MetS in the IARS population (OR 4.956 95% CI 2.504–9.810; P<.0001 followed by hsCRP (OR 1.324 95% CI 1.070–1.638; P=.010. In conclusion, oxLDL is a candidate predictor for MetS in the Asian Indian population.

  10. Cardiovascular disease-related parameters and oxidative stress in SHROB rats, a model for metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Eunice Molinar-Toribio

    Full Text Available SHROB rats have been suggested as a model for metabolic syndrome (MetS as a situation prior to the onset of CVD or type-2 diabetes, but information on descriptive biochemical parameters for this model is limited. Here, we extensively evaluate parameters related to CVD and oxidative stress (OS in SHROB rats. SHROB rats were monitored for 15 weeks and compared to a control group of Wistar rats. Body weight was recorded weekly. At the end of the study, parameters related to CVD and OS were evaluated in plasma, urine and different organs. SHROB rats presented statistically significant differences from Wistar rats in CVD risk factors: total cholesterol, LDL-cholesterol, triglycerides, apoA1, apoB100, abdominal fat, insulin, blood pressure, C-reactive protein, ICAM-1 and PAI-1. In adipose tissue, liver and brain, the endogenous antioxidant systems were activated, yet there was no significant oxidative damage to lipids (MDA or proteins (carbonylation. We conclude that SHROB rats present significant alterations in parameters related to inflammation, endothelial dysfunction, thrombotic activity, insulin resistance and OS measured in plasma as well as enhanced redox defence systems in vital organs that will be useful as markers of MetS and CVD for nutrition interventions.

  11. Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles

    Directory of Open Access Journals (Sweden)

    Cassandra Collins

    2017-09-01

    Full Text Available Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein, indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

  12. Effects of simultaneous and optimized sequential cardiac resynchronization therapy on myocardial oxidative metabolism and efficiency.

    Science.gov (United States)

    Christenson, Stuart D; Chareonthaitawee, Panithaya; Burnes, John E; Hill, Michael R S; Kemp, Brad J; Khandheria, Bijoy K; Hayes, David L; Gibbons, Raymond J

    2008-02-01

    Cardiac resynchronization therapy (CRT) can improve left ventricular (LV) hemodynamics and function. Recent data suggest the energy cost of such improvement is favorable. The effects of sequential CRT on myocardial oxidative metabolism (MVO(2)) and efficiency have not been previously assessed. Eight patients with NYHA class III heart failure were studied 196 +/- 180 days after CRT implant. Dynamic [(11)C]acetate positron emission tomography (PET) and echocardiography were performed after 1 hour of: 1) AAI pacing, 2) simultaneous CRT, and 3) sequential CRT. MVO(2) was calculated using the monoexponential clearance rate of [(11)C]acetate (k(mono)). Myocardial efficiency was expressed in terms of the work metabolic index (WMI). P values represent overall significance from repeated measures analysis. Global LV and right ventricular (RV) MVO(2) were not significantly different between pacing modes, but the septal/lateral MVO(2) ratio differed significantly with the change in pacing mode (AAI pacing = 0.696 +/- 0.094 min(-1), simultaneous CRT = 0.975 +/- 0.143 min(-1), and sequential CRT = 0.938 +/- 0.189 min(-1); overall P = 0.001). Stroke volume index (SVI) (AAI pacing = 26.7 +/- 10.4 mL/m(2), simultaneous CRT = 30.6 +/- 11.2 mL/m(2), sequential CRT = 33.5 +/- 12.2 mL/m(2); overall P simultaneous CRT = 4.29 +/- 1.72 mmHg*mL/m(2)*10(6), sequential CRT = 4.79 +/- 1.92 mmHg*mL/m(2)*10(6); overall P = 0.002) also differed between pacing modes. Compared with simultaneous CRT, additional changes in septal/lateral MVO(2), SVI, and WMI with sequential CRT were not statistically significant on post hoc analysis. In this small selected population, CRT increases LV SVI without increasing MVO(2), resulting in improved myocardial efficiency. Additional improvements in LV work, oxidative metabolism, and efficiency from simultaneous to sequential CRT were not significant.

  13. An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: A nutrigenomics approach

    NARCIS (Netherlands)

    Bakker, G.C.M.; Erk, M.J. van; Pellis, L.; Wopereis, S.; Rubingh, C.M.; Cnubben, N.H.P.; Kooistra, T.; Ommen, B. van; Hendriks, H.F.J.

    2010-01-01

    Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products

  14. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity

    NARCIS (Netherlands)

    Cantó, Carles; Houtkooper, Riekelt H.; Pirinen, Eija; Youn, Dou Y.; Oosterveer, Maaike H.; Cen, Yana; Fernandez-Marcos, Pablo J.; Yamamoto, Hiroyasu; Andreux, Pénélope A.; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A.; Auwerx, Johan

    2012-01-01

    As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+)

  15. Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S-mephenytoin oxidation in Tanzanians

    DEFF Research Database (Denmark)

    Skjelbo, E; Mutabingwa, T K; Bygbjerg, Ib Christian

    1996-01-01

    S-Mephenytoin and chloroguanide (proguanil) oxidation was studied in 216 tanzanians. The mephenytoin S/R ratio in urine ranged from 0.9, were arbitrarily defined as poor metabolizers of mephenytoin. The chloroguanide/cycloguanil ratio ranged from 0.82 to 249. There was a significant correlation b...

  16. Expression profiling feline peripheral blood monocytes identifies a transcriptional signature associated with type two diabetes mellitus.

    Science.gov (United States)

    O'Leary, Caroline A; Sedhom, Mamdouh; Reeve-Johnson, Mia; Mallyon, John; Irvine, Katharine M

    2017-04-01

    Diabetes mellitus is a common disease of cats and is similar to type 2 diabetes (T2D) in humans, especially with respect to the role of obesity-induced insulin resistance, glucose toxicity, decreased number of pancreatic β-cells and pancreatic amyloid deposition. Cats have thus been proposed as a valuable translational model of T2D. In humans, inflammation associated with adipose tissue is believed to be central to T2D development, and peripheral blood monocytes (PBM) are important in the inflammatory cascade which leads to insulin resistance and β-cell failure. PBM may thus provide a useful window to study the pathogenesis of diabetes mellitus in cats, however feline monocytes are poorly characterised. In this study, we used the Affymetrix Feline 1.0ST array to profile peripheral blood monocytes from 3 domestic cats with T2D and 3 cats with normal glucose tolerance. Feline monocytes were enriched for genes expressed in human monocytes, and, despite heterogeneous gene expression, we identified a T2D-associated expression signature associated with cell cycle perturbations, DNA repair and the unfolded protein response, oxidative phosphorylation and inflammatory responses. Our data provide novel insights into the feline monocyte transcriptome, and support the hypothesis that inflammatory monocytes contribute to T2D pathogenesis in cats as well as in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Cognitive impairment and Alzheimer’s disease: Links with oxidative stress and cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Alejandra Sekler

    2008-08-01

    Full Text Available Alejandra Sekler1,2, José M Jiménez2, Leonel Rojo2, Edgard Pastene3, Patricio Fuentes4, Andrea Slachevsky4, Ricardo B Maccioni1,21Center of Cognitive Neurosciences, International Center for Biomedicine (ICC, Santiago, Chile; 2Laboratory of Cellular, Molecular Biology and Neurosciences, Faculty of Sciences, Universidad de Chile, Santiago, Chile; 3Department of Pharmacy, Faculty of Pharmacy, University of Concepcion, Concepción, Chile; 4Unidad de Neurología Cognitiva y Demencias, Servicio de Neurología, Hospital del Salvador, Santiago, ChileAbstract: Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer’s disease (AD, Parkinson’s disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP, plasma malondialdehyde and total antioxidative capacity (TAC, as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59 and a control group of neurologically normal subjects (n = 29, attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery, while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC of

  18. Oxidative stress and metabolic syndrome: Effects of a natural antioxidants enriched diet on insulin resistance.

    Science.gov (United States)

    Mancini, Antonio; Martorana, Giuseppe Ettore; Magini, Marinella; Festa, Roberto; Raimondo, Sebastiano; Silvestrini, Andrea; Nicolotti, Nicola; Mordente, Alvaro; Mele, Maria Cristina; Miggiano, Giacinto Abele Donato; Meucci, Elisabetta

    2015-04-01

    Oxidative stress (OS) could play a role in metabolic syndrome-related manifestations contributing to insulin resistance (IR). The aim of the present study was to gain insight the relationships between OS, IR and other hormones involved in caloric balance, explaining the effects of a natural antioxidant-enriched diet in patients affected by metabolic syndrome. We investigated the effects of dietary antioxidants on IR, studying 53 obese (20 males and 33 females, 18-66 years old, BMI 36.3 ± 5.5 kg/m 2 ), with IR evaluated by Homeostasis Model Assessment (HOMA)-index, comparing 4 treatments: hypocaloric diet alone (group A) or plus metformin 1000 mg/daily (group B), natural antioxidants-enriched hypocaloric diet alone (group C) or plus metformin (group D). A personalized program, with calculated antioxidant intake of 800-1000 mg/daily, from fruit and vegetables, was administered to group C and D. The glycemic and insulinemic response to oral glucose load, and concentrations of total-, LDL- and HDL-cholesterol, triglycerides, uric acid, C reactive protein, fT3, fT4, TSH, insulin-like growth factor 1 were evaluated before and after 3-months. Plasma Total antioxidant capacity was determined by H 2 O 2 -metmyoglobin system, which interacting with the chromogen ABTS generates a radical with latency time (LAG) proportional to antioxidant content. Despite a similar BMI decrease, we found a significant decrease of HOMA and insulin peak only in group B and D. Insulin response (AUC) showed the greatest decrease in group D (25.60  ±  8.96%) and was significantly lower in group D vs B. No differences were observed in glucose response, lipid metabolism and TAC (expressed as LAG values). TSH values were significantly suppressed in group D vs B. These data suggest that dietary antioxidants ameliorate insulin-sensitivity in obese subjects with IR by enhancing the effect of insulin-sensitizing drugs albeit with molecular mechanisms which remain yet to be elucidated

  19. Caenorhabditis elegans: A Useful Model for Studying Metabolic Disorders in Which Oxidative Stress Is a Contributing Factor

    Directory of Open Access Journals (Sweden)

    Elizabeth Moreno-Arriola

    2014-01-01

    Full Text Available Caenorhabditis elegans is a powerful model organism that is invaluable for experimental research because it can be used to recapitulate most human diseases at either the metabolic or genomic level in vivo. This organism contains many key components related to metabolic and oxidative stress networks that could conceivably allow us to increase and integrate information to understand the causes and mechanisms of complex diseases. Oxidative stress is an etiological factor that influences numerous human diseases, including diabetes. C. elegans displays remarkably similar molecular bases and cellular pathways to those of mammals. Defects in the insulin/insulin-like growth factor-1 signaling pathway or increased ROS levels induce the conserved phase II detoxification response via the SKN-1 pathway to fight against oxidative stress. However, it is noteworthy that, aside from the detrimental effects of ROS, they have been proposed as second messengers that trigger the mitohormetic response to attenuate the adverse effects of oxidative stress. Herein, we briefly describe the importance of C. elegans as an experimental model system for studying metabolic disorders related to oxidative stress and the molecular mechanisms that underlie their pathophysiology.

  20. The nucleic acid metabolism in rat liver after single and long-term administration of tritium oxide

    International Nuclear Information System (INIS)

    Shorokhova, V.B.

    1984-01-01

    It was shown that after a single administration of tritiUm oxide in a dose of 22.2 MBq/g body mass the liver mass increased, the concentration of nucleic acids decreased and the biosynthesjs rate increased dUring a one-month observation. By the end of the observation period (the first year) the parameters under study were normalized. The long-term administration of tritium oxide in daily doses of 0.37, 0.925 and 1.85 MBq/g body mass caused changes in the nucleac acid metabolism which were less manifest (at early times), than in the case of a single injection. At the same time, the long-term administration of tritium oxide in the dose of 0.925 MBq/g caused a substantial disturbance of the nucleic acid metabolism at later times (after 2-9 months)

  1. A Model of Oxidative Stress Management: Moderation of Carbohydrate Metabolizing Enzymes in SOD1-Null Drosophila melanogaster

    Science.gov (United States)

    Bernard, Kristine E.; Parkes, Tony L.; Merritt, Thomas J. S.

    2011-01-01

    The response to oxidative stress involves numerous genes and mutations in these genes often manifest in pleiotropic ways that presumably reflect perturbations in ROS-mediated physiology. The Drosophila melanogaster SOD1-null allele (cSODn108) is proposed to result in oxidative stress by preventing superoxide breakdown. In SOD1-null flies, oxidative stress management is thought to be reliant on the glutathione-dependent antioxidants that utilize NADPH to cycle between reduced and oxidized form. Previous studies suggest that SOD1-null Drosophila rely on lipid catabolism for energy rather than carbohydrate metabolism. We tested these connections by comparing the activity of carbohydrate metabolizing enzymes, lipid and triglyceride concentration, and steady state NADPH:NADP+ in SOD1-null and control transgenic rescue flies. We find a negative shift in the activity of carbohydrate metabolizing enzymes in SOD1-nulls and the NADP+-reducing enzymes were found to have significantly lower activity than the other enzymes assayed. Little evidence for the catabolism of lipids as preferential energy source was found, as the concentration of lipids and triglycerides were not significantly lower in SOD1-nulls compared with controls. Using a starvation assay to impact lipids and triglycerides, we found that lipids were indeed depleted in both genotypes when under starvation stress, suggesting that oxidative damage was not preventing the catabolism of lipids in SOD1-null flies. Remarkably, SOD1-nulls were also found to be relatively resistant to starvation. Age profiles of enzyme activity, triglyceride and lipid concentration indicates that the trends observed are consistent over the average lifespan of the SOD1-nulls. Based on our results, we propose a model of physiological response in which organisms under oxidative stress limit the production of ROS through the down-regulation of carbohydrate metabolism in order to moderate the products exiting the electron transport chain. PMID

  2. Assessment of right ventricular oxidative metabolism by PET in patients with idiopathic dilated cardiomyopathy undergoing cardiac resynchronisation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Knuuti, Juhani; Naum, Alexandru; Stolen, Kira Q.; Kalliokoski, Riikka [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); Sundell, Jan [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); University of Turku, Department of Medicine, Turku (Finland); Engblom, Erik; Koistinen, Juhani; Airaksinen, K.E. Juhani [University of Turku, Department of Medicine, Turku (Finland); Ylitalo, Antti [Satakunta Central Hospital, Department of Medicine, Pori (Finland); Nekolla, Stephan G. [Klinikum rechts der Isar der Technischen Universitaet Muenchen, Klinik und Poliklinik fuer Nuklearmedizin, Munich (Germany); Bax, K.E. Jeroen J. [Leiden University, Department of Cardiology, Leiden (Netherlands)

    2004-12-01

    Right ventricular (RV) performance is known to have prognostic value in patients with congestive heart failure (CHF). Cardiac resynchronisation therapy (CRT) has been found to enhance left ventricular (LV) energetics and metabolic reserve in patients with heart failure. The interplay between the LV and RV may play an important role in CRT response. The purpose of the study was to investigate RV oxidative metabolism, metabolic reserve and the effects of CRT in patients with CHF and left bundle brach block. In addition, the role of the RV in the response to CRT was evaluated. Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of a biventricular pacemaker 8{+-}5 months earlier were studied under two conditions: CRT ON and after CRT had been switched OFF for 24 h. Oxidative metabolism was measured using [{sup 11}C]acetate positron emission tomography (K{sub mono}). The measurements were performed at rest and during dobutamine-induced stress (5 {mu}g/kg per minute). LV performance and interventricular mechanical delay (interventricular asynchrony) were measured using echocardiography. CRT had no effect on RV K{sub mono} at rest (ON: 0.052{+-}0.014, OFF: 0.047{+-}0.018, NS). Dobutamine-induced stress increased RV K{sub mono} significantly under both conditions but oxidative metabolism was more enhanced when CRT was ON (0.076{+-}0.026 vs 0.065{+-}0.027, p=0.003). CRT shortened interventricular delay significantly (45{+-}33 vs 19{+-}35 ms, p=0.05). In five patients the response to CRT was striking (32% increase in mean LV stroke volume, range 18-36%), while in the other five patients no response was observed (mean change +2%, range -6% to +4%). RV K{sub mono} and LV stroke volume response to CRT correlated inversely (r=-0.66, p=0.034). None of the other measured parameters, including all LV parameters and electromechanical parameters, were associated with the response to CRT. In responders, RV K{sub mono} with CRT OFF was significantly lower

  3. Fe biomineralization mirrors individual metabolic activity in a nitrate-dependent Fe(II-oxidizer

    Directory of Open Access Journals (Sweden)

    Jennyfer eMIOT

    2015-09-01

    Full Text Available Microbial biomineralization sometimes leads to periplasmic encrustation, which is predicted to enhance microorganism preservation in the fossil record. Mineral precipitation within the periplasm is however thought to induce death, as a result of permeability loss preventing nutrient and waste transit across the cell wall. This hypothesis had however never been investigated down to the single cell level. Here, we cultured the nitrate reducing Fe(II oxidizing bacteria Acidovorax sp. strain BoFeN1 that have been previously shown to promote the precipitation of a diversity of Fe minerals (lepidocrocite, goethite, Fe phosphate encrusting the periplasm. We investigated the connection of Fe biomineralization with carbon assimilation at the single cell level, using a combination of electron microscopy and Nano-Secondary Ion Mass Spectrometry (NanoSIMS. Our analyses revealed strong individual heterogeneities of Fe biomineralization. Noteworthy, a small proportion of cells remaining free of any precipitate persisted even at advanced stages of biomineralization. Using pulse chase experiments with 13C-acetate, we provide evidences of individual phenotypic heterogeneities of carbon assimilation, correlated with the level of Fe biomineralization. Whereas non- and moderately encrusted cells were able to assimilate acetate, higher levels of periplasm encrustation prevented any carbon incorporation. Carbon assimilation only depended on the level of Fe encrustation and not on the nature of Fe minerals precipitated in the cell wall. Carbon assimilation decreased exponentially with increasing cell-associated Fe content. Persistence of a small proportion of non-mineralized and metabolically active cells might constitute a strategy of survival in highly ferruginous environments. Eventually, our results suggest that periplasmic Fe biomineralization may provide a signature of individual metabolic status, which could be looked for in the fossil record and in modern

  4. Improving metabolic efficiency of the reverse beta-oxidation cycle by balancing redox cofactor requirement.

    Science.gov (United States)

    Wu, Junjun; Zhang, Xia; Zhou, Peng; Huang, Jiaying; Xia, Xiudong; Li, Wei; Zhou, Ziyu; Chen, Yue; Liu, Yinghao; Dong, Mingsheng

    2017-11-01

    Previous studies have made many exciting achievements on pushing the functional reversal of beta-oxidation cycle (r-BOX) to more widespread adoption for synthesis of a wide variety of fuels and chemicals. However, the redox cofactor requirement for the efficient operation of r-BOX remains unclear. In this work, the metabolic efficiency of r-BOX for medium-chain fatty acid (C 6 -C 10 , MCFA) production was optimized by redox cofactor engineering. Stoichiometric analysis of the r-BOX pathway and further experimental examination identified NADH as a crucial determinant of r-BOX process yield. Furthermore, the introduction of formate dehydrogenase from Candida boidinii using fermentative inhibitor byproduct formate as a redox NADH sink improved MCFA titer from initial 1.2g/L to 3.1g/L. Moreover, coupling of increasing the supply of acetyl-CoA with NADH to achieve fermentative redox balance enabled product synthesis at maximum titers. To this end, the acetate re-assimilation pathway was further optimized to increase acetyl-CoA availability associated with the new supply of NADH. It was found that the acetyl-CoA synthetase activity and intracellular ATP levels constrained the activity of acetate re-assimilation pathway, and 4.7g/L of MCFA titer was finally achieved after alleviating these two limiting factors. To the best of our knowledge, this represented the highest titer reported to date. These results demonstrated that the key constraint of r-BOX was redox imbalance and redox engineering could further unleash the lipogenic potential of this cycle. The redox engineering strategies could be applied to acetyl-CoA-derived products or other bio-products requiring multiple redox cofactors for biosynthesis. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  5. Understanding the determinants of selectivity in drug metabolism through modeling of dextromethorphan oxidation by cytochrome P450

    Science.gov (United States)

    Oláh, Julianna; Mulholland, Adrian J.; Harvey, Jeremy N.

    2011-01-01

    Cytochrome P450 enzymes play key roles in the metabolism of the majority of drugs. Improved models for prediction of likely metabolites will contribute to drug development. In this work, two possible metabolic routes (aromatic carbon oxidation and O-demethylation) of dextromethorphan are compared using molecular dynamics (MD) simulations and density functional theory (DFT). The DFT results on a small active site model suggest that both reactions might occur competitively. Docking and MD studies of dextromethorphan in the active site of P450 2D6 show that the dextromethorphan is located close to heme oxygen in a geometry apparently consistent with competitive metabolism. In contrast, calculations of the reaction path in a large protein model [using a hybrid quantum mechanical–molecular mechanics (QM/MM) method] show a very strong preference for O-demethylation, in accordance with experimental results. The aromatic carbon oxidation reaction is predicted to have a high activation energy, due to the active site preventing formation of a favorable transition-state structure. Hence, the QM/MM calculations demonstrate a crucial role of many active site residues in determining reactivity of dextromethorphan in P450 2D6. Beyond substrate binding orientation and reactivity of Compound I, successful metabolite predictions must take into account the detailed mechanism of oxidation in the protein. These results demonstrate the potential of QM/MM methods to investigate specificity in drug metabolism. PMID:21444768

  6. Short communication: Characterizing metabolic and oxidant status of pastured dairy cows postpartum in an automatic milking system.

    Science.gov (United States)

    Elischer, M F; Sordillo, L M; Siegford, J M; Karcher, E L

    2015-10-01

    The periparturient period represents a stressful time for dairy cows as they transition from late gestation to early lactation. Undesirable fluctuations in metabolites and impaired immune defense mechanisms near parturition can severely affect cow health and have residual effects on performance and longevity. Metabolic and oxidative stress profiles of multiparous and primiparous dairy cows in traditional parlor and feeding systems are well characterized, but status of these profiles in alternative management systems, such as grazing cows managed with an automatic milking system (AMS), are poorly characterized. Therefore, the objective of this case study was to characterize the metabolic and oxidant status of pastured cows milked with an AMS. It was hypothesized that primiparous and multiparous cows milked with an AMS would experience changes in oxidative and metabolic status after parturition; however, these changes would not impair cow health or production. Blood was collected from 14 multiparous and 8 primiparous Friesian-cross dairy cows at 1, 7, 14, and 21 d relative to calving for concentrations of insulin, glucose, nonesterified fatty acids (NEFA), β-hydroxybutyrate, reduced glutathione, oxidized glutathione, and antioxidant potential. Milk production and milking frequency data were collected postpartum. Milk production differed on d 7 and 14 between primiparous and multiparous cows and frequency was not affected by parity. Primiparous cows had higher levels of glucose than multiparous cows. No differences in insulin, NEFA, or β-hydroxybutyrate concentrations were noted between multiparous and primiparous cows postpartum, though days relative to calving significantly affected insulin and NEFA. Primiparous cows also had higher antioxidant potential than multiparous cows during the postpartum period. Results from this study show that, although responses were within expected ranges, periparturient multiparous cows responded differently than periparturient

  7. Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

    DEFF Research Database (Denmark)

    Sørensen, A L; Hey, A S; Kharazmi, A

    1994-01-01

    In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes...... towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63...... in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished...

  8. Age Increases Monocyte Adhesion on Collagen

    Science.gov (United States)

    Khalaji, Samira; Zondler, Lisa; Kleinjan, Fenneke; Nolte, Ulla; Mulaw, Medhanie A.; Danzer, Karin M.; Weishaupt, Jochen H.; Gottschalk, Kay-E.

    2017-05-01

    Adhesion of monocytes to micro-injuries on arterial walls is an important early step in the occurrence and development of degenerative atherosclerotic lesions. At these injuries, collagen is exposed to the blood stream. We are interested whether age influences monocyte adhesion to collagen under flow, and hence influences the susceptibility to arteriosclerotic lesions. Therefore, we studied adhesion and rolling of human peripheral blood monocytes from old and young individuals on collagen type I coated surface under shear flow. We find that firm adhesion of monocytes to collagen type I is elevated in old individuals. Pre-stimulation by lipopolysaccharide increases the firm adhesion of monocytes homogeneously in older individuals, but heterogeneously in young individuals. Blocking integrin αx showed that adhesion of monocytes to collagen type I is specific to the main collagen binding integrin αxβ2. Surprisingly, we find no significant age-dependent difference in gene expression of integrin αx or integrin β2. However, if all integrins are activated from the outside, no differences exist between the age groups. Altered integrin activation therefore causes the increased adhesion. Our results show that the basal increase in integrin activation in monocytes from old individuals increases monocyte adhesion to collagen and therefore the risk for arteriosclerotic plaques.

  9. Intermediate Monocytes but Not TIE2-Expressing Monocytes Are a Sensitive Diagnostic Indicator for Colorectal Cancer

    Science.gov (United States)

    Schauer, Dominic; Starlinger, Patrick; Reiter, Christian; Jahn, Nikolaus; Zajc, Philipp; Buchberger, Elisabeth; Bachleitner-Hofmann, Thomas; Bergmann, Michael; Stift, Anton; Gruenberger, Thomas; Brostjan, Christine

    2012-01-01

    We have conducted the first study to determine the diagnostic potential of the CD14++CD16+ intermediate monocytes as compared to the pro-angiogenic subset of CD14++CD16+TIE2+ TIE2-expressing monocytes (TEMs) in cancer. These monocyte populations were investigated by flow cytometry in healthy volunteers (N = 32) and in colorectal carcinoma patients with localized (N = 24) or metastatic (N = 37) disease. We further determined blood levels of cytokines associated with monocyte regulation. The results revealed the intermediate monocyte subset to be significantly elevated in colorectal cancer patients and to show the highest frequencies in localized disease. Multivariate regression analysis identified intermediate monocytes as a significant independent variable in cancer prediction. With a cut-off value at 0.37% (intermediate monocytes of total leukocytes) the diagnostic sensitivity and specificity ranged at 69% and 81%, respectively. In contrast, TEM levels were elevated in localized cancer but did not differ significantly between groups and none of the cytokines correlated with monocyte subpopulations. Of interest, in vitro analyses supported the observation that intermediate monocytes were more potently induced by primary as opposed to metastatic cancer cells which may relate to the immunosuppressive milieu established in the advanced stage of metastatic disease. In conclusion, intermediate monocytes as compared to TIE2-expressing monocytes are a more sensitive diagnostic indicator of colorectal cancer. PMID:22973451

  10. Intermediate monocytes but not TIE2-expressing monocytes are a sensitive diagnostic indicator for colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Dominic Schauer

    Full Text Available We have conducted the first study to determine the diagnostic potential of the CD14++CD16+ intermediate monocytes as compared to the pro-angiogenic subset of CD14++CD16+TIE2+ TIE2-expressing monocytes (TEMs in cancer. These monocyte populations were investigated by flow cytometry in healthy volunteers (N = 32 and in colorectal carcinoma patients with localized (N = 24 or metastatic (N = 37 disease. We further determined blood levels of cytokines associated with monocyte regulation. The results revealed the intermediate monocyte subset to be significantly elevated in colorectal cancer patients and to show the highest frequencies in localized disease. Multivariate regression analysis identified intermediate monocytes as a significant independent variable in cancer prediction. With a cut-off value at 0.37% (intermediate monocytes of total leukocytes the diagnostic sensitivity and specificity ranged at 69% and 81%, respectively. In contrast, TEM levels were elevated in localized cancer but did not differ significantly between groups and none of the cytokines correlated with monocyte subpopulations. Of interest, in vitro analyses supported the observation that intermediate monocytes were more potently induced by primary as opposed to metastatic cancer cells which may relate to the immunosuppressive milieu established in the advanced stage of metastatic disease. In conclusion, intermediate monocytes as compared to TIE2-expressing monocytes are a more sensitive diagnostic indicator of colorectal cancer.

  11. Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults

    Directory of Open Access Journals (Sweden)

    Trautwein Christian

    2010-06-01

    Full Text Available Abstract Background Recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during ageing, potentially influencing their functionality and contributing to immunosenescence. Results Circulating monocyte subsets, surface marker and chemokine receptor expression were analyzed in 181 healthy volunteers (median age 42, range 18-88. Unlike the unaffected total leukocyte or total monocyte counts, non-classical CD14+CD16+ monocytes significantly increased with age, but displayed reduced HLA-DR and CX3CR1 surface expression in the elderly. Classical CD14++CD16- monocyte counts did not vary dependent on age. Serum MCP-1 (CCL2, but not MIP1α (CCL3, MIP1β (CCL4 or fractalkine (CX3CL1 concentrations increased with age. Monocyte-derived macrophages from old or young individuals did not differ with respect to cytokine release in vitro at steady state or upon LPS stimulation. Conclusions Our study demonstrates dynamic changes of circulating monocytes during ageing in humans. The expansion of the non-classical CD14+CD16+ subtype, alterations of surface protein and chemokine receptor expression as well as circulating monocyte-related chemokines possibly contribute to the preserved functionality of the monocyte pool throughout adulthood.

  12. Effects of pistachio nuts on body composition, metabolic, inflammatory and oxidative stress parameters in Asian Indians with metabolic syndrome: a 24-wk, randomized control trial.

    Science.gov (United States)

    Gulati, Seema; Misra, Anoop; Pandey, Ravindra Mohan; Bhatt, Surya Prakash; Saluja, Shelza

    2014-02-01

    The aim of this study was to evaluate the effects of pistachio nuts as an adjunct to diet and exercise on body composition, metabolic, inflammatory, and oxidative stress parameters in Asian Indians with metabolic syndrome. In this 24-wk randomized control trial, 60 individuals with the metabolic syndrome were randomized to either pistachio (intervention group) or control group (diet as per weight and physical activity profile, modulated according to dietary guidelines for Asian Indians) after 3 wk of a diet and exercise run in. In the first group, unsalted pistachios (20% energy) were given daily. A standard diet and exercise protocol was followed for both groups. Body weight, waist circumference (WC), magnetic resonance imaging estimation of intraabdominal adipose tissue and subcutaneous abdominal adipose tissue, fasting blood glucose (FBG), fasting serum insulin, glycosylated hemoglobin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), adiponectin, free fatty acids (FFAs), tumor necrosis factor (TNF)-α, leptin, and thiobarbituric acid reactive substances (TBARS) were assessed before and after the intervention. Statistically significant improvement in mean values for various parameters in the intervention group compared with control group were as follows: WC (P pistachios leads to beneficial effects on the cardiometabolic profile of Asian Indians with metabolic syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Tiamulin selectively inhibits oxidative hepatic steroid and drug metabolism in vitro in the pig.

    Science.gov (United States)

    Witkamp, R F; Nijmeijer, S M; Csikó, G; van Miert, A S

    1994-08-01

    The simultaneous use of the antibiotic tiamulin with certain ionophoric antibiotics (monensin, salinomycin) may give rise to a toxic interaction in pigs and poultry. In the present study, effects of tiamulin on hepatic cytochrome P450 activities in vitro were studied using pig liver microsomes. When tiamulin was added to the incubation medium the N-demethylation rate of ethylmorphine and the hydroxylation of testosterone at the 6 beta- and 11 alpha-positions was strongly inhibited. Tiamulin inhibited these activities more than SKF525A or cimetidine, but less than ketoconazole. The microsomal N-demethylation rate of erythromycin and the hydroxylation of testosterone at the 2 beta-position were inhibited to a lesser degree, whereas the ethoxyresorufin-O-deethylation, aniline hydroxylation and testosterone hydroxylations at the 15 alpha- and 15 beta-positions were not affected by tiamulin. No in vitro complexation by tiamulin of cytochrome P450 resulting in a loss of CO-binding capacity could be demonstrated. Results from the present study suggest a selective inhibition of cytochrome P450 enzymes in pigs, probably belonging to the P4503A subfamily. The mechanism of this interaction is still unclear. However, interactions between tiamulin and those veterinary drugs or endogenous compounds which undergo oxidative metabolism by P450 enzymes must be considered. More research is needed to reveal which of the P450 enzymes are affected by tiamulin in order to improve the understanding and probably the predictability of this interaction.

  14. Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia

    Science.gov (United States)

    Kuhn, Viktoria; Diederich, Lukas; Keller, T.C. Stevenson; Kramer, Christian M.; Lückstädt, Wiebke; Panknin, Christina; Suvorava, Tatsiana; Isakson, Brant E.; Kelm, Malte

    2017-01-01

    Abstract Significance: Recent clinical evidence identified anemia to be correlated with severe complications of cardiovascular disease (CVD) such as bleeding, thromboembolic events, stroke, hypertension, arrhythmias, and inflammation, particularly in elderly patients. The underlying mechanisms of these complications are largely unidentified. Recent Advances: Previously, red blood cells (RBCs) were considered exclusively as transporters of oxygen and nutrients to the tissues. More recent experimental evidence indicates that RBCs are important interorgan communication systems with additional functions, including participation in control of systemic nitric oxide metabolism, redox regulation, blood rheology, and viscosity. In this article, we aim to revise and discuss the potential impact of these noncanonical functions of RBCs and their dysfunction in the cardiovascular system and in anemia. Critical Issues: The mechanistic links between changes of RBC functional properties and cardiovascular complications related to anemia have not been untangled so far. Future Directions: To allow a better understanding of the complications associated with anemia in CVD, basic and translational science studies should be focused on identifying the role of noncanonical functions of RBCs in the cardiovascular system and on defining intrinsic and/or systemic dysfunction of RBCs in anemia and its relationship to CVD both in animal models and clinical settings. Antioxid. Redox Signal. 26, 718–742. PMID:27889956

  15. Lipid Peroxidation, Nitric Oxide Metabolites, and Their Ratio in a Group of Subjects with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Gregorio Caimi

    2014-01-01

    Full Text Available Our aim was to evaluate lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS, nitric oxide metabolites (nitrite + nitrate expressed as NOx, and TBARS/NOx ratio in a group of subjects with metabolic syndrome (MS. In this regard we enrolled 106 subjects with MS defined according to the IDF criteria, subsequently subdivided into diabetic (DMS and nondiabetic (NDMS and also into subjects with a low triglycerides/HDL-cholesterol (TG/HDL-C index or with a high TG/HDL-C index. In the entire group and in the four subgroups of MS subjects we found an increase in TBARS and NOx levels and a decrease in TBARS/NOx ratio in comparison with normal controls. Regarding all these parameters no statistical difference between DMS and NDMS was evident, but a significant increase in NOx was present in subjects with a high TG/HDL-C index in comparison with those with a low index. In MS subjects we also found a negative correlation between TBARS/NOx ratio and TG/HDL-C index. Considering the hyperactivity of the inducible NO synthase in MS, these data confirm the altered redox and inflammatory status that characterizes the MS and suggest a link between lipid peroxidation, inflammation, and insulin resistance, evaluated as TG/HDL-C index.

  16. Effects of Hormone Therapy on Oxidative Stress in Postmenopausal Women with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Martha A. Sánchez-Rodríguez

    2016-08-01

    Full Text Available The aim of this study was to determine the effect of oral hormone therapy (HT on oxidative stress (OS in postmenopausal women with metabolic syndrome (MetS. A randomized, double blind, placebo-controlled trial was carried out. We formed four groups of 25 women each; healthy (HW and MetS women (MSW were assigned to HT (1 mg/day of estradiol valerate plus 5 mg/10 day of medroxiprogesterone or placebo. We measured plasma lipoperoxides, erythrocyte superoxide dismutase and glutathione peroxidase, total plasma antioxidant status and uric acid, as OS markers. Alternative cut-off values of each parameter were defined and a stress score (SS ranging from 0 to 7 was used as total OS. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII criteria. Participants were seen at baseline, 3 and 6 months. After 6 months, MetS decreased in MSW-HT (48%, their triglycerides and high-density lipoprotein cholesterol (HDL-c improved; in the other groups no difference was found. SS in MSW-HT decreased (3.8 ± 0.3 to 1.7 ± 0.3, p < 0.05 and OS was also reduced (44%, this effect was evident since 3 mo. HW-HT with high OS also decreased (40%. In placebo groups there was no change. Our findings suggest that HT improve lipids and OS associated to MetS in postmenopausal women.

  17. Mitogen-activated protein kinase phosphatase 1 (MKP-1) in macrophage biology and cardiovascular disease. A redox-regulated master controller of monocyte function and macrophage phenotype.

    Science.gov (United States)

    Kim, Hong Seok; Asmis, Reto

    2017-08-01

    MAPK pathways play a critical role in the activation of monocytes and macrophages by pathogens, signaling molecules and environmental cues and in the regulation of macrophage function and plasticity. MAPK phosphatase 1 (MKP-1) has emerged as the main counter-regulator of MAPK signaling in monocytes and macrophages. Loss of MKP-1 in monocytes and macrophages in response to metabolic stress leads to dysregulation of monocyte adhesion and migration, and gives rise to dysfunctional, proatherogenic monocyte-derived macrophages. Here we review the properties of this redox-regulated dual-specificity MAPK phosphatase and the role of MKP-1 in monocyte and macrophage biology and cardiovascular diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Metabolic responses of Beauveria bassiana to hydrogen peroxide-induced oxidative stress using an LC-MS-based metabolomics approach.

