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Sample records for maintains redox homeostasis

  1. Ergothioneine Maintains Redox and Bioenergetic Homeostasis Essential for Drug Susceptibility and Virulence of Mycobacterium tuberculosis

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    Vikram Saini

    2016-01-01

    Full Text Available The mechanisms by which Mycobacterium tuberculosis (Mtb maintains metabolic equilibrium to survive during infection and upon exposure to antimycobacterial drugs are poorly characterized. Ergothioneine (EGT and mycothiol (MSH are the major redox buffers present in Mtb, but the contribution of EGT to Mtb redox homeostasis and virulence remains unknown. We report that Mtb WhiB3, a 4Fe-4S redox sensor protein, regulates EGT production and maintains bioenergetic homeostasis. We show that central carbon metabolism and lipid precursors regulate EGT production and that EGT modulates drug sensitivity. Notably, EGT and MSH are both essential for redox and bioenergetic homeostasis. Transcriptomic analyses of EGT and MSH mutants indicate overlapping but distinct functions of EGT and MSH. Last, we show that EGT is critical for Mtb survival in both macrophages and mice. This study has uncovered a dynamic balance between Mtb redox and bioenergetic homeostasis, which critically influences Mtb drug susceptibility and pathogenicity.

  2. A Wheat SIMILAR TO RCD-ONE Gene Enhances Seedling Growth and Abiotic Stress Resistance by Modulating Redox Homeostasis and Maintaining Genomic Integrity[C][W

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    Liu, Shuantao; Liu, Shuwei; Wang, Mei; Wei, Tiandi; Meng, Chen; Wang, Meng; Xia, Guangmin

    2014-01-01

    Plant growth inhibition is a common response to salinity. Under saline conditions, Shanrong No. 3 (SR3), a bread wheat (Triticum aestivum) introgression line, performs better than its parent wheat variety Jinan 177 (JN177) with respect to both seedling growth and abiotic stress tolerance. Furthermore, the endogenous reactive oxygen species (ROS) was also elevated in SR3 relative to JN177. The SR3 allele of sro1, a gene encoding a poly(ADP ribose) polymerase (PARP) domain protein, was identified to be crucial for both aspects of its superior performance. Unlike RADICAL-INDUCED CELL DEATH1 and other Arabidopsis thaliana SIMILAR TO RCD-ONE (SRO) proteins, sro1 has PARP activity. Both the overexpression of Ta-sro1 in wheat and its heterologous expression in Arabidopsis promote the accumulation of ROS, mainly by enhancing the activity of NADPH oxidase and the expression of NAD(P)H dehydrogenase, in conjunction with the suppression of alternative oxidase expression. Moreover, it promotes the activity of ascorbate-GSH cycle enzymes and GSH peroxidase cycle enzymes, which regulate ROS content and cellular redox homeostasis. sro1 is also found to be involved in the maintenance of genomic integrity. We show here that the wheat SRO has PARP activity; such activity could be manipulated to improve the growth of seedlings exposed to salinity stress by modulating redox homeostasis and maintaining genomic stability. PMID:24443520

  3. Zinc and the modulation of redox homeostasis

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    Oteiza, Patricia I.

    2012-01-01

    Zinc, a redox inactive metal, has been long viewed as a component of the antioxidant network, and growing evidence points to its involvement in redox-regulated signaling. These actions are exerted through several mechanisms based on the unique chemical and functional properties of zinc. Overall, zinc contributes to maintain the cell redox balance through different mechanisms including: i) the regulation of oxidant production and metal-induced oxidative damage; ii) the dynamic association of zinc with sulfur in protein cysteine clusters, from which the metal can be released by nitric oxide, peroxides, oxidized glutathione and other thiol oxidant species; iii) zinc-mediated induction of the zinc-binding protein metallothionein, which releases the metal under oxidative conditions and act per se scavenging oxidants; iv) the involvement of zinc in the regulation of glutathione metabolism and of the overall protein thiol redox status; and v) a direct or indirect regulation of redox signaling. Findings of oxidative stress, altered redox signaling, and associated cell/tissue disfunction in cell and animal models of zinc deficiency, stress the relevant role of zinc in the preservation of cell redox homeostasis. However, while the participation of zinc in antioxidant protection, redox sensing, and redox-regulated signaling is accepted, the involved molecules, targets and mechanisms are still partially known and the subject of active research. PMID:22960578