    Science.gov (United States)

    Zhang, Chen; Wang, Wei; Lu, Ruili; Jin, Song; Chen, Yihui; Fan, Meizhen; Huang, Bo; Li, Zengzhi; Hu, Fenglin

    2016-06-01

    The entomopathogenic fungus, Beauveria bassiana, is commonly used as a biological agent for pest control. Environmental and biological factors expose the fungus to oxidative stress; as a result, B. bassiana has adopted a number of anti-oxidant mechanisms. In this study, we investigated metabolites of B. bassiana that are formed in response to oxidative stress from hydrogen peroxide (H2O2) by using a liquid chromatography mass spectrometry (LC-MS) approach. Partial least-squares discriminant analysis (PLS-DA) revealed differences between the control and the H2O2-treated groups. Hierarchical cluster analysis (HCA) showed 18 up-regulated metabolites and 25 down-regulated metabolites in the H2O2-treated fungus. Pathway analysis indicated that B. bassiana may be able to alleviate oxidative stress by enhancing lipid catabolism and glycometabolism, thus decreasing membrane polarity and preventing polar H2O2 or ROS from permeating into fungal cells and protecting cells against oxidative injury. Meanwhile, most of the unsaturated fatty acids that are derived from glycerophospholipids hydrolysis can convert into oxylipins through autoxidation, which can prevent the reactive oxygen of H2O2 from attacking important macromolecules of the fungus. Results showed also that H2O2 treatment can enhance mycotoxins production which implies that oxidative stress may be able to increase the virulence of the fungus. In comparison to the control group, citric acid and UDP-N-acetylglucosamine were down-regulated, which suggested that metabolic flux was occurring to the TCA cycle and enhancing carbohydrate metabolism. The findings from this study will contribute to the understanding of how the molecular mechanisms of fungus respond to environmental and biological stress factors as well as how the manipulation of such metabolisms may lead to selection of more effective fungal strains for pest control. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Daily consumption of white tea (Camellia sinensis (L.)) improves the cerebral cortex metabolic and oxidative profile in prediabetic Wistar rats.

    Science.gov (United States)

    Nunes, Ana R; Alves, Marco G; Tomás, Gonçalo D; Conde, Vanessa R; Cristóvão, Ana C; Moreira, Paula I; Oliveira, Pedro F; Silva, Branca M

    2015-03-14

    Diabetes mellitus (DM) is a major public health problem and its incidence is rising dramatically. The brain, particularly the cerebral cortex, is very susceptible to glucose fluctuations and hyperglycaemia-induced oxidative stress. Tea (Camellia sinensis (L.)) is widely consumed; however, the antidiabetic properties of white tea remain largely unexplored. In the present study, we investigated the effects of daily consumption of white tea on the cerebral cortex of prediabetic rats. The cerebral cortex metabolic profile was evaluated, and the expression levels of GLUT, phosphofructokinase-1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were assessed. LDH activity was also determined. The cerebral cortex oxidative profile was determined by evaluating its antioxidant power, lipid peroxidation and protein oxidation levels. Catalase, glutathione, glutamate, N-acetylaspartate, aspartate, choline, γ-aminobutyric acid, taurine and valine contents were determined. Daily consumption of white tea ameliorated glucose tolerance and insulin sensitivity. Moreover, white tea altered the cortex glycolytic profile, modulating GLUT expression and lactate and alanine contents. Finally, white tea consumption restored protein oxidation and lipid peroxidation levels and catalase expression, and improved antioxidant capacity. In conclusion, daily consumption of white tea improved the cerebral cortex metabolic and oxidative profile in prediabetic rats, suggesting it as a good, safe and inexpensive strategy to prevent DM-related effects in the cerebral cortex.

  20. Protein energy malnutrition increases arginase activity in monocytes and macrophages.

    Science.gov (United States)

    Corware, Karina; Yardley, Vanessa; Mack, Christopher; Schuster, Steffen; Al-Hassi, Hafid; Herath, Shanthi; Bergin, Philip; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Kropf, Pascale

    2014-01-01

    Protein energy malnutrition is commonly associated with immune dysfunctions and is a major factor in susceptibility to infectious diseases. In this study, we evaluated the impact of protein energy malnutrition on the capacity of monocytes and macrophages to upregulate arginase, an enzyme associated with immunosuppression and increased pathogen replication. Our results show that monocytes and macrophages are significantly increased in the bone marrow and blood of mice fed on a protein low diet. No alteration in the capacity of bone marrow derived macrophages isolated from malnourished mice to phagocytose particles, to produce the microbicidal molecule nitric oxide and to kill intracellular Leishmania parasites was detected. However, macrophages and monocytes from malnourished mice express significantly more arginase both in vitro and in vivo. Using an experimental model of visceral leishmaniasis, we show that following protein energy malnutrition, the increased parasite burden measured in the spleen of these mice coincided with increased arginase activity and that macrophages provide a more permissive environment for parasite growth. Taken together, these results identify a novel mechanism in protein energy malnutrition that might contributes to increased susceptibility to infectious diseases by upregulating arginase activity in myeloid cells.

  1. Kaempferol impedes IL-32-induced monocyte-macrophage differentiation.

    Science.gov (United States)

    Nam, Sun-Young; Jeong, Hyun-Ja; Kim, Hyung-Min

    2017-08-25

    Kaempferol possesses a wide range of therapeutic properties, including antioxidant, anti-inflammatory, and anticancer properties. The present study sought to evaluate the effects and possible pharmacological mechanisms of kaempferol on interleukin (IL)-32-induced monocyte-macrophage differentiation. In this study, we performed flow cytometry assay, immunocytochemical staining, quantitative real-time PCR, enzyme-linked immuno sorbent assay, caspase-1 assay, and Western blotting to observe the effects and underlying mechanisms of kaempferol using the human monocyte cell line THP-1. The flow cytometry, immunocytochemical staining, and real-time PCR results show that kaempferol attenuated IL-32-induced monocyte differentiation to product macrophage-like cells. Kaempferol decreased the production and mRNA expression of pro-inflammatory cytokines, in this case thymic stromal lymphopoietin (TSLP), IL-1β, tumor necrosis factor (TNF)-α, and IL-8. Furthermore, kaempferol inhibited the IL-32-induced activation of p38 and nuclear factor-κB in a dose-dependent manner in THP-1 cells. Kaempferol also ameliorated the lipopolysaccharide-induced production of the inflammatory mediators TSLP, IL-1β, TNF-α, IL-8, and nitric oxide of macrophage-like cells differentiated by IL-32. In brief, our findings may provide new mechanistic insights into the anti-inflammatory effects of kaempferol. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Solar photocatalytic oxidation of recalcitrant natural metabolic by-products of amoxicillin biodegradation

    OpenAIRE

    João Pereira; Ana Reis; Vera Homem; José Silva; Arminda Alves; Maria Teresa Borges; Rui Boaventura; Vítor Vilar; Olga Pastor Nunes

    2014-01-01

    The contamination of the aquatic environment by non-metabolized and metabolized antibiotic residues has brought the necessity of alternative treatment steps to current water decontamination technologies. This work assessed the feasibility of using a multi-stage treatment system for amoxicillin (AMX) spiked solutions combining: i) a biological treatment process using an enriched culture to metabolize AMX, with ii) a solar photocatalytic system to achieve the removal of the metabolized transfor...

  3. Weekend ethanol consumption and high-sucrose diet: resveratrol effects on energy expenditure, substrate oxidation, lipid profile, oxidative stress and hepatic energy metabolism.

    Science.gov (United States)

    Rocha, Katiucha Karolina Honório Ribeiro; Souza, Gisele Aparecida; Seiva, Fábio Rodrigues Ferreira; Ebaid, Geovana Xavier; Novelli, Ethel Lourenzi Barbosa

    2011-01-01

    The present study analyzed the association between weekend ethanol and high-sucrose diet on oxygen consumption, lipid profile, oxidative stress and hepatic energy metabolism. Because resveratrol (RS, 3,5,4'-trans-trihydroxystilbene) has been implicated as a modulator of alcohol-independent cardiovascular protection attributed to red wine, we also determined whether RS could change the damage done by this lifestyle. Male Wistar 24 rats receiving standard chow were divided into four groups (n = 6/group): (C) water throughout the experimental period; (E) 30% ethanol 3 days/week, water 4 days/week; (ES) a mixture of 30% ethanol and 30% sucrose 3 days/week, drinking 30% sucrose 4 days/week; (ESR) 30% ethanol and 30% sucrose containing 6 mg/l RS 3 days/week, drinking 30% sucrose 4 days/week. After 70 days the body weight was highest in ESR rats. E rats had higher energy expenditure (resting metabolic rate), oxygen consumption (VO(2)), fat oxidation, serum triacylglycerol (TG) and very low-density lipoprotein (VLDL) than C. ES rats normalized calorimetric parameters and enhanced carbohydrate oxidation. ESR ameliorated calorimetric parameters, reduced TG, VLDL and lipid hydroperoxide/total antioxidant substances, as well enhanced high-density lipoprotein (HDL) and HDL/TG ratio. Hepatic hydroxyacyl coenzyme-A dehydrogenase (OHADH)/citrate synthase ratio was lower in E and ES rats than in C. OHADH was highest in ESR rats. The present study brought new insights on weekend alcohol consumption, demonstrating for the first time, that this pattern of ethanol exposure induced dyslipidemic profile, calorimetric and hepatic metabolic changes which resemble that of the alcoholism. No synergistic effects were found with weekend ethanol and high-sucrose intake. RS was advantageous in weekend drinking and high-sucrose intake condition ameliorating hepatic metabolism and improving risk factors for cardiovascular damage.

  4. The effect of right ventricular pacing on myocardial oxidative metabolism and efficiency: relation with left ventricular dyssynchrony

    Energy Technology Data Exchange (ETDEWEB)

    Ukkonen, Heikki; Saraste, Antti; Koistinen, Juhani [Turku University Hospital, Department of Medicine, P.O. Box 52, Turku (Finland); Tops, Laurens; Bax, Jeroen [Leiden University Medical Center, Leiden (Netherlands); Naum, Alexander [University of Turku, Turku PET Centre, Turku (Finland); Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Turku University Hospital, Turku PET Centre, P.O. Box 52, Turku (Finland)

    2009-12-15

    Right ventricular (RV) apical pacing induces dyssynchrony by a left bundle branch block type electrical activation sequence in the heart and may impair left ventricular (LV) function. Whether these functional changes are accompanied by changes in myocardial perfusion, oxidative metabolism and efficiency, and the relation with the induction of LV dyssynchrony are unknown. Our study was designed to investigate the acute effects of RV pacing on these parameters. Ten patients with normal LV ejection fraction and VVI/DDD pacemaker were studied during AAI pacing/sinus rhythm without RV pacing (pacing-OFF) and with RV pacing (pacing-ON) at the same heart rate. Dynamic [{sup 15}O]water and [{sup 11}C]acetate positron emission tomography was used to measure perfusion and oxidative metabolism (k{sub mono}) of the LV. An echocardiographic examination was used to assess LV stroke volume (SV) and LV dyssynchrony. Myocardial efficiency of forward work was calculated as systolic blood pressure x cardiac output/LV mass/k{sub mono}. RV pacing decreased SV in all subjects (mean decrease 13%, from 76 {+-} 7 to 66 {+-} 7 ml, p = 0.004), but global perfusion and k{sub mono} were unchanged. The efficiency tended to be lower with pacing-ON (70 {+-} 20 vs 81 {+-} 21 mmHg l/g, p = 0.066). In patients with dyssynchrony during pacing (n = 6) efficiency decreased by 23% (from 78 {+-} 25 to 60 {+-} 14 mmHg l/g, p = 0.02), but in patients without dyssynchrony no change in efficiency was detected. Accordingly, heterogeneity in myocardial perfusion and oxidative metabolism was detected during pacing in patients with dyssynchrony but not in those without dyssynchrony. RV pacing resulted in a significant decrease in SV. However, deleterious effects on LV oxidative metabolism and efficiency were observed only in patients with dyssynchrony during RV pacing. (orig.)

  5. Monocyte matrix metalloproteinase production in Type 2 diabetes and controls – a cross sectional study

    Directory of Open Access Journals (Sweden)

    Davies Isabel R

    2003-03-01

    Full Text Available Abstract Background Coronary plaque rupture may result from localised over expression of matrix metalloproteinases (MMPs within the plaque by infiltrating monocyte – macrophages. As MMP expression can be promoted by the modified lipoproteins, oxidative stress and hyperglycaemia that characterises Type 2 diabetes, we hypothesised that peripheral monocytes in these patients, exposed to these factors in vivo, would demonstrate increased MMP production compared to controls. Methods We examined peripheral venous monocyte expression of MMP and tissue inhibitor of metalloproteinase-1 (TIMP-1 in 18 controls and 22 subjects with Type 2 diabetes and no previous cardiovascular complications. Results No significant difference in MMP-1, 3 or 9 or TIMP-1 production was observed between control and diabetes groups. Conclusions Monocyte MMP-1, 3, and 9, and TIMP-1, production are not abnormal in Type 2 diabetes. This data cannot be extrapolated to monocyte – macrophage behaviour in the vessel wall, but it does suggest MMP and TIMP-1 expression prior to monocyte infiltration and transformation are not abnormal in Type 2 diabetes.

  6. Toxicity of nanotitanium dioxide (TiO2-NP) on human monocytes and their mitochondria.

    Science.gov (United States)

    Ghanbary, Fatemeh; Seydi, Enaytollah; Naserzadeh, Parvaneh; Salimi, Ahmad

    2018-03-01

    The effect of nanotitanium dioxide (TiO 2 -NP) in human monocytes is still unknown. Therefore, an understanding of probable cytotoxicity of TiO 2 -NP on human monocytes and underlining the mechanisms involved is of significant interest. The aim of this study was to assess the cytotoxicity of TiO 2 -NP on human monocytes. Using biochemical and flow cytometry assessments, we demonstrated that addition of TiO 2 -NP at 10 μg/ml concentration to monocytes induced cytotoxicity following 12 h. The TiO 2 -NP-induced cytotoxicity on monocytes was associated with intracellular reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) collapse, lysosomal membrane injury, lipid peroxidation, and depletion of glutathione. According to our results, TiO 2 -NP triggers oxidative stress and organelles damages in monocytes which are important cells in defense against foreign agents. Finally, our findings suggest that use of antioxidants and mitochondrial/lysosomal protective agents could be of benefit for the people in the exposure with TiO 2 -NP.

  7. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Science.gov (United States)

    Feng, Jianghua; Liu, Huili; Zhang, Limin; Bhakoo, Kishore; Lu, Lehui

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  8. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianghua [Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, 361005 (China); Liu Huili; Zhang Limin [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Bhakoo, Kishore [Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A-STAR) 138667 (Singapore); Lu Lehui, E-mail: jianghua.feng@hotmail.com, E-mail: jianghua.feng@wipm.ac.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China)

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary {alpha}-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary {alpha}-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies ({beta}-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of

  9. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    International Nuclear Information System (INIS)

    Feng Jianghua; Liu Huili; Zhang Limin; Bhakoo, Kishore; Lu Lehui

    2010-01-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  10. Biofluid metabotyping of occupationally exposed subjects to air pollution demonstrates high oxidative stress and deregulated amino acid metabolism

    Science.gov (United States)

    Pradhan, Surya Narayan; Das, Aleena; Meena, Ramovatar; Nanda, Ranjan Kumar; Rajamani, Paulraj

    2016-10-01

    Occupational exposure to air pollution induces oxidative stress and prolonged exposure increases susceptibility to cardiovascular and respiratory diseases in several working groups. Biofluid of these subjects may reflect perturbed metabolic phenotypes. In this study we carried out a comparative molecular profiling study using parallel biofluids collected from subjects (n = 85) belonging to auto rickshaw drivers (ARD), traffic cops (TC) and office workers (OW). Higher levels of oxidative stress and inflammation markers in serum of ARD subjects were observed as compared to OW and TC. Uni and multivariate analyses of metabolites identified in urine by 1H NMR revealed 11 deregulated molecules in ARD subjects and involved in phenylalanine, histidine, arginine and proline metabolism. Despite contribution of confounding factors like exposure period, dietary factors including smoking and alcohol status, our results demonstrate existence of exposure specific metabotypes in biofluids of ARD, OW and TC groups. Monitoring serum oxidative stress and inflammation markers and urine metabolites by NMR may be useful to characterize perturbed metabolic phenotypes in populations exposed to urban traffic air pollution.

  11. High Uric Acid Activates the ROS-AMPK Pathway, Impairs CD68 Expression and Inhibits OxLDL-Induced Foam-Cell Formation in a Human Monocytic Cell Line, THP-1

    Directory of Open Access Journals (Sweden)

    Chaohuan Luo

    2016-11-01

    Full Text Available Background/Aims: Hyperuricemia is part of the metabolic-syndrome cluster of abdominal obesity, impaired glucose tolerance, insulin resistance, dyslipidemia, and hypertension. Monocytes/macrophages are critical in the development of metabolic syndrome, including gout, obesity and atherosclerosis. However, how high uric acid (HUA exposure affects monocyte/macrophage function remains unclear. In this study, we investigated the molecular mechanism of HUA exposure in monocytes/macrophages and its impact on oxidized low-density lipoprotein (oxLDL-induced foam-cell formation in a human monocytic cell line, THP-1. Methods: We primed THP-1 cells with phorbol-12-myristate-13-acetate (PMA for differentiation, then exposed cells to HUA and detected the production of reactive oxygen species (ROS and analyzed the level of phospho-AMPKα. THP-1 cells were pre-incubated with Compound C, an AMPK inhibitor, or N-acetyl-L-cysteine (NAC, a ROS scavenger, or HUA before PMA, to assess CD68 expression and phospho-AMPKα level. PMA-primed THP-1 cells were pre-treated with oxLDL before Compound C and HUA treatment. Western blot analysis was used to examine the levels of phospho-AMPKα, CD68, ABCG1, ABCA1, cyclooxygenase-2 (COX-2 and NF-κB (p65. Flow cytometry was used to assess ROS production and CD68 expression in live cells. Oil-red O staining was used to observe oxLDL uptake in cells. Results: HUA treatment increased ROS production in PMA-primed THP-1 cells; NAC blocked HUA-induced oxidative stress. HUA treatment time-dependently increased phospho-AMPKα level in PMA-primed THP-1 cells. The HUA-induced oxidative stress increased phospho-AMPKα levels, which was blocked by NAC. HUA treatment impaired CD68 expression during cell differentiation by activating the AMPK pathway, which was reversed by Compound C treatment. Finally, HUA treatment inhibited oxLDL uptake in the formation of foam cells in THP-1 cells, which was blocked by Compound C treatment. HUA treatment

  12. [Oxidative metabolism of main and accessory olfactory bulbs, limpic system and hypothalamus during the estral cycle of the rat (author's transl)].

    Science.gov (United States)

    Sánchez-Criado, J E

    1979-06-01

    The in vitro oxidative metabolism of hypothalamus, olfactory and limbic systems from female rats in the estrous cycle have been measured. The accessory olfactory bulb becomes most active during diestrous when the hypothalamus reaches its lowest values.

  13. Effect of Tiaoxin Recipe (调心方) on Spatial Memory and Energy Metabolism of Oxidation Injured Alzheimer's Disease Rats

    Institute of Scientific and Technical Information of China (English)

    邱宏; 金国琴; 赵伟康; 张学礼

    2003-01-01

    Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in treating AD. Methods: Eighty-eight SD rats were randomly divided into five groups (normal group, operative group, "AD" model group,TXR group and Aricept group). An oxygen free radical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate, DHF-FeCl3-ADP) was used to create oxidation injured rat models mimic to AD; spatial learning and memory impairment (Morris water maze method), the activity of Succinate-oxidase, NADH-oxidase, CytC-oxidase (Clark oxygen electrode method) and the expression of cytochrome oxidase (CO)ⅡmRNA (in situ hybridization method) were observed. Results: Compared with the normal group, the spatial memory, activity of CytC-oxidase and COⅡmRNA expression of oxidation injured "AD" rats were obviously decreased; TXR, however, could improve these functions in "AD" rat models obviously. Conclusion: The mechanism of the action of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mitochondrial energy metabolism.

  14. MONOCYTES AND MACROPHAGES IN PREGNANCY AND PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Marijke M Faas

    2014-06-01

    Full Text Available Preeclampsia is an important complication in pregnancy, characterized byhypertension and proteinuria in the second half of pregnancy. Generalizedactivation of the inflammatory response is thought to play a role in thepathogenesis of preeclampsia. Monocytes may play a central role in thisinflammatory response. Monocytes are short lived cells, that mature in thecirculation and invade into tissues upon an inflammatory stimulus anddevelop into macrophages. Macrophages are abundantly present in theendometrium and play a role in implantation and placentation in normalpregnancy. In preeclampsia, these macrophages appear to be present in largernumbers and are also activated. In the present review we focused on the roleof monocytes and macrophages in the pathophysiology of preeclampsia.

  15. Strenuous physical exercise adversely affects monocyte chemotaxis

    DEFF Research Database (Denmark)

    Czepluch, Frauke S; Barres, Romain; Caidahl, Kenneth

    2011-01-01

    Physical exercise is important for proper cardiovascular function and disease prevention, but it may influence the immune system. We evaluated the effect of strenuous exercise on monocyte chemotaxis. Monocytes were isolated from blood of 13 young, healthy, sedentary individuals participating...... in a three-week training program which consisted of repeated exercise bouts. Monocyte chemotaxis and serological biomarkers were investigated at baseline, after three weeks training and after four weeks recovery. Chemotaxis towards vascular endothelial growth factor-A (VEGF-A) and transforming growth factor...

  16. Assessment of nitric oxide (NO) redox reactions contribution to nitrous oxide (N2 O) formation during nitrification using a multispecies metabolic network model.

    Science.gov (United States)

    Perez-Garcia, Octavio; Chandran, Kartik; Villas-Boas, Silas G; Singhal, Naresh

    2016-05-01

    Over the coming decades nitrous oxide (N2O) is expected to become a dominant greenhouse gas and atmospheric ozone depleting substance. In wastewater treatment systems, N2O is majorly produced by nitrifying microbes through biochemical reduction of nitrite (NO2(-)) and nitric oxide (NO). However it is unknown if the amount of N2O formed is affected by alternative NO redox reactions catalyzed by oxidative nitrite oxidoreductase (NirK), cytochromes (i.e., P460 [CytP460] and 554 [Cyt554 ]) and flavohemoglobins (Hmp) in ammonia- and nitrite-oxidizing bacteria (AOB and NOB, respectively). In this study, a mathematical model is developed to assess how N2O formation is affected by such alternative nitrogen redox transformations. The developed multispecies metabolic network model captures the nitrogen respiratory pathways inferred from genomes of eight AOB and NOB species. The performance of model variants, obtained as different combinations of active NO redox reactions, was assessed against nine experimental datasets for nitrifying cultures producing N2O at different concentration of electron donor and acceptor. Model predicted metabolic fluxes show that only variants that included NO oxidation to NO2(-) by CytP460 and Hmp in AOB gave statistically similar estimates to observed production rates of N2O, NO, NO2(-) and nitrate (NO3(-)), together with fractions of AOB and NOB species in biomass. Simulations showed that NO oxidation to NO2(-) decreased N2O formation by 60% without changing culture's NO2(-) production rate. Model variants including NO reduction to N2O by Cyt554 and cNor in NOB did not improve the accuracy of experimental datasets estimates, suggesting null N2O production by NOB during nitrification. Finally, the analysis shows that in nitrifying cultures transitioning from dissolved oxygen levels above 3.8 ± 0.38 to <1.5 ± 0.8 mg/L, NOB cells can oxidize the NO produced by AOB through reactions catalyzed by oxidative NirK. © 2015 Wiley Periodicals, Inc.

  17. Monocyte Trafficking, Engraftment, and Delivery of Nanoparticles and an Exogenous Gene into the Acutely Inflamed Brain Tissue - Evaluations on Monocyte-Based Delivery System for the Central Nervous System.

    Directory of Open Access Journals (Sweden)

    Hsin-I Tong

    Full Text Available The ability of monocytes and monocyte-derived macrophages (MDM to travel towards chemotactic gradient, traverse tissue barriers, and accumulate precisely at diseased sites makes them attractive candidates as drug carriers and therapeutic gene delivery vehicles targeting the brain, where treatments are often hampered by the blockade of the blood brain barrier (BBB. This study was designed to fully establish an optimized cell-based delivery system using monocytes and MDM, by evaluating their homing efficiency, engraftment potential, as well as carriage and delivery ability to transport nano-scaled particles and exogenous genes into the brain, following the non-invasive intravenous (IV cell adoptive transfer in an acute neuroinflammation mouse model induced by intracranial injection of Escherichia coli lipopolysaccharides. We demonstrated that freshly isolated monocytes had superior inflamed-brain homing ability over MDM cultured in the presence of macrophage colony stimulating factor. In addition, brain trafficking of IV infused monocytes was positively correlated with the number of adoptive transferred cells, and could be further enhanced by transient disruption of the BBB with IV administration of Mannitol, Bradykinin or Serotonin right before cell infusion. A small portion of transmigrated cells was detected to differentiate into IBA-1 positive cells with microglia morphology in the brain. Finally, with the use of superparamagnetic iron oxide nanoparticles SHP30, the ability of nanoscale agent-carriage monocytes to enter the inflamed brain region was validated. In addition, lentiviral vector DHIV-101 was used to introduce green fluorescent protein (GFP gene into monocytes, and the exogenous GFP gene was detected in the brain at 48 hours following IV infusion of the transduced monocytes. All together, our study has set up the optimized conditions for the more-in-depth tests and development of monocyte-mediated delivery, and our data supported

  18. Military training elicits marked increases in plasma metabolomic signatures of energy metabolism, lipolysis, fatty acid oxidation, and ketogenesis.

    Science.gov (United States)

    Karl, J Philip; Margolis, Lee M; Murphy, Nancy E; Carrigan, Christopher T; Castellani, John W; Madslien, Elisabeth H; Teien, Hilde-Kristin; Martini, Svein; Montain, Scott J; Pasiakos, Stefan M

    2017-09-01

    Military training studies provide unique insight into metabolic responses to extreme physiologic stress induced by multiple stressor environments, and the impacts of nutrition in mediating these responses. Advances in metabolomics have provided new approaches for extending current understanding of factors modulating dynamic metabolic responses in these environments. In this study, whole-body metabolic responses to strenuous military training were explored in relation to energy balance and macronutrient intake by performing nontargeted global metabolite profiling on plasma collected from 25 male soldiers before and after completing a 4-day, 51-km cross-country ski march that produced high total daily energy expenditures (25.4 MJ/day [SD 2.3]) and severe energy deficits (13.6 MJ/day [SD 2.5]). Of 737 identified metabolites, 478 changed during the training. Increases in 88% of the free fatty acids and 91% of the acylcarnitines, and decreases in 88% of the mono- and diacylglycerols detected within lipid metabolism pathways were observed. Smaller increases in 75% of the tricarboxylic acid cycle intermediates, and 50% of the branched-chain amino acid metabolites detected were also observed. Changes in multiple metabolites related to lipid metabolism were correlated with body mass loss and energy balance, but not with energy and macronutrient intakes or energy expenditure. These findings are consistent with an increase in energy metabolism, lipolysis, fatty acid oxidation, ketogenesis, and branched-chain amino acid catabolism during strenuous military training. The magnitude of the energy deficit induced by undereating relative to high energy expenditure, rather than macronutrient intake, appeared to drive these changes, particularly within lipid metabolism pathways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  19. Lipopolysaccharide-induced expression of cell surface receptors and cell activation of neutrophils and monocytes in whole human blood

    Directory of Open Access Journals (Sweden)

    N.E. Gomes

    2010-09-01

    Full Text Available Lipopolysaccharide (LPS activates neutrophils and monocytes, inducing a wide array of biological activities. LPS rough (R and smooth (S forms signal through Toll-like receptor 4 (TLR4, but differ in their requirement for CD14. Since the R-form LPS can interact with TLR4 independent of CD14 and the differential expression of CD14 on neutrophils and monocytes, we used the S-form LPS from Salmonella abortus equi and the R-form LPS from Salmonella minnesota mutants to evaluate LPS-induced activation of human neutrophils and monocytes in whole blood from healthy volunteers. Expression of cell surface receptors and reactive oxygen species (ROS and nitric oxide (NO generation were measured by flow cytometry in whole blood monocytes and neutrophils. The oxidative burst was quantified by measuring the oxidation of 2',7'-dichlorofluorescein diacetate and the NO production was quantified by measuring the oxidation of 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate. A small increase of TLR4 expression by monocytes was observed after 6 h of LPS stimulation. Monocyte CD14 modulation by LPS was biphasic, with an initial 30% increase followed by a 40% decrease in expression after 6 h of incubation. Expression of CD11b was rapidly up-regulated, doubling after 5 min on monocytes, while down-regulation of CXCR2 was observed on neutrophils, reaching a 50% reduction after 6 h. LPS induced low production of ROS and NO. This study shows a complex LPS-induced cell surface receptor modulation on human monocytes and neutrophils, with up- and down-regulation depending on the receptor. R- and S-form LPS activate human neutrophils similarly, despite the low CD14 expression, if the stimulation occurs in whole blood.

  20. NDRG2 overexpression suppresses hepatoma cells survival during metabolic stress through disturbing the activation of fatty acid oxidation

    International Nuclear Information System (INIS)

    Pan, Tao; Zhang, Mei; Zhang, Fang; Yan, Guang; Ru, Yi; Wang, Qinhao; Zhang, Yao; Wei, Xuehui; Xu, Xinyuan; Shen, Lan; Zhang, Jian; Wu, Kaichun; Yao, Libo; Li, Xia

    2017-01-01

    Because of the high nutrient consumption and inadequate vascularization, solid tumor constantly undergoes metabolic stress during tumor development. Oncogenes and tumor suppressor genes participated in cancer cells' metabolic reprogramming. N-Myc downstream regulated gene 2 (NDRG2) is a recently identified tumor suppressor gene, but its function in cancer metabolism, particularly during metabolic stress, remains unclear. In this study, we found that NDRG2 overexpression significantly reduced hepatoma cell proliferation and enhanced cell apoptosis under glucose limitation. Moreover, NDRG2 overexpression aggravated energy imbalance and oxidative stress by decreasing the intracellular ATP and NADPH generation and increasing ROS levels. Strikingly, NDRG2 inhibited the activation of fatty acid oxidation (FAO), which preserves ATP and NADPH purveyance in the absence of glucose. Finally, mechanistic investigation showed that NDRG2 overexpression suppressed the glucose-deprivation induced AMPK/ACC pathway activation in hepatoma cells, whereas the expression of a constitutively active form of AMPK abrogated glucose-deprivation induced AMPK activation and cell apoptosis. Thus, as a negative regulator of AMPK, NDRG2 disturbs the induction of FAO genes by glucose limitation, leading to dysregulation of ATP and NADPH, and thus reduces the tolerance of hepatoma cells to glucose limitation. - Highlights: • NDRG2 overexpression reduces the tolerance of hepatoma cells to glucose limitation. • NDRG2 overexpression aggravates energy imbalance and oxidative stress under glucose deprivation. • NDRG2 overexpression disturbs the activation of FAO in hepatoma cells under glucose limitation. • NDRG2 overexpression inhibits the activation of AMPK/ACC pathway in hepatoma cells during glucose starvation.

  1. Relation between both oxidative and metabolic-osmotic cell damages and initial injury severity in bombing casualties

    Directory of Open Access Journals (Sweden)

    Vučeljić Marina

    2006-01-01

    Full Text Available Background/Aim. We have recently reported the development of oxidative cell damages in bombing casualties within a very early period after the initial injury. The aim of this study, was to investigate malondialdehyde (MDA, as an indicator of lipid peroxidation, and osmolal gap (OG, as a good indicator of metabolic cell damages and to assess their relationship with the initial severity of the injury in bombing casualties. Methods. The study included the males (n = 52, injured during the bombing with the Injury Severity Score (ISS ranging from 3 to 66. The whole group of casualties was devided into a group of less severely (ISS < 25, n = 24 and a group of severely (ISS ≥ 26, n = 28 injured males. The uninjured volunteers (n = 10 were the controls. Osmolality, MDA, sodium, glucose, urea, creatinine, total bilirubin and total protein levels were measured in the venous blood, sampled daily, within a ten-day period. Results. In both groups of casualties, MDA and OG levels increased, total protein levels decreased, while other parameters were within the control limits. MDA alterations correlated with ISS (r = 0.414, p < 0.01, while a statistically significant correlation between OG and ISS was not obtained. Interestingly, in spite of some differences in MDA and OG trends, at the end of the examined period they were at the similar level in both groups. Conclusion. The initial oxidative damages of the cellular membrane with intracellular metabolic disorders contributed to the gradual development of metabolic-osmotic damages of cells, which, consequently caused the OG increase. In the bombing casualties, oxidative cell damages were dependent on the initial injury severity, while metabolic-osmotic cell damages were not.

  2. Investigation of cytokines, oxidative stress, metabolic, and inflammatory biomarkers after orange juice consumption by normal and overweight subjects

    Directory of Open Access Journals (Sweden)

    Grace K. Z. S. Dourado

    2015-10-01

    Full Text Available Background: Abdominal adiposity has been linked to metabolic abnormalities, including dyslipidemia, oxidative stress, and low-grade inflammation. Objective: To test the hypothesis that consumption of 100% orange juice (OJ would improve metabolic, oxidative, and inflammatory biomarkers and cytokine levels in normal and overweight subjects with increased waist circumference. Design: Subjects were divided into two groups in accordance with their body mass index: normal and overweight. Both groups of individuals consumed 750 mL of OJ daily for 8 weeks. Body composition (weight, height, percentage of fat mass, and waist circumference; metabolic biomarkers (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], triglycerides, glucose, insulin, HOMA-IR, and glycated hemoglobin; oxidative biomarkers (malondialdehyde and DPPH•; inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP]; cytokines (IL-4, IL-10, IL-12, TNF-α, and IFN-γ; and diet were evaluated before and after consumption of OJ for 8 weeks. Results: The major findings of this study were: 1 no alteration in body composition in either group; 2 improvement of the lipid profile, evidenced by a reduction in total cholesterol and LDL-C; 3 a potential stimulation of the immune response due to increase in IL-12; 4 anti-inflammatory effect as a result of a marked reduction in hsCRP; and 5 antioxidant action by the enhancement of total antioxidant capacity and the reduction of lipid peroxidation, in both normal and overweight subjects. Conclusions: OJ consumption has a positive effect on important biomarkers of health status in normal and overweight subjects, thereby supporting evidence that OJ acts as functional food and could be consumed as part of a healthy diet to prevent metabolic and chronic diseases.

  3. Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria.

    Science.gov (United States)

    Filipović, Dragana; Costina, Victor; Perić, Ivana; Stanisavljević, Andrijana; Findeisen, Peter

    2017-03-15

    Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15mg/kg) was administered daily to adult male Wistar rats for 3weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO. Our comparative study revealed that in cytosolic and nonsynaptic mitochondrial fractions, 60 and 3 proteins respectively, were down-regulated, and 23 and 60 proteins, respectively, were up-regulated. Proteins differentially regulated in cytosolic and nonsynaptic mitochondrial fractions were primarily related to cellular and metabolic processes. Of the identified proteins, the expressions of calretinin and parvalbumine were confirmed. The predominant molecular functions of differentially expressed proteins in both cell hippocampal fractions were binding and catalytic activity. Most differentially expressed proteins in nonsynaptic mitochondria were catalytic enzymes involved in the pyruvate metabolism, citric acid cycle, oxidative phosphorylation, ATP synthesis, ATP transduction and glutamate metabolism. Results indicate that chronic Flx treatment may influence proteins involved in calcium signaling, cytoskeletal structure, chaperone system and stimulates energy metabolism via the upregulation of GAPDH expression in cytoplasm, as well as directing energy metabolism toward the citric acid cycle and oxidative phosphorylation in nonsynaptic mitochondria. This approach provides new insight into the chronic effects of Flx treatment on protein expression in a key brain region associated with stress response and memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Nitrous oxide and perioperative outcomes.

    Science.gov (United States)

    Ko, Hanjo; Kaye, Alan David; Urman, Richard D

    2014-06-01

    There is emerging evidence related to the effects of nitrous oxide on important perioperative patient outcomes. Proposed mechanisms include metabolic effects linked to elevated homocysteine levels and endothelial dysfunction, inhibition of deoxyribonucleic acid and protein formation, and depression of chemotactic migration by monocytes. Newer large studies point to possible risks associated with the use of nitrous oxide, although data are often equivocal and inconclusive. Cardiovascular outcomes such as stroke or myocardial infarction were shown to be unchanged in previous studies, but the more recent Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia I trial shows possible associations between nitrous oxide and increased cardiovascular and pulmonary complications. There are also possible effects on postoperative wound infections and neuropsychological function, although the multifactorial nature of these complications should be considered. Teratogenicity linked to nitrous oxide use has not been firmly established. The use of nitrous oxide for routine anesthetic care may be associated with significant costs if complications such as nausea, vomiting, and wound infections are taken into consideration. Overall, definitive data regarding the effect of nitrous oxide on major perioperative outcomes are lacking. There are ongoing prospective studies that may further elucidate its role. The use of nitrous oxide in daily practice should be individualized to each patient's medical conditions and risk factors.

  5. Effect of Feeding Oxidized Soybean Oil against Antioxidant role of Pomegranate Seed on Physiology and Metabolism of Periparturient Saanen Goats

    Directory of Open Access Journals (Sweden)

    Seyyed Ehsan Ghiasi

    2016-08-01

    Full Text Available Introduction Oxidative stress is metabolic and physiologic status caused by imbalance between free radical production and antioxidant defense of body. In some physiological status such as rapid growth, parturition, disease and high production rate that imbalance would occur. High producing dairy animals are suspected to oxidative stress and require to antioxidant supplementation. Negative energy balance in early lactation force the nutrition specialist to apply oil and high NFC diet to exceed the requirement of high producing dairy animals such as Holstein cows and Saanen goats. In recent years, the attention to the use of herbal or organic antioxidant in animal nutrition has increased. This study was carried out to investigate the effects of feeding oxidized soybean oil (OSO plus pomegranate seed (PS as a natural antioxidant, on metabolism and physiology of Preparturient Saanen Goats. Materials and Methods Eighteen Saanen dairy goats with initial body weight of 47 ± 9 kg were assigned to three dietary treatments in a completely randomized design with repeated measurements for 21 days before anticipated parturition. Experimental treatments including: 1 base diet and 4% fresh soybean oil (FSO, 2 base diet and 4% oxidized soybean oil (DM basis respectively, and 3 base diet plus 4% OSO and 8% Pomegranate seed (OSO-PS. After 2 weeks of feeding trial diets, goats were sampled for blood, rumen liquor, faeces and urine for measuring parameters of blood glucose, BHBA, lipid and nitrogen profile, rumen liquor ammonia nitrogen, urine pH and volume, faeces qualitative and quantitative variables and other responses such as nutrients digestibility. The GLM procedure of SAS software v.9.2 were used for statistical analysis. Initial body weight and metabolic variables were used as covariate in the model. Results and discussion All nutrients digestibility, Ruminal ammonia nitrogen and voluntary feed intake were decreased by OSO (p

  6. Effect of grape seed extract on postprandial oxidative status and metabolic responses in men and women with the metabolic syndrome - randomized, cross-over, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Indika Edirisinghe

    2012-12-01

    Full Text Available Objective: This investigation was undertaken to determine whether a grape seed extract (GSE that is rich in mono-, oligo- and poly- meric polyphenols would modify postprandial oxidative stress and inflammation in individuals with the metabolic syndrome (MetS.Background: MetS is known to be associated with impaired glucose tolerance and poor glycemic control. Consumption of a meal high in readily available carbohydrates and fat causes postprandial increases in glycemia and lipidemia and markers of oxidative stress, inflammation and insulin resistance. Materials/methods: After an overnight fast, twelve subjects with MetS (5 men and 7 women consumed a breakfast meal high in fat and carbohydrate in a cross-over design. A GSE (300 mg or placebo capsule was administrated 1 hr before the meal (-1 hr. Changes in plasma insulin, glucose, oxidative stress and inflammatory markers were measured hourly for 6 hr. Results: Plasma hydrophilic oxygen radical absorbance capacity (ORAC measured as the positive incremental area under the curve (-1 to 5 hr was significantly increased when the meal was preceded by GSE compared with placebo (P0.05. No changes in inflammatory markers were evident. Conclusion: These data suggest that GSE enhances postprandial plasma antioxidant status and reduces the glycemic response to a meal, high in fat and carbohydrate in subjects with the MetS.

  7. Aged mice have increased inflammatory monocyte concentration ...

    Indian Academy of Sciences (India)

    monocytes from old as compared with those from young mice. The increased classic .... several instances where the isotype control antibodies stained in a similar position but at a ..... responses in young and older adults. J. Infect. Dis. 195.

  8. Epigenetic Regulation of Monocyte and Macrophage Function

    NARCIS (Netherlands)

    Hoeksema, Marten A.; de Winther, Menno P. J.

    2016-01-01

    Monocytes and macrophages are key players in tissue homeostasis and immune responses. Epigenetic processes tightly regulate cellular functioning in health and disease. Recent Advances: Recent technical developments have allowed detailed characterizations of the transcriptional circuitry underlying

  9. Monocyte scintigraphy in rheumatoid arthritis: the dynamics of monocyte migration in immune-mediated inflammatory disease.

    Directory of Open Access Journals (Sweden)

    Rogier M Thurlings

    2009-11-01

    Full Text Available Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA, a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man.We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT. We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99mTc-HMPAO. Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4 x 10(-3 (0.95-5.1 x 10(-3 % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion.The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention.

  10. Age-Specific Determinants of Pulse Wave Velocity among Metabolic Syndrome Components, Inflammatory Markers, and Oxidative Stress.

    Science.gov (United States)

    Kim, Minkyung; Kim, Minjoo; Yoo, Hye Jin; Lee, Seung Yeon; Lee, Sang-Hyun; Lee, Jong Ho

    2018-02-01

    Pulse wave velocity (PWV) is thought to have different relationships with metabolic syndrome (MS) components, inflammatory markers, and oxidative stress, according to age. However, age-specific determinants of PWV have not yet been studied. We investigated age-dependent relationships among PWV and MS components, inflammatory markers, and oxidative stress. A total of 4,318 subjects were divided into 4 groups: 19-34 y (n=687), 35-44 y (n=1,413), 45-54 y (n=1,384), and 55-79 y (n=834). MS components, brachial-ankle PWV (baPWV), high-sensitivity C-reactive protein (hs-CRP), and oxidative stress markers were measured. There were age-related increases in MS, body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic BP (DBP), triglycerides, glucose, hs-CRP, oxidized low-density lipoprotein (LDL), 8-epi-prostaglandin F 2α (8-epi-PGF 2α ), and baPWV. BaPWV was significantly associated with sex and elevated BP in the 19-34 y group; with age, sex, BMI, elevated BP and triglycerides in the 35-44 y group; with age, sex, elevated BP, fasting glucose, hs-CRP and oxidized LDL in the 45-54 y group; and with age, BMI, elevated BP, fasting glucose and oxidized LDL in the 55-79 y group. Our results show that age-related increases in baPWV are associated with age-related changes in MS components, inflammatory markers, and oxidative stress. However, each of these factors has an age-specific, different impact on arterial stiffness. In particular, oxidative stress may be independently associated with arterial stiffness in individuals older than 45 y.

  11. Osteopontin Prevents Monocyte Recirculation and Apoptosis

    OpenAIRE

    Burdo, Tricia H.; Wood, Malcolm R.; Fox, Howard S.

    2007-01-01

    Cells of the monocyte/macrophage lineage have been shown to be the principal targets for productive HIV-1 replication within the central nervous system. In addition, HIV-1-associated dementia (HAD) has been shown to correlate with macrophage abundance in the brain. While increased entry of monocytes into the brain is thought to initiate this process, mechanisms that prevent macrophage egress from the brain and means that prevent macrophage death may also contribute to cell accumulation. We hy...

  12. Induction of autophagy is essential for monocyte-macrophage differentiation

    OpenAIRE

    Zhang, Yan; Morgan, Michael J.; Chen, Kun; Choksi, Swati; Liu, Zheng-gang

    2012-01-01

    Monocytes are programmed to undergo apoptosis in the absence of stimulation. Stimuli that promote monocyte-macrophage differentiation not only cause cellular changes, but also prevent the default apoptosis of monocytes. In the present study, we demonstrate that autophagy is induced when monocytes are triggered to differentiate and that the induction of autophagy is pivotal for the survival and differentiation of monocytes. We also show that inhibition of autophagy results in apoptosis of cell...

  13. HIV-1 Latency in Monocytes/Macrophages

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2014-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

  14. Effects of glucose metabolism pathways on sperm motility and oxidative status during long-term liquid storage of goat semen.

    Science.gov (United States)

    Qiu, Jian-Hua; Li, You-Wei; Xie, Hong-Li; Li, Qing; Dong, Hai-Bo; Sun, Ming-Ju; Gao, Wei-Qiang; Tan, Jing-He

    2016-08-01

    Although great efforts were made to prolong the fertility of liquid-stored semen, limited improvements have been achieved in different species. Although it is expected that energy supply and the redox potential will play an essential role in sperm function, there are few reports on the impact of specific energy substrates on spermatozoa during liquid semen storage. Furthermore, although it is accepted that glucose metabolism through glycolysis provides energy, roles of pentose phosphate pathway (PPP) and tricarboxylic acid cycle remain to be unequivocally found in spermatozoa. We have studied the pathways by which spermatozoa metabolize glucose during long-term liquid storage of goat semen. The results indicated that among the substrates tested, glucose and pyruvate were better than lactate in maintaining goat sperm motility. Although both glycolysis and PPP were essential, PPP was more important than glycolysis to maintain sperm motility. Pentose phosphate pathway reduced oxidative stress and provided glycolysis with more intermediate products such as fructose-6-phosphate. Pyruvate entered goat spermatozoa through monocarboxylate transporters and was oxidized by the tricarboxylic acid cycle and electron transfer to sustain sperm motility. Long-term liquid semen storage can be used as a good model to study sperm glucose metabolism. The data are important for an optimal control of sperm survival during semen handling and preservation not only in the goat but also in other species. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Oxidative stress protection and glutathione metabolism in response to hydrogen peroxide and menadione in riboflavinogenic fungus Ashbya gossypii.

    Science.gov (United States)

    Kavitha, S; Chandra, T S

    2014-11-01

    Ashbya gossypii is a plant pathogen and a natural overproducer of riboflavin and is used for industrial riboflavin production. A few literature reports depict a link between riboflavin overproduction and stress in this fungus. However, the stress protection mechanisms and glutathione metabolism are not much explored in A. gossypii. In the present study, an increase in the activity of catalase and superoxide dismutase was observed in response to hydrogen peroxide and menadione. The lipid peroxide and membrane lipid peroxide levels were increased by H2O2 and menadione, indicating oxidative damage. The glutathione metabolism was altered with a significant increase in oxidized glutathione (GSSG), glutathione peroxidase (GPX), glutathione S transferase (GST), and glutathione reductase (GR) and a decrease in reduced glutathione (GSH) levels in the presence of H2O2 and menadione. Expression of the genes involved in stress mechanism was analyzed in response to the stressors by semiquantitative RT-PCR. The messenger RNA (mRNA) levels of CTT1, SOD1, GSH1, YAP1, and RIB3 were increased by H2O2 and menadione, indicating the effect of stress at the transcriptional level. A preliminary bioinformatics study for the presence of stress response elements (STRE)/Yap response elements (YRE) depicted that the glutathione metabolic genes, stress genes, and the RIB genes hosted either STRE/YRE, which may enable induction of these genes during stress.

  16. A PGC-1α- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Skov, Vibe; Petersson, Stine Juhl

    2014-01-01

    Insulin resistance in obesity and type 2 diabetes is related to abnormalities in mitochondrial oxidative phosphorylation (OxPhos) in skeletal muscle. We tested the hypothesis that mitochondrial oxidative metabolism is impaired in muscle of patients with inherited insulin resistance and defective...

  17. Role of nitric oxide synthase uncoupling at rostral ventrolateral medulla in redox-sensitive hypertension associated with metabolic syndrome.

    Science.gov (United States)

    Wu, Kay L H; Chao, Yung-Mei; Tsay, Shiow-Jen; Chen, Chen Hsiu; Chan, Samuel H H; Dovinova, Ima; Chan, Julie Y H

    2014-10-01

    Metabolic syndrome (MetS), which is rapidly becoming prevalent worldwide, is long known to be associated with hypertension and recently with oxidative stress. Of note is that oxidative stress in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons reside, contributes to sympathoexcitation and hypertension. This study sought to identify the source of tissue oxidative stress in RVLM and their roles in neural mechanism of hypertension associated with MetS. Adult normotensive rats subjected to a high-fructose diet for 8 weeks developed metabolic traits of MetS, alongside increases in sympathetic vasomotor activity and blood pressure. In RVLM of these MetS rats, the tissue level of reactive oxygen species was increased, nitric oxide (NO) was decreased, and mitochondrial electron transport capacity was reduced. Whereas the protein expression of neuronal NO synthase (nNOS) or protein inhibitor of nNOS was increased, the ratio of nNOS dimer/monomer was significantly decreased. Oral intake of pioglitazone or intracisternal infusion of tempol or coenzyme Q10 significantly abrogated all those molecular events in high-fructose diet-fed rats and ameliorated sympathoexcitation and hypertension. Gene silencing of protein inhibitor of nNOS mRNA in RVLM using lentivirus carrying small hairpin RNA inhibited protein inhibitor of nNOS expression, increased the ratio of nNOS dimer/monomer, restored NO content, and alleviated oxidative stress in RVLM of high-fructose diet-fed rats, alongside significantly reduced sympathoexcitation and hypertension. These results suggest that redox-sensitive and protein inhibitor of nNOS-mediated nNOS uncoupling is engaged in a vicious cycle that sustains the production of reactive oxygen species in RVLM, resulting in sympathoexcitation and hypertension associated with MetS. © 2014 American Heart Association, Inc.

  18. A Metagenomics-Based Metabolic Model of Nitrate-Dependent Anaerobic Oxidation of Methane by Methanoperedens-Like Archaea

    Science.gov (United States)

    Arshad, Arslan; Speth, Daan R.; de Graaf, Rob M.; Op den Camp, Huub J. M.; Jetten, Mike S. M.; Welte, Cornelia U.

    2015-01-01

    Methane oxidation is an important process to mitigate the emission of the greenhouse gas methane and further exacerbating of climate forcing. Both aerobic and anaerobic microorganisms have been reported to catalyze methane oxidation with only a few possible electron acceptors. Recently, new microorganisms were identified that could couple the oxidation of methane to nitrate or nitrite reduction. Here we investigated such an enrichment culture at the (meta) genomic level to establish a metabolic model of nitrate-driven anaerobic oxidation of methane (nitrate-AOM). Nitrate-AOM is catalyzed by an archaeon closely related to (reverse) methanogens that belongs to the ANME-2d clade, tentatively named Methanoperedens nitroreducens. Methane may be activated by methyl-CoM reductase and subsequently undergo full oxidation to carbon dioxide via reverse methanogenesis. All enzymes of this pathway were present and expressed in the investigated culture. The genome of the archaeal enrichment culture encoded a variety of enzymes involved in an electron transport chain similar to those found in Methanosarcina species with additional features not previously found in methane-converting archaea. Nitrate reduction to nitrite seems to be located in the pseudoperiplasm and may be catalyzed by an unusual Nar-like protein complex. A small part of the resulting nitrite is reduced to ammonium which may be catalyzed by a Nrf-type nitrite reductase. One of the key questions is how electrons from cytoplasmically located reverse methanogenesis reach the nitrate reductase in the pseudoperiplasm. Electron transport in M. nitroreducens probably involves cofactor F420 in the cytoplasm, quinones in the cytoplasmic membrane and cytochrome c in the pseudoperiplasm. The membrane-bound electron transport chain includes F420H2 dehydrogenase and an unusual Rieske/cytochrome b complex. Based on genome and transcriptome studies a tentative model of how central energy metabolism of nitrate-AOM could work is

  19. Ameliorative effects of oleanolic acid on fluoride induced metabolic and oxidative dysfunctions in rat brain: Experimental and biochemical studies.

    Science.gov (United States)

    Sarkar, Chaitali; Pal, Sudipta; Das, Niranjan; Dinda, Biswanath

    2014-04-01

    Beneficial effects of oleanolic acid on fluoride-induced oxidative stress and certain metabolic dysfunctions were studied in four regions of rat brain. Male Wistar rats were treated with sodium fluoride at a dose of 20 mg/kg b.w./day (orally) for 30 days. Results indicate marked reduction in acidic, basic and neutral protein contents due to fluoride toxicity in cerebrum, cerebellum, pons and medulla. DNA, RNA contents significantly decreased in those regions after fluoride exposure. Activities of proteolytic enzymes (such as cathepsin, trypsin and pronase) were inhibited by fluoride, whereas transaminase enzyme (GOT and GPT) activities increased significantly in brain tissue. Fluoride appreciably elevated brain malondialdehyde level, free amino acid nitrogen, NO content and free OH radical generation. Additionally, fluoride perturbed GSH content and markedly reduced SOD, GPx, GR and CAT activities in brain tissues. Oral supplementation of oleanolic acid (a plant triterpenoid), at a dose of 5mg/kgb.w./day for last 14 days of fluoride treatment appreciably ameliorated fluoride-induced alteration of brain metabolic functions. Appreciable counteractive effects of oleanolic acid against fluoride-induced changes in protein and nucleic acid contents, proteolytic enzyme activities and other oxidative stress parameters indicate that oleanolic acid has potential antioxidative effects against fluoride-induced oxidative brain damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

    Directory of Open Access Journals (Sweden)

    Oluwafeyisetan O. Adebiyi

    2015-12-01

    Full Text Available Nucleoside Reverse Transcriptase Inhibitors (NRTIs have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7 were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT (groups I, II III, 50 mg/kg stavudine (d4T (groups IV, V, VI and 3 mL/kg of distilled water (group VII. Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy.

  1. Metabolic encephalopathy and lipid storage myopathy associated with a presumptive mitochondrial fatty acid oxidation defect in a dog

    Directory of Open Access Journals (Sweden)

    Vanessa R Biegen

    2015-11-01

    Full Text Available A 1-year-old spayed female Shih Tzu presented for episodic abnormalities of posture and mentation. Neurologic examination was consistent with a bilaterally symmetric multifocal encephalopathy. The dog had a waxing-and-waning hyperlactemia and hypoglycemia. Magnetic resonance imaging revealed bilaterally symmetric cavitated lesions of the caudate nuclei with less severe abnormalities in the cerebellar nuclei. Empirical therapy was unsuccessful and the patient was euthanized. Post-mortem histopathology revealed bilaterally symmetric necrotic lesions of the caudate and cerebellar nuclei and multi-organ lipid accumulation, including a lipid storage myopathy. Malonic aciduria and ketonuria were found on urinary organic acid screen. Plasma acylcarnitine analysis suggested a fatty acid oxidation defect. Fatty acid oxidation disorders are inborn errors of metabolism documented in humans, but poorly described in dogs. Although neurologic signs have been described in humans with this group of diseases, descriptions of advanced imaging and histopathology are severely lacking. This report suggests that abnormalities of fatty acid metabolism may cause severe, bilateral gray matter necrosis and lipid accumulation in multiple organs including the skeletal muscles, liver, and kidneys. Veterinarians should be aware that fatty acid oxidation disorders, although potentially fatal, may be treatable. A timely definitive diagnosis is essential in guiding therapy.

  2. Assessment of myocardial metabolism with iodine-123 heptadecanoic acid: effect of decreased fatty acid oxidation on deiodination

    International Nuclear Information System (INIS)

    Luethy, P.C.; Chatelain, P.; Papageorgiou, I.; Schubiger, A.; Lerch, R.A.

    1988-01-01

    Terminally radioiodinated fatty acid analogs are of potential use for the noninvasive delineation of regional alterations of fatty acid metabolism by gamma imaging. Since radioactivity from extracted iodine-123 heptadecanoic acid [( 123I]HDA) is released from the myocardium in form of free radioiodide (123I-) the present study was performed to determine whether deiodination of [123I]HDA is related to free fatty acid metabolism. Myocardial production of free radioiodide was measured in rat hearts in vitro and in vivo both under control conditions and after inhibition of fatty acid oxidation. In isolated rat hearts perfused at constant flow with a medium containing [123I]HDA, release of 123I- was markedly reduced during cardioplegia and pharmacologic inhibition of mitochondrial fatty acid transfer with POCA by 67% (p less than 0.005) and 72% (p less than 0.005), respectively. In fasted rats in vivo, 1 min after i.v. injection of [123I]HDA, 51 +/- 5% of myocardial radioactivity was recovered in the aqueous phase, containing free iodide, of myocardial lipid extracts. Aqueous activity was significantly decreased in fed (20 +/- 2%; p less than 0.002) and POCA pretreated (30 +/- 3.7%; p less than 0.05) animals exhibiting reduced oxidation of [14C]palmitate. Thus, deiodination of [123I]HDA was consistently reduced during inhibition of fatty acid oxidation in vitro and in vivo. The results apply to the interpretation of myocardial clearance curves of terminally radioiodinated fatty acid analogs

  3. Effects of extra virgin olive oil and fish oil on lipid profile and oxidative stress in patients with metabolic syndrome.

    Science.gov (United States)

    Venturini, Danielle; Simão, Andréa Name Colado; Urbano, Mariana Ragassi; Dichi, Isaias

    2015-06-01

    The aim of this study was to verify if extra virgin olive oil and fish oil have a synergistic effect on lipid and oxidative stress parameters in patients with metabolic syndrome (MetS). This intervention study included 102 patients (81 women and 21 men) with MetS (mean age 51.45 ± 8.27 y) from the ambulatory center of the University Hospital of Londrina, Paraná, Brazil. Patients were randomly assigned to one of four groups: Patients in the control group (CG) were instructed to maintain their usual diet; the second group (fish oil group [FO]) received 3 g/d of fish oil ω-3 fatty acids (10 capsules); the third group (extra virgin olive oil group [OO]) received 10 mL/d of extra virgin olive oil at lunch and dinner; and the fourth group (fish oil and extra virgin olive oil group [FOO]) received 3 g/d of fish oil ω-3 fatty acids and 10 mL/d of extra virgin olive oil. MetS related markers and oxidative stress were measured at baseline and after 90 d. Differences across treatment groups showed a statistically significant decrease (P virgin olive oil have beneficial synergistic effects on lipid metabolism and oxidative stress in patients with MetS. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Formation of quinones by one-electron oxidation in the metabolism of benzo[a]pyrene and 6-fluorobenzo[a]pyrene

    International Nuclear Information System (INIS)

    Cavalieri, E.; Wong, A.; Cremonesi, P.; Warner, C.; Rogan, E.

    1986-01-01

    Metabolic activation of polycyclic aromatic hydrocarbons (PAH), as well as other chemical carcinogens, occurs by two major pathways: One-electron oxidation and two-electron oxidation, or monooxygenation. One-electron oxidation generates radical cations or radicals, depending on the molecule in which the oxidation occurs, whereas two-electron oxidation produces oxygenated metabolites. Radical cations of PAH are ultimate electrophilic metabolites capable of binding to cellular macromolecules to initiate the tumor process. In this paper the authors will provide evidence that one-electron oxidation is involved not only in PAH carcinogenesis, but also in the formation of certain metabolites. Metabolism of benzo[a]pyrene (BP) by cytochrome P-450 monooxygenase yields three classes of products: phenols, dihydrodiols and the quinones, 1,6-, 3,6- and 6,12- dione

  5. The effects of exogenous fatty acids and niacin on human monocyte-macrophage plasticity.

    Science.gov (United States)

    Montserrat-de la Paz, Sergio; Rodriguez, Dolores; Cardelo, Magdalena P; Naranjo, Maria C; Bermudez, Beatriz; Abia, Rocio; Muriana, Francisco J G; Lopez, Sergio

    2017-08-01

    Macrophage plasticity allows adapting to different environments, having a dual activity in inflammatory-related diseases. Our hypothesis is that the type of dietary fatty acids into human postprandial triglyceride-rich lipoproteins (TRLs), alone or in combination with niacin (vitamin B3), could modulate the plasticity of monocytes-macrophages. We isolated TRLs at the postprandial peak from blood samples of healthy volunteers after the ingestion of a meal rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). Autologous monocytes isolated at fasting were first induced to differentiate into naïve macrophages. We observed that postprandial TRL-MUFAs, particularly in combination with niacin, enhance competence to monocytes to differentiate and polarise into M2 macrophages. Postprandial TRL-SFAs made polarised macrophages prone to an M1 phenotype. In contrast to dietary SFAs, dietary MUFAs in the meals plus immediate-release niacin primed circulating monocytes for a reduced postprandial pro-inflammatory profile. Our study underlines a role of postprandial TRLs as a metabolic entity in regulating the plasticity of the monocyte-macrophage lineage and also brings an understanding of the mechanisms by which dietary fatty acids are environmental factors fostering the innate immune responsiveness in humans. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation.

    Science.gov (United States)

    Lozoya, Oswaldo A; Martinez-Reyes, Inmaculada; Wang, Tianyuan; Grenet, Dagoberto; Bushel, Pierre; Li, Jianying; Chandel, Navdeep; Woychik, Richard P; Santos, Janine H

    2018-04-18

    Mitochondrial function affects many aspects of cellular physiology, and, most recently, its role in epigenetics has been reported. Mechanistically, how mitochondrial function alters DNA methylation patterns in the nucleus remains ill defined. Using a cell culture model of induced mitochondrial DNA (mtDNA) depletion, in this study we show that progressive mitochondrial dysfunction leads to an early transcriptional and metabolic program centered on the metabolism of various amino acids, including those involved in the methionine cycle. We find that this program also increases DNA methylation, which occurs primarily in the genes that are differentially expressed. Maintenance of mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation in the context of mtDNA loss rescues methionine salvage and polyamine synthesis and prevents changes in DNA methylation and gene expression but does not affect serine/folate metabolism or transsulfuration. This work provides a novel mechanistic link between mitochondrial function and epigenetic regulation of gene expression that involves polyamine and methionine metabolism responding to changes in the tricarboxylic acid (TCA) cycle. Given the implications of these findings, future studies across different physiological contexts and in vivo are warranted.

  7. Metabolomics reveals reduction of metabolic oxidation in women with polycystic ovary syndrome after pioglitazone-flutamide-metformin polytherapy.

    Directory of Open Access Journals (Sweden)

    Maria Vinaixa

    Full Text Available Polycystic ovary syndrome (PCOS is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients.

  8. Effects of Combined Low Glutathione with Mild Oxidative and Low Phosphorus Stress on the Metabolism of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Atsushi Fukushima

    2017-08-01

    Full Text Available Plants possess highly sensitive mechanisms that monitor environmental stress levels for a dose-dependent fine-tuning of their growth and development. Differences in plant responses to severe and mild abiotic stresses have been recognized. Although many studies have revealed that glutathione can contribute to plant tolerance to various environmental stresses, little is known about the relationship between glutathione and mild abiotic stress, especially the effect of stress-induced altered glutathione levels on the metabolism. Here, we applied a systems biology approach to identify key pathways involved in the gene-to-metabolite networks perturbed by low glutathione content under mild abiotic stress in Arabidopsis thaliana. We used glutathione synthesis mutants (cad2-1 and pad2-1 and plants overexpressing the gene encoding γ-glutamylcysteine synthetase, the first enzyme of the glutathione biosynthetic pathway. The plants were exposed to two mild stress conditions—oxidative stress elicited by methyl viologen and stress induced by the limited availability of phosphate. We observed that the mutants and transgenic plants showed similar shoot growth as that of the wild-type plants under mild abiotic stress. We then selected the synthesis mutants and performed multi-platform metabolomics and microarray experiments to evaluate the possible effects on the overall metabolome and the transcriptome. As a common oxidative stress response, several flavonoids that we assessed showed overaccumulation, whereas the mild phosphate stress resulted in increased levels of specific kaempferol- and quercetin-glycosides. Remarkably, in addition to a significant increased level of sugar, osmolytes, and lipids as mild oxidative stress-responsive metabolites, short-chain aliphatic glucosinolates over-accumulated in the mutants, whereas the level of long-chain aliphatic glucosinolates and specific lipids decreased. Coordinated gene expressions related to glucosinolate and

  9. Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation

    DEFF Research Database (Denmark)

    Aamand, Rasmus; Dalsgaard, Thomas; Jensen, Frank Bo

    2009-01-01

    In catalyzing the reversible hydration of CO2 to bicarbonate and protons, the ubiquitous enzyme carbonic anhydrase (CA) plays a crucial role in CO2 transport, in acid-base balance, and in linking local acidosis to O2 unloading from hemoglobin. Considering the structural similarity between...... bicarbonate and nitrite, we hypothesized that CA uses nitrite as a substrate to produce the potent vasodilator nitric oxide (NO) to increase local blood flow to metabolically active tissues. Here we show that CA readily reacts with nitrite to generate NO, particularly at low pH, and that the NO produced...

  10. [The role of oxidative metabolism disturbance in the development of NO-related endothelial dysfunction during chronic hearth failure].

    Science.gov (United States)

    Goishvili, N; Kakauridze, N; Sanikidze, T

    2005-05-01

    The aim of the work was to establish the oxidative metabolism changes and NO data in Chronic Hearth Failure (HF). 52 patients were included in the investigation, among them 37 patients with CHD and chronic HF (II-IV functional class by NIHA) and 17 without it (control group). For revealing of organism redox-status (ceruloplasmine, Fe3+-transfferine, Mn2+, methemoglobine) the blood paramagnetic centers was studied by electron paramagnetic resonance method. For revealing of blood free NO, the diethyldithiocarbamat (SIGMA) was used. In chronic HF the oxidative process intensification and organism compensate reaction reduction with low Fe3+-transferine levels, increased Mn2++, methaemoglobin and inactivation of erythrocytes membranes adrenergic receptors were revealed. In chronic HF the accumulation of reactive oxygen levels provoke NO transformation in peroxynitrote with following decreases of blood free NO and develop the endothelial dysfunction.

  11. Genetically Determined Insulin Resistance is Characterized by Down-Regulation of Mitochondrial Oxidative Metabolism in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas M; Skov, Vibe; Wojtaszewski, Jørgen

    2010-01-01

    Transcriptional profiling of skeletal muscle from patients with type 2 diabetes and high-risk individuals have demonstrated a co-ordinated down-regulation of oxidative phosphorylation (OxPhos) genes, suggesting a link between insulin resistance and mitochondrial dysfunction. However, whether...... mitochondrial dysfunction is a cause or consequence of insulin resistance remains to be clarified. In the present study, we tested the hypothesis that mitochondrial oxidative metabolism was down-regulated in skeletal muscle of patients with genetically determined insulin resistance. Skeletal muscle biopsies.......02), and complex V (ATP5B; p=0.005). Our data demonstrate that genetically determined insulin resistance is associated with a co-ordinated down-regulation of OxPhos components both at the transcriptional and translational level. These findings suggest that an impaired biological response to insulin in skeletal...

  12. Metabolic alkene labeling and in vitro detection of histone acylation via the aqueous oxidative Heck reaction

    NARCIS (Netherlands)

    Ourailidou, Maria E; Dockerty, Paul; Witte, Martin; Poelarends, Gerrit J; Dekker, Frank J

    2015-01-01

    The detection of protein lysine acylations remains a challenge due to lack of specific antibodies for acylations with various chain lengths. This problem can be addressed by metabolic labeling techniques using carboxylates with reactive functionalities. Subsequent chemoselective reactions with a

  13. Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

    Science.gov (United States)

    Whigham, Leah D.; Butz, Daniel E.; Dashti, Hesam; Tonelli, Marco; Johnson, LuAnn K.; Cook, Mark E.; Porter, Warren P.; Eghbalnia, Hamid R.; Markley, John L.; Lindheim, Steven R.; Schoeller, Dale A.; Abbott, David H.; Assadi-Porter, Fariba M.

    2014-01-01

    Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (pglucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain. PMID:24765590

  14. CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48

    OpenAIRE

    Holm, Niels Bjerre; Nielsen, Line Marie; Linnet, Kristian

    2015-01-01

    Synthetic cannabinoid designer drugs have emerged as drugs of abuse during the last decade, and acute intoxication cases are documented in the scientific literature. Synthetic cannabinoids are extensively metabolized, but our knowledge of the involved enzymes is limited. Here, we investigated the metabolism of N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), a compound identified in herbal blends from 2012 and onwards. We screened for metabolite formation using a panel of nine rec...

  15. Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

    OpenAIRE

    Whigham, Leah D.; Butz, Daniel E.; Dashti, Hesam; Tonelli, Marco; Johnson, LuAnn K.; Cook, Mark E.; Porter, Warren P.; Eghbalnia, Hamid R.; Markley, John L.; Lindheim, Steven R.; Schoeller, Dale A.; Abbott, David H.; Assadi-Porter, Fariba M.

    2014-01-01

    Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p

  16. Effects of a Physical Activity Program on Markers of Endothelial Dysfunction, Oxidative Stress, and Metabolic Status in Adolescents with Metabolic Syndrome

    Science.gov (United States)

    Camarillo-Romero, Eneida; Dominguez-Garcia, Ma Victoria; Amaya-Chavez, Araceli; Camarillo-Romero, Maria del Socorro; Talavera-Piña, Juan; Huitron-Bravo, Gerardo; Majluf-Cruz, Abraham

    2012-01-01

    The metabolic syndrome (MetS) is a precursor of diabetes. Physical activity (PA) improves endothelial dysfunction and may benefit patients with MetS. Aims. To evaluate the effect of a physical activity (PA) program on markers of endothelial dysfunction and oxidative stress in adolescents with (MetS). Methods. We carried out a cohort study of 38 adolescents with and without MetS (18 females and 20 males). All participants completed a 3-month PA program. All variables of the MetS as well as markers of endothelial dysfunction and oxidative stress tests were evaluated. Results. Females with and without MetS showed significant differences for almost all components of the MetS, whereas males were significantly different in half of the components. After the PA program, components of the MetS were not different from baseline values except for HDL-C levels. Some baseline endothelial dysfunction markers were significantly different among adolescents with and without MetS; however, after the PA program, most of these markers significantly improved in subjects with and without MetS. Conclusion. PA improves the markers of endothelial dysfunction in adolescents with MetS although other changes in the components of the MetS were not observed. Perhaps the benefits of PA on all components of MetS would appear after a PA program with a longer duration. PMID:22888450

  17. Coping with Salt Water Habitats: Metabolic and Oxidative Responses to Salt Intake in the Rufous-Collared Sparrow

    Directory of Open Access Journals (Sweden)

    Pablo Sabat

    2017-09-01

    Full Text Available Many physiological adjustments occur in response to salt intake in several marine taxa, which manifest at different scales from changes in the concentration of individual molecules to physical traits of whole organisms. Little is known about the influence of salinity on the distribution, physiological performance, and ecology of passerines; specifically, the impact of drinking water salinity on the oxidative status of birds has been largely ignored. In this study, we evaluated whether experimental variations in the salt intake of a widely-distributed passerine (Zontotrichia capensis could generate differences in basal (BMR and maximum metabolic rates (Msum, as well as affect metabolic enzyme activity and oxidative status. We measured rates of energy expenditure of birds after 30-d acclimation to drink salt (SW or tap (fresh water (TW and assessed changes in the activity of mitochondrial enzymes (cytochrome c oxidase and citrate synthase in skeletal muscle, heart, and kidney. Finally, we evaluated the oxidative status of bird tissues by means of total antioxidant capacity (TAC and superoxide dismutase activities and lipid oxidative damage (Malondialdehyde, MDA. The results revealed a significant increase in BMR but not Msum, which resulted in a reduction in factorial aerobic scope in SW- vs. TW-acclimated birds. These changes were paralleled with increased kidney and intestine masses and catabolic activities in tissues, especially in pectoralis muscle. We also found that TAC and MDA concentrations were ~120 and ~400% higher, respectively in the liver of animals acclimated to the SW- vs. TW-treatment. Our study is the first to document changes in the oxidative status in birds that persistently drink saltwater, and shows that they undergo several physiological adjustments that range that range in scale from biochemical capacities (e.g., TAC and MDA to whole organism traits (e.g., metabolic rates. We propose that the physiological changes observed

  18. Metabolism and Whole-Body Fat Oxidation Following Post-Exercise Carbohydrate or Protein Intake

    DEFF Research Database (Denmark)

    Hall, Ulrika Andersson; Pettersson, Stefan; Edin, Fredrik

    2018-01-01

    : Protein supplementation immediately post-exercise did not affect the doubling in whole body fat oxidation seen during a subsequent exercise trial 2 hours later. Neither did it affect resting fat oxidation during the post-exercise period despite increased insulin levels and attenuated ketosis. Carbohydrate...

  19. All-trans retinoic acid increases oxidative metabolism in mature adipocytes

    DEFF Research Database (Denmark)

    Mercader, Josep; Madsen, Lise; Felipe, Francisco

    2007-01-01

    ), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). These changes paralleled inactivation of the retinoblastoma protein and were...

  20. Metabolism of styrene-7,8-oxide in human liver in vitro: interindividual variation and stereochemistry

    NARCIS (Netherlands)

    Wenker, M. A.; Kezić, S.; Monster, A. C.; de Wolff, F. A.

    2000-01-01

    Styrene is an industrial solvent which is mainly oxidized by cytochrome P450 to an electrophilic, chiral epoxide metabolite: styrene-7,8-oxide (SO). SO has cytotoxic and genotoxic properties; the (R)-enantiomer is more mutagenic to Salmonella typhimurium TA 100 in the Ames test than the

  1. Coenzyme Q10, α-Tocopherol, and Oxidative Stress Could Be Important Metabolic Biomarkers of Male Infertility

    Directory of Open Access Journals (Sweden)

    Anna Gvozdjáková

    2015-01-01

    Full Text Available Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule in infertile men on sperm parameters, concentration of antioxidants (coenzyme Q10,  CoQ10-TOTAL, γ, and α-tocopherols, and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp. and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of CoQ10-TOTAL (ubiquinone + ubiquinol and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, CoQ10-TOTAL, and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.