  4. Redox homeostasis: The Golden Mean of healthy living.

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    Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

    2016-08-01

    The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve "reactive oxygen species" rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary

  5. Redox homeostasis: The Golden Mean of healthy living

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    Fulvio Ursini

    2016-08-01

    Full Text Available The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve “reactive oxygen species” rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles

  6. Mitochondrial redox biology and homeostasis in plants.

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    Noctor, Graham; De Paepe, Rosine; Foyer, Christine H

    2007-03-01

    Mitochondria are key players in plant cell redox homeostasis and signalling. Earlier concepts that regarded mitochondria as secondary to chloroplasts as the powerhouses of photosynthetic cells, with roles in cell proliferation, death and ageing described largely by analogy to animal paradigms, have been replaced by the new philosophy of integrated cellular energy and redox metabolism involving mitochondria and chloroplasts. Thanks to oxygenic photosynthesis, plant mitochondria often operate in an oxygen- and carbohydrate-rich environment. This rather unique environment necessitates extensive flexibility in electron transport pathways and associated NAD(P)-linked enzymes. In this review, mitochondrial redox metabolism is discussed in relation to the integrated cellular energy and redox function that controls plant cell biology and fate.

  7. Tuning of redox regulatory mechanisms, reactive oxygen species and redox homeostasis under salinity stress

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    Hossain eSazzad

    2016-05-01

    Full Text Available Soil salinity is a crucial environmental constraint which limits biomass production at many sites on a global scale. Saline growth conditions cause osmotic and ionic imbalances, oxidative stress and perturb metabolism, e.g. the photosynthetic electron flow. The plant ability to tolerate salinity is determined by multiple biochemical and physiological mechanisms protecting cell functions, in particular by regulating proper water relations and maintaining ion homeostasis. Redox homeostasis is a fundamental cell property. Its regulation includes control of reactive oxygen species (ROS generation, sensing deviation from and readjustment of the cellular redox state. All these redox related functions have been recognized as decisive factors in salinity acclimation and adaptation. This review focuses on the core response of plants to overcome the challenges of salinity stress through regulation of ROS generation and detoxification systems and to maintain redox homeostasis. Emphasis is given to the role of NADH oxidase (RBOH, alternative oxidase (AOX, the plastid terminal oxidase (PTOX and the malate valve with the malate dehydrogenase isoforms under salt stress. Overwhelming evidence assigns an essential auxiliary function of ROS and redox homeostasis to salinity acclimation of plants.

  8. Glutathione in Cellular Redox Homeostasis: Association with the Excitatory Amino Acid Carrier 1 (EAAC1

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    Koji Aoyama

    2015-05-01

    Full Text Available Reactive oxygen species (ROS are by-products of the cellular metabolism of oxygen consumption, produced mainly in the mitochondria. ROS are known to be highly reactive ions or free radicals containing oxygen that impair redox homeostasis and cellular functions, leading to cell death. Under physiological conditions, a variety of antioxidant systems scavenge ROS to maintain the intracellular redox homeostasis and normal cellular functions. This review focuses on the antioxidant system’s roles in maintaining redox homeostasis. Especially, glutathione (GSH is the most important thiol-containing molecule, as it functions as a redox buffer, antioxidant, and enzyme cofactor against oxidative stress. In the brain, dysfunction of GSH synthesis leading to GSH depletion exacerbates oxidative stress, which is linked to a pathogenesis of aging-related neurodegenerative diseases. Excitatory amino acid carrier 1 (EAAC1 plays a pivotal role in neuronal GSH synthesis. The regulatory mechanism of EAAC1 is also discussed.