  2. The Oxidative Metabolism of Fossil Hydrocarbons and Sulfide Minerals by the Lithobiontic Microbial Community Inhabiting Deep Subterrestrial Kupferschiefer Black Shale

    Directory of Open Access Journals (Sweden)

    Agnieszka Włodarczyk

    2018-05-01

    Full Text Available Black shales are one of the largest reservoirs of fossil organic carbon and inorganic reduced sulfur on Earth. It is assumed that microorganisms play an important role in the transformations of these sedimentary rocks and contribute to the return of organic carbon and inorganic sulfur to the global geochemical cycles. An outcrop of deep subterrestrial ~256-million-year-old Kupferschiefer black shale was studied to define the metabolic processes of the deep biosphere important in transformations of organic carbon and inorganic reduced sulfur compounds. This outcrop was created during mining activity 12 years ago and since then it has been exposed to the activity of oxygen and microorganisms. The microbial processes were described based on metagenome and metaproteome studies as well as on the geochemistry of the rock. The microorganisms inhabiting the subterrestrial black shale were dominated by bacterial genera such as Pseudomonas, Limnobacter, Yonghaparkia, Thiobacillus, Bradyrhizobium, and Sulfuricaulis. This study on black shale was the first to detect archaea and fungi, represented by Nitrososphaera and Aspergillus genera, respectively. The enzymatic oxidation of fossil aliphatic and aromatic hydrocarbons was mediated mostly by chemoorganotrophic bacteria, but also by archaea and fungi. The dissimilative enzymatic oxidation of primary reduced sulfur compounds was performed by chemolithotrophic bacteria. The geochemical consequences of microbial activity were the oxidation and dehydrogenation of kerogen, as well as oxidation of sulfide minerals.

  3. Sodium acetate induces a metabolic alkalosis but not the increase in fatty acid oxidation observed following bicarbonate ingestion in humans.

    Science.gov (United States)

    Smith, Gordon I; Jeukendrup, Asker E; Ball, Derek

    2007-07-01

    We conducted this study to quantify the oxidation of exogenous acetate and to determine the effect of increased acetate availability upon fat and carbohydrate utilization in humans at rest. Eight healthy volunteers (6 males and 2 females) completed 2 separate trials, 7 d apart in a single-blind, randomized, crossover design. On each occasion, respiratory gas and arterialized venous blood samples were taken before and during 180 min following consumption of a drink containing either sodium acetate (NaAc) or NaHCO3 at a dose of 2 mmol/kg body mass. Labeled [1,2 -13C] NaAc was added to the NaAc drink to quantify acetate oxidation. Both sodium salts induced a mild metabolic alkalosis and increased energy expenditure (P < 0.05) to a similar magnitude. NaHCO3 ingestion increased fat utilization from 587 +/- 83 kJ/180 min to 693 +/- 101 kJ/180 min (P = 0.01) with no change in carbohydrate utilization. Following ingestion of NaAc, the amount of fat and carbohydrate utilized did not differ from the preingestion values. However, oxidation of the exogenous acetate almost entirely (90%) replaced the additional fat that had been oxidized during the bicarbonate trial. We determined that 80.1 +/- 2.3% of an exogenous source of acetate is oxidized in humans at rest. Whereas NaHCO3 ingestion increased fat oxidation, a similar response did not occur following NaAc ingestion despite the fact both sodium salts induced a similar increase in energy expenditure and shift in acid-base balance.

  4. Oxidative Stress and Antioxidant Defense Mechanisms Linked to Exercise During Cardiopulmonary and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Kelsey Fisher-Wellman

    2009-01-01

    Full Text Available Oxidative stress has been implicated in the pathophysiology of multiple human diseases, in addition to the aging process. Although various stimuli exist, acute exercise is known to induce a transient increase in reactive oxygen and nitrogen species (RONS, evident by several reports of increased oxidative damage following acute bouts of aerobic and anaerobic exercise. Although the results are somewhat mixed and appear disease dependent, individuals with chronic disease experience an exacerbation in oxidative stress following acute exercise when compared to healthy individuals. However, this increased oxidant stress may serve as a necessary “signal” for the upregulation in antioxidant defenses, thereby providing protection against subsequent exposure to prooxidant environments within susceptible individuals. Here we present studies related to both acute exercise-induced oxidative stress in those with disease, in addition to studies focused on adaptations resulting from increased RONS exposure associated with chronic exercise training in persons with disease.

  5. The monocyte counts to HDL cholesterol ratio in obese and lean patients with polycystic ovary syndrome.

    Science.gov (United States)

    Usta, Akin; Avci, Eyup; Bulbul, Cagla Bahar; Kadi, Hasan; Adali, Ertan

    2018-04-10

    Women with polycystic ovary syndrome are more likely to suffer from obesity, insulin resistance, and chronic low-grade inflammation. In fact, the excessive activation of monocytes exacerbates oxidative stress and inflammation. However, high-density lipoprotein cholesterol neutralizes the pro-inflammatory and pro-oxidant effects of monocytes. The aim of this study is to investigate whether monocyte counts to high-density lipoprotein cholesterol ratio can predict the inflammatory condition in patients with polycystic ovary syndrome. In this cross-sectional study, a total of 124 women (61 of them with polycystic ovary syndrome and 63 age-matched healthy volunteers) were included in the study population. Obese polycystic ovary syndrome patients (n = 30) with a body mass index of ≥25 kg/m 2 and lean polycystic ovary syndrome patients (n = 31) with a body mass index of polycystic ovary syndrome were significantly higher than in control subjects (p = 0.0018). Moreover, a regression analysis revealed that body mass index, the homeostasis model assessment of insulin resistance and the high sensitivity C-reactive protein levels were confounding factors that affected the monocyte counts to high density lipoprotein cholesterol values. Additionally, a univariate and multivariate logistic regression analysis demonstrated that the increased monocyte counts to high density lipoprotein cholesterol values were more sensitive than the other known risk factors (such as increased body mass index, homeostasis model assessment of insulin resistance and high sensitive C-reactive protein levels) in the prediction of the inflammation in patients with polycystic ovary syndrome. The present study demonstrated that the monocyte count to high density lipoprotein cholesterol may be a novel and useful predictor of the presence of polycystic ovary syndrome.

  6. Protective Role of Flaxseed Oil and Flaxseed Lignan Secoisolariciresinol Diglucoside Against Oxidative Stress in Rats with Metabolic Syndrome.

    Science.gov (United States)

    Pilar, Bruna; Güllich, Angélica; Oliveira, Patrícia; Ströher, Deise; Piccoli, Jacqueline; Manfredini, Vanusa

    2017-12-01

    This study evaluated the protective effect of flaxseed oil (FO) and flaxseed lignan secoisolariciresinol diglucoside (SDG) against oxidative stress in rats with metabolic syndrome (MS). 48 rats were allocated into the following 6 groups: Groups 1 (control), 5 (FO), and 6 (SDG) received water and were treated daily orally with saline, FO, and SDG, respectively. Groups 2 (MS), 3 (MS+FO), and 4 (MS+SDG) received 30% fructose in drinking water for MS induction and were treated daily orally with saline, FO, and SDG, respectively. After 30 d, animals were sacrificed, and blood was collected for biochemical and oxidative analysis. Body weight was recorded weekly. Systolic blood pressure (SBP) was measured before and after treatment. Fructose could produce MS and oxidative stress. FO and SDG prevented changes in SBP, lipids, and glucose. FO and SDG prevented oxidative damage to lipids, and only FO prevented oxidative damage to proteins associated to MS. FO and SDG improved enzymatic antioxidants defenses and reduced glutathione levels, which was greater with SDG. Total polyphenol levels were enhanced in groups that received SDG. Thus, the results of this study demonstrated that treatment with a 30% fructose solution for 30 d is effective for MS induction and the oxidative stress is involved in the pathophysiology of MS induced by fructose-rich diets. Furthermore, we demonstrated that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content especially that of SDG, suggesting that this compound can be used in isolation to prevent oxidative stress associated with MS. We report that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content, especially that of secoisolariciresinol diglucoside. This is significant because suggests that this compound can be used in isolation to prevent oxidative stress associated with MS. Furthermore, this study was the only one to perform a comparison of the abilities of 2 components

  7. Increased oxidative metabolism and myoglobin expression in zebrafish muscle during chronic hypoxia

    Directory of Open Access Journals (Sweden)

    Richard T. Jaspers

    2014-07-01

    Full Text Available Fish may be extremely hypoxia resistant. We investigated how muscle fibre size and oxidative capacity in zebrafish (Danio rerio adapt during severe chronic hypoxia. Zebrafish were kept for either 3 or 6 weeks under chronic constant hypoxia (CCH (10% air/90%N2 saturated water. We analyzed cross-sectional area (CSA, succinate dehydrogenase (SDH activity, capillarization, myonuclear density, myoglobin (Mb concentration and Mb mRNA expression of high and low oxidative muscle fibres. After 3 weeks of CCH, CSA, SDH activity, Mb concentration, capillary and myonuclear density of both muscle fibre types were similar as under normoxia. In contrast, staining intensity for Mb mRNA of hypoxic high oxidative muscle fibres was 94% higher than that of normoxic controls (P<0.001. Between 3 and 6 weeks of CCH, CSA of high and low oxidative muscle fibres increased by 25 and 30%, respectively. This was similar to normoxic controls. Capillary and myonuclear density were not changed by CCH. However, in high oxidative muscle fibres of fish maintained under CCH, SDH activity, Mb concentration as well as Mb mRNA content were higher by 86%, 138% and 90%, respectively, than in muscle fibres of fish kept under normoxia (P<0.001. In low oxidative muscle fibres, SDH activity, Mb and Mb mRNA content were not significantly changed. Under normoxia, the calculated interstitial oxygen tension required to prevent anoxic cores in muscle fibres (PO2crit of high oxidative muscle fibres was between 1.0 and 1.7 mmHg. These values were similar at 3 and 6 weeks CCH. We conclude that high oxidative skeletal muscle fibres of zebrafish continue to grow and increase oxidative capacity during CCH. Oxygen supply to mitochondria in these fibres may be facilitated by an increased Mb concentration, which is regulated by an increase in Mb mRNA content per myonucleus.

  8. Foliar-applied urea modulates nitric oxide synthesis metabolism and glycinebetaine accumulation in drought-stressed maize

    International Nuclear Information System (INIS)

    Zhang, L.; Tian, L.; Lai, J.; Zheng, P.; Liang, Z.; Alva, A

    2014-01-01

    Foliar urea has been proved to play a better positive role in enhancing accumulation of nitric oxide (NO) and glycinebetaine (GB) in maize (Zea mays L.) under drought stress (DS). However, it is unclear how foliar urea affects biosynthetic metabolism of NO and its relationship with GB accumulation. This study was on investigating the effect of foliar- applied urea on seedlings of maize cultivar Zhengdan 958 grown in a hydroponic medium under DS or No DS. Contents of NO and GB and nitric oxide synthase (NOS) activity increased and peaked 12 h after the treatment. Nitrate reductase activity (NRA) followed the similar pattern 6h after the treatment. Under DS foliar urea application increased NR and NOS activity and, thereby, increased NO formation. Therefore, enhancement in activities of both NRA and NOS resulted in an increase of NO accumulation. Foliar- applied urea could induce an increased NO burst by enhanced NO synthesis metabolism as a nitrogen signal, possibly resulting in GB accumulation under DS. (author)

  9. Systemic down-regulation of delta-9 desaturase promotes muscle oxidative metabolism and accelerates muscle function recovery following nerve injury.

    Directory of Open Access Journals (Sweden)

    Ghulam Hussain

    Full Text Available The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS. Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles.

  10. Expanded metabolic versatility of ubiquitous nitrite-oxidizing bacteria from the genus Nitrospira

    DEFF Research Database (Denmark)

    Koch, Hanna; Lücker, Sebastian; Albertsen, Mads

    2015-01-01

    , we identified ecophysiological traits that contribute to the ecological success of Nitrospira. Unexpectedly, N. moscoviensis possesses genes coding for a urease and cleaves urea to ammonia and CO2. Ureolysis was not observed yet in nitrite oxidizers and enables N. moscoviensis to supply ammonia...... oxidizers lacking urease with ammonia from urea, which is fully nitrified by this consortium through reciprocal feeding. The presence of highly similar urease genes in Nitrospira lenta from activated sludge, in metagenomes from soils and freshwater habitats, and of other ureases in marine nitrite oxidizers...

  11. Tryptophan Oxidative Metabolism Catalyzed by : A Thermophile Isolated from Kuwait Soil Contaminated with Petroleum Hydrocarbons

    Directory of Open Access Journals (Sweden)

    Jassim M. Al-Hassan

    2011-01-01

    Full Text Available Tryptophan metabolism has been extensively studied in humans as well as in soil. Its metabolism takes place mainly through kynurenine pathway yielding hydroxylated, deaminated and many other products of physiological significance. However, tryptophan metabolism has not been studied in an isolated thermophilic bacterium. Geobacillus stearothermophilus is a local thermophile isolated from Kuwait desert soil contaminated with petroleum hydrocarbons. The bacterium grows well at 65 °C in 0.05 M phosphate buffer (pH 7, when supplied with organic compounds as a carbon source and has a good potential for transformation of steroids and related molecules. In the present study, we used tryptophan ethyl ester as a carbon source for the bacterium to study the catabolism of the amino acid at pH 5 and pH 7. In this endeavor, we have resolved twenty one transformation products of tryptophan by GC/LC and have identified them through their mass spectral fragmentation.

  12. Endothelial dysfunction in metabolic diseases: role of oxidation and possible therapeutic employment of N-acetylcysteine.

    Science.gov (United States)

    Masha, A; Martina, V

    2014-01-01

    Several metabolic diseases present a high cardiovascular mortality due to endothelial dysfunction consequences. In the last years of the past century, it has come to light that the endothelial cells, previously considered as inert in what regards an eventual secretion activity, play a pivotal role in regulating different aspects of the vascular function (endothelial function). It was clearly demonstrated that the endothelium acts as a real active organ, owning endocrine, paracrine and autocrine modulation activities by means of which it is able to regulate the vascular homeostasis. The present review will investigate the relationship between some metabolic diseases and the endothelial dysfunction and in particular the mechanisms underlying the effects of metabolic pathologies on the endothelium. Furthermore, it will consider the possible therapeutic employment of the N-acetilcysteine in such conditions.

  13. Effect of aspirin and prostaglandins on the carbohydrate metabolism in albino rats.: glucose oxidation through different pathways and glycolytic enzymes

    International Nuclear Information System (INIS)

    Balasubramanian, A.; Ramakrishnan, S.

    1980-01-01

    The effect of chronic and acute doses of aspirin and prostaglandins F2α and E2 individually on the oxidation of glucose through Embden Meyerhof-TCA cycle and pentose phosphate pathways and some key glycolytic enzymes of liver were studied in male albino rats. Studies were extended to find the combined effect of PGF2α and E2 with an acute dose of aspirin. There was increased utilisation of both 1- 14 C glucose and 6- 14 C glucose on aspirin treatment. However, the metabolism through the EM-TCA pathway was more pronounced as shown by a reduced ratio of 14 CO 2 from 1- 14 C and 6- 14 C glucose. Two hepatic key glycolytic enzymes viz. hexokinase and pyruvate kinase were increased due to aspirin treatment. Withdrawal of aspirin corrected the above impaired carbohydrate metabolism in liver. Prostaglandin F2α also caused a reduction in the utilisation of 1- 14 C glucose, while PGE2 recorded an increase in the utilisation of both 1- 14 C and 6- 14 C glucose when compared to controls, indicating that different members of prostaglandins could affect metabolisms and differently. Administration of the PGs and aspirin together showed an increase in the utilisation of 6- 14 C glucose. (auth.)

  14. Kinetic analysis of human CYP24A1 metabolism of vitamin D via the C24-oxidation pathway.

    Science.gov (United States)

    Tieu, Elaine W; Tang, Edith K Y; Tuckey, Robert C

    2014-07-01

    CYP24A1 is the multicatalytic cytochrome P450 responsible for the catabolism of vitamin D via the C23- and C24-oxidation pathways. We successfully expressed the labile human enzyme in Escherichia coli and partially purified it in an active state that permitted detailed characterization of its metabolism of 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] and the intermediates of the C24-oxidation pathway in a phospholipid-vesicle reconstituted system. The C24-oxidation pathway intermediates, 1,24,25-trihydroxyvitamin D3, 24-oxo-1,25-dihydroxyvitamin D3, 24-oxo-1,23,25-trihydroxyvitamin D3 and tetranor-1,23-dihydroxyvitamin D3, were enzymatically produced from 1,25(OH)2 D3 using rat CYP24A1. Both 1,25(OH)2 D3 and 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3 were found to partition strongly into the phospholipid bilayer when in aqueous medium. Changes to the phospholipid concentration did not affect the kinetic parameters for the metabolism of 1,25(OH)2 D3 by CYP24A1, indicating that it is the concentration of substrates in the membrane phase (mol substrate·mol phospholipid(-1) ) that determines their rate of metabolism. CYP24A1 exhibited Km values for the different C24-intermediates ranging from 0.34 to 15 mmol·mol phospholipid(-1) , with 24-oxo-1,23,25-trihydroxyvitamin D3 [24-oxo-1,23,25(OH)3 D3] displaying the lowest and 1,24,25-trihydroxyvitamin D3 [1,24,25(OH)3 D3] displaying the highest. The kcat values varied by up to 3.8-fold, with 1,24,25(OH)3 D3 displaying the highest kcat (34 min(-1) ) and 24-oxo-1,23,25(OH)3 D3 the lowest. The data show that the cleavage of the side chain of 24-oxo-1,23,25(OH)3 D3 occurs with the highest catalytic efficiency (kcat /Km ) and produces 1-hydroxy-23-oxo-24,25,26,27-tetranorvitamin D3 and not 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3, as the primary product. These kinetic analyses also show that intermediates of the C24-oxidation pathway effectively compete with precursor substrates for binding to the active site of the

  15. Effects of lemongrass oil and citral on hepatic drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in rats

    Directory of Open Access Journals (Sweden)

    Chien-Chun Li

    2018-01-01

    Full Text Available The essential oil from a lemongrass variety of Cymbopogon flexuosus [lemongrass oil (LO] is used in various food and aroma industry products and exhibits biological activities, such as anticancer and antimicrobial activities. To investigate the effects of 200 LO (200 mg/kg and 400 LO (400 mg/kg and its major component, citral (240 mg/kg, on drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in the liver, male Sprague-Dawley rats were fed a pelleted diet and administered LO or citral by gavage for 2 weeks. After 2 weeks of feeding, the effects of LO and citral on the metabolism and toxicity of acetaminophen were determined. The results showed that rats treated with 400 LO or citral had significantly reduced hepatic testosterone 6β-hydroxylation and ethoxyresorufin O-deethylation activities. In addition, NAD(PH:quinone oxidoreductase 1 activity was significantly increased by citral, and Uridine 5′-diphospho (UDP glucurosyltransferase activity was significantly increased by 400 LO in the rat liver. Treatment with 400 LO or citral reduced lipid peroxidation and reactive oxygen species levels in the liver. After acetaminophen treatment, however, LO and citral treatment resulted in little or no change in plasma alanine aminotransferase activity and acetaminophen-protein adducts content in the liver. Our results indicate that LO and citral may change the activities of drug-metabolizing enzymes and reduce oxidative stress in the liver. However, LO and citral may not affect the detoxification of acetaminophen.

  16. Foliar urea application affects nitric oxide burst and glycine betaine metabolism in two maize cultivars under drought

    International Nuclear Information System (INIS)

    Zhang, L.; Zhang, X.; Wang, K.; Zhao, Y.; Zhai, Y.; Gao, M.

    2011-01-01

    Foliar urea has been proved to act a better role in alleviation of the negative effects of drought stress (DS). However, the modulation mechanism of foliar urea are not conclusive in view of nitric oxide (NO) burst and glycine betaine metabolism and their relationship. Two maize ( Zea mays L.) cultivars (Zhengdan 958, JD958, Jundan 20, ZD20) were grown in hydroponic medium, which were treated with spraying of urea concentration of 15 g L/sup -1/ and two water regimes (non-stress and DS simulated by the addition of polyethylene glycol (PEG, 15% w/v, MW 6000). The ten-day DS treatment increased betaine aldehyde dehydrogenase (BADH) activity, choline content and nitric oxide (NO) content acted as the key enzyme, initial substrate and a nitrogenous signal substance respectively in GB synthesis metabolism, thus, induced to great GB accumulation. The accumulation of NO reached the summit earlier than that of GB. The more positive/less negative responses were recorded in JD958 as compared with ZD20 to DS. Addition of foliar ur ea could increase accumulation of choline and BADH activity as well as NO content, thereby, increase GB accumulation under DS. These positive effects of urea applying foliarly on all parameters measured were more pronounced in cultivar JD20 than those in ZD958 under drought. It is, therefore, concluded that increases of both BADH activity and choline content possibly resulted in enhancement of GB accumulation. Foliar urea application could provoke better GB accumulation by modulation of GB metabolism, possibly mediating by NO burst as a signal molecule during drought, especially in the drought sensitive maize cultivar. (author)

  17. Effects of lemongrass oil and citral on hepatic drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in rats.

    Science.gov (United States)

    Li, Chien-Chun; Yu, Hsiang-Fu; Chang, Chun-Hua; Liu, Yun-Ta; Yao, Hsien-Tsung

    2018-01-01

    The essential oil from a lemongrass variety of Cymbopogon flexuosus [lemongrass oil (LO)] is used in various food and aroma industry products and exhibits biological activities, such as anticancer and antimicrobial activities. To investigate the effects of 200 LO (200 mg/kg) and 400 LO (400 mg/kg) and its major component, citral (240 mg/kg), on drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in the liver, male Sprague-Dawley rats were fed a pelleted diet and administered LO or citral by gavage for 2 weeks. After 2 weeks of feeding, the effects of LO and citral on the metabolism and toxicity of acetaminophen were determined. The results showed that rats treated with 400 LO or citral had significantly reduced hepatic testosterone 6β-hydroxylation and ethoxyresorufin O-deethylation activities. In addition, NAD(P)H:quinone oxidoreductase 1 activity was significantly increased by citral, and Uridine 5'-diphospho (UDP) glucurosyltransferase activity was significantly increased by 400 LO in the rat liver. Treatment with 400 LO or citral reduced lipid peroxidation and reactive oxygen species levels in the liver. After acetaminophen treatment, however, LO and citral treatment resulted in little or no change in plasma alanine aminotransferase activity and acetaminophen-protein adducts content in the liver. Our results indicate that LO and citral may change the activities of drug-metabolizing enzymes and reduce oxidative stress in the liver. However, LO and citral may not affect the detoxification of acetaminophen. Copyright © 2017. Published by Elsevier B.V.

  18. β-oxidation and rapid metabolism, but not uptake regulate brain eicosapentaenoic acid levels.

    Science.gov (United States)

    Chen, Chuck T; Bazinet, Richard P

    2015-01-01

    The brain has a unique polyunsaturated fatty acid composition, with high levels of arachidonic and docosahexaenoic acids (DHA) while levels of eicosapentaenoic acid (EPA) are several orders of magnitude lower. As evidence accumulated that fatty acid entry into the brain was not selective and, in fact, that DHA and EPA enter the brain at similar rates, new mechanisms were required to explain their large concentration differences in the brain. Here we summarize recent research demonstrating that EPA is rapidly and extensively β-oxidized upon entry into the brain. Although the ATP generated from the β-oxidation of EPA is low compared to the use of glucose, fatty acid β-oxidation may serve to regulate brain fatty acid levels in the absence of selective transportation. Furthermore, when β-oxidation of EPA is blocked, desaturation of EPA increases and Land׳s recycling decreases to maintain low EPA levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Oxidation kinetics of model compounds of metabolic waste in supercritical water

    Science.gov (United States)

    Webley, Paul A.; Holgate, Henry R.; Stevenson, David M.; Tester, Jefferson W.

    1990-01-01

    In this NASA-funded study, the oxidation kinetics of methanol and ammonia in supercritical water have been experimentally determined in an isothermal plug flow reactor. Theoretical studies have also been carried out to characterize key reaction pathways. Methanol oxidation rates were found to be proportional to the first power of methanol concentration and independent of oxygen concentration and were highly activated with an activation energy of approximately 98 kcal/mole over the temperature range 480 to 540 C at 246 bar. The oxidation of ammonia was found to be catalytic with an activation energy of 38 kcal/mole over temperatures ranging from 640 to 700 C. An elementary reaction model for methanol oxidation was applied after correction for the effect of high pressure on the rate constants. The conversion of methanol predicted by the model was in good agreement with experimental data.

  20. Mechanisms and evolution of oxidative sulfur metabolism in green sulfur bacteria

    DEFF Research Database (Denmark)

    Gregersen, Lea Haarup; Bryant, Donald A.; Frigaard, Niels-Ulrik

    2011-01-01

    Green sulfur bacteria (GSB) constitute a closely related group of photoautotrophic and thiotrophic bacteria with limited phenotypic variation. They typically oxidize sulfide and thiosulfate to sulfate with sulfur globules as an intermediate. Based on genome sequence information from 15 strains...... product is further oxidized to sulfite by the dissimilatory sulfite reductase (DSR) system. This system consists of components horizontally acquired partly from sulfide-oxidizing and partly from sulfate-reducing bacteria. Depending on the strain, the sulfite is probably oxidized to sulfate by one of two...... in sulfate formation in other bacteria has been replaced by the DSR system in GSB. Sequence analyses suggested that the conserved soxJXYZAKBW gene cluster was horizontally acquired by Chlorobium phaeovibrioides DSM 265 from the Chlorobaculum lineage and that this acquisition was mediated by a mobile genetic...

  1. Nitrous oxide metabolism in nitrate-reducing bacteria: Physiology and regulatory mechanisms

    OpenAIRE

    Torres, Maria; Simon, Jorg; Rowley, Gary; Bedmar, Eulogio; Richardson, David; Gates, Andrew; Delgado, Maria

    2016-01-01

    Nitrous oxide (N2O) is an important greenhouse gas (GHG) with substantial global warming potential and also contributes to ozone depletion through photochemical nit- ric oxide (NO) production in the stratosphere. The negative effects of N2O on climate and stratospheric ozone make N2O mitigation an international challenge. More than 60% of global N2O emissions are emitted from agricultural soils mainly due to the appli- cation of synthetic nitrogen-containing fertilizers. Thus, mitigation stra...

  2. Impaired metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martin; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina

    2014-01-01

    Accumulation of damaged macromolecules, including irreversibly oxidized proteins, is a hallmark of cellular and organismal ageing. Failure of protein homesotasis is a major contributor to the age-related accumulation of damaged proteins. In skeletal muscle, tissue maintenance and regeneration...... phenotype. In addition, these findings highlight the molecular mechanisms implicated in satellite cells dysfunction during ageing, paving the road for future therapeutic interventions aimed at preventing oxidative modifications of proteins and/or stimulating their elimination....

  3. Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75

    OpenAIRE

    Cáceres, Lucía; Necakov, Aleksandar S.; Schwartz, Carol; Kimber, Sandra; Roberts, Ian J.H.; Krause, Henry M.

    2011-01-01

    Nitric oxide gas acts as a short-range signaling molecule in a vast array of important physiological processes, many of which include major changes in gene expression. How these genomic responses are induced, however, is poorly understood. Here, using genetic and chemical manipulations, we show that nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer part...

  4. Role of glutathione metabolism status in the definition of some cellular parameters and oxidative stress tolerance of Saccharomyces cerevisiae cells growing as biofilms.

    Science.gov (United States)

    Gales, Grégoire; Penninckx, Michel; Block, Jean-Claude; Leroy, Pierre

    2008-08-01

    The resistance of Saccharomyces cerevisiae to oxidative stress (H(2)O(2) and Cd(2+)) was compared in biofilms and planktonic cells, with the help of yeast mutants deleted of genes related to glutathione metabolism and oxidative stress. Biofilm-forming cells were found predominantly in the G1 stage of the cell cycle. This might explain their higher tolerance to oxidative stress and the young replicative age of these cells in an old culture. The reduced glutathione status of S. cerevisiae was affected by the growth phase and apparently plays an important role in oxidative stress tolerance in cells growing as a biofilm.

  5. Interpretation of metabolic memory phenomenon using a physiological systems model: What drives oxidative stress following glucose normalization?

    Science.gov (United States)

    Voronova, Veronika; Zhudenkov, Kirill; Helmlinger, Gabriel; Peskov, Kirill

    2017-01-01

    Hyperglycemia is generally associated with oxidative stress, which plays a key role in diabetes-related complications. A complex, quantitative relationship has been established between glucose levels and oxidative stress, both in vitro and in vivo. For example, oxidative stress is known to persist after glucose normalization, a phenomenon described as metabolic memory. Also, uncontrolled glucose levels appear to be more detrimental to patients with diabetes (non-constant glucose levels) vs. patients with high, constant glucose levels. The objective of the current study was to delineate the mechanisms underlying such behaviors, using a mechanistic physiological systems modeling approach that captures and integrates essential underlying pathophysiological processes. The proposed model was based on a system of ordinary differential equations. It describes the interplay between reactive oxygen species production potential (ROS), ROS-induced cell alterations, and subsequent adaptation mechanisms. Model parameters were calibrated using different sources of experimental information, including ROS production in cell cultures exposed to various concentration profiles of constant and oscillating glucose levels. The model adequately reproduced the ROS excess generation after glucose normalization. Such behavior appeared to be driven by positive feedback regulations between ROS and ROS-induced cell alterations. The further oxidative stress-related detrimental effect as induced by unstable glucose levels can be explained by inability of cells to adapt to dynamic environment. Cell adaptation to instable high glucose declines during glucose normalization phases, and further glucose increase promotes similar or higher oxidative stress. In contrast, gradual ROS production potential decrease, driven by adaptation, is observed in cells exposed to constant high glucose.

  6. Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism.

    Science.gov (United States)

    Wegman, Martin P; Guo, Michael H; Bennion, Douglas M; Shankar, Meena N; Chrzanowski, Stephen M; Goldberg, Leslie A; Xu, Jinze; Williams, Tiffany A; Lu, Xiaomin; Hsu, Stephen I; Anton, Stephen D; Leeuwenburgh, Christiaan; Brantly, Mark L

    2015-04-01

    Caloric restriction has consistently been shown to extend life span and ameliorate aging-related diseases. These effects may be due to diet-induced reactive oxygen species acting to up-regulate sirtuins and related protective pathways, which research suggests may be partially inhibited by dietary anti-oxidant supplementation. Because caloric restriction is not sustainable long term for most humans, we investigated an alternative dietary approach, intermittent fasting (IF), which is proposed to act on similar biological pathways. We hypothesized that a modified IF diet, where participants maintain overall energy balance by alternating between days of fasting (25% of normal caloric intake) and feasting (175% of normal), would increase expression of genes associated with aging and reduce oxidative stress and that these effects would be suppressed by anti-oxidant supplementation. To assess the tolerability of the diet and to explore effects on biological mechanisms related to aging and metabolism, we recruited a cohort of 24 healthy individuals in a double-crossover, double-blinded, randomized clinical trial. Study participants underwent two 3-week treatment periods-IF and IF with anti-oxidant (vitamins C and E) supplementation. We found strict adherence to study-provided diets and that participants found the diet tolerable, with no adverse clinical findings or weight change. We detected a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers analyzed. We also found that IF decreased plasma insulin levels (1.01 μU/mL). Although our study suggests that the IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks.

  7. Positive effect of combined exercise training in a model of metabolic syndrome and menopause: autonomic, inflammatory, and oxidative stress evaluations.

    Science.gov (United States)

    Conti, Filipe Fernandes; Brito, Janaina de Oliveira; Bernardes, Nathalia; Dias, Danielle da Silva; Malfitano, Christiane; Morris, Mariana; Llesuy, Susana Francisca; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2015-12-15

    It is now well established that after menopause cardiometabolic disorders become more common. Recently, resistance exercise has been recommended as a complement to aerobic (combined training, CT) for the treatment of cardiometabolic diseases. The aim of this study was to evaluate the effects of CT in hypertensive ovariectomized rats undergoing fructose overload in blood pressure variability (BPV), inflammation, and oxidative stress parameters. Female rats were divided into the following groups (n = 8/group): sedentary normotensive Wistar rats (C), and sedentary (FHO) or trained (FHOT) ovariectomized spontaneously hypertensive rats undergoing and fructose overload. CT was performed on a treadmill and ladder adapted to rats in alternate days (8 wk; 40-60% maximal capacity). Arterial pressure (AP) was directly measured. Oxidative stress and inflammation were measured on cardiac and renal tissues. The association of risk factors (hypertension + ovariectomy + fructose) promoted increase in insulin resistance, mean AP (FHO: 174 ± 4 vs. C: 108 ± 1 mmHg), heart rate (FHO: 403 ± 12 vs. C: 352 ± 11 beats/min), BPV, cardiac inflammation (tumor necrosis factor-α-FHO: 65.8 ± 9.9 vs. C: 23.3 ± 4.3 pg/mg protein), and oxidative stress cardiac and renal tissues. However, CT was able to reduce mean AP (FHOT: 158 ± 4 mmHg), heart rate (FHOT: 303 ± 5 beats/min), insulin resistance, and sympathetic modulation. Moreover, the trained rats presented increased nitric oxide bioavailability, reduced tumor necrosis factor-α (FHOT: 33.1 ± 4.9 pg/mg protein), increased IL-10 in cardiac tissue and reduced lipoperoxidation, and increased antioxidant defenses in cardiac and renal tissues. In conclusion, the association of risk factors promoted an additional impairment in metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters and combined exercise training was able to attenuate these dysfunctions. Copyright © 2015 the American Physiological Society.

  8. Effect of in vitro digested cod liver oil of different quality on oxidative, proteomic and inflammatory responses in the yeast Saccharomyces cerevisiae and human monocyte-derived dendritic cells

    DEFF Research Database (Denmark)

    Larsson, Karin; Istenič, Katja; Wulff, Tune

    2015-01-01

    BACKGROUND: Upon oxidation of the polyunsaturated fatty acids in fish oil, either before ingestion or, as recently shown, during the gastro-intestinal passage, a cascade of potentially cytotoxic peroxidation products, such as malondialdehyde and 4-hydroxy-2-hexenal, can form. In this study, we di...... in yeast and immunomodulation of dendritic cells....

  9. Enhanced metabolic versatility of planktonic sulfur-oxidizing γ-proteobacteria in an oxygen-deficient coastal ecosystem

    Directory of Open Access Journals (Sweden)

    Alejandro A. Murillo

    2014-07-01

    Full Text Available Sulfur-oxidizing Gamma-proteobacteria are abundant in marine oxygen-deficient waters, and appear to play a key role in a previously unrecognized cryptic sulfur cycle. Metagenomic analyses of members of the uncultured SUP05 lineage in the Canadian seasonally anoxic fjord Saanich Inlet (SI, hydrothermal plumes in the Guaymas Basin (GB and single cell genomics analysis of two ARCTIC96BD-19 representatives from the South Atlantic Sub-Tropical Gyre (SASG have shown them to be metabolically versatile. However, SI and GB SUP05 bacteria seem to be obligate chemolithoautotrophs, whereas ARCTIC96BD-19 has the genetic potential for aerobic respiration. Here, we present results of a metagenomic analysis of sulfur-oxidizing Gamma-proteobacteria (GSO, closely related to the SUP05/ARCTIC96BD-19 clade, from a coastal ecosystem in the eastern South Pacific (ESP. This ecosystem experiences seasonal anoxia and accumulation of nitrite and ammonium at depth, with a corresponding increase in the abundance of GSO representatives. The ESP-GSOs appear to have a significantly different gene complement than those from Saanich Inlet, Guaymas Basin and SASG. Genomic analyses of de novo assembled contigs indicate the presence of a complete aerobic respiratory complex based on the cytochrome bc1 oxidase. Furthermore, they appear to encode a complete TCA cycle and several transporters for dissolved organic carbon species, suggesting a mixotrophic lifestyle. Thus, the success of sulfur-oxidizing Gamma-proteobacteria in oxygen-deficient marine ecosystems appears due not only to their previously recognized anaerobic metabolic versatility, but also to their capacity to function under aerobic conditions using different carbon sources. Finally, members of ESP-GSO cluster also have the genetic potential for reducing nitrate to ammonium based on the nirBD genes, and may therefore facilitate a tighter coupling of the nitrogen and sulfur cycles in oxygen-deficient waters.

  10. AMPK activation through mitochondrial regulation results in increased substrate oxidation and improved metabolic parameters in models of diabetes.