  9. Maintaining homeostasis by decision-making.

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    Christoph W Korn

    2015-05-01

    Full Text Available Living organisms need to maintain energetic homeostasis. For many species, this implies taking actions with delayed consequences. For example, humans may have to decide between foraging for high-calorie but hard-to-get, and low-calorie but easy-to-get food, under threat of starvation. Homeostatic principles prescribe decisions that maximize the probability of sustaining appropriate energy levels across the entire foraging trajectory. Here, predictions from biological principles contrast with predictions from economic decision-making models based on maximizing the utility of the endpoint outcome of a choice. To empirically arbitrate between the predictions of biological and economic models for individual human decision-making, we devised a virtual foraging task in which players chose repeatedly between two foraging environments, lost energy by the passage of time, and gained energy probabilistically according to the statistics of the environment they chose. Reaching zero energy was framed as starvation. We used the mathematics of random walks to derive endpoint outcome distributions of the choices. This also furnished equivalent lotteries, presented in a purely economic, casino-like frame, in which starvation corresponded to winning nothing. Bayesian model comparison showed that--in both the foraging and the casino frames--participants' choices depended jointly on the probability of starvation and the expected endpoint value of the outcome, but could not be explained by economic models based on combinations of statistical moments or on rank-dependent utility. This implies that under precisely defined constraints biological principles are better suited to explain human decision-making than economic models based on endpoint utility maximization.

  10. A genome-wide screen in yeast identifies specific oxidative stress genes required for the maintenance of sub-cellular redox homeostasis

    NARCIS (Netherlands)

    Ayer, A.; Fellermeier, S.; Fife, C.; Li, S.S.; Smits, G.; Meyer, A.J.; Dawes, I.W.; Perrone, G.G.

    2012-01-01

    Maintenance of an optimal redox environment is critical for appropriate functioning of cellular processes and cell survival. Despite the importance of maintaining redox homeostasis, it is not clear how the optimal redox potential is sensed and set, and the processes that impact redox on a

  11. Redox Homeostasis in Pancreatic beta Cells

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Dlasková, Andrea; Plecitá-Hlavatá, Lydie

    2012-01-01

    Roč. 2012, č. 2012 (2012), s. 932838 ISSN 1942-0900 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GPP304/10/P204 Institutional support: RVO:67985823 Keywords : beta cells * reactive oxygen species homeostasis * mitochondria Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.393, year: 2012

  12. Redox homeostasis: the linchpin in stem cell self-renewal and differentiation.

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    Wang, Kui; Zhang, Tao; Dong, Qiang; Nice, Edouard Collins; Huang, Canhua; Wei, Yuquan

    2013-03-14

    Stem cells are characterized by their unique ability of self-renewal to maintain the so-called stem cell pool. Over the past decades, reactive oxygen species (ROS) have been recognized as toxic aerobic metabolism byproducts that are harmful to stem cells, leading to DNA damage, senescence or cell death. Recently, a growing body of literature has shown that stem cells reside in redox niches with low ROS levels. The balance of Redox homeostasis facilitates stem cell self-renewal by an intricate network. Thus, to fully decipher the underlying molecular mechanisms involved in the maintenance of stem cell self-renewal, it is critical to address the important role of redox homeostasis in the regulation of self-renewal and differentiation of stem cells. In this regard, we will discuss the regulatory mechanisms involved in the subtly orchestrated balance of redox status in stem cells by scavenger antioxidant enzyme systems that are well monitored by the hypoxia niches and crucial redox regulators including forkhead homeobox type O family (FoxOs), apurinic/apyrimidinic (AP) endonuclease1/redox factor-1 (APE1/Ref-1), nuclear factor erythroid-2-related factor 2 (Nrf2) and ataxia telangiectasia mutated (ATM). We will also introduce several pivotal ROS-sensitive molecules, such as hypoxia-inducible factors, p38 mitogen-activated protein kinase (p38) and p53, involved in the redox-regulated stem cell self-renewal. Specifically, all the aforementioned molecules can act as 'redox sensors' by virtue of redox modifications of their cysteine residues, which are critically important in the control of protein function. Given the importance of redox homeostasis in the regulation of stem cell self-renewal, understanding the underlying molecular mechanisms involved will provide important new insights into stem cell biology.