    Directory of Open Access Journals (Sweden)

    Yonchu Jenkins

    Full Text Available Modulation of mitochondrial function through inhibiting respiratory complex I activates a key sensor of cellular energy status, the 5'-AMP-activated protein kinase (AMPK. Activation of AMPK results in the mobilization of nutrient uptake and catabolism for mitochondrial ATP generation to restore energy homeostasis. How these nutrient pathways are affected in the presence of a potent modulator of mitochondrial function and the role of AMPK activation in these effects remain unclear. We have identified a molecule, named R419, that activates AMPK in vitro via complex I inhibition at much lower concentrations than metformin (IC50 100 nM vs 27 mM, respectively. R419 potently increased myocyte glucose uptake that was dependent on AMPK activation, while its ability to suppress hepatic glucose production in vitro was not. In addition, R419 treatment of mouse primary hepatocytes increased fatty acid oxidation and inhibited lipogenesis in an AMPK-dependent fashion. We have performed an extensive metabolic characterization of its effects in the db/db mouse diabetes model. In vivo metabolite profiling of R419-treated db/db mice showed a clear upregulation of fatty acid oxidation and catabolism of branched chain amino acids. Additionally, analyses performed using both (13C-palmitate and (13C-glucose tracers revealed that R419 induces complete oxidation of both glucose and palmitate to CO2 in skeletal muscle, liver, and adipose tissue, confirming that the compound increases mitochondrial function in vivo. Taken together, our results show that R419 is a potent inhibitor of complex I and modulates mitochondrial function in vitro and in diabetic animals in vivo. R419 may serve as a valuable molecular tool for investigating the impact of modulating mitochondrial function on nutrient metabolism in multiple tissues and on glucose and lipid homeostasis in diabetic animal models.

  11. Effect on oxidative stress, hepatic chemical metabolizing parameters, and genotoxic damage of mad honey intake in rats.

    Science.gov (United States)

    Eraslan, G; Kanbur, M; Karabacak, M; Arslan, K; Siliğ, Y; Soyer Sarica, Z; Tekeli, M Y; Taş, A

    2017-01-01

    A total of 66 male Wistar rats were used and six groups (control: 10 animals and experimental: 12 animals) were formed. While a separate control group was established for each study period, mad honey application to the animals in the experimental group was carried out with a single dose (12.5 g kg -1 body weight (b.w.); acute stage), at a dose of 7.5 g kg -1 b.w. for 21 days (subacute stage), and at a dose of 5 g kg -1 b.w. for 60 days (chronic stage). Tissue and blood oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), 4-hydroxynonenal (HNE), superoxide dismutase, catalase, glutathione (GSH) peroxidase, and glucose-6-phosphate dehydrogenase), hepatic chemical metabolizing parameters in the liver (cytochrome P450 2E1, nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase, nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase (CYTC), GSH S-transferase (GST), and GSH), and micronucleus and comet test in some samples were examined. Findings from the study showed that single and repeated doses given over the period increased MDA, NO, and HNE levels while decreasing/increasing tissue and blood antioxidant enzyme activities. From hepatic chemical metabolizing parameters, GST activity increased in the subacute and chronic stages and CYTC activity increased in the acute period, whereas GSH level decreased in the subacute stage. Changes in tail and head intensities were found in most of the comet results. Mad honey caused oxidative stresses for each exposure period and made some significant changes on the comet test in certain periods for some samples obtained. In other words, according to the available research results obtained, careless consumption of mad honey for different medical purposes is not appropriate.

  12. Pitfall in metabolic screening in a patient with fatal peroxisomal beta-oxidation defect

    NARCIS (Netherlands)

    Rosewich, H.; Waterham, H. R.; Wanders, R. J. A.; Ferdinandusse, S.; Henneke, M.; Hunneman, D.; Gärtner, J.

    2006-01-01

    We present a rare case of peroxisomal acyl-CoA oxidase deficiency that was not detected by the common metabolic screening program for peroxisomal disorders. The patient presented with a typical MRI pattern showing pachygyria, perisylvian polymicrogyria, cerebral and cerebellar white matter

  13. Glutamate dehydrogenase is essential to sustain neuronal oxidative energy metabolism during stimulation

    DEFF Research Database (Denmark)

    Hohnholt, Michaela C; Andersen, Vibe H; Andersen, Jens V

    2017-01-01

    by glutamate was significantly lower in brain mitochondria from GDH KO mice and synaptosomes were not able to increase their respiration upon an elevated energy demand. The role of GDH for metabolism of glutamine and the respiratory capacity underscore the importance of GDH for neurons particularly during...

  14. Metabolic evidence of diminished lipid oxidation in women with polycystic ovary syndrome

    Science.gov (United States)

    Complex diseases, such as polycystic ovary syndrome (PCOS), are not limited to specific genes, pathogens, toxicoses, or identifiable environmental influences. PCOS still remains a diagnosis of exclusion despite being the most common female endocrinopathy and the leading cause of metabolic syndrome, ...

  15. C1 Metabolism in Corynebacterium glutamicum: an Endogenous Pathway for Oxidation of Methanol to Carbon Dioxide

    Science.gov (United States)

    Witthoff, Sabrina; Mühlroth, Alice

    2013-01-01

    Methanol is considered an interesting carbon source in “bio-based” microbial production processes. Since Corynebacterium glutamicum is an important host in industrial biotechnology, in particular for amino acid production, we performed studies of the response of this organism to methanol. The C. glutamicum wild type was able to convert 13C-labeled methanol to 13CO2. Analysis of global gene expression in the presence of methanol revealed several genes of ethanol catabolism to be upregulated, indicating that some of the corresponding enzymes are involved in methanol oxidation. Indeed, a mutant lacking the alcohol dehydrogenase gene adhA showed a 62% reduced methanol consumption rate, indicating that AdhA is mainly responsible for methanol oxidation to formaldehyde. Further studies revealed that oxidation of formaldehyde to formate is catalyzed predominantly by two enzymes, the acetaldehyde dehydrogenase Ald and the mycothiol-dependent formaldehyde dehydrogenase AdhE. The Δald ΔadhE and Δald ΔmshC deletion mutants were severely impaired in their ability to oxidize formaldehyde, but residual methanol oxidation to CO2 was still possible. The oxidation of formate to CO2 is catalyzed by the formate dehydrogenase FdhF, recently identified by us. Similar to the case with ethanol, methanol catabolism is subject to carbon catabolite repression in the presence of glucose and is dependent on the transcriptional regulator RamA, which was previously shown to be essential for expression of adhA and ald. In conclusion, we were able to show that C. glutamicum possesses an endogenous pathway for methanol oxidation to CO2 and to identify the enzymes and a transcriptional regulator involved in this pathway. PMID:24014532

  16. Maturation and demise of human primary monocytes by carbon nanotubes

    KAUST Repository

    De Nicola, Milena D.; Mirabile Gattia, Daniele; Traversa, Enrico; Ghibelli, Lina

    2013-01-01

    -competent monocytes by mechanisms related to the presence of large nanoparticle aggregates, suggesting phenomena of bulk toxicity possibly consisting of frustrated phagocytosis. At the same time, MWCNT stimulate adhesion of the phagocytosis-incompetent monocytes

  17. Solar photocatalytic oxidation of recalcitrant natural metabolic by-products of amoxicillin biodegradation.

    Science.gov (United States)

    Pereira, João H O S; Reis, Ana C; Homem, Vera; Silva, José A; Alves, Arminda; Borges, Maria T; Boaventura, Rui A R; Vilar, Vítor J P; Nunes, Olga C

    2014-11-15

    The contamination of the aquatic environment by non-metabolized and metabolized antibiotic residues has brought the necessity of alternative treatment steps to current water decontamination technologies. This work assessed the feasibility of using a multistage treatment system for amoxicillin (AMX) spiked solutions combining: i) a biological treatment process using an enriched culture to metabolize AMX, with ii) a solar photocatalytic system to achieve the removal of the metabolized transformation products (TPs) identified via LC-MS, recalcitrant to further biological degradation. Firstly, a mixed culture (MC) was obtained through the enrichment of an activated sludge sample collected in an urban wastewater treatment plant (WWTP). Secondly, different aqueous matrices spiked with AMX were treated with the MC and the metabolic transformation products were identified. Thirdly, the efficiency of two solar assisted photocatalytic processes (TiO2/UV or Fe(3+)/Oxalate/H2O2/UV-Vis) was assessed in the degradation of the obtained TPs using a lab-scale prototype photoreactor equipped with a compound parabolic collector (CPC). Highest AMX specific biodegradation rates were obtained in buffer and urban wastewater (WW) media (0.10 ± 0.01 and 0.13 ± 0.07 g(AMX) g(biomass)(-1) h(-1), respectively). The resulting TPs, which no longer presented antibacterial activity, were identified as amoxicilloic acid (m/z = 384). The performance of the Fe(3+)/Oxalate/H2O2/UV-Vis system in the removal of the TPs from WW medium was superior to the TiO2/UV process (TPs no longer detected after 40 min (QUV = 2.6 kJ L(-1)), against incomplete TPs removal after 240 min (QUV = 14.9 kJ L(-1)), respectively). Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Oxidative stress and homocyteine metabolism following coronary artery grafting by on pump and off pump CABG techniques

    International Nuclear Information System (INIS)

    Parvizi, R.; Noubar, R.; Salmasi, H.S.

    2007-01-01

    To compare the effect of on-pump and off-pump CABG on the induction of the oxidative stress and the metabolism of homocysteine, which is involved in the synthesis of glutathione. This retrospective study was performed in Shahid Madani Heart Hospital in Tabriz, Iran in 2004 using a questionnaire. Plasma homocysteine, folate total antioxidant capacity (TAC) and malonedialdehyde (MDA) were determined on blood samples obtained from 40 patients undergoing CABG, preoperatively and at 0,12,48,120 hours and 6 months after surgery. The patients were divided into two matched groups, one off-pump and the other on-pump CABG. A marked reduction of homocysteine, folate and significant elevation of MDA were noticed at 0, 12, 48 hours after operation in the both groups (P<0.05). A negative and marked correlation between homocysteine and TAC but a positive and significant between homocysteinc and MDA were observed (P<0.05 in the both groups). In CABG operation because of oxidative stress and consumption of GSH immediate reduction in the plasma levels of homocyticine occurs in the both techniques. However using off pump CABG induction of oxidative stress and changes in plasma levels of homocysteine are not as high as on- pump CABG. (author)

  19. The possible influences of dietary oil supplementation in ameliorating metabolic disturbances and oxidative stress in Alloxan injected rats

    International Nuclear Information System (INIS)

    Farag, M.F.S.; Osman, N.N.; Darwish, M.M.

    2005-01-01

    Diabetes mellitus (DM) is a multifactor disease that is associated with a number of different metabolic abnormalities. Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with DM. The present work was conducted to examine the protective or treating effects of two different dietary oils rich in medium chain fatty acids (MCFA) as coconut oil (CO) or omega-3-polyunsaturated fatty acids (ω-3-PUFAs)as flaxseed oil (FO) on the severity of DM induced experimentally by alloxan injection. Wistar strain albino rats (17 Og) were fed commercial rat chow diet supplemented with either CO or FO for four weeks. A single dose of alloxan (150 mg/kg) resulted in hyperglycemia, decreases in serum insulin, thyroxine (T 4 ), and high density lipoprotein-cholesterol levels, elevated triglycerides, total cholesterol and low density lipoprotein-cholesterol concentrations. Concurrent with those changes, an increased liver malonaldehyde (MDA) level was observed. This oxidative stress was related to decreases in superoxide dismutase (SOD) activity and glutathione (GSH) content in the liver of alloxan diabetic rats. Oils supplementation after diabetes induction ameliorated hyperglycemia, increased insulin and thyroxine hormone levels, improved lipid profiles, blunted the increase in MDA, modulated the levels of hepatic SOD activity and GSH content of alloxan treated rats. It could be suggested that each of CO or FO could be used as antidiabetic complement in case of DM. This may be related to their anti oxidative properties

  20. Macrophage Interaction with Paracoccidioides brasiliensis Yeast Cells Modulates Fungal Metabolism and Generates a Response to Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Juliana Alves Parente-Rocha

    Full Text Available Macrophages are key players during Paracoccidioides brasiliensis infection. However, the relative contribution of the fungal response to counteracting macrophage activity remains poorly understood. In this work, we evaluated the P. brasiliensis proteomic response to macrophage internalization. A total of 308 differentially expressed proteins were detected in P. brasiliensis during infection. The positively regulated proteins included those involved in alternative carbon metabolism, such as enzymes involved in gluconeogenesis, beta-oxidation of fatty acids and amino acids catabolism. The down-regulated proteins during P. brasiliensis internalization in macrophages included those related to glycolysis and protein synthesis. Proteins involved in the oxidative stress response in P. brasiliensis yeast cells were also up-regulated during macrophage infection, including superoxide dismutases (SOD, thioredoxins (THX and cytochrome c peroxidase (CCP. Antisense knockdown mutants evaluated the importance of CCP during macrophage infection. The results suggested that CCP is involved in a complex system of protection against oxidative stress and that gene silencing of this component of the antioxidant system diminished the survival of P. brasiliensis in macrophages and in a murine model of infection.

  1. Immediate effects of chest physiotherapy on hemodynamic, metabolic, and oxidative stress parameters in subjects with septic shock.

    Science.gov (United States)

    dos Santos, Rafael S; Donadio, Márcio V F; da Silva, Gabriela V; Blattner, Clarissa N; Melo, Denizar A S; Nunes, Fernanda B; Dias, Fernando S; Squizani, Eamim D; Pedrazza, Leonardo; Gadegast, Isabella; de Oliveira, Jarbas R

    2014-09-01

    Septic shock presents as a continuum of infectious events, generating tissue hypoxia and hypovolemia, and increased oxidative stress. Chest physiotherapy helps reduce secretion, improving dynamic and static compliance, as well as improving secretion clearance and preventing pulmonary complications. The purpose of this study was to evaluate the immediate effect of chest physiotherapy on hemodynamic, metabolic, inflammatory, and oxidative stress parameters in subjects in septic shock. We conducted a quasi-experimental study in 30 subjects in septic shock, who underwent chest physiotherapy, without associated heart diseases and with vasopressors stress were evaluated before and 15 min after physiotherapy. Thirty subjects with a mean age of 61.8 ± 15.9 y and Sequential Organ Failure Assessment of 8 (range 6-10) were included. Chest physiotherapy caused a normalization of pH (P = .046) and P(aCO2) (P = .008); reduction of lactate (P = .001); and an increase in P(aO2) (P = .03), arterial oxygen saturation (P = .02), and P(aO2)/F(IO2) (P = .034), 15 min after it was applied. The results indicate that chest physiotherapy has immediate effects, improving oxygenation and reducing lactate and oxidative damage in subjects in septic shock. However, it does not cause alterations in the inflammatory and hemodynamic parameters. Copyright © 2014 by Daedalus Enterprises.

  2. Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells.

    Science.gov (United States)

    Kim, Yong-Dae; Lantz-McPeak, Susan M; Ali, Syed F; Kleinman, Michael T; Choi, Young-Sook; Kim, Heon

    2014-05-01

    A major constituent of urban air pollution is diesel exhaust, a complex mixture of gases, chemicals, and particles. Recent evidence suggests that exposure to air pollution can increase the risk of a fatal stroke, cause cerebrovascular damage, and induce neuroinflammation and oxidative stress that may trigger neurodegenerative diseases, such as Parkinson's disease. The specific aim of this study was to determine whether ultrafine diesel exhaust particles (DEPs), the particle component of exhaust from diesel engines, can induce oxidative stress and effect dopamine metabolism in PC-12 cells. After 24 h exposure to DEPs of 200 nm or smaller, cell viability, ROS and nitric oxide (NO(2)) generation, and levels of dopamine (DA) and its metabolites, (dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)), were evaluated. Results indicated cell viability was not significantly changed by DEP exposure. However, ROS showed dramatic dose-dependent changes after DEP exposure (2.4 fold increase compared to control at 200 μg/mL). NO(2) levels were also dose-dependently increased after DEP exposure. Although not in a dose-dependent manner, upon DEP exposure, intracellular DA levels were increased while DOPAC and HVA levels decreased when compared to control. Results suggest that ultrafine DEPs lead to dopamine accumulation in the cytoplasm of PC-12 cells, possibly contributing to ROS formation. Further studies are warranted to elucidate this mechanism. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Specific Kv1.3 blockade modulates key cholesterol-metabolism-associated molecules in human macrophages exposed to ox-LDL.

    Science.gov (United States)

    Yang, Yong; Wang, Yan-Fu; Yang, Xiao-Fang; Wang, Zhao-Hui; Lian, Yi-Tian; Yang, Ying; Li, Xiao-Wei; Gao, Xiang; Chen, Jian; Shu, Yan-Wen; Cheng, Long-Xian; Liao, Yu-Hua; Liu, Kun

    2013-01-01

    Cholesterol-metabolism-associated molecules, including scavenger receptor class A (SR-A), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD36, ACAT1, ABCA1, ABCG1, and scavenger receptor class B type I, can modulate cholesterol metabolism in the transformation from macrophages to foam cells. Voltage-gated potassium channel Kv1.3 has increasingly been demonstrated to play an important role in the modulation of macrophage function. Here, we investigate the role of Kv1.3 in modulating cholesterol-metabolism-associated molecules in human acute monocytic leukemia cell-derived macrophages (THP-1 macrophages) and human monocyte-derived macrophages exposed to oxidized LDL (ox-LDL). Human Kv1.3 and Kv1.5 channels (hKv1.3 and hKv1.5) are expressed in macrophages and form a heteromultimeric channel. The hKv1.3-E314 antibody that we had generated as a specific hKv1.3 blocker inhibited outward delayed rectifier potassium currents, whereas the hKv1.5-E313 antibody that we had generated as a specific hKv1.5 blocker failed. Accordingly, the hKv1.3-E314 antibody reduced percentage of cholesterol ester and enhanced apoA-I-mediated cholesterol efflux in THP-1 macrophages and human monocyte-derived macrophages exposed to ox-LDL. The hKv1.3-E314 antibody downregulated SR-A, LOX-1, and ACAT1 expression and upregulated ABCA1 expression in THP-1 macrophages and human monocyte-derived macrophages. Our results reveal that specific Kv1.3 blockade represents a novel strategy modulating cholesterol metabolism in macrophages, which benefits the treatment of atherosclerotic lesions.

  4. Specific Kv1.3 blockade modulates key cholesterol-metabolism-associated molecules in human macrophages exposed to ox-LDL[S

    Science.gov (United States)

    Yang, Yong; Wang, Yan-Fu; Yang, Xiao-Fang; Wang, Zhao-Hui; Lian, Yi-Tian; Yang, Ying; Li, Xiao-Wei; Gao, Xiang; Chen, Jian; Shu, Yan-Wen; Cheng, Long-Xian; Liao, Yu-Hua; Liu, Kun

    2013-01-01

    Cholesterol-metabolism-associated molecules, including scavenger receptor class A (SR-A), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD36, ACAT1, ABCA1, ABCG1, and scavenger receptor class B type I, can modulate cholesterol metabolism in the transformation from macrophages to foam cells. Voltage-gated potassium channel Kv1.3 has increasingly been demonstrated to play an important role in the modulation of macrophage function. Here, we investigate the role of Kv1.3 in modulating cholesterol-metabolism-associated molecules in human acute monocytic leukemia cell-derived macrophages (THP-1 macrophages) and human monocyte-derived macrophages exposed to oxidized LDL (ox-LDL). Human Kv1.3 and Kv1.5 channels (hKv1.3 and hKv1.5) are expressed in macrophages and form a heteromultimeric channel. The hKv1.3-E314 antibody that we had generated as a specific hKv1.3 blocker inhibited outward delayed rectifier potassium currents, whereas the hKv1.5-E313 antibody that we had generated as a specific hKv1.5 blocker failed. Accordingly, the hKv1.3-E314 antibody reduced percentage of cholesterol ester and enhanced apoA-I-mediated cholesterol efflux in THP-1 macrophages and human monocyte-derived macrophages exposed to ox-LDL. The hKv1.3-E314 antibody downregulated SR-A, LOX-1, and ACAT1 expression and upregulated ABCA1 expression in THP-1 macrophages and human monocyte-derived macrophages. Our results reveal that specific Kv1.3 blockade represents a novel strategy modulating cholesterol metabolism in macrophages, which benefits the treatment of atherosclerotic lesions. PMID:23099443

  5. A high-fat meal promotes lipid-load and apolipoprotein B-48 receptor transcriptional activity in circulating monocytes.

    Science.gov (United States)

    Varela, Lourdes M; Ortega, Almudena; Bermudez, Beatriz; Lopez, Sergio; Pacheco, Yolanda M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G

    2011-05-01

    The postprandial metabolism of dietary fats results in the production of apolipoprotein B-48 (apoB48)-containing triglyceride-rich lipoproteins (TRLs), which cause rapid receptor-mediated macrophage lipid engorgement via the apoB48 cell surface receptor (apoB48R). Monocytes circulate together with apoB48-containing TRLs in the postprandial bloodstream and may start accumulating lipids even before their migration to tissues and differentiation to macrophages. We sought to determine whether circulating monocytes are equipped with apoB48R and whether, in the postprandial state, circulating monocytes accumulate lipids and modulate apoB48R transcriptional activity after intake of a high-fat meal. In a crossover design, we studied the effect of a high-fat meal on fasting and postprandial concentrations of triglycerides, free fatty acids, cholesterol, and insulin in 12 healthy men. TRLs and monocytes were freshly isolated at fasting, hourly until the postprandial peak, and at the late postprandial phase. TRLs were subjected to triglycerides, apoB48, and apolipoprotein B-100 analyses; and lipid accumulation and apoB48R mRNA expression levels were measured in monocytes. Monocytes showed a time-dependent lipid accumulation in response to the high-fat meal, which was paralleled by an increase in apoB48R mRNA expression levels. These effects were coincident only with an increase in apoB48-containing TRLs in the postprandial phase and were also observed ex vivo in freshly isolated monocytes incubated with apoB48-containing TRLs. In a setting of abundant plasma apoB48-containing TRLs, these findings highlight the role of dietary fat in inducing lipid accumulation and apoB48R gene transcription in circulating monocytes.

  6. Triglyceride-rich lipoprotein regulates APOB48 receptor gene expression in human THP-1 monocytes and macrophages.

    Science.gov (United States)

    Bermudez, Beatriz; Lopez, Sergio; Varela, Lourdes M; Ortega, Almudena; Pacheco, Yolanda M; Moreda, Wenceslao; Moreno-Luna, Rafael; Abia, Rocio; Muriana, Francisco J G

    2012-02-01

    The postprandial metabolism of dietary fats implies that the production of TG-rich lipoproteins (TRL) contributes to the progression of plaque development. TRL and their remnants cause rapid receptor-mediated monocyte/macrophage lipid engorgement via the cell surface apoB48 receptor (apoB48R). However, the mechanistic basis for apoB48 receptor (APOB48R) regulation by postprandial TRL in monocytes and macrophages is not well established. In this study, we investigated the effects of postprandial TRL from healthy volunteers on the expression of APOB48R mRNA and lipid uptake in human THP-1 monocytes and THP-1-derived macrophages. The expression of APOB48R mRNA was upregulated in THP-1 monocytes, but downregulated in THP-1-derived macrophages when treated with postprandial TRL (P < 0.05), in a dose- and time-dependent manner. TG and free cholesterol were dramatically increased in THP-1-derived macrophages (140 and 50%, respectively; P < 0.05) and in THP-1 monocytes (160 and 95%, respectively; P < 0.05). This lipid accumulation was severely decreased (~50%; P < 0.05) in THP-1-derived macrophages by small interfering RNA (siRNA) targeting of APOB48R. Using PPAR and retinoid X receptor (RXR) agonists, antagonists, and siRNA, our data indicate that PPARα, PPARγ, and RXRα are involved in postprandial TRL-induced APOB48R transcriptional regulation. Co-incubation with acyl-CoA synthetase or acyl-CoA:cholesterol acyltransferase inhibitors potentiated the effects of postprandial TRL on the expression of APOB48R mRNA in THP-1 monocytes and THP-1-derived macrophages. Our findings collectively suggest that APOB48R represents a molecular target of postprandial TRL via PPAR-dependent pathways in human THP-1 monocytes and macrophages and advance a potentially important link between postprandial metabolism of dietary fats and atherogenesis.

  7. All-trans retinoic acid increases oxidative metabolism in mature adipocytes

    DEFF Research Database (Denmark)

    Mercader, Josep; Madsen, Lise; Felipe, Francisco

    2007-01-01

    BACKGROUND/AIMS: In rodents, retinoic acid (RA) treatment favors loss of body fat mass and the acquisition of brown fat features in white fat depots. In this work, we sought to examine to what extent these RA effects are cell autonomous or dependent on systemic factors. METHODS: Parameters of lipid......), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). These changes paralleled inactivation of the retinoblastoma protein and were...

  8. Metabolism of clebopride in vitro. Identification of N-oxidized products.

    Science.gov (United States)

    Huizing, G; Beckett, A H

    1980-01-01

    1. N-(1'-Benzyl-4'-piperidyl-N-oxide)-4-amino-5-chloro-2-methoxybenzamide, N-(4'-(N-hydroxylpiperidyl)-4-amino-5-chloro-2-methoxybenzamide and N-(4'-(delta 1'-piperidyl-N-oxide))-4-amino-5-chloro-2-methoxybenzamide were obtained from chloroform extracts of incubation mixtures of clebopride or desbenzyl clebopride with 9000 g supernatant of liver homogenates of male NZW rabbits. 2. These metabolites were identified using electron impact (low and high resolution) and field desorption mass spectrometry, and computer averaged time proton magnetic resonance spectroscopy.

  9. Deuterium oxide as a tool for the study of amino acid metabolism

    International Nuclear Information System (INIS)

    Mitra, R.; Burton, J.; Varner, J.E.

    1976-01-01

    We have used deuterium oxide in nontoxic concentrations to study, in intact seedlings, the biosynthesis of amino acids. The extent and pattern of deuteration, as determined by a gas--liquid chromatograph--mass spectrometer system, permits conclusions about the biosynthesis of individual amino acids and also about their exposure to transaminases and other enzymes that might introduce deuterium into specific positions of the amino acid by exchange. This method could be used to study amino acid biogenesis in any organism that can tolerate 20 to 40 percent deuterium oxide for a period of a few hours to a few days

  10. Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75.

    Science.gov (United States)

    Cáceres, Lucía; Necakov, Aleksandar S; Schwartz, Carol; Kimber, Sandra; Roberts, Ian J H; Krause, Henry M

    2011-07-15

    Nitric oxide gas acts as a short-range signaling molecule in a vast array of important physiological processes, many of which include major changes in gene expression. How these genomic responses are induced, however, is poorly understood. Here, using genetic and chemical manipulations, we show that nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer partner, Drosophila hormone receptor 3 (DHR3). Manipulation of these interactions leads to gross alterations in feeding behavior, fat deposition, and developmental timing. These neuroendocrine interactions and consequences appear to be conserved in vertebrates.

  11. Acute effect of glucose on cerebral blood flow, blood oxygenation, and oxidative metabolism.

    Science.gov (United States)

    Xu, Feng; Liu, Peiying; Pascual, Juan M; Xiao, Guanghua; Huang, Hao; Lu, Hanzhang

    2015-02-01

    While it is known that specific nuclei of the brain, for example hypothalamus, contain glucose-sensing neurons thus their activity is affected by blood glucose level, the effect of glucose modulation on whole-brain metabolism is not completely understood. Several recent reports have elucidated the long-term impact of caloric restriction on the brain, showing that animals under caloric restriction had enhanced rate of tricarboxylic acid cycle (TCA) cycle flux accompanied by extended life span. However, acute effect of postprandial blood glucose increase has not been addressed in detail, partly due to a scarcity and complexity of measurement techniques. In this study, using a recently developed noninvasive MR technique, we measured dynamic changes in global cerebral metabolic rate of O2 (CMRO2 ) following a 50 g glucose ingestion (N = 10). A time dependent decrease in CMRO2 was observed, which was accompanied by a reduction in oxygen extraction fraction (OEF) with unaltered cerebral blood flow (CBF). At 40 min post-ingestion, the amount of CMRO2 reduction was 7.8 ± 1.6%. A control study without glucose ingestion was performed (N = 10), which revealed no changes in CMRO2 , CBF, or OEF, suggesting that the observations in the glucose study was not due to subject drowsiness or fatigue after staying inside the scanner. These findings suggest that ingestion of glucose may alter the rate of cerebral metabolism of oxygen in an acute setting. © 2014 Wiley Periodicals, Inc.

  12. In vitro metabolism of nitric oxide-donating aspirin: the effect of positional isomerism.

    Science.gov (United States)

    Gao, Jianjun; Kashfi, Khosrow; Rigas, Basil

    2005-03-01

    NO-donating aspirin (NO-ASA) is a potentially important chemopreventive agent against cancer. Since positional isomerism affects strongly its potency in inhibiting colon cancer cell growth, we studied the metabolic transformations of its ortho-, meta-, and para-isomers in rat liver and colon cytosolic, microsomal, and mitochondrial fractions as well as in intact HT-29 human colon cancer cells. NO-ASA and metabolites were determined by high-performance liquid chromatography and products identified by mass spectroscopy, as required. For all three isomers, the acetyl group on the ASA moiety was hydrolyzed rapidly. This was followed by hydrolysis of the ester bond linking the salicylate anion to the spacer. The ortho- and para-isomers produced salicylic acid and a putative intermediate consisting of the remainder of the molecule, which via a rapid step generated nitrate, (hydroxymethyl)phenol, and a conjugate of spacer with glutathione. The meta-isomer, in contrast, generated salicylic acid and (nitroxymethyl)phenol, the latter leading to (hydroxymethyl)phenol and the glutathione-spacer conjugate. This metabolic pathway takes place in its entirety only in the cytosolic fraction of the tissues tested and in intact human colon cancer cells, perhaps reflecting exposure to the cytosolic glutathione S-transferase, which catalyzes the formation of the spacer-glutathione conjugate. Thus, the three positional isomers of NO-ASA differ in their metabolism and these differences correlate with their differential effects on cancer cell growth, underscoring the importance of positional isomerism in modulating drug effects.

  13. COPPER AND COPPER-CONTAINING PESTICIDES: METABOLISM, TOXICITY AND OXIDATIVE STRESS

    Directory of Open Access Journals (Sweden)

    Viktor Husak

    2015-05-01

    Full Text Available The purpose of this paper is to provide a brief review of the current knowledge regarding metabolism and toxicity of copper and copper-based pesticides in living organisms. Copper is an essential trace element in all living organisms (bacteria, fungi, plants, and animals, because it participates in different metabolic processes and maintain functions of organisms. The transport and metabolism of copper in living organisms is currently the subject of many studies. Copper is absorbed, transported, distributed, stored, and excreted in the body via the complex of homeostatic processes, which provide organisms with a needed constant level of this micronutrient and avoid excessive amounts. Many aspects of copper homeostasis were studied at the molecular level. Copper based-pesticides, in particularly fungicides, bacteriocides and herbicides, are widely used in agricultural practice throughout the world. Copper is an integral part of antioxidant enzymes, particularly copper-zinc superoxide dismutase (Cu,Zn-SOD, and plays prominent roles in iron homeostasis. On the other hand, excess of copper in organism has deleterious effect, because it stimulates free radical production in the cell, induces lipid peroxidation, and disturbs the total antioxidant capacity of the body. The mechanisms of copper toxicity are discussed in this review also.

  14. Unveiling the oxidative metabolism of Rhipicephalus microplus (Acari: Ixodidae) experimentally exposed to entomopathogenic fungi.

    Science.gov (United States)

    Tunholi-Alves, Vinícius Menezes; Tunholi Alves, Victor Menezes; da Silva, Jairo Pinheiro; Nora Castro, Rosane; Salgueiro, Fernanda Barbosa; Perinotto, Wendell Marcelo de Souza; Gôlo, Patrícia Silva; Camargo, Mariana Guedes; Angelo, Isabele da Costa; Bittencourt, Vânia Rita Elias Pinheiro

    2016-10-01

    Rhipicephalus microplus is an important tick in tropical regions due to the high economic losses caused by its parasitism. Metarhizium anisopliae and Beauveria bassiana are well-known entomopathogenic fungi that can afflict R. microplus ticks. The development of new targets and strategies to control this parasite can be driven by studies of this tick's physiology. Recently, it was reported that when exposed to adverse physiological conditions, ticks can activate fermentative pathways, indicating transition from aerobic to anaerobic metabolism. Nevertheless, the precise mechanism by which entomopathogenic fungi influence R. microplus metabolism has not been clarified, limiting understanding of the tick-fungus association. Thus, the present study aimed to evaluate the effect of infection of ticks by M. anisopliae and B. bassiana on the amount of selected carboxylic acids present in the hemolymph, enabling increased understanding of changes previously reported. The results showed preservation in the concentrations of oxalic, lactic, and pyruvic acids in the hemolymph 24 and 48 h after dropping from cattle; while there were variations in the concentration of these carboxylic acids after infection of female ticks to M. anisopliae and B. bassiana. Significant increases were observed in the concentration of oxalic and lactic acids and significant reduction of pyruvic acid for both observation times (24 and 48 h) after infection by entomopathogenic fungi. These results indicate that B. bassiana and M. anisopliae infection alters the basal metabolism of R. microplus females, resulting in the activation of fermentative pathways.

  15. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects

    International Nuclear Information System (INIS)

    Fox, P.T.; Raichle, M.E.

    1986-01-01

    Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) was studied using multiple sequential administrations of 15 O-labeled radiotracers and positron emission tomography. In the resting state an excellent correlation between CBF and CMRO 2 was found when paired measurements of CBF and CMRO 2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO 2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO 2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized

  16. Oxidative stress status, antioxidant metabolism and polypeptide patterns in Juncus maritimus shoots exhibiting differential mercury burdens in Ria de Aveiro coastal lagoon (Portugal).

    Science.gov (United States)

    Anjum, Naser A; Duarte, Armando C; Pereira, Eduarda; Ahmad, Iqbal

    2014-05-01

    This study assessed the oxidative stress status, antioxidant metabolism and polypeptide patterns in salt marsh macrophyte Juncus maritimus shoots exhibiting differential mercury burdens in Ria de Aveiro coastal lagoon at reference and the sites with highest, moderate and the lowest mercury contamination. In order to achieve these goals, shoot-mercury burden and the responses of representative oxidative stress indices, and the components of both non-glutathione- and glutathione-based H2O2-metabolizing systems were analyzed and cross-talked with shoot-polypeptide patterns. Compared to the reference site, significant elevations in J. maritimus shoot mercury and the oxidative stress indices such as H2O2, lipid peroxidation, electrolyte leakage and reactive carbonyls were maximum at the site with highest followed by moderate and the lowest mercury contamination. Significantly elevated activity of non-glutathione-based H2O2-metabolizing enzymes such as ascorbate peroxidase and catalase accompanied the studied damage-endpoint responses, whereas the activity of glutathione-based H2O2-scavenging enzymes glutathione peroxidase and glutathione sulfo-transferase was inhibited. Concomitantly, significantly enhanced glutathione reductase activity and the contents of both reduced and oxidized glutathione were perceptible in high mercury-exhibiting shoots. It is inferred that high mercury-accrued elevations in oxidative stress indices were obvious, where non-glutathione-based H2O2-decomposing enzyme system was dominant over the glutathione-based H2O2-scavenging enzyme system. In particular, the glutathione-based H2O2-scavenging system failed to coordinate with elevated glutathione reductase which in turn resulted into increased pool of oxidized glutathione and the ratio of oxidized glutathione-to-reduced glutathione. The substantiation of the studied oxidative stress indices and antioxidant metabolism with approximately 53-kDa polypeptide warrants further studies.

  17. Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome

    NARCIS (Netherlands)

    Schreurs, M.; Kuipers, F.; van der Leij, F. R.

    P>Insulin sensitizers like metformin generally act through pathways triggered by adenosine monophosphate-activated protein kinase. Carnitine palmitoyltransferase 1 (CPT1) controls mitochondrial beta-oxidation and is inhibited by malonyl-CoA, the product of acetyl-CoA carboxylase (ACC). The adenosine

  18. Ripening, storage temperature, ethylene action, and oxidative stress alter apple peel phytosterol metabolism

    Science.gov (United States)

    The chilling conditions of apple cold storage can provoke an economically significant necrotic peel disorder called superficial scald (scald) in susceptible cultivars. Disorder development can be reduced by inhibiting ethylene action or oxidative stress. We found previously that scald is preceded b...

  19. Establishment of oxidative D-xylose metabolism in Pseudomonas putida S12

    NARCIS (Netherlands)

    Meijnen, J.P.; Winde, J.H. de; Ruijssenaars, H.J.

    2009-01-01

    The oxidative D-xylose catabolic pathway of Caulobacter crescentus, encoded by the xylXABCD operon, was expressed in the gram-negative bacterium Pseudomonas putida S12. This engineered transformant strain was able to grow on D-xylose as a sole carbon source with a biomass yield of 53% (based on g

  20. Comparison of amino acid oxidation and urea metabolism in haemodialysis patients during fasting and meal intake

    NARCIS (Netherlands)

    Veeneman, JM; Kingma, HA; Stellaard, F; de Jong, PE; Reijngoud, DJ; Huisman, RM

    Background. The PNA (protein equivalent of nitrogen appearance) is used to calculate protein intake from urea kinetics. One of the essential assumptions in the calculation of PNA is that urea accumulation in haemodialysis (HD) patients is equivalent to amino acid oxidation. However, urea is

  1. Impaired energy metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martín A; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina

    2016-01-01

    Accumulation of oxidized proteins is a hallmark of cellular and organismal aging. Adult muscle stem cell (or satellite cell) replication and differentiation is compromised with age contributing to sarcopenia. However, the molecular events related to satellite cell dysfunction during aging are not...