  13. Wine consumption and intestinal redox homeostasis

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    Biasi, Fiorella; Deiana, Monica; Guina, Tina; Gamba, Paola; Leonarduzzi, Gabriella; Poli, Giuseppe

    2014-01-01

    Regular consumption of moderate doses of wine is an integral part of the Mediterranean diet, which has long been considered to provide remarkable health benefits. Wine׳s beneficial effect has been attributed principally to its non-alcoholic portion, which has antioxidant properties, and contains a wide variety of phenolics, generally called polyphenols. Wine phenolics may prevent or delay the progression of intestinal diseases characterized by oxidative stress and inflammation, especially because they reach higher concentrations in the gut than in other tissues. They act as both free radical scavengers and modulators of specific inflammation-related genes involved in cellular redox signaling. In addition, the importance of wine polyphenols has recently been stressed for their ability to act as prebiotics and antimicrobial agents. Wine components have been proposed as an alternative natural approach to prevent or treat inflammatory bowel diseases. The difficulty remains to distinguish whether these positive properties are due only to polyphenols in wine or also to the alcohol intake, since many studies have reported ethanol to possess various beneficial effects. Our knowledge of the use of wine components in managing human intestinal inflammatory diseases is still quite limited, and further clinical studies may afford more solid evidence of their beneficial effects. PMID:25009781

  14. Energy and Redox Homeostasis in Tumor Cells

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    Marcus Fernandes de Oliveira

    2012-01-01

    Full Text Available Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1. The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg’s original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.

  15. Redox Homeostasis in Plants under Abiotic Stress: Role of electron carriers, energy metabolism mediators and proteinaceous thiols

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    Dhriti Kapoor

    2015-03-01

    Full Text Available Contemporaneous presence of both oxidized and reduced forms of electron carriers is mandatory in efficient flux by plant electron transport cascades. This requirement is considered as redox poising that involves the movement of electron from multiple sites in respiratory and photosynthetic electron transport chains to molecular oxygen. This flux triggers the formation of superoxide, consequently give rise to other reactive oxygen species (ROS under adverse environmental conditions like drought, high or low temperature, heavy metal stress etc. that plants owing during their life span. Plant cells synthesize ascorbate, an additional hydrophilic redox buffer, which protect the plants against oxidative challenge. Large pools of antioxidants also preside over the redox homeostasis. Besides, tocopherol is a liposoluble redox buffer, which efficiently scavenges the ROS like singlet oxygen. In addition, proteinaceous thiol members such as thioredoxin, peroxiredoxin and glutaredoxin, electron carriers and energy metabolism mediators phosphorylated (NADP and non-phosphorylated (NAD+ coenzyme forms interact with ROS, metabolize and maintain redox homeostasis.

  16. Engineering redox homeostasis to develop efficient alcohol-producing microbial cell factories.

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    Zhao, Chunhua; Zhao, Qiuwei; Li, Yin; Zhang, Yanping

    2017-06-24

    The biosynthetic pathways of most alcohols are linked to intracellular redox homeostasis, which is crucial for life. This crucial balance is primarily controlled by the generation of reducing equivalents, as well as the (reduction)-oxidation metabolic cycle and the thiol redox homeostasis system. As a main oxidation pathway of reducing equivalents, the biosynthesis of most alcohols includes redox reactions, which are dependent on cofactors such as NADH or NADPH. Thus, when engineering alcohol-producing strains, the availability of cofactors and redox homeostasis must be considered. In this review, recent advances on the engineering of cellular redox homeostasis systems to accelerate alcohol biosynthesis are summarized. Recent approaches include improving cofactor availability, manipulating the affinity of redox enzymes to specific cofactors, as well as globally controlling redox reactions, indicating the power of these approaches, and opening a path towards improving the production of a number of different industrially-relevant alcohols in the near future.

  17. Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling

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    Parker, Lewan; Shaw, Christopher S.; Stepto, Nigel K.; Levinger, Itamar

    2017-01-01

    Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis. PMID:28529499

  18. AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

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    Chen, Peili; Li, Yan Chun; Toback, F Gary

    2015-01-01

    Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

  19. AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

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    Peili Chen

    Full Text Available Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD. We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

  20. Creatine maintains intestinal homeostasis and protects against colitis.

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    Turer, Emre; McAlpine, William; Wang, Kuan-Wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R; Beutler, Bruce

    2017-02-14

    Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N -ethyl- N -nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted ( Gatm c/c ) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatm c/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatm c/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury.