  2. Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Chung-Wei Kao

    2018-05-01

    Full Text Available Atherosclerosis is a multifactorial inflammatory disease that may progress silently for long period, and it is also widely accepted as the main cause of cardiovascular diseases. To prevent atherosclerotic plaques from generating, imaging early molecular markers and quantifying the extent of disease progression are desired. During inflammation, circulating monocytes leave the bloodstream and migrate into incipient lipid accumulation in the artery wall, following conditioning by local growth factors and proinflammatory cytokines; therefore, monocyte accumulation in the arterial wall can be observed in fatty streaks, rupture-prone plaques, and experimental atherosclerosis. In this work, we synthesized monocyte-targeting iron oxide magnetic nanoparticles (MNPs, which were incorporated with the peptides derived from the chemokine receptor C-C chemokine receptor type 2 (CCR2-binding motif of monocytes chemoattractant protein-1 (MCP-1 as a diagnostic tool for potential atherosclerosis. MCP-1-motif MNPs co-localized with monocytes in in vitro fluorescence imaging. In addition, with MNPs injection in ApoE knockout mice (ApoE KO mice, the well-characterized animal model of atherosclerosis, MNPs were found in specific organs or regions which had monocytes accumulation, especially the aorta of atherosclerosis model mice, through in vivo imaging system (IVIS imaging and magnetic resonance imaging (MRI. We also performed Oil Red O staining and Prussian Blue staining to confirm the co-localization of MCP-1-motif MNPs and atherosclerosis. The results showed the promising potential of MCP-1-motif MNPs as a diagnostic agent of atherosclerosis.

  3. Free Radical Oxidation Induced by Iron Metabolism Disorder in Femoral and Pelvic Fractures and Potential for Its Correction

    Directory of Open Access Journals (Sweden)

    Y. P. Orlov

    2016-01-01

    Full Text Available Objective: To determine the pathogenic significance of iron ions in the activation of free radical oxidation in trau matic disease and valuate the efficacy of Desferal in the complex therapy of patients with femoral and pelvic fractions.Materials and methods. Iron metabolism and the intensity of free radical oxidation have been studed in 30 patients with traumas. The patients were randomized into two groups by gender, age and the severity of injury. Group I (n=15 included the injured patients who received the standard intensive therapy. Group II (n=15 included the patients who were treated with Desferal of 8 mg/kg twice daily in 12 hours along with the intensive therapy. The control group comprized of 10 healthy individuals of the same age. The concentration of total and free hemoglobine, serum iron, transferrin, total antioxidant activity of blood serum, the intensity of free radical oxida tion by the Fe2+induced chemiluminescence and hemostatic parameters were studied on admittance as well as on 3rd and 5th day of hospitalization. The parameters of sistemic hemodyamics were checked by integral rheovasog raphy. Statistical processing of data was carried out using Biostat and MS Excel software. The results were pre sented as a mean and standart deviation (M±δ. The Student’s (t and MannWhitney tests were used to prove the hypotheses. The critical level of significance was P=0.05.Results. It was determined that the disorders of iron metabolism in patients with traumatic disease were accompanied by intra and extravascular hemolysis, the excess off reduced iron ions catalizing the free radical oxidation, and failure of antioxidant system and disorders of hemostatic system and central hemodynamics. Desferal lowered the level of reduced iron in blood serum, diminished the intensity of free radical oxidation and eliminated the disorders in hemostasis and systemic hemodynamics.Conclusion. Data confirm the pathogenic role of iron ions in the

  4. Mycobacterium leprae upregulates IRGM expression in monocytes and monocyte-derived macrophages.

    Science.gov (United States)

    Yang, Degang; Chen, Jia; Zhang, Linglin; Cha, Zhanshan; Han, Song; Shi, Weiwei; Ding, Ru; Ma, Lan; Xiao, Hong; Shi, Chao; Jing, Zhichun; Song, Ningjing

    2014-08-01

    Leprosy is caused by the infection of Mycobacterium leprae, which evokes a strong inflammatory response and leads to nerve damage. Immunity-related GTPase family M protein (IRGM) plays critical roles in controlling inflammation. The objective of the study was to investigate whether IRGM is involved in the infection of M. leprae. Levels of IRGM were assessed in M. leprae-infected CD4(+) T cells, monocytes, and monocyte-derived macrophages. Data revealed that both protein and mRNA levels of IRGM were increased in monocytes after M. leprae infection. Interestingly, monocyte-derived macrophages showed more prominent IRGM expression with M. leprae infection, whereas the bacteria did not affect IRGM in CD4(+) T cells. Furthermore, we assessed levels of IRGM in CD4(+) T cells and monocytes from 78 leprosy patients and 40 healthy controls, and observed upregulated protein level of IRGM in the monocytes from leprosy patients. Also, IRGM expression was inversely correlated with the severity of the disease. These findings suggested a close involvement of IRGM in M. leprae infection and indicated a potential mechanism of defending M. leprae infection.

  5. TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium.

    Directory of Open Access Journals (Sweden)

    Seung Jin Lee

    Full Text Available Toll-like receptor 4 (TLR4 is known to mediate monocyte adhesion to endothelial cells, however, its role on the expression of monocyte adhesion molecules is unclear. In the present study, we investigated the role of TLR4 on the expression of monocyte adhesion molecules, and determined the functional role of TLR4-induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1 monocytes were stimulated with Kdo2-Lipid A (KLA, a specific TLR4 agonist, Mac-1 expression was markedly increased in association with an increased adhesion of monocytes to endothelial cells. These were attenuated by anti-Mac-1 antibody, suggesting a functional role of TLR4-induced Mac-1 on monocyte adhesion to endothelial cells. In monocytes treated with MK886, a 5-lipoxygenase (LO inhibitor, both Mac-1 expression and monocyte adhesion to endothelial cells induced by KLA were markedly attenuated. Moreover, KLA increased the expression of mRNA and protein of 5-LO, suggesting a pivotal role of 5-LO on these processes. In in vivo studies, KLA increased monocyte adhesion to aortic endothelium of wild-type (WT mice, which was attenuated in WT mice treated with anti-Mac-1 antibody as well as in TLR4-deficient mice. Taken together, TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis.

  6. Brain oxidative metabolism of the newborn dog: correlation between 31P NMR spectroscopy and pyridine nucleotide redox state.

    Science.gov (United States)

    Mayevsky, A; Nioka, S; Subramanian, V H; Chance, B

    1988-04-01

    The effects of both anoxia and short- and long-term hypoxia on brain oxidative metabolism were studied in newborn dogs. Oxidative metabolism was evaluated by two independent measures: in vivo continuous monitoring of mitochondrial NADH redox state and energy stores as calculated from the phosphocreatine (PCr)/Pi levels measured by 31P nuclear magnetic resonance (NMR) spectroscopy. The hemodynamic response to low oxygen supply was further evaluated by measuring the changes in the reflected light intensity at 366 nm (the excitation wavelength for NADH). The animal underwent surgery and was prepared for monitoring of the two signals (NADH and PCr/Pi). It was then placed inside a Phosphoenergetics 260-80 NMR spectrometer magnet with a 31-cm bore. Each animal (1-21 days old) was exposed to short-term anoxia or hypoxia as well as to long-term hypoxia (1-2 h). The results can be summarized as follow: (a) In the normoxic brain, the ratio between PCr and Pi was greater than 1 (1.2-1.4), while under hypoxia or asphyxia a significant decrease that was correlated to the FiO2 levels was recorded. (b) A clear correlation was found between the decrease in PCr/Pi values and the increased NADH redox state developed under decreased O2 supply to the brain. (c) Exposing the animal to moderately long-term hypoxia led to a stabilized low-energy state of the brain with a good recovery after rebreathing normal air. (d) Under long-term and severe hypoxia, the microcirculatory autoregulatory mechanism was damaged and massive vasoconstriction was optically recorded simultaneously with a significant decrease in PCr/Pi values.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Abnormal iron metabolism and oxidative stress in mice expressing a mutant form of the ferritin light polypeptide gene

    Science.gov (United States)

    Barbeito, Ana G.; Garringer, Holly J.; Baraibar, Martin A.; Gao, Xiaoying; Arredondo, Miguel; Núñez, Marco T.; Smith, Mark A.; Ghetti, Bernardino; Vidal, Ruben

    2009-01-01

    Insertional mutations in exon 4 of the ferritin light chain (FTL) gene are associated with hereditary ferritinopathy (HF) or neuroferritinopathy, an autosomal dominant neurodegenerative disease characterized by progressive impairment of motor and cognitive functions. To determine the pathogenic mechanisms by which mutations in FTL lead to neurodegeneration, we investigated iron metabolism and markers of oxidative stress in the brain of transgenic (Tg) mice that express the mutant human FTL498-499InsTC cDNA. Compared with wild-type mice, brain extracts from Tg (FTL-Tg) mice showed an increase in the cytoplasmic levels of both FTL and ferritin heavy chain polypeptides, a decrease in the protein and mRNA levels of transferrin receptor-1, and a significant increase in iron levels. Transgenic mice also showed the presence of markers for lipid peroxidation, protein carbonyls, and nitrone–protein adducts in the brain. However, gene expression analysis of iron management proteins in the liver of Tg mice indicates that the FTL-Tg mouse liver is iron deficient. Our data suggest that disruption of iron metabolism in the brain has a primary role in the process of neurodegeneration in HF and that the pathogenesis of HF is likely to result from a combination of reduction in iron storage function and enhanced toxicity associated with iron-induced ferritin aggregates in the brain. PMID:19519778

  8. NMR-based metabonomic analyses of the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) on macrophage metabolism

    Science.gov (United States)

    Feng, Jianghua; Zhao, Jing; Hao, Fuhua; Chen, Chang; Bhakoo, Kishore; Tang, Huiru

    2011-05-01

    The metabonomic changes in murine RAW264.7 macrophage-like cell line induced by ultrasmall superparamagnetic particles of iron oxides (USPIO) have been investigated, by analyzing both the cells and culture media, using high-resolution NMR in conjunction with multivariate statistical methods. Upon treatment with USPIO, macrophage cells showed a significant decrease in the levels of triglycerides, essential amino acids such as valine, isoleucine, and choline metabolites together with an increase of glycerophospholipids, tyrosine, phenylalanine, lysine, glycine, and glutamate. Such cellular responses to USPIO were also detectable in compositional changes of cell media, showing an obvious depletion of the primary nutrition molecules, such as glucose and amino acids and the production of end-products of glycolysis, such as pyruvate, acetate, and lactate and intermediates of TCA cycle such as succinate and citrate. At 48 h treatment, there was a differential response to incubation with USPIO in both cell metabonome and medium components, indicating that USPIO are phagocytosed and released by macrophages. Furthermore, information on cell membrane modification can be derived from the changes in choline-like metabolites. These results not only suggest that NMR-based metabonomic methods have sufficient sensitivity to identify the metabolic consequences of murine RAW264.7 macrophage-like cell line response to USPIO in vitro, but also provide useful information on the effects of USPIO on cellular metabolism.

  9. NMR-based metabonomic analyses of the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) on macrophage metabolism

    International Nuclear Information System (INIS)

    Feng Jianghua; Zhao Jing; Hao Fuhua; Chen Chang; Bhakoo, Kishore; Tang, Huiru

    2011-01-01

    The metabonomic changes in murine RAW264.7 macrophage-like cell line induced by ultrasmall superparamagnetic particles of iron oxides (USPIO) have been investigated, by analyzing both the cells and culture media, using high-resolution NMR in conjunction with multivariate statistical methods. Upon treatment with USPIO, macrophage cells showed a significant decrease in the levels of triglycerides, essential amino acids such as valine, isoleucine, and choline metabolites together with an increase of glycerophospholipids, tyrosine, phenylalanine, lysine, glycine, and glutamate. Such cellular responses to USPIO were also detectable in compositional changes of cell media, showing an obvious depletion of the primary nutrition molecules, such as glucose and amino acids and the production of end-products of glycolysis, such as pyruvate, acetate, and lactate and intermediates of TCA cycle such as succinate and citrate. At 48 h treatment, there was a differential response to incubation with USPIO in both cell metabonome and medium components, indicating that USPIO are phagocytosed and released by macrophages. Furthermore, information on cell membrane modification can be derived from the changes in choline-like metabolites. These results not only suggest that NMR-based metabonomic methods have sufficient sensitivity to identify the metabolic consequences of murine RAW264.7 macrophage-like cell line response to USPIO in vitro, but also provide useful information on the effects of USPIO on cellular metabolism.

  10. Cerebral blood flow, oxidative metabolism and cerebrovascular carbon dioxide reactivity in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Møller, Kirsten; Strauss, Gitte Irene; Thomsen, Gerda

    2002-01-01

    BACKGROUND: The optimal arterial carbon dioxide tension (P(a)CO(2)) in patients with acute bacterial meningitis (ABM) is unknown and controversial. The objective of this study was to measure global cerebral blood flow (CBF), cerebrovascular CO(2) reactivity (CO(2)R), and cerebral metabolic rates...... and hyperventilation with single-photon emission computed tomography (SPECT) (14 patients) and/or the Kety-Schmidt technique (KS) (11 patients and all controls). In KS studies, CMR was measured by multiplying the arterial to jugular venous concentration difference (a-v D) by CBF. RESULTS: CBF did not differ...

  11. Nitrous Oxide Metabolism in Nitrate-Reducing Bacteria: Physiology and Regulatory Mechanisms.

    Science.gov (United States)

    Torres, M J; Simon, J; Rowley, G; Bedmar, E J; Richardson, D J; Gates, A J; Delgado, M J

    2016-01-01

    Nitrous oxide (N2O) is an important greenhouse gas (GHG) with substantial global warming potential and also contributes to ozone depletion through photochemical nitric oxide (NO) production in the stratosphere. The negative effects of N2O on climate and stratospheric ozone make N2O mitigation an international challenge. More than 60% of global N2O emissions are emitted from agricultural soils mainly due to the application of synthetic nitrogen-containing fertilizers. Thus, mitigation strategies must be developed which increase (or at least do not negatively impact) on agricultural efficiency whilst decrease the levels of N2O released. This aim is particularly important in the context of the ever expanding population and subsequent increased burden on the food chain. More than two-thirds of N2O emissions from soils can be attributed to bacterial and fungal denitrification and nitrification processes. In ammonia-oxidizing bacteria, N2O is formed through the oxidation of hydroxylamine to nitrite. In denitrifiers, nitrate is reduced to N2 via nitrite, NO and N2O production. In addition to denitrification, respiratory nitrate ammonification (also termed dissimilatory nitrate reduction to ammonium) is another important nitrate-reducing mechanism in soil, responsible for the loss of nitrate and production of N2O from reduction of NO that is formed as a by-product of the reduction process. This review will synthesize our current understanding of the environmental, regulatory and biochemical control of N2O emissions by nitrate-reducing bacteria and point to new solutions for agricultural GHG mitigation. © 2016 Elsevier Ltd. All rights reserved.

  12. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism

    OpenAIRE

    Lee, Jieun; Wolfgang, Michael J

    2012-01-01

    Abstract Background Carnitine Palmitoyltransferase-1c (CPT1c) is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to...

  13. Enhanced sulfamethoxazole degradation through ammonia oxidizing bacteria co-metabolism and fate of transformation products.

    Science.gov (United States)

    Kassotaki, Elissavet; Buttiglieri, Gianluigi; Ferrando-Climent, Laura; Rodriguez-Roda, Ignasi; Pijuan, Maite

    2016-05-01

    The occurrence of the widely-used antibiotic sulfamethoxazole (SFX) in wastewaters and surface waters has been reported in a large number of studies. However, the results obtained up-to-date have pointed out disparities in its removal. This manuscript explores the enhanced biodegradation potential of an enriched culture of Ammonia Oxidizing Bacteria (AOB) towards SFX. Several sets of batch tests were conducted to establish a link between SFX degradation and specific ammonia oxidation rate. The occurrence, degradation and generation of SFX and some of its transformation products (4-Nitro SFX, Desamino-SFX and N(4)-Acetyl-SFX) was also monitored. A clear link between the degradation of SFX and the nitrification rate was found, resulting in an increased SFX removal at higher specific ammonia oxidation rates. Moreover, experiments conducted under the presence of allylthiourea (ATU) did not present any removal of SFX, suggesting a connection between the AMO enzyme and SFX degradation. Long term experiments (up to 10 weeks) were also conducted adding two different concentrations (10 and 100 μg/L) of SFX in the influent of a partial nitrification sequencing batch reactor, resulting in up to 98% removal. Finally, the formation of transformation products during SFX degradation represented up to 32%, being 4-Nitro-SFX the most abundant. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Effects of Ropivacaine and Bupivacaine on Rabbit Myocardial Energetic Metabolism and Mitochondria Oxidation

    Institute of Scientific and Technical Information of China (English)

    张诗海; 姚尚龙; 李晴

    2003-01-01

    Summary: To compare the cardiotoxicity induced by ropivacaine and bupivacaine and to investigatethe mechanism of cardiotoxicity, 24 mature New Zealand rabbits were divided randomly into controlgroup (group C), ropivacaine group (group R) and bupivacaine group (group B). Hearts were drawnout rapidly from the anesthetized animals and cardiac perfusion was performed immediately. Ropiva-caine 500 ng/ml (group R) or bupivacaine 500 ng/ml (group B) was added to the perfusion solution.Ventricular myocardial ATP, ADP and AMP were measured with high performance liquid chro-matogram. The ability of myocardial mitochondria oxidation to pyruvate or palmitoylcarnitine wasdetected with Clark electrode. Our results showed that myocardial ATP and ADP decreased signifi-cantly (P<0. 05) in group R and most significantly (P<0. 01) in group B as compared with groupC. Myocardial ATP and ADP decreased most significantly (P<0. 01) in group B as compared withgroup R. The changes of myocardial AMP revealed significant difference among three groups. Thechanges of pyruvate oxidation exibited no significant difference among the three groups. Palmitoyl-carnitine oxidation decreased markedly (P<0. 05) in group R and most significantly (P<0. 01) ingroup B as compared with group C. The present study indicated that the inhibition of lipid substrateoxidation may be responsible for the cardiotoxicity induced by bupivacaine and ropivacaine. The car-diotoxicity induced by ropivacaine is far more less than bupivacaine.

  15. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    Science.gov (United States)

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

    2015-01-01

    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  16. The proliferative human monocyte subpopulation contains osteoclast precursors

    Science.gov (United States)

    Lari, Roya; Kitchener, Peter D; Hamilton, John A

    2009-01-01

    Introduction Immediate precursors of bone-resorbing osteoclasts are cells of the monocyte/macrophage lineage. Particularly during clinical conditions showing bone loss, it would appear that osteoclast precursors are mobilized from bone marrow into the circulation prior to entering tissues undergoing such loss. The observed heterogeneity of peripheral blood monocytes has led to the notion that different monocyte subpopulations may have special or restricted functions, including as osteoclast precursors. Methods Human peripheral blood monocytes were sorted based upon their degree of proliferation and cultured in macrophage colony-stimulating factor (M-CSF or CSF-1) and receptor activator of nuclear factor-kappa-B ligand (RANKL). Results The monocyte subpopulation that is capable of proliferation gave rise to significantly more multinucleated, bone-resorbing osteoclasts than the bulk of the monocytes. Conclusions Human peripheral blood osteoclast precursors reside in the proliferative monocyte subpopulation. PMID:19222861

  17. Type-2 diabetes mellitus reduces cortical thickness and decreases oxidative metabolism in sensorimotor regions after stroke.

    Science.gov (United States)

    Ferris, Jennifer K; Peters, Sue; Brown, Katlyn E; Tourigny, Katherine; Boyd, Lara A

    2018-05-01

    Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with stroke and diabetes had lower cortical thickness bilaterally in the primary somatosensory cortex, and primary and secondary motor cortices. Individuals with stroke and diabetes also showed reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional primary and secondary motor cortex thicknesses were negatively related to sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group such that those with thinner primary and secondary motor cortices had better motor function. These data suggest that type-2 diabetes alters cerebral energy metabolism, and is associated with thinning of sensorimotor cortex after stroke. These factors may influence motor outcomes after stroke.

  18. MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligo.

    Science.gov (United States)

    Sahoo, Anupama; Lee, Bongyong; Boniface, Katia; Seneschal, Julien; Sahoo, Sanjaya K; Seki, Tatsuya; Wang, Chunyan; Das, Soumen; Han, Xianlin; Steppie, Michael; Seal, Sudipta; Taieb, Alain; Perera, Ranjan J

    2017-09-01

    Vitiligo is a common chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical causes, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. In this study we characterized the human vitiligo cell line PIG3V and the normal human melanocyte line HEM-l by RNA sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched microRNA-211, a known metabolic switch in nonpigmented melanoma cells, was severely down-regulated in vitiligo cell line PIG3V and skin biopsy samples from vitiligo patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were reciprocally up-regulated. microRNA-211 binds to PGC1-α 3' untranslated region locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated microRNA-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of microRNA-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Early metabolic adaptation in C57BL/6 mice resistant to high fat diet induced weight gain involves an activation of mitochondrial oxidative pathways.

    Science.gov (United States)

    Boulangé, Claire L; Claus, Sandrine P; Chou, Chieh J; Collino, Sebastiano; Montoliu, Ivan; Kochhar, Sunil; Holmes, Elaine; Rezzi, Serge; Nicholson, Jeremy K; Dumas, Marc E; Martin, François-Pierre J

    2013-04-05

    We investigated the short-term (7 days) and long-term (60 days) metabolic effect of high fat diet induced obesity (DIO) and weight gain in isogenic C57BL/6 mice and examined the specific metabolic differentiation between mice that were either strong-responders (SR), or non-responders (NR) to weight gain. Mice (n = 80) were fed a standard chow diet for 7 days prior to randomization into a high-fat (HF) (n = 56) or a low-fat (LF) (n = 24) diet group. The (1)H NMR urinary metabolic profiles of LF and HF mice were recorded 7 and 60 days after the diet switch. On the basis of the body weight gain (BWG) distribution of HF group, we identified NR mice (n = 10) and SR mice (n = 14) to DIO. Compared with LF, HF feeding increased urinary excretion of glycine conjugates of β-oxidation intermediate (hexanoylglycine), branched chain amino acid (BCAA) catabolism intermediates (isovalerylglycine, α-keto-β-methylvalerate and α-ketoisovalerate) and end-products of nicotinamide adenine dinucleotide (NAD) metabolism (N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide) suggesting up-regulation of mitochondrial oxidative pathways. In the HF group, NR mice excreted relatively more hexanoylglycine, isovalerylglycine, and fewer tricarboxylic acid (TCA) cycle intermediate (succinate) in comparison to SR mice. Thus, subtle regulation of ketogenic pathways in DIO may alleviate the saturation of the TCA cycle and mitochondrial oxidative metabolism.

  20. The effects of resveratrol on hepatic oxidative stress in metabolic syndrome model induced by high fructose diet.

    Science.gov (United States)

    Yilmaz Demirtas, C; Bircan, F S; Pasaoglu, O T; Turkozkan, N

    2018-01-01

    The purpose of this study was to evaluate probable protective effects of resveratrol treatment on hepatic oxidative events in a rat model of metabolic syndrome (MetS). Thirty-two male adult rats were randomly divided into 4 groups: control, fructose, resveratrol, and fructose plus resveratrol. To induce MetS, fructose solution (20 % in drinking water) was used. Resveratrol (10 mg/kg/day) was given by oral gavage. All treatments were given for 8 weeks. Serum lipid profile, glucose and insulin levels, liver total oxidant status (TOS) levels and paraoxonase (PON), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were analyzed. Fructose-fed rats displayed statistically significant increases in TOS levels, and decreases in PON activity compared to the control group. Resveratrol treatment moderately prevented the decrease in liver PON activity caused by fructose. On the other hand, resveratrol, alone or in combination with fructose, did not change the TOS levels when compared to the fructose group. The SOD and CAT activities in all groups did not change. In this experimental design, high-fructose consumption led to elevated TOS levels and low PON activities. The resveratrol therapy shown beneficial effects on PON activity. However, it was found to behave like a prooxidant when administered together with fructose and alone in some parameters. Our results can inspire the development of new clinical therapy in patients with MetS (Tab. 2, Ref. 34).

  1. The Effects Of Two Fitness Programs With Different Metabolic Demands On Oxidative Stress In The Blood Of Young Females

    Directory of Open Access Journals (Sweden)

    Djordjevic Dusica

    2015-06-01

    Full Text Available The aim of the present study was to assess the effects of two metabolically different exercise programs on the redox state of women who were physically inactive before the beginning of the study. For this purpose, participants (women 25±5 years old chose one of two popular fitness programs, Pilates or Tae Bo, and attended it 3 times a week for 12 weeks. At the beginning and end of the study, body composition analysis and venous blood sampling were performed. The levels of superoxide anion radical, hydrogen peroxide, nitric oxide and lipid peroxidation were measured in plasma, and the levels of reduced glutathione and the activity of superoxide dismutase and catalase were measured in erythrocytes. Only the Tae Bo program induced changes (positive in body composition, whereas both exercise programs induced slight oxidative stress in exercisers. In the Tae Bo group, the levels of hydrogen peroxide were significantly increased, whereas the levels of reduced glutathione were decreased after three months of training. In the Pilates group, hydrogen peroxide and catalase activity were increased, and nitrites decreased. However, at the end of the study, those two groups had no significantly different values for any pro/antioxidant compared with the subjects who served as controls. This finding suggests that moderate physical activity, such as recreational fitness programs, may induce the increased production of reactive oxygen species but do not lead to a serious disturbance of the redox homeostasis of exercisers.

  2. Low density lipoprotein for oxidation and metabolic studies. Isolation from small volumes of plasma using a tabletop ultracentrifuge.

    Science.gov (United States)

    Himber, J; Bühler, E; Moll, D; Moser, U K

    1995-01-01

    A rapid method is described for the isolation of small volumes of plasma low density lipoprotein (LDL) free of plasma protein contaminants using the TL-100 Tabletop Ultracentrifuge (Beckman). The isolation of LDL was achieved by a 25 min discontinuous gradient density centrifugation between the density range of 1.006 and 1.21 g/ml, recovery of LDL by tube slicing followed by a 90 min flotation step (d = 1.12 g/ml). The purity of LDL and apolipoprotein B100 (apo B100) were monitored by agarose electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), radial immunodiffusion and micropreparative fast protein liquid chromatography (FPLC). The ability of LDL oxidation was assessed by following absorbance at 234 nm after addition of copper ions. The functional integrity of the isolated LDL was checked by clearance kinetics after injection of [125I]-labelled LDL in estrogen-treated rats. The additional purification step led to LDL fractions free of protein contamination and left apo B100, alpha-tocopherol and beta-carotene intact. The LDL prepared in this way was free of albumin, as evident from analytic tests and from its enhanced oxidative modification by copper ions. Used for analytical purposes, this method allows LDL preparations from plasma volumes up to 570 microliters. This method is also convenient for metabolic studies in small animals, especially those relating to the determination of kinetic parameters of LDL in which LDL-apo B100 has to be specifically radiolabelled.

  3. The incidences of oxidative –stress occurrence following two metabolic support measures in critically ill patients

    Directory of Open Access Journals (Sweden)

    Mojtaba Mojtahedzadeh

    2013-02-01

    Full Text Available Background: A high percentage of patients admitted to the intensive care unit (ICU have systemic inflammatory response syndrome (SIRS criteria. Free radicals play an important role in initiation and development of SIRS. The purpose of this study was to assess and compare the molecular changes of cellular antioxidant power in patients with SIRS who received enteral nutrition (EN or EN combined with parenteral nutrition (PN. Methods: Two groups of 10 patients were enrolled in this randomized, controlled clinical trial. Those in the treatment group received EN+PN and the control group received only EN. Venous blood samples were taken just prior to initiation of nutritional support and then 24, 48 and 72 hours following entry into the study for examination of antioxidant parameters including total thiol, total antioxidant capacity and lipid peroxidation. Results: The two supportive regimens had different affects on total antioxidant capacity (P=0.005. In the EN group the amount of total antioxidant capacity was not significantly different in different days (P>0.05, but in the EN+PN group it was significantly different on third and forth days as compared to the first day. The two other parameters had no significant differences between the two groups. Conclusion: These results are suggesting that an increase in oxidative stress bio-markers are not necessarily related to the route of pharmaconutrition and may occur independently during metabolic support measures. Keywords: Parenteral Nutrition, Enteral Nitrition, Systemic Inflammatory Response Syndrome, Oxidative stress

  4. Oxidative and nonoxidative metabolism of polycyclic aromatic hydrocarbons in rabbit and chicken aortas and in human fetal smooth-muscle cells

    International Nuclear Information System (INIS)

    Bond, J.A.; Kocan, R.M.; Benditt, E.P.; Juchau, M.R.

    1980-01-01

    A description of the various enzyme systems in aortas of rabbits and chickens and in human fetal smooth muscle cells in culture which are responsible overall for the metabolism of F, 12-dimethylbenz(a)anthracene and benzo(a)pyrene-4, 5-oxide are provided

  5. Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung.

    Science.gov (United States)

    Grasemann, C; Herrmann, R; Starschinova, J; Gertsen, M; Palmert, M R; Grasemann, H

    2017-02-20

    Alterations in the L-arginine/nitric oxide (NO) metabolism contribute to diseases such as obesity, metabolic syndrome and airway dysfunction. The impact of early-life exposures on the L-arginine/NO metabolism in lung later in life is not well understood. The objective of this work was to study the effects of intrauterine exposures to maternal hyperglycemia and high-fat diet (HFD) on pulmonary L-arginine/NO metabolism in mice. We used two murine models of intrauterine exposures to maternal (a) hyperglycemia and (b) HFD to study the effects of these exposures on the L-arginine/NO metabolism in lung in normal chow-fed offspring. Both intrauterine exposures resulted in NO deficiency in the lung of the offspring at 6 weeks of age. However, each of the exposures leading to different metabolic phenotypes caused a distinct alteration in the L-arginine/NO metabolism. Maternal hyperglycemia leading to impaired glucose tolerance but no obesity in the offspring resulted in increased levels of asymmetric dimethylarginine and impairment of NO synthases. Although maternal HFD led to obesity without impairment in glucose tolerance in the offspring, it resulted in increased expression and activity of arginase in the lung of the normal chow-fed offspring. These data suggest that maternal hyperglycemia and HFD can cause alterations in the pulmonary L-arginine/NO metabolism in offspring.

  6. Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone

    DEFF Research Database (Denmark)

    Petersson, Stine J; Christensen, Louise L; Kristensen, Jonas M

    2014-01-01

    therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels. METHODS: Skeletal muscle biopsies were obtained before and after treatment with either testosterone gel (n=12) or placebo (n=13......) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic-hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative......: The beneficial effect of testosterone treatment on lipid oxidation is not explained by increased abundance or phosphorylation-dependent activity of enzymes known to regulate mitochondrial biogenesis or markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable...

  7. Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids.

    Science.gov (United States)

    Trenteseaux, Charlotte; Gaston, Anh-Thu; Aguesse, Audrey; Poupeau, Guillaume; de Coppet, Pierre; Andriantsitohaina, Ramaroson; Laschet, Jamila; Amarger, Valérie; Krempf, Michel; Nobecourt-Dupuy, Estelle; Ouguerram, Khadija

    2017-11-01

    Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E-deficient mice and the underlying mechanism. Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E-deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and Fmo3 hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic Scarb1 and Cyp7a1 but higher Nr1h4 gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in Scarb1 and Ldlr gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower Cyp7a1 gene expression compared with female born to normocholesterolemic mothers. DNA methylation of Fmo3, Scarb1 , and Ldlr promoter regions was slightly modified and may explain the mRNA expression modulation. Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and

  8. Paraquat administration in Drosophila for use in metabolic studies of oxidative stress.

    Science.gov (United States)

    Rzezniczak, T Z; Douglas, L A; Watterson, J H; Merritt, T J S

    2011-12-15

    Paraquat (PQ) is widely used in the laboratory to induce in vivo oxidative stress, particularly in the fruit fly, Drosophila melanogaster. PQ administration to the fly traditionally involves feeding in a 1% sucrose solution; however, a diet high in sucrose can itself be stressful. We examined a novel method of PQ administration: incorporation into the fly's standard cornmeal-sucrose-yeast diet. This method successfully delivers PQ to the fly at concentrations similar to those of the traditional method but with fewer possibly confounding complications. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Propolis Supplementation and the Changes in the Oxidative Metabolism of Blood Platelets Exposed to Electromagnetic Radiation

    Directory of Open Access Journals (Sweden)

    Henrykowska Gabriela

    2015-03-01

    Full Text Available Introduction. Electromagnetic radiation (EMR that has an effect on living organisms may be a source of oxidative stress. A lack of proper compensation by antioxidant defences on the part of proteins leading to an uncontrolled growth of reactive forms of oxygen, which may give rise to numerous health conditions. Various scientific studies have indicated that propolis has multiple valuable medicinal properties: antibacterial, anti-inflammatory, antioxidant, protective - in relation to liver parenchyma, as well as anti-cancer. Nonetheless, the results of studies concerned with its antioxidant capabilities are not explicit and require further tests and analyses.

  10. Effect of metabolic gases and water vapor, perfluorocarbon emulsions, and nitric oxide on tissue bubbles during decompression sickness.

    Science.gov (United States)

    Randsøe, Thomas

    2016-05-01

    In aviation and diving, fast decrease in ambient pressure, such as during accidental loss of cabin pressure or when a diver decompresses too fast to sea level, may cause nitrogen (N2) bubble formation in blood and tissue resulting in decompression sickness (DCS). Conventional treatment of DCS is oxygen (O2) breathing combined with recompression.  However, bubble kinetic models suggest, that metabolic gases, i.e. O2 and carbon dioxide (CO2), and water vapor contribute significantly to DCS bubble volume and growth at hypobaric altitude exposures. Further, perfluorocarbon emulsions (PFC) and nitric oxide (NO) donors have, on an experimental basis, demonstrated therapeutic properties both as treatment and prophylactic intervention against DCS. The effect was ascribed to solubility of respiratory gases in PFC, plausible NO elicited nuclei demise and/or N2 washout through enhanced blood flow rate. Accordingly, by means of monitoring injected bubbles in exposed adipose tissue or measurements of spinal evoked potentials (SEPs) in anaesthetized rats, the aim of this study was to: 1) evaluate the contribution of metabolic gases and water vapor to bubble volume at different barometrical altitude exposures, 2) clarify the O2 contribution and N2 solubility from bubbles during administration of PFC at normo- and hypobaric conditions and, 3) test the effect of different NO donors on SEPs during DCS upon a hyperbaric air dive and, to study the influence of  NO on tissue bubbles at high altitude exposures. The results support the bubble kinetic models and indicate that metabolic gases and water vapor contribute significantly to bubble volume at 25 kPa (~10,376 m above sea level) and constitute a threshold for bubble stabilization or decay at the interval of 47-36 kPa (~6,036 and ~7,920 m above sea level). The effect of the metabolic gases and water vapor seemed to compromise the therapeutic properties of both PFC and NO at altitude, while PFC significantly increased bubble

  11. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats.

    Directory of Open Access Journals (Sweden)

    Nady Braidy

    2011-04-01

    Full Text Available The cofactor nicotinamide adenine dinucleotide (NAD+ has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose polymerase (PARP, an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD:NADH ratio in all organs by middle age (i.e.12 months compared to young (i.e. 3 month old rats. These changes in [NAD(H] occurred in parallel with an increase in lipid peroxidation and protein carbonyls (o- and m- tyrosine formation and decline in total antioxidant capacity in these organs. An age dependent increase in DNA damage (phosphorylated H2AX was also observed in these same organs. Decreased Sirt1 activity and increased acetylated p53 were observed in organ tissues in parallel with the drop in NAD+ and moderate over-expression of Sirt1 protein. Reduced mitochondrial activity of complex I-IV was also observed in aging animals, impacting both redox status and ATP production. The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor.

  12. The effects of vitamin-E on oxidative stress and metabolic imbalance induced by acute unilateral ureteral obstruction in anaesthetized rats

    Directory of Open Access Journals (Sweden)

    Shirazi M

    2008-12-01

    Full Text Available "nBackground: Obstructive nephropathy has been associated with disorders in metabolism state and oxidative balance of kidney. Stress oxidative play a key role in the pathophysiological processes of renal diseases. The objective of this study was to investigate effects of vitamin-E, as a powerful antioxidant, on renal oxidative stress and metabolism defect induced by 24-hr unilateral ureteral obstruction (UUO. "nMethods: Anesthetized male Sprague-Dawley rats (n=10 in each group were sterilely operated to occlude the left ureter. In UUO+NS, we had a single dose normal saline injection and in UUO+VitE and UUO+OO groups, D-α-tocopherol (50 mg/kg, the main component of vitamin-E, and its vehicle (Olive Oil, respectively, were twicely infused I.P. before and after UUO-induction. There were also sham-operated and control groups. 24-hr after of UUO-induction, both kidneys were removed and stored in -70°C. To determine metabolism condition, the levels of ATP and ADP; and to evaluate redox state, the levels of malondialdehyde (MDA and ferric reducing/antioxidant power (FRAP of kidneys were assessed. "nResults: The comparisons between UUO+NS and sham groups indicated that UUO increased MDA (p<0.001 and ADP (p<0.05, but decreased FRAP, and ATP/ADP ratio in obstructed kidney (all p<0.001. In UUO+VitE group, MDA and FRAP were equal to their levels in sham group, while ATP, ADP and ATP/ADP ratio were not different from those of UUO+NS group in obstructed kidney. "nConclusion: Twenty four hour of UUO caused renal reduction in oxidative metabolism and elevations in reactive oxygen species; and administration of vitamin-E, although considerably ameliorated the oxidative stress, could not improve the defected metabolism.

  13. Nitro-Oleic Acid Reduces J774A.1 Macrophage Oxidative Status and Triglyceride Mass: Involvement of Paraoxonase2 and Triglyceride Metabolizing Enzymes.

    Science.gov (United States)

    Rosenblat, Mira; Rom, Oren; Volkova, Nina; Aviram, Michael

    2016-08-01

    Nitro-fatty acids possess anti-atherogenic properties, but their effects on macrophage oxidative status and lipid metabolism that play important roles in atherosclerosis development are unclear. This study compared the effects of nitro-oleic acid (OLA-NO2) with those of native oleic acid (OLA) on intracellular reactive oxygen species (ROS) generation, anti-oxidants and metabolism of triglycerides and cholesterol in J774A.1 macrophages. Upon incubating the cells with physiological concentrations of OLA-NO2 (0-1 µM) or with equivalent levels of OLA, ROS levels measured by 2, 7-dichlorofluorescein diacetate, decreased dose-dependently, but the anti-oxidative effects of OLA-NO2 were significantly augmented. Copper ion addition increased ROS generation in OLA treated macrophages without affecting OLA-NO2 treated cells. These effects could be attributed to elevated glutathione levels and to increased activity and expression of paraoxonase2 that were observed in OLA-NO2 vs OLA treated cells. Beneficial effects on triglyceride metabolism were noted in OLA-NO2 vs OLA treated macrophages in which cellular triglycerides were reduced due to attenuated biosynthesis and accelerated hydrolysis of triglycerides. Accordingly, OLA-NO2 treated cells demonstrated down-regulation of diacylglycerol acyltransferase1, the key enzyme in triglyceride biosynthesis, and increased expression of hormone-sensitive lipase and adipose triglyceride lipase that regulate triglyceride hydrolysis. Finally, OLA-NO2 vs OLA treatment resulted in modest but significant beneficial effects on macrophage cholesterol metabolism, reducing cholesterol biosynthesis rate and low density lipoprotein influx into the cells, while increasing high density lipoprotein-mediated cholesterol efflux from the macrophages. Collectively, compared with OLA, OLA-NO2 modestly but significantly reduces macrophage oxidative status and cellular triglyceride content via modulation of cellular anti-oxidants and triglyceride

  14. Sympathetic, Metabolic Adaptations, and Oxidative Stress in Autism Spectrum Disorders: How Far From Physiology?

    Directory of Open Access Journals (Sweden)

    Antonietta Messina

    2018-03-01

    Full Text Available Autism spectrum disorders (ASD is a complex and multifaceted neurobehavioral syndrome with no specific cause still identified, despite the worldwide increasing (prevalence for 1,000 children from 6.7 to 14.6, between 2000 and 2012. Many biological and instrumental markers have been suggested as potential predictive factors for the precocious diagnosis during infancy and/or pediatric age. Many studies reported structural and functional abnormalities in the autonomic system in subjects with ASD. Sleep problems in ASD are a prominent feature, having an impact on the social interaction of the patient. Considering the role of orexins (A and B in wake-sleep circadian rhythm, we could speculate that ASD subjects may present a dysregulation in orexinergic neurotransmission. Conversely, oxidative stress is implicated in the pathophysiology of many neurological disorders. Nonetheless, little is known about the linkage between oxidative stress and the occurrence or the progress of autism and autonomic functioning; some markers, such as heart rate (HR, heart rate variability (HRV, body temperature, and galvanic skin response (GSR, may be altered in the patient with this so complex disorder. In the present paper, we analyzed an autism case report, focusing on the rule of the sympathetic activity with the aim to suggest that it may be considered an important tool in ASD evaluation. The results of this case confirm our hypothesis even if further studies needed.

  15. Mechanistic aspects of ingested chlorine dioxide on thyroid function: impact of oxidants on iodide metabolism

    International Nuclear Information System (INIS)

    Bercz, J.P.; Jones, L.L.; Harrington, R.M.; Bawa, R.; Condie, L.

    1986-01-01

    Toxicological studies dealing with recent findings of health effects of drinking water disinfectants are reviewed. Experiments with monkeys and rodents indicate that the biological activity of ingested disinfectants is expressed via their chemical interaction with the mucosal epithelia, secretory products, and nutritional contents of the alimentary tract. Evidence exists that a principal partner of this redox interaction is the iodide of nutritional origin that is ubiquitous in the gastrointestinal tract. Thus the observation that subchronic exposure to chlorine dioxide (ClO 2 ) in drinking water decreases serum thyroxine levels in mammalian species can be best explained with changes produced in the chemical form of the bioavailable iodide. Ongoing and previously reported mechanistic studies indicate that oxidizing agents such as chlorine-based disinfectants oxidize the basal iodide content of the gastrointestinal tract. The resulting reactive iodine species readily attaches to organic matter by covalent bonding. Evidence suggests that the extent to which such iodinated organics are formed is proportional to the magnitude of the electromotive force and stoichiometry of the redox couple between iodide and the disinfectant. Because the extent of thyroid uptake of the bioavailable iodide does not decrease during ClO 2 ingestion, it seems that ClO 2 does not cause iodide deficiency of sufficient magnitude to account for the decease in hormonogenesis. Absorption of one or more of iodinated molecules, e.g., nutrient, hormones, or cellular constituents of the alimentary tract having thyromimetic or thyroid inhibitory properties, is a better hypothesis for the effects seen

  16. Oxidative effects, nutrients and metabolic changes in aquatic macrophyte, Elodea nuttallii, following exposure to lanthanum.

    Science.gov (United States)

    Zhang, Jingjing; Zhang, Tingting; Lu, Qianqian; Cai, Sanjuan; Chu, Weiyue; Qiu, Han; Xu, Ting; Li, Feifei; Xu, Qinsong

    2015-05-01

    We investigated the phytoremediation potential of Elodea nuttallii to remove rare earth metals from contaminated water. The laboratory experiments were designed to assess the responses induced by lanthanum (5-20mgL(-1)) in E. nuttallii over a period of 7 days. The results showed that most La (approximately 85%) was associated with the cell wall. The addition of La to the culture medium reduced the concentration of K, Ca, Cu, Mg, and Mn. However, O2(·-) levels increased with a concomitant increase in the malondialdehyde (MDA) concentration as the La concentration increased, which indicated that the cells were under oxidative stress. Significant reductions in the levels of chlorophyll (Chl) a, b, and carotenoids (Car) were observed in a concentration-dependent manner. However, the levels of reduced glutathione (GSH), total non-protein thiols (TNP-SH) and phytochelatins (PCs) increased for all La concentrations. The results suggested that La was toxic to E. nuttallii because it induced oxidative stress and disturbed mineral uptake. However, E. nuttallii was able to combat La induced damage via an immobilization mechanism, which involved the cell wall and the activation of non-enzymatic antioxidant. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The metabolic enhancer piracetam attenuates mitochondrion-specific endonuclease G translocation and oxidative DNA fragmentation.

    Science.gov (United States)

    Gupta, Sonam; Verma, Dinesh Kumar; Biswas, Joyshree; Rama Raju, K Siva; Joshi, Neeraj; Wahajuddin; Singh, Sarika

    2014-08-01

    This study was performed to investigate the involvement of mitochondrion-specific endonuclease G in piracetam (P)-induced protective mechanisms. Studies have shown the antiapoptotic effects of piracetam but the mechanism of action of piracetam is still an enigma. To assess the involvement of endonuclease G in piracetam-induced protective effects, astrocyte glial cells were treated with lipopolysaccharide (LPS) and piracetam. LPS treatment caused significantly decreased viability, mitochondrial activity, oxidative stress, chromatin condensation, and DNA fragmentation, which were attenuated by piracetam cotreatment. Cotreatment of astrocytes with piracetam showed its significantly time-dependent absorption as observed with high-performance liquid chromatography. Astrocytes treated with piracetam alone showed enhanced mitochondrial membrane potential (MMP) in comparison to control astrocytes. However, in LPS-treated cells no significant alteration in MMP was observed in comparison to control cells. Protein and mRNA levels of the terminal executor of the caspase-mediated pathway, caspase-3, were not altered significantly in LPS or LPS + piracetam-treated astrocytes, whereas endonuclease G was significantly translocated to the nucleus in LPS-treated astrocytes. Piracetam cotreatment attenuated the LPS-induced endonuclease G translocation. In conclusion this study indicates that LPS treatment of astrocytes caused decreased viability, oxidative stress, mitochondrial dysfunction, chromatin condensation, DNA damage, and translocation of endonuclease G to the nucleus, which was inhibited by piracetam cotreatment, confirming that the mitochondrion-specific endonuclease G is one of the factors involved in piracetam-induced protective mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults

    Science.gov (United States)

    Shepherd, Sam O.; Wilson, Oliver J.; Adlan, Ahmed M.; Wagenmakers, Anton J. M.; Shaw, Christopher S.; Lord, Janet M.

    2017-01-01

    Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on immune function in sedentary adults. Twenty-seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function. PMID:28656073

  19. Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults

    Directory of Open Access Journals (Sweden)

    David B. Bartlett

    2017-01-01

    Full Text Available Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT and moderate-intensity continuous training (MICT on immune function in sedentary adults. Twenty-seven (43 ± 11 years healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate or MICT (70% maximum heart rate group training program. Aerobic capacity (VO2peak, neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function.

  20. Prion protein induced signaling cascades in monocytes

    International Nuclear Information System (INIS)

    Krebs, Bjarne; Dorner-Ciossek, Cornelia; Schmalzbauer, Ruediger; Vassallo, Neville; Herms, Jochen; Kretzschmar, Hans A.

    2006-01-01

    Prion proteins play a central role in transmission and pathogenesis of transmissible spongiform encephalopathies. The cellular prion protein (PrP C ), whose physiological function remains elusive, is anchored to the surface of a variety of cell types including neurons and cells of the lymphoreticular system. In this study, we investigated the response of a mouse monocyte/macrophage cell line to exposure with PrP C fusion proteins synthesized with a human Fc-tag. PrP C fusion proteins showed an attachment to the surface of monocyte/macrophages in nanomolar concentrations. This was accompanied by an increase of cellular tyrosine phosphorylation as a result of activated signaling pathways. Detailed investigations exhibited activation of downstream pathways through a stimulation with PrP fusion proteins, which include phosphorylation of ERK 1,2 and Akt kinase. Macrophages opsonize and present antigenic structures, contact lymphocytes, and deliver cytokines. The findings reported here may become the basis of understanding the molecular function of PrP C in monocytes and macrophages

  1. Statins attenuate polymethylmethacrylate-mediated monocyte activation.

    LENUS (Irish Health Repository)

    Laing, Alan J

    2012-02-03

    BACKGROUND: Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation. METHODS: We used an in vitro model of the human monocyte\\/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF-alpha and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed. RESULTS: We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF-alpha and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway. INTERPRETATION: We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.

  2. Effect of isolated hepatic ischemia on organic anion clearance and oxidative metabolism.

    Science.gov (United States)

    Minard, G; Bynoe, R; Wood, G C; Fabian, T C; Croce, M; Kudsk, K A

    1992-04-01

    Hepatic failure is frequently seen following severe hemorrhagic shock, sepsis, and trauma. Clearance of various drugs has been used to evaluate hepatocellular dysfunction, including indocyanine green (ICG), an organic anionic dye that is transported similarly to bilirubin, and antipyrine (AP), a marker of oxidative phosphorylation. Previous investigators have noted a decrease in ICG excretion following systemic hemorrhage. The effect of isolated hepatic ischemia on the clearances of ICG and AP was studied in 16 pigs after 90 minutes of vascular occlusion to the liver. Antipyrine clearance decreased almost 50% from baseline values at 24 and 72 hours after the ischemia procedure, indicating a significant depression in the cytochrome P-450 system. On the other hand, ICG clearance did not change significantly. In conclusion, ICG clearance is not depressed after isolated hepatic ischemia in pigs. Changes in organic anion clearance after systemic hemorrhage may be because of release of toxic products from ischemic peripheral tissue.

  3. The Role of Propolis in Oxidative Stress and Lipid Metabolism: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Verónica Mujica

    2017-01-01

    Full Text Available Although there is evidence of the benefits of propolis on human health, the vast majority of studies have been conducted using animal models. The present study includes the chemical characterization and clinical evaluation of the effects of the oral administration of propolis solution on the oxidative status and modulation of lipids in a human population in Talca, Chile. Chemical characterization of propolis, total phenol, flavonoids, and total antioxidant capacity were determined by ORAC. Identification of phenols and flavonoids in propolis was assessed by HPLC-DAD. A double-blind, placebo-controlled clinical trial was conducted. Subjects provided informed consent form and the Bioethics Committee of the Universidad de Talca approved protocol. Eligible subjects (n=67 were randomized in two groups: propolis (n=35 and placebo (n=32. All subjects were evaluated at 0 (baseline, 45, and 90 days. In the propolis group, we observed that increases in HDL-c went from 53.9 ± 11.9 to 65.8 ± 16.7 mg/dL (p<0.001 from baseline to 90 days. Compared to placebo subjects, consumption of propolis induced a net increase in GSH levels (p<0.0001 and a decrease (p<0.001 in TBARS levels for the propolis group. Our findings indicate potential benefits of propolis use in human health. The use of propolis appears to have positive effects on oxidative status and improvement of HDL-c, both of which contribute to a reduced risk of cardiovascular disease.

  4. Effects of mercury and selenium on glutathione metabolism and oxidative stress in mallard ducks

    Science.gov (United States)

    Hoffman, D.J.; Heinz, G.H.

    1998-01-01

    Earlier studies reported on the toxicity and related oxidative stress of different forms of Se, including seleno-D,L-methionine, in mallards (Anas platyrhynchos). This study compares the effects of Se (seleno-D,L-methionine) and Hg (methylmercury chloride) separately and in combination. Mallard drakes received one of the following diets: untreated feed (controls), or feed containing 10 ppm Se, 10 ppm Hg, or 10 ppm Se in combination with 10 ppm Hg. After 10 weeks, blood, liver, and brain samples were collected for biochemical assays. The following clinical and biochemical alterations occurred in response to mercury exposure: hematocrit and hemoglobin concentrations decreased; activities of the enzymes glutathione (GSH) peroxidase (plasma and liver), glutathione-S-transferase (liver), and glucose-6-phosphate dehydrogenase (G-6-PDH) (liver and brain) decreased; hepatic oxidized glutathione (GSSG) concentration increased relative to reduced glutathione (GSH); and lipid peroxidation in the brain was evident as detected by increased thiobarbituric reactive substances (TBARS). Effects of Se alone included increased hepatic GSSG reductase activity and brain TBARS concentration. Se in combination with Hg partially or totally alleviated effects of Hg on GSH peroxidase, G-6-PDH, and GSSG. These findings are compared in relation to field observations for diving ducks and other aquatic birds. It is concluded that since both Hg and excess Se can affect thiol status, measurement of associated enzymes in conjunction with thiol status may be a useful bioindicator to discriminate between Hg and Se effects. The ability of Se to restore the activities of G-6-PDH, GSH peroxidase, and glutathione status involved in antioxidative defense mechanisms may be crucial to biological protection from the toxic effects of methyl mercury.

  5. Role of ultraviolet irradiation and oxidative stress in cataract formation-medical prevention by nutritional antioxidants and metabolic agonists.

    Science.gov (United States)

    Varma, Shambhu D; Kovtun, Svitlana; Hegde, Kavita R

    2011-07-01

    Cataract is a significant cause of visual disability with relatively high incidence. It has been proposed that such high incidence is related to oxidative stress induced by continued intraocular penetration of light and consequent photochemical generation of reactive oxygen species, such as superoxide and singlet oxygen and their derivatization to other oxidants, such as hydrogen peroxide and hydroxyl radical. The latter two can also interact to generate singlet oxygen by Haber-Weiss reaction. It has been proposed that in addition to the endogenous enzymatic antioxidant enzymes, the process can be inhibited by many nutritional and metabolic oxyradical scavengers, such as ascorbate, vitamin E, pyruvate, and xanthine alkaloids, such as caffeine. Initial verification of the hypothesis has been done primarily by rat and mouse lens organ culture studies under ambient as well as ultraviolet (UV) light irradiation and determining the effect of such irradiation on its physiology in terms of its efficiency of active membrane transport activity and the levels of certain metabolites such as glutathione and adenosine triphosphate as well as in terms of apoptotic cell death. In vivo studies on the possible prevention of oxidative stress and cataract formation have been conducted by administering pyruvate and caffeine orally in drinking water and by their topical application using diabetic and galactosemic animal models. Photosensitized damage to lens caused by exposure to visible light and UVA has been found to be significantly prevented by ascorbate and pyruvate. Caffeine has been found be effective against UVA and UVB. Oral or topical application of pyruvate has been found to inhibit the formation of cataracts induced by diabetes and galactosemia. Caffeine has also been found to inhibit cataract induced by sodium selenite and high levels of galactose. Studies with diabetes are in progress. Various in vitro and in vivo studies summarized in this review strongly support the

  6. Altered Cellular Metabolism Drives Trained Immunity.

    Science.gov (United States)

    Sohrabi, Yahya; Godfrey, Rinesh; Findeisen, Hannes M

    2018-04-04

    Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions.

    Directory of Open Access Journals (Sweden)

    Ana Carolina eAriza

    2012-02-01

    Full Text Available The succinate receptor (also known as GPR91 is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin-angiotensin system, starts to unfold: The succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients.

  8. Corruption of coronary collateral growth in metabolic syndrome: Role of oxidative stress.

    Science.gov (United States)

    Pung, Yuh Fen; Chilian, William M

    2010-12-26

    The myocardium adapts to ischemic insults in a variety of ways. One adaptation is the phenomenon of acute preconditioning, which can greatly ameliorate ischemic damage. However, this effect wanes within a few hours and does not confer chronic protection. A more chronic adaptation is the so-called second window of preconditioning, which enables protection for a few days. The most potent adaptation invoked by the myocardium to minimize the effects of ischemia is the growth of blood vessels in the heart, angiogenesis and arteriogenesis (collateral growth), which prevent the development of ischemia by enabling flow to a jeopardized region of the heart. This brief review examines the mechanisms underlying angiogenesis and arteriogenesis in the heart. The concept of a redox window, which is an optimal redox state for vascular growth, is discussed along with signaling mechanisms invoked by reactive oxygen species that are stimulated during ischemia-reperfusion. Finally, the review discusses of some of the pathologies, especially the metabolic syndrome, that negatively affect collateral growth through the corruption of redox signaling processes.

  9. Study on oxidative metabolism of S180 cells induced by meretrix glycopeptide

    Science.gov (United States)

    Wu, Jielian; Wang, Ping; Kang, Huizhu

    2017-03-01

    Previous in vitro researches have showed that MGP0501, a natural glycopeptide isolated from Meretrix meretrix, can inhibit proliferation or induce apoptosis in human gastric carcinoma, lung cance (A549), Leukemia K562, mouse melanoma B16, hepatoma or breast cancer cells (MDA-MB-231). In this study, we performed an in vivo study to investigate the anti-tumor effect and mechanisms of MGP0501 on xenografted sarcoma 180 (S180) in mice. Results revealed that the inhibition rates of S180 on solid tumors were 69.72%, with a concentration of 6 mg/kg MGP0501,which was significantly higher than that of CTX. In addition, the biochemical metabolism analysis showed that MGP0501 could enhance the activities of glutathione tablets (GSH-Px) and catalase (CAT) and supersxide dismutase (SOD) in liver of mice. The content of malondialdehyde (MDA) in liver, on the contrary, was decreased. The promotion to antioxidation and the elimination of free radical in liver also attribute the antitumor activity of MGP0501. These results indicated that in vivo antitumor activity is associated with enhanced antioxidant capacity in S180 xenografts-bearing mice.

  10. Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids, carbohydrates and lipids as well as oxidative stress.

    Science.gov (United States)

    Long, Yue; Dong, Xin; Yuan, Yawei; Huang, Jinqiang; Song, Jiangang; Sun, Yumin; Lu, Zhijie; Yang, Liqun; Yu, Weifeng

    2015-07-01

    The study examined the global metabolic and some biochemical changes in rats with cholestasis induced by bile duct ligation (BDL). Serum samples were collected in male Wistar rats with BDL (n = 8) and sham surgery (n = 8) at day 3 after surgery for metabolomics analysis using a combination of reversed phase chromatography and hydrophilic interaction chromatography (HILIC) and quadrupole-time-of-flight mass spectrometry (Q-TOF MS). The serum levels of malondialdehyde (MDA), total antioxidative capacity (T-AOC), glutathione (GSH) and glutathione disulfide (GSSG), the activities of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) were measured to estimate the oxidative stress state. Key changes after BDL included increased levels of l-phenylalanine, l-glutamate, l-tyrosine, kynurenine, l-lactic acid, LysoPC(c) (14:0), glycine and succinic acid and decreased levels of l-valine, PC(b) (19:0/0:0), taurine, palmitic acid, l-isoleucine and citric acid metabolism products. And treatment with BDL significantly decreased the levels of GSH, T-AOC as well as SOD, GSH-Px activities, and upregulated MDA levels. The changes could be mapped to metabolism of amino acids and lipids, Krebs cycle and glycolysis, as well as increased oxidative stress and decreased antioxidant capability. Our study indicated that BDL induces major changes in the metabolism of all 3 major energy substances, as well as oxidative stress.

  11. Low dose/low fluence ionizing radiation-induced biological effects: The role of intercellular communication and oxidative metabolism

    Science.gov (United States)

    Azzam, Edouard

    Mechanistic investigations have been considered critical to understanding the health risks of exposure to ionizing radiation. To gain greater insight in the biological effects of exposure to low dose/low fluence space radiations with different linear energy transfer (LET) properties, we examined short and long-term biological responses to energetic protons and high charge (Z) and high energy (E) ions (HZE particles) in human cells maintained in culture and in targeted and non-targeted tissues of irradiated rodents. Particular focus of the studies has been on mod-ulation of gene expression, proliferative capacity, induction of DNA damage and perturbations in oxidative metabolism. Exposure to mean doses of 1000 MeV/nucleon iron ions, by which a small to moderate proportion of cells in an exposed population is targeted through the nucleus by an HZE particle, induced stressful effects in the irradiated and non-irradiated cells in the population. Direct intercellular communication via gap-junctions was a primary mediator of the propagation of stressful effects from irradiated to non-irradiated cells. Compromised prolif-erative capacity, elevated level of DNA damage and oxidative stress evaluated by measurements of protein carbonylation, lipid peroxidation and activity of metabolic enzymes persisted in the progeny of irradiated and non-irradiated cells. In contrast, progeny of cells exposed to high or low doses from 150-1000 MeV protons retained the ability to form colonies and harbored similar levels of micronuclei, a surrogate form of DNA damage, as control, which correlated with normal reactive oxygen species (ROS) levels. Importantly, a significant increase in the spontaneous neoplastic transformation frequency was observed in progeny of bystander mouse embryo fibroblasts (MEFs) co-cultured with MEFs irradiated with energetic iron ions but not protons. Of particular significance, stressful effects were detected in non-targeted tissues of rats that received partial

  12. EMMPRIN (CD147/basigin) mediates platelet-monocyte interactions in vivo and augments monocyte recruitment to the vascular wall.

    Science.gov (United States)

    Schulz, C; von Brühl, M-L; Barocke, V; Cullen, P; Mayer, K; Okrojek, R; Steinhart, A; Ahmad, Z; Kremmer, E; Nieswandt, B; Frampton, J; Massberg, S; Schmidt, R

    2011-05-01

    Platelets play a central role in hemostasis, in inflammatory diseases such as atherosclerosis, and during thrombus formation following vascular injury. Thereby, platelets interact intensively with monocytes and enhance their recruitment to the vascular wall. To investigate the role of the extracellular matrix metalloproteinase inducer (EMMPRIN) in platelet-monocyte interactions. Isolated human monocytes were perfused in vitro over firmly adherent platelets to allow investigation of the role of EMMPRIN in platelet-monocyte interactions under flow conditions. Monocytes readily bound to surface-adherent platelets. Both antibody blockade and gene silencing of monocyte EMMPRIN substantially attenuated firm adhesion of monocytes to platelets at arterial and venous shear rates. In vivo, platelet interactions with the murine monocyte cell line ANA-1 were significantly decreased when ANA-1 cells were pretreated with EMMPRIN-silencing small interfering RNA prior to injection into wild-type mice. Using intravital microscopy, we showed that recruitment of EMMPRIN-silenced ANA-1 to the injured carotid artery was significantly reduced as compared with control cells. Further silencing of EMMPRIN resulted in significantly fewer ANA-1-platelet aggregates in the mouse circulation as determined by flow cytometry. Finally, we identified glycoprotein (GP)VI as a critical corresponding receptor on platelets that mediates interaction with monocyte EMMPRIN. Thus, blocking of GPVI inhibited the effect of EMMPRIN on firm monocyte adhesion to platelets under arterial flow conditions in vitro, and abrogated EMMPRIN-mediated platelet-monocyte aggregate formation in vivo. EMMPRIN supports platelet-monocyte interactions and promotes monocyte recruitment to the arterial wall. Therefore, EMMPRIN might represent a novel target to reduce vascular inflammation and atherosclerotic lesion development. © 2011 International Society on Thrombosis and Haemostasis.

  13. The Modulatory Role of Vitis vinifera in Oxidative Stress and Carbohydrate Metabolism of Irradiated Rats

    International Nuclear Information System (INIS)

    El Tahawy, N.A.; Salama, S.F.; Ashry, O.M.

    2008-01-01

    Proanthocyanidins are naturally occurring antioxidants found in grape seed extract (GSPE) of Vitis vinifera. The present study aims at assessing the protective effects of GSPI against free radicals induced by ionizing radiation on the antioxidant status, the process of carbohydrate metabolism, and some hematological parameters in adult rats. Catalase (CAT) activity and reduced glutathione (GSH) concentration along with lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) were determined in liver and muscle tissues, The activity of glucose-6)-phosphatase was determined in liver tissues and glucose level in serum. Erythrocytes count (RBCs), hemoglobin content (Hb) and haematocrit value (Hct %) were also determined. Rats received daily GSPE by gavage in concentration of 100 mg/Kg body weight for 15 consecutive days before exposure to 5 Gy dose of whole body gamma irradiation. The experimental investigations were carried out on the second and third weeks post irradiation.The results indicate that ingestion of GSPE is safe and had no significant effect on the levels of the parameters studied. Exposure to radiation produced a significant decrease in CAT activity and GSH content along with significant increase of TEARS levels in liver and muscle tissues. Liver glucose-6-phosphatase activity increased 2 and 3 weeks post irradiation concomitant with a significant increase of serum glucose level. Blood RBCs, Hb and Hct levels were significantly depressed. Administration of GSPE ameliorated the severity of changes in all the parameters measured. It could be concluded that proanthocyanidins might play a considerable role in ameliorating the radiation induced changes in antioxidant status and carbohydrate metabolites

  14. Longitudinal relationship of diet and oxidative stress with depressive symptoms in patients with metabolic syndrome after following a weight loss treatment: the RESMENA project.

    Science.gov (United States)

    Perez-Cornago, Aurora; Lopez-Legarrea, Patricia; de la Iglesia, Rocio; Lahortiga, Francisca; Martinez, J Alfredo; Zulet, M Angeles

    2014-12-01

    Metabolic syndrome and depression seem to share some common underlying mechanisms, although less is known about the impact of metabolic syndrome dietary treatments on depression. This study examined the association between a hypocaloric treatment designed to reduce metabolic syndrome features in self-perceived depression and the potential involvement of dietary components and oxidative stress changes. Analyses were based on volunteers (n = 55) with metabolic syndrome (age 50 ± 1 y.o.; 38M/17F), where depressive symptoms were assessed using the Beck Depression Inventory. Participants followed two hypocaloric diets (control diet and RESMENA diet) with the same energy restriction (-30% TCV) for six months. Depressive symptoms, dietary records, anthropometrical measurements, biochemical parameters and oxidative stress levels were analysed. Both diets improved self-perceived depression similarly (p = 0.528). Participants with lower depressive symptoms at baseline reported a significantly higher intake of omega-3 polyunsaturated fatty acids (p trend = 0.002). Interestingly, after adjusting for potential confounders, the increase in folate consumption (p = 0.011) and the decrease in plasma malondialdehyde levels (p = 0.012) throughout the intervention, were associated with the improvement in depressive symptoms. A higher intake of folate and a decline in malondialdehyde plasma levels during a weight loss intervention, were related to improvements in manifestations of depression (www.clinicaltrials.gov; NCT01087086). Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis

    Directory of Open Access Journals (Sweden)

    Ling-Yu Wang

    2016-09-01

    Full Text Available The histone lysine demethylase KDM4A/JMJD2A has been implicated in prostate carcinogenesis through its role in transcriptional regulation. Here, we describe KDM4A as a E2F1 coactivator and demonstrate a functional role for the E2F1-KDM4A complex in the control of tumor metabolism. KDM4A associates with E2F1 on target gene promoters and enhances E2F1 chromatin binding and transcriptional activity, thereby modulating the transcriptional profile essential for cancer cell proliferation and survival. The pyruvate dehydrogenase kinases (PDKs PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial oxidation. Downregulation of KDM4A leads to elevated activity of pyruvate dehydrogenase and mitochondrial oxidation, resulting in excessive accumulation of reactive oxygen species. The altered metabolic phenotypes can be partially rescued by ectopic expression of PDK1 and PDK3, indicating a KDM4A-dependent tumor metabolic regulation via PDK. Our results suggest that KDM4A is a key regulator of tumor metabolism and a potential therapeutic target for prostate cancer.

  16. Effects of methylmercury exposure on glutathione metabolism, oxidative stress, and chromosomal damage in captive-reared common loon (Gavia immer) chicks

    International Nuclear Information System (INIS)

    Kenow, Kevin P.; Hoffman, David J.; Hines, Randy K.; Meyer, Michael W.; Bickham, John W.; Matson, Cole W.; Stebbins, Katie R.; Montagna, Paul; Elfessi, Abdulaziz

    2008-01-01

    We quantified the level of dietary mercury (Hg), delivered as methylmercury chloride (CH 3 HgCl), associated with negative effects on organ and plasma biochemistries related to glutathione (GSH) metabolism and oxidative stress, and chromosomal damage in captive-reared common loon (Gavia immer) chicks reared from hatch to 105 days. Mercury-associated effects related to oxidative stress and altered glutathione metabolism occurred at 1.2 μg Hg/g and 0.4 μg Hg/g, an ecologically relevant dietary mercury level, but not at 0.08 μg Hg/g. Among the variables that contributed most to dissimilarities in tissue chemistries between control and treatment groups were increased levels of oxidized glutathione (GSSG), GSH peroxidase, and the ratio of GSSG to GSH in brain tissue; increased levels of hepatic GSH; and decreased levels of hepatic glucose-6-phosphate dehydrogenase (G-6-PDH). Our results also suggest that chronic exposure to environmentally relevant dietary Hg levels did not result in statistically significant somatic chromosomal damage in common loon chicks. - Oxidative stress and altered glutathione metabolism were evident in common loon chicks exposed to ≥0.4 μg Hg as CH 3 HgCl per gram wet food intake

  17. Effects of methylmercury exposure on glutathione metabolism, oxidative stress, and chromosomal damage in captive-reared common loon (Gavia immer) chicks

    Energy Technology Data Exchange (ETDEWEB)

    Kenow, Kevin P. [U.S. Geological Survey, Upper Midwest Environmental Sciences Center, 2630 Fanta Reed Road, La Crosse, WI 54603 (United States)], E-mail: kkenow@usgs.gov; Hoffman, David J. [U.S. Geological Survey, Patuxent Wildlife Research Center, 10300 Baltimore Avenue, Beltsville, MD 20705 (United States)], E-mail: djhoffman@usgs.gov; Hines, Randy K. [U.S. Geological Survey, Upper Midwest Environmental Sciences Center, 2630 Fanta Reed Road, La Crosse, WI 54603 (United States)], E-mail: rkhines@usgs.gov; Meyer, Michael W. [Wisconsin Department of Natural Resources, 107 Sutliff Avenue, Rhinelander, WI 54501 (United States)], E-mail: michael.meyer@dnr.state.wi.us; Bickham, John W. [Center for the Environment and Department of Forestry and Natural Resources, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: bickham@purdue.edu; Matson, Cole W. [Integrated Toxicology and Environmental Health Program, Duke University, Durham, NC 27708 (United States)], E-mail: matson@duke.edu; Stebbins, Katie R. [U.S. Geological Survey, Patuxent Wildlife Research Center, 10300 Baltimore Avenue, Beltsville, MD 20705 (United States); Montagna, Paul [Texas A and M University-Corpus Christi, Harte Research Institute, Corpus Christi, TX (United States)], E-mail: paul.montagna@tamucc.edu; Elfessi, Abdulaziz [University of Wisconsin-La Crosse, La Crosse, WI 54601 (United States)], E-mail: elfessi.abdu@uwlax.edu

    2008-12-15

    We quantified the level of dietary mercury (Hg), delivered as methylmercury chloride (CH{sub 3}HgCl), associated with negative effects on organ and plasma biochemistries related to glutathione (GSH) metabolism and oxidative stress, and chromosomal damage in captive-reared common loon (Gavia immer) chicks reared from hatch to 105 days. Mercury-associated effects related to oxidative stress and altered glutathione metabolism occurred at 1.2 {mu}g Hg/g and 0.4 {mu}g Hg/g, an ecologically relevant dietary mercury level, but not at 0.08 {mu}g Hg/g. Among the variables that contributed most to dissimilarities in tissue chemistries between control and treatment groups were increased levels of oxidized glutathione (GSSG), GSH peroxidase, and the ratio of GSSG to GSH in brain tissue; increased levels of hepatic GSH; and decreased levels of hepatic glucose-6-phosphate dehydrogenase (G-6-PDH). Our results also suggest that chronic exposure to environmentally relevant dietary Hg levels did not result in statistically significant somatic chromosomal damage in common loon chicks. - Oxidative stress and altered glutathione metabolism were evident in common loon chicks exposed to {>=}0.4 {mu}g Hg as CH{sub 3}HgCl per gram wet food intake.

  18. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Lykke, Kasper; Bryk, Jaroslaw; Stridh, Malin H; Zaganas, Ioannis; Skytt, Dorte M; Schousboe, Arne; Bak, Lasse K; Enard, Wolfgang; Pääbo, Svante; Waagepetersen, Helle S

    2017-03-01

    A key enzyme in brain glutamate homeostasis is glutamate dehydrogenase (GDH) which links carbohydrate and amino acid metabolism mediating glutamate degradation to CO 2 and expanding tricarboxylic acid (TCA) cycle capacity with intermediates, i.e. anaplerosis. Humans express two GDH isoforms, GDH1 and 2, whereas most other mammals express only GDH1. hGDH1 is widely expressed in human brain while hGDH2 is confined to astrocytes. The two isoforms display different enzymatic properties and the nature of these supports that hGDH2 expression in astrocytes potentially increases glutamate oxidation and supports the TCA cycle during energy-demanding processes such as high intensity glutamatergic signaling. However, little is known about how expression of hGDH2 affects the handling of glutamate and TCA cycle metabolism in astrocytes. Therefore, we cultured astrocytes from cerebral cortical tissue of hGDH2-expressing transgenic mice. We measured glutamate uptake and metabolism using [ 3 H]glutamate, while the effect on metabolic pathways of glutamate and glucose was evaluated by use of 13 C and 14 C substrates and analysis by mass spectrometry and determination of radioactively labeled metabolites including CO 2 , respectively. We conclude that hGDH2 expression increases capacity for uptake and oxidative metabolism of glutamate, particularly during increased workload and aglycemia. Additionally, hGDH2 expression increased utilization of branched-chain amino acids (BCAA) during aglycemia and caused a general decrease in oxidative glucose metabolism. We speculate, that expression of hGDH2 allows astrocytes to spare glucose and utilize BCAAs during substrate shortages. These findings support the proposed role of hGDH2 in astrocytes as an important fail-safe during situations of intense glutamatergic activity. GLIA 2017;65:474-488. © 2016 Wiley Periodicals, Inc.

  19. Prostaglandin E2 and thromboxane B2 release from human monocytes treated with bacterial lipopolysaccharide

    International Nuclear Information System (INIS)

    Nichols, F.C.; Garrison, S.W.; Davis, H.W.

    1988-01-01

    We investigated the capacity of counterflow-isolated human monocytes to independently synthesize thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) when stimulated with bacterial lipopolysaccharide (LPS). Independent metabolism was confirmed by establishing different specific activities (dpm/ng) of TxB2 and PGE2 released from LPS-treated cells. For metabolites released during the initial 2-hr treatment period, the specific activity of PGE2 was approximately threefold higher than that of TxB2 regardless of labeling with [3H]arachidonic acid (AA) or [14C]AA. Cells that were pulse-labeled for 2 hr with [3H]AA demonstrated a decreasing PGE2 specific activity over 24 hr, whereas the TxB2 specific activity remained unchanged. In contrast, cells continuously exposed to [14C]AA demonstrated an increasing TxB2 specific activity that approached the level of PGE2 by 24 hr. These results suggest the presence of at least 2 cyclooxygenase metabolic compartments in counterflow-isolated monocytes. Although freshly isolated monocytes have been reported to contain variable numbers of adherent platelets, additional experiments demonstrated that counterflow-isolated platelets are not capable of releasing elevated levels of TxB2 or PGE2 when treated with LPS. It is proposed from these findings that at least two subsets of monocytes exist in peripheral blood that can be distinguished on the basis of independent conversion of AA to TxB2 and PGE2

  20. Females Are Protected From Iron-Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress.

    Science.gov (United States)

    Das, Subhash K; Patel, Vaibhav B; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y

    2017-01-23

    Sex-related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron-overload cardiomyopathy is poorly understood. Male and female wild-type and hemojuvelin-null mice were injected and fed with a high-iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron-overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron-overloaded mice based on echocardiographic and invasive pressure-volume analyses. Female mice demonstrated a marked suppression of iron-mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron-overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron-induced upregulation of ferritin, decreased myocardial SERCA2a levels, and increased NCX1 levels. 17β-Estradiol therapy rescued the iron-overload cardiomyopathy in male wild-type mice. The responses in wild-type and hemojuvelin-null female mice were remarkably similar, highlighting a conserved mechanism of sex-dependent protection from iron-overload-mediated cardiac injury. Male and female mice respond differently to iron-overload-mediated effects on heart structure and function, and females are markedly protected from iron-overload cardiomyopathy. Ovariectomy in female mice exacerbated iron-induced myocardial injury and precipitated severe cardiac dysfunction during iron-overload conditions, whereas 17β-estradiol therapy was protective in male iron-overloaded mice.

  1. Water addition regulates the metabolic activity of ammonia oxidizers responding to environmental perturbations in dry subhumid ecosystems.

    Science.gov (United States)

    Hu, Hang-Wei; Macdonald, Catriona A; Trivedi, Pankaj; Holmes, Bronwyn; Bodrossy, Levente; He, Ji-Zheng; Singh, Brajesh K

    2015-02-01

    Terrestrial arid and semi-arid ecosystems (drylands) constitute about 41% of the Earth's land surface and are predicted to experience increasing fluctuations in water and nitrogen availability. Mounting evidence has confirmed the significant importance of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in nitrification, plant nitrogen availability and atmospheric N2 O emissions, but their responses to environmental perturbations in drylands remain largely unknown. Here we evaluate how the factorial combinations of irrigation and fertilization in forests and land-use change from grassland to forest affects the dynamics of AOA and AOB following a 6-year dryland field study. Potential nitrification rates and AOA and AOB abundances were significantly higher in the irrigated plots, accompanied by considerable changes in community compositions, but their responses to fertilization alone were not significant. DNA-stable isotope probing results showed increased (13) CO2 incorporation into the amoA gene of AOA, but not of AOB, in plots receiving water addition, coupled with significantly higher net mineralization and nitrification rates. High-throughput microarray analysis revealed that active AOA assemblages belonging to Nitrosopumilus and Nitrosotalea were increasingly labelled by (13) CO2 following irrigation. However, no obvious effects of land-use changes on nitrification rates or metabolic activity of AOA and AOB could be observed under dry conditions. We provide evidence that water addition had more important roles than nitrogen fertilization in influencing the autotrophic nitrification in dryland ecosystems, and AOA are increasingly involved in ammonia oxidation when dry soils become wetted. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  2. Effect of α-lipoic acid combined with nerve growth factor on bone metabolism, oxidative stress and nerve conduction function after femoral fracture surgery

    Directory of Open Access Journals (Sweden)

    An-Jun Cao

    2017-11-01

    Full Text Available Objective: To discuss the effect of 毩 -lipoic acid combined with nerve growth factor on bone metabolism, oxidative stress and nerve conduction function after femoral fracture surgery. Methods: A total of 110 patients with femoral fracture who received surgical treatment in the hospital between January 2015 and January 2017 were collected and divided into the control group (n=55 and study group (n=55 by random number table. Control group received postoperative nerve growth factor therapy, and study group received postoperative 毩 -lipoic acid combined with nerve growth factor therapy. The differences in the contents of bone metabolism and oxidative stress indexes as well as the levels of nerve conduction function indexes were compared between the two groups before and after treatment. Results: Before treatment, the differences in the contents of bone metabolism and oxidative stress indexes as well as the levels of nerve conduction function indexes were not statistically significant between the two groups. After treatment, serum bone metabolism indexes BGP and PⅠNP contents of study group were higher than those of control group while CTX-Ⅰ and TRAP contents were lower than those of control group; serum oxidative stress indexes TAC, CAT and SOD contents of study group were higher than those of control group while MDA content was lower than that of control group; limb nerve conduction velocity SCV and MCV levels of study group were higher than those of control group. Conclusion: 毩 -lipoic acid combined with nerve growth factor therapy after femoral fracture surgery can effectively balance osteoblast/ osteoclast activity, reduce oxidative stress and improve limb nerve conduction velocity.

  3. Possible effect of pentoxifylline on oxidative stress and certain metabolic disorders in gamma irradiated rats

    International Nuclear Information System (INIS)

    Ashry, O.M.; Salama, S.F.; El Tahawy, N.A.

    2007-01-01

    Pentoxifylline (PTX) is a methylxanthine derivative and phospho-di esterase inhibitor used to treat cerebral, diabetic or functional disorders of vascular system. It lowers blood viscosity and improves erythrocyte flexibility and it has anti-oxidant properties and anti-inflammatory activity. In this study, PTX effects on antioxidant status of cerebral cortex and certain organ functions in rats subjected to 2 fractionated irradiation doses 4 and 8 Gy were investigated. Animals were divided into 4 groups: Group 1: which served as a control. Group 2: in which PTX was administered (1200 mg/ L daily for 6 rats) in drinking water for 8 and 16 days. Group 3: which was irradiated with fractionated irradiation at dose levels of 4 and 8 Gy (2 Gy every 4 days) for 8 and 16 days. Group 4: in which PTX was administered together with fractionated irradiation 4 and 8 Gy for 8 and 16 days. The cerebral cortex levels of reduced glutathione (GSH) and malonaldehyde (MDA) levels as well as superoxide dismutase (SOD) and catalase (CAT) activities, were determined. Serum ALT and AST activities and contents of glucose, uric acid and liver glycogen were also measured. Fractionated irradiation of 4 and 8 Gy significantly elevated GSH and MDA contents and SOD activity in cerebral cortex, while CAT activity was depressed. Exposure to fractionated dose level of 8 Gy caused significant elevation of serum ALT and AST activities, as well as liver glycogen contents and depressed uric acid level. PTX depressed MDA level and elevated the activity of antioxidant enzymes in cerebral cortex. ALT, AST activities and levels of uric acid and liver glycogen were lowered by PTX administration. Serum glucose was significantly decreased by all treatments applied. PTX might hold promise, as a useful therapeutic intervention, reducing late radiation injury via antioxidant pathway

  4. Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice.

    Science.gov (United States)

    Kim, Juyoung; Kim, Juhae; Kwon, Young Hye

    2016-08-01

    Changes in nutritional status during gestation and lactation have detrimental effects on offspring metabolism. Several animal studies have shown that maternal high-fat diet (HFD) can predispose the offspring to development of obesity and metabolic diseases, however the mechanisms underlying these transgenerational effects are poorly understood. Therefore, we examined the effect of maternal HFD consumption on metabolic phenotype and hepatic expression of involved genes in dams to determine whether any of these parameters were associated with the metabolic outcomes in the offspring. Female C57BL/6 mice were fed a low-fat diet (LFD: 10% calories from fat) or a high-fat diet (HFD: 45% calories from fat) for three weeks before mating, and during pregnancy and lactation. Dams and their male offspring were studied at weaning. Dams fed an HFD had significantly higher body and adipose tissue weights and higher serum triglyceride and cholesterol levels than dams fed an LFD. Hepatic lipid levels and mRNA levels of genes involved in lipid metabolism, including LXRα, SREBP-2, FXR, LDLR, and ABCG8 were significantly changed by maternal HFD intake. Significantly lower total liver DNA and protein contents were observed in dams fed an HFD, implicating the disturbed liver adaptation in the pregnancy-related metabolic demand. HFD feeding also induced significant oxidative stress in serum and liver of dams. Offspring of dams fed an HFD had significantly higher serum cholesterol levels, which were negatively correlated with liver weights of dams and positively correlated with hepatic lipid peroxide levels in dams. Maternal HFD consumption induced metabolic dysfunction, including altered liver growth and oxidative stress in dams, which may contribute to the disturbed cholesterol homeostasis in the early life of male mice offspring.

  5. Immunological and biochemical parameters of patients with metabolic syndrome and the participation of oxidative and nitroactive stress

    Directory of Open Access Journals (Sweden)

    A.N.C. Simão

    2011-07-01

    Full Text Available Metabolic syndrome (MS is a multifactorial disease involving inflammatory activity and endothelial dysfunction. The aim of the present study was to evaluate the relationship between the changes in lipoperoxidation, in immunological and biochemical parameters and nitric oxide metabolite (NOx levels in MS patients. Fifty patients with MS (4 males/46 females and 50 controls (3 males/47 females were studied. Compared to control (Mann-Whitney test, MS patients presented higher serum levels (P < 0.05 of fibrinogen: 314 (185-489 vs 262 (188-314 mg/dL, C-reactive protein (CRP: 7.80 (1.10-46.50 vs 0.70 (0.16-5.20 mg/dL, interleukin-6: 3.96 (3.04-28.18 vs 3.33 (2.55-9.63 pg/mL, uric acid: 5.45 (3.15-9.65 vs 3.81 (2.70-5.90 mg/dL, and hydroperoxides: 20,689 (19,076-67,182 vs 18,636 (15,926-19,731 cpm. In contrast, they presented lower (P < 0.05 adiponectin: 7.11 (3.19-18.22 vs 12.31 (9.11-27.27 µg/mL, and NOx levels: 5.69 (2.36-8.18 vs 6.72 (5.14-12.43 µM. NOx was inversely associated (Spearman’s rank correlation with body mass index (r = -0.2858, P = 0.0191, insulin resistance determined by the homeostasis model assessment (r = -0.2530, P = 0.0315, CRP (r = -0.2843, P = 0.0171 and fibrinogen (r = -0.2464, P = 0.0413, and positively correlated with hydroperoxides (r = 0.2506, P = 0.0408. In conclusion, NOx levels are associated with obesity, insulin resistance, oxidative stress, and inflammatory markers. The high uric acid levels together with reactive oxygen species generation may be responsible for the reduced NO levels, which in turn lead to endothelial dysfunction. The elevated plasma chemiluminescence reflecting both increased plasma oxidation and reduced antioxidant capacity may play a role in the MS mechanism.

  6. Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and apoptosis in liver cancer cells and suppresses hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Meng-Xi; Jin, Lei; Sun, Si-Jia; Liu, Peng; Feng, Xu; Cheng, Zhou-Li; Liu, Wei-Ren; Guan, Kun-Liang; Shi, Ying-Hong; Yuan, Hai-Xin; Xiong, Yue

    2018-03-01

    Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively. Increased expressions of both PCK genes are found in cancer of several organs, including colon, lung, and skin, and linked to increased anabolic metabolism and cell proliferation. Here, we report that the expressions of both PCK1 and PCK2 genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC. Forced expression of either PCK1 or PCK2 in liver cancer cell lines results in severe apoptosis under the condition of glucose deprivation and suppressed liver tumorigenesis in mice. Mechanistically, we show that the pro-apoptotic effect of PCK1 requires its catalytic activity. We demonstrate that forced PCK1 expression in glucose-starved liver cancer cells induced TCA cataplerosis, leading to energy crisis and oxidative stress. Replenishing TCA intermediate α-ketoglutarate or inhibition of reactive oxygen species production blocked the cell death caused by PCK expression. Taken together, our data reveal that PCK1 is detrimental to malignant hepatocytes and suggest activating PCK1 expression as a potential treatment strategy for patients with HCC.

  7. Benign Effect of Extremely Low-Frequency Electromagnetic Field on Brain Plasticity Assessed by Nitric Oxide Metabolism during Poststroke Rehabilitation

    Directory of Open Access Journals (Sweden)

    Natalia Cichoń

    2017-01-01

    Full Text Available Nitric oxide (NO is one of the most important signal molecules, involved in both physiological and pathological processes. As a neurotransmitter in the central nervous system, NO regulates cerebral blood flow, neurogenesis, and synaptic plasticity. The aim of our study was to investigate the effect of the extremely low-frequency electromagnetic field (ELF-EMF on generation and metabolism of NO, as a neurotransmitter, in the rehabilitation of poststroke patients. Forty-eight patients were divided into two groups: ELF-EMF and non-ELF-EMF. Both groups underwent the same 4-week rehabilitation program. Additionally, the ELF-EMF group was exposed to an extremely low-frequency electromagnetic field of 40 Hz, 7 mT, for 15 min/day. Levels of 3-nitrotyrosine, nitrate/nitrite, and TNFα in plasma samples were measured, and NOS2 expression was determined in whole blood samples. Functional status was evaluated before and after a series of treatments, using the Activity Daily Living, Geriatric Depression Scale, and Mini-Mental State Examination. We observed that application of ELF-EMF significantly increased 3-nitrotyrosine and nitrate/nitrite levels, while expression of NOS2 was insignificantly decreased in both groups. The results also show that ELF-EMF treatments improved functional and mental status. We conclude that ELF-EMF therapy is capable of promoting recovery in poststroke patients.

  8. Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water.

    Science.gov (United States)

    Chen, Baowei; Arnold, Lora L; Cohen, Samuel M; Thomas, David J; Le, X Chris

    2011-12-01

    Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic (iAs) producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated arsenicals may contribute to toxicity associated with exposure to inorganic arsenic. Here, adult female wild-type (WT) C57BL/6 mice and female As3mt knockout (KO) mice received drinking water that contained 1, 10, or 25 ppm (mg/l) of arsenite for 33 days and blood, liver, kidney, and lung were taken for arsenic speciation. Genotype markedly affected concentrations of arsenicals in tissues. Summed concentrations of arsenicals in plasma were higher in WT than in KO mice; in red blood cells, summed concentrations of arsenicals were higher in KO than in WT mice. In liver, kidney, and lung, summed concentrations of arsenicals were greater in KO than in WT mice. Although capacity for arsenic methylation is much reduced in KO mice, some mono-, di-, and tri-methylated arsenicals were found in tissues of KO mice, likely reflecting the activity of other tissue methyltransferases or preabsorptive metabolism by the microbiota of the gastrointestinal tract. These results show that the genotype for arsenic methylation determines the phenotypes of arsenic retention and distribution and affects the dose- and organ-dependent toxicity associated with exposure to inorganic arsenic.

  9. Beneficial Effects of the RESMENA Dietary Pattern on Oxidative Stress in Patients Suffering from Metabolic Syndrome with Hyperglycemia Are Associated to Dietary TAC and Fruit Consumption

    Directory of Open Access Journals (Sweden)

    J. Alfredo Martinez

    2013-03-01

    Full Text Available Hyperglycemia and oxidative stress are conditions directly related to the metabolic syndrome (MetS, whose prevalence is increasing worldwide. This study aimed to evaluate the effectiveness of a new weight-loss dietary pattern on improving the oxidative stress status on patients suffering MetS with hyperglycemia. Seventy-nine volunteers were randomly assigned to two low-calorie diets (−30% Energy: the control diet based on the American Health Association criteria and the RESMENA diet based on a different macronutrient distribution (30% proteins, 30% lipids, 40% carbohydrates, which was characterized by an increase of the meal frequency (seven-times/day, low glycemic load, high antioxidant capacity (TAC and high n-3 fatty acids content. Dietary records, anthropometrical measurements, biochemical parameters and oxidative stress biomarkers were analyzed before and after the six-month-long study. The RESMENA (Metabolic Syndrome Reduction in Navarra diet specifically reduced the android fat mass and demonstrated more effectiveness on improving general oxidative stress through a greater decrease of oxidized LDL (oxLDL values and protection against arylesterase depletion. Interestingly, oxLDL values were associated with dietary TAC and fruit consumption and with changes on body mass index (BMI, waist circumference, fat mass and triacilglyceride (TG levels. In conclusion, the antioxidant properties of the RESMENA diet provide further benefits to those attributable to weight loss on patients suffering Mets with hyperglycemia.

  10. Beneficial effects of the RESMENA dietary pattern on oxidative stress in patients suffering from metabolic syndrome with hyperglycemia are associated to dietary TAC and fruit consumption.

    Science.gov (United States)

    de la Iglesia, Rocio; Lopez-Legarrea, Patricia; Celada, Paloma; Sánchez-Muniz, Francisco J; Martinez, J Alfredo; Zulet, M Angeles

    2013-03-27

    Hyperglycemia and oxidative stress are conditions directly related to the metabolic syndrome (MetS), whose prevalence is increasing worldwide. This study aimed to evaluate the effectiveness of a new weight-loss dietary pattern on improving the oxidative stress status on patients suffering MetS with hyperglycemia. Seventy-nine volunteers were randomly assigned to two low-calorie diets (-30% Energy): the control diet based on the American Health Association criteria and the RESMENA diet based on a different macronutrient distribution (30% proteins, 30% lipids, 40% carbohydrates), which was characterized by an increase of the meal frequency (seven-times/day), low glycemic load, high antioxidant capacity (TAC) and high n-3 fatty acids content. Dietary records, anthropometrical measurements, biochemical parameters and oxidative stress biomarkers were analyzed before and after the six-month-long study. The RESMENA (Metabolic Syndrome Reduction in Navarra) diet specifically reduced the android fat mass and demonstrated more effectiveness on improving general oxidative stress through a greater decrease of oxidized LDL (oxLDL) values and protection against arylesterase depletion. Interestingly, oxLDL values were associated with dietary TAC and fruit consumption and with changes on body mass index (BMI), waist circumference, fat mass and triacilglyceride (TG) levels. In conclusion, the antioxidant properties of the RESMENA diet provide further benefits to those attributable to weight loss on patients suffering Mets with hyperglycemia.

  11. Abnormal monocyte recruitment and collateral artery formation in monocyte chemoattractant protein-1 deficient mice

    NARCIS (Netherlands)

    Voskuil, Michiel; Hoefer, Imo E.; van Royen, Niels; Hua, Jing; de Graaf, Stijn; Bode, Christoph; Buschmann, Ivo R.; Piek, Jan J.

    2004-01-01

    Monocyte chemoattractant protein 1 (MCP-1) has been shown to be effective for the stimulation of collateral artery formation in small and large animal models. The availability of a genetic knockout mouse enables evaluation of the importance of the role of MCP-1 in the natural course of collateral

  12. Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

    2007-01-01

    Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). In patients with type 2 diabetes, insulin resistance in skeletal muscle is associated with abnormalities in insulin signaling, fatty acid metabolism......, and mitochondrial oxidative phosphorylation (OXPHOS). In PCOS patients, the molecular mechanisms of insulin resistance are, however, less well characterized. To identify biological pathways of importance for the pathogenesis of insulin resistance in PCOS, we compared gene expression in skeletal muscle...... of metabolically characterized PCOS patients (n = 16) and healthy control subjects (n = 13) using two different approaches for global pathway analysis: gene set enrichment analysis (GSEA 1.0) and gene map annotator and pathway profiler (GenMAPP 2.0). We demonstrate that impaired insulin-stimulated total, oxidative...

  13. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows

    Science.gov (United States)

    Derno, Michael; Otten, Winfried; Mielenz, Manfred; Nürnberg, Gerd

    2015-01-01

    High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS) and one pair-fed (PF) at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1), cows were challenged for 6 days (P2) by heat stress (temperature humidity index (THI) = 76) or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows. PMID:25938406

  14. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows.

    Science.gov (United States)

    Lamp, Ole; Derno, Michael; Otten, Winfried; Mielenz, Manfred; Nürnberg, Gerd; Kuhla, Björn

    2015-01-01

    High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS) and one pair-fed (PF) at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1), cows were challenged for 6 days (P2) by heat stress (temperature humidity index (THI) = 76) or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows.

  15. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows.

    Directory of Open Access Journals (Sweden)

    Ole Lamp

    Full Text Available High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS and one pair-fed (PF at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1, cows were challenged for 6 days (P2 by heat stress (temperature humidity index (THI = 76 or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows.

  16. The Role of ?786T/C Polymorphism in the Endothelial Nitric Oxide Synthase Gene in Males with Clinical and Biochemical Features of the Metabolic Syndrome

    OpenAIRE

    Misiak, Blazej; Krolik, Marta; Kukowka, Anna; Lewera, Anna; Leszczynski, Przemyslaw; Stankiewicz-Olczyk, Joanna; Slezak, Ryszard

    2011-01-01

    Background. Extensive evidence, arising from models of endothelial nitric oxide synthase gene (NOS3)-knockout mice supports the role of endothelial malfunction in the pathogenesis of the metabolic syndrome (MS). Aims. The aim of this study was to evaluate the role of −786T/C polymorphism in the etiology of MS and assess previously reported interaction with cigarette smoking. Methods. Based on International Diabetes Federation 2005 criteria, we recruited randomly 152 subjects with MS and 75 su...

  17. Enzymatic oxidation of 2-phenylethylamine to phenylacetic acid and 2-phenylethanol with special reference to the metabolism of its intermediate phenylacetaldehyde.

    Science.gov (United States)

    Panoutsopoulos, Georgios I; Kouretas, Demetrios; Gounaris, Elias G; Beedham, Christine

    2004-12-01

    2-phenylethylamine is an endogenous constituent of the human brain and is implicated in cerebral transmission. This bioactive amine is also present in certain foodstuffs such as chocolate, cheese and wine and may cause undesirable side effects in susceptible individuals. Metabolism of 2-phenylethylamine to phenylacetaldehyde is catalysed by monoamine oxidase B but the oxidation to its acid is usually ascribed to aldehyde dehydrogenase and the contribution of aldehyde oxidase and xanthine oxidase, if any, is ignored. The objective of this study was to elucidate the role of the molybdenum hydroxylases, aldehyde oxidase and xanthine oxidase, in the metabolism of phenylacetaldehyde derived from its parent biogenic amine. Treatments of 2-phenylethylamine with monoamine oxidase were carried out for the production of phenylacetaldehyde, as well as treatments of synthetic or enzymatic-generated phenylacetaldehyde with aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase. The results indicated that phenylacetaldehyde is metabolised mainly to phenylacetic acid with lower concentrations of 2-phenylethanol by all three oxidising enzymes. Aldehyde dehydrogenase was the predominant enzyme involved in phenylacetaldehyde oxidation and thus it has a major role in 2-phenylethylamine metabolism with aldehyde oxidase playing a less prominent role. Xanthine oxidase does not contribute to the oxidation of phenylacetaldehyde due to low amounts being present in guinea pig. Thus aldehyde dehydrogenase is not the only enzyme oxidising xenobiotic and endobiotic aldehydes and the role of aldehyde oxidase in such reactions should not be ignored.

  18. Effect of continuous subcutaneous insulin pump infusion on glucolipid metabolism as well as inflammation and oxidative stress in placenta of patients with GDM

    Directory of Open Access Journals (Sweden)

    Liu Jie

    2017-05-01

    Full Text Available Objective: To study the effect of continuous subcutaneous insulin pump infusion on glucolipid metabolism as well as inflammation and oxidative stress in placenta of patients with gestational diabetes mellitus (GDM. Methods: Patients with GDM who received insulin therapy between March 2013 and May 2016 were selected as the research subjects and randomly divided into multiple subcutaneous insulin injection (MSII group and continuous subcutaneous insulin pump infusion (CSII group. Before and after treatment, serum glucolipid metabolism as well as inflammation and oxidative stress inexes in placenta were determined respectively. Results: 2 weeks and 4 weeks after treatment, FBG, 1hPBG, 2hPBG, Chemerin, Vaspin and Visfatin levels of both groups of patients were significantly lower than those before treatment and FBG, 1hPBG, 2hPBG, Chemerin, Vaspin and Visfatin levels of CSII group were significantly lower than those of MSII group; after delivery, TNF-α, IL-6, ROS and AGEs levels in placenta of CSII group were significantly lower than those of MSII group. Conclusion: Continuous subcutaneous insulin infusion can more effectively improve the glucolipid metabolism and inhibit the inflammation and oxidative stress in placenta of patients with GDM than multiple subcutaneous insulin injection.

  19. Dioscoreophyllum cumminsii (Stapf) Diels leaves halt high-fructose induced metabolic syndrome: Hyperglycemia, insulin resistance, inflammation and oxidative stress.

    Science.gov (United States)

    Ajiboye, T O; Aliyu, H; Tanimu, M A; Muhammad, R M; Ibitoye, O B

    2016-11-04

    extract. Data generated in this study further laid credence to the hypoglycemic activity of aqueous leaf extract of D. cumminsii as evident from the reversal of hyperglycemia, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPARγ activation in high fructose diet-induced metabolic syndrome.

    Science.gov (United States)

    Cannizzaro, Luca; Rossoni, Giuseppe; Savi, Federica; Altomare, Alessandra; Marinello, Cristina; Saethang, Thammakorn; Carini, Marina; Payne, D Michael; Pisitkun, Trairak; Aldini, Giancarlo; Leelahavanichkul, Asada

    2017-01-01

    The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ). Rats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half. Rats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented. Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by

  1. A simple method for human peripheral blood monocyte Isolation

    Directory of Open Access Journals (Sweden)

    Marcos C de Almeida

    2000-04-01

    Full Text Available We describe a simple method using percoll gradient for isolation of highly enriched human monocytes. High numbers of fully functional cells are obtained from whole blood or buffy coat cells. The use of simple laboratory equipment and a relatively cheap reagent makes the described method a convenient approach to obtaining human monocytes.

  2. Monocyte function is severely impaired by the fluorochrome calcein acetomethylester

    International Nuclear Information System (INIS)

    Czepluch, Frauke S.; Olieslagers, Serve J.F.; Waltenberger, Johannes

    2007-01-01

    For rapid chemotaxis quantification, cell prelabelling is often performed with the fluorochrome calcein acetomethylester (calcein AM). We investigated whether calcein AM-prelabelling is reliable for monocyte migration analysis. Human monocytes were either preexposed to calcein AM or unlabelled. Monocyte migration towards the potent chemoattractants transforming growth factor-β1 (TGF-β1) and N-formyl-Methionin-Leucin-Phenylalanin (fMLP) was assessed using a 48-well micro-chemotaxis chamber. For quantification, cells were visualized by light microscopy and counted. Surprisingly, random migration of calcein AM-prelabelled cells was significantly impaired compared to the unlabelled control. Accordingly, monocyte chemotaxis towards either TGF-β1 or fMLP dramatically declined. Adherence of calcein AM-labelled monocytes on plastic was also significantly decreased compared to control cells. As adhesion is regarded as an essential component of monocyte migration, the reduced migration observed in calcein AM-labelled monocytes might be explained by a fluorochrome-induced adhesion defect. Therefore, use of the fluorochrome calcein AM cannot be recommended for functional testing of monocytes

  3. Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Jamille Souza Fernandes

    2014-01-01

    Full Text Available A major issue with Schistosoma mansoni infection is the development of periportal fibrosis, which is predominantly caused by the host immune response to egg antigens. Experimental studies have pointed to the participation of monocytes in the pathogenesis of liver fibrosis. The aim of this study was to characterize the subsets of monocytes in individuals with different degrees of periportal fibrosis secondary to schistosomiasis. Monocytes were classified into classical (CD14++CD16−, intermediate (CD14++CD16+, and nonclassical (CD14+CD16++. The expressions of monocyte markers and cytokines were assessed using flow cytometry. The frequency of classical monocytes was higher than the other subsets. The expression of HLA-DR, IL-6, TNF-α, and TGF-β was higher in monocytes from individuals with moderate to severe fibrosis as compared to other groups. Although no differences were observed in receptors expression (IL-4R and IL-10R between groups of patients, the expression of IL-12 was lower in monocytes from individuals with moderate to severe fibrosis, suggesting a protective role of this cytokine in the development of fibrosis. Our data support the hypothesis that the three different monocyte populations participate in the immunopathogenesis of periportal fibrosis, since they express high levels of proinflammatory and profibrotic cytokines and low levels of regulatory markers.

  4. D-Serine exposure resulted in gene expression changes indicative of activation of fibrogenic pathways and down-regulation of energy metabolism and oxidative stress response

    International Nuclear Information System (INIS)

    Soto, Armando; DelRaso, Nicholas J.; Schlager, John J.; Chan, Victor T.

    2008-01-01

    , metabolism and transport, inflammatory response, proteasome-mediated degradation of oxidatively damaged cytosolic proteins, Ras protein signal transduction, TGF-beta signaling pathway and mRNA transcription, processing, splicing and transport. On the other hand, major metabolic pathways, which include carbohydrate metabolism, TCA cycle, oxidative phosphorylation, ATP synthesis coupled electron transport, amino acid metabolism and transport, lipid metabolism, nucleotide metabolism, and vitamin metabolism, and oxidative stress response including induction of antioxidant genes and glutathione metabolism are down-regulated. As tubular epithelia have strong energy demand for normal functions, down-regulation of energy metabolism after D-serine treatment may be related to the mechanism of its nephrotoxicity. In addition, hydrogen peroxide, a reactive oxygen species, is produced as a byproduct of the metabolism of D-serine by D-amino acid oxidase in the peroxisomes of the tubular epithelia. Down-regulation of pathways for antioxidant genes induction and glutathione metabolism will likely exacerbate the cytotoxicity of this reactive oxygen species. The observation that the genes involved in apoptosis, DNA repair, proteasome pathway for the degradation of oxidatively damaged cytosolic proteins were up-regulated lends some supports to this premise. Up-regulation of pathways of cell proliferation cycle, DNA replication and gene expression process, including mRNA transcription, processing, splicing, transport, translation initiation, and protein transport along with protein complex assembly, suggests ongoing tissue repair and regeneration. Consistent with the fibrogenic function of the TGF-beta signaling pathway in various experimental renal diseases, genes encoding major extracellular matrix components such as collagens, laminins, fibronectin 1 and tenascins are also strongly up-regulated. Taken together, the results of this study provide important insights into the molecular mechanism

  5. Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

    Directory of Open Access Journals (Sweden)

    Ojaimi Caroline

    2010-08-01

    Full Text Available Abstract Background The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM have not been defined completely. We have shown in conscious dogs with DM that: 1 baseline coronary blood flow (CBF was significantly decreased, 2 endothelium-dependent (ACh coronary vasodilation was impaired, and 3 reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes. Methods Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4. Results The array data revealed that 797 genes were differentially expressed (P 2+ cycling genes (ryanodine receptor; SERCA2 Calcium ATPase, structural proteins (actin alpha. Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase, which were markedly down regulated. Conclusion our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.

  6. Nitric Oxide Mediates the Hormonal Control of Crassulacean Acid Metabolism Expression in Young Pineapple Plants1[W][OA

    Science.gov (United States)

    Freschi, Luciano; Rodrigues, Maria Aurineide; Domingues, Douglas Silva; Purgatto, Eduardo; Van Sluys, Marie-Anne; Magalhaes, Jose Ronaldo; Kaiser, Werner M.; Mercier, Helenice

    2010-01-01

    Genotypic, developmental, and environmental factors converge to determine the degree of Crassulacean acid metabolism (CAM) expression. To characterize the signaling events controlling CAM expression in young pineapple (Ananas comosus) plants, this photosynthetic pathway was modulated through manipulations in water availability. Rapid, intense, and completely reversible up-regulation in CAM expression was triggered by water deficit, as indicated by the rise in nocturnal malate accumulation and in the expression and activity of important CAM enzymes. During both up- and down-regulation of CAM, the degree of CAM expression was positively and negatively correlated with the endogenous levels of abscisic acid (ABA) and cytokinins, respectively. When exogenously applied, ABA stimulated and cytokinins repressed the expression of CAM. However, inhibition of water deficit-induced ABA accumulation did not block the up-regulation of CAM, suggesting that a parallel, non-ABA-dependent signaling route was also operating. Moreover, strong evidence revealed that nitric oxide (NO) may fulfill an important role during CAM signaling. Up-regulation of CAM was clearly observed in NO-treated plants, and a conspicuous temporal and spatial correlation was also evident between NO production and CAM expression. Removal of NO from the tissues either by adding NO scavenger or by inhibiting NO production significantly impaired ABA-induced up-regulation of CAM, indicating that NO likely acts as a key downstream component in the ABA-dependent signaling pathway. Finally, tungstate or glutamine inhibition of the NO-generating enzyme nitrate reductase completely blocked NO production during ABA-induced up-regulation of CAM, characterizing this enzyme as responsible for NO synthesis during CAM signaling in pineapple plants. PMID:20147491

  7. The relationship of thioredoxin-1 and cisplatin resistance: its impact on ROS and oxidative metabolism in lung cancer cells.

    Science.gov (United States)

    Wangpaichitr, Medhi; Sullivan, Elizabeth J; Theodoropoulos, George; Wu, Chunjing; You, Min; Feun, Lynn G; Lampidis, Theodore J; Kuo, Macus T; Savaraj, Niramol

    2012-03-01

    Elimination of cisplatin-resistant lung cancer cells remains a major obstacle. We have shown that cisplatin-resistant tumors have higher reactive oxygen species (ROS) levels and can be exploited for targeted therapy. Here, we show that increased secretion of the antioxidant thioredoxin-1 (TRX1) resulted in lowered intracellular TRX1 and contributed to higher ROS in cisplatin-resistant tumors in vivo and in vitro. By reconstituting TRX1 protein in cisplatin-resistant cells, we increased sensitivity to cisplatin but decreased sensitivity to elesclomol (ROS inducer). Conversely, decreased TRX1 protein in parental cells reduced the sensitivity to cisplatin but increased sensitivity to elesclomol. Cisplatin-resistant cells had increased endogenous oxygen consumption and mitochondrial activity but decreased lactic acid production. They also exhibited higher levels of argininosuccinate synthetase (ASS) and fumarase mRNA, which contributed to oxidative metabolism (OXMET) when compared with parental cells. Restoring intracellular TRX1 protein in cisplatin-resistant cells resulted in lowering ASS and fumarase mRNAs, which in turn sensitized them to arginine deprivation. Interestingly, cisplatin-resistant cells also had significantly higher basal levels of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Overexpressing TRX1 lowered ACC and FAS proteins expressions in cisplatin-resistant cells. Chemical inhibition and short interfering RNA of ACC resulted in significant cell death in cisplatin-resistant compared with parental cells. Conversely, TRX1 overexpressed cisplatin-resistant cells resisted 5-(tetradecyloxy)-2-furoic acid (TOFA)-induced death. Collectively, lowering TRX1 expression through increased secretion leads cisplatin-resistant cells to higher ROS production and increased dependency on OXMET. These changes raise an intriguing therapeutic potential for future therapy in cisplatin-resistant lung cancer.

  8. EXPERIMENTAL WORK AND RESEARCH Effect of Tiaoxin Recipe(调心方)on Spatial Memory and Energy Metabolism of Oxidation Injured Alzheimers Disease Rats

    Institute of Scientific and Technical Information of China (English)

    QIUHong; ZHAOWei-kang; 等

    2003-01-01

    Objective:To observe the effect of Tiaoxin Recipe(TXR) on the spatial memory,brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease(AD) rats,and to explore the mechanism of TXR in treating AD.Methods:Eighty-eight SD rats were randomly divided into five groups (normal group,operative group,“AD”model group,TXR group and Aricept group).An oxygen free rad-ical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate,DHF-FeCl3-ADP)was used to create oxidation injured rat models mimic to AD; spatial learning and memeory impairment (Morris water maze method),the activity of Succinate-oxidase,NADH-oxidase,CytC-oxidase(Clark ox-ygen electrode method)and the expression of cytochrome oxidase(CO)ⅡmRNA(in situ hybridization method)were observed.Results:Compared with the normal group,the spatial memory,activity of CytC-oxidase and COⅡmRNA expression of oxidation injured“AD”rats were obviously decreased;TXR,how-ever,could improve these functions in “AD”rat models obviously.Conclusion:The mechanism of the ac-tion of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mi-tochondrial energy metabolism.

  9. Phenotypic heterogeneity of peripheral monocytes in healthy dogs.

    Science.gov (United States)

    Gibbons, Natalie; Goulart, Michelle R