  1. Microbiota-stimulated immune mechanisms to maintain gut homeostasis.

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    Chung, Hachung; Kasper, Dennis Lee

    2010-08-01

    In recent years there has been an explosion of interest to identify microbial inhabitants of human and understand their beneficial role in health. In the gut, a symbiotic host-microbial interaction has coevolved as bacteria make essential contributions to human metabolism and bacteria in turn benefits from the nutrient-rich niche in the intestine. To maintain host-microbe coexistence, the host must protect itself against microbial invasion, injury, and overreactions to foreign food antigens, and gut microbes need protection against competing microbes and the host immune system. Perturbation of this homeostatic coexistence has been strongly associated with human disease. This review discusses how gut bacteria regulate host innate and adaptive immunity, with emphasis on how this regulation contributes to host-microbe homeostasis in the gut. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. Alterations in redox homeostasis in the elite endurance athlete.

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    Lewis, Nathan A; Howatson, Glyn; Morton, Katie; Hill, Jessica; Pedlar, Charles R

    2015-03-01

    The production of reactive oxygen (ROS) and nitrogen species (RNS) is a fundamental feature of mammalian physiology, cellular respiration and cell signalling, and essential for muscle function and training adaptation. Aerobic and anaerobic exercise results in alterations in redox homeostasis (ARH) in untrained, trained and well trained athletes. Low to moderate doses of ROS and RNS play a role in muscle adaptation to endurance training, but an overwhelming increase in RNS and ROS may lead to increased cell apoptosis and immunosuppression, fatigued states and underperformance. The objectives of this systematic review are: (a) to test the hypotheses that ARH occur in elite endurance athletes; following an acute exercise bout, in an endurance race or competition; across a micro-, meso- or macro-training cycle; following a training taper; before, during and after altitude training; in females with amenorrhoea versus eumenorrhoea; and in non-functional over-reaching (NFOR) and overtraining states (OTS); (b) to report any relationship between ARH and training load and ARH and performance; and (c) to apply critical difference values for measures of oxidative stress/ARH to address whether there is any evidence of ARH being of physiological significance (not just statistical) and thus relevant to health and performance in the elite athlete. Electronic databases, Embase, MEDLINE, and SPORTDiscus were searched for relevant articles. Only studies that were observational articles of cross-sectional or longitudinal design, and included elite athletes competing at national or international level in endurance sports were included. Studies had to include biomarkers of ARH; oxidative damage, antioxidant enzymes, antioxidant capacity, and antioxidant vitamins and nutrients in urine, serum, plasma, whole blood, red blood cells (RBCs) and white blood cells (WBCs). A total of 3,057 articles were identified from the electronic searches. Twenty-eight articles met the inclusion criteria

  3. Two functionally distinct NADP+-dependent ferredoxin oxidoreductases maintain the primary redox balance of Pyrococcus furiosus.

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    Nguyen, Diep M N; Schut, Gerrit J; Zadvornyy, Oleg A; Tokmina-Lukaszewska, Monika; Poudel, Saroj; Lipscomb, Gina L; Adams, Leslie A; Dinsmore, Jessica T; Nixon, William J; Boyd, Eric S; Bothner, Brian; Peters, John W; Adams, Michael W W

    2017-09-01

    Electron bifurcation has recently gained acceptance as the third mechanism of energy conservation in which energy is conserved through the coupling of exergonic and endergonic reactions. A structure-based mechanism of bifurcation has been elucidated recently for the flavin-based enzyme NADH-dependent ferredoxin NADP + oxidoreductase I (NfnI) from the hyperthermophillic archaeon Pyrococcus furiosus. NfnI is thought to be involved in maintaining the cellular redox balance, producing NADPH for biosynthesis by recycling the two other primary redox carriers, NADH and ferredoxin. The P. furiosus genome encodes an NfnI paralog termed NfnII, and the two are differentially expressed, depending on the growth conditions. In this study, we show that deletion of the genes encoding either NfnI or NfnII affects the cellular concentrations of NAD(P)H and particularly NADPH. This results in a moderate to severe growth phenotype in deletion mutants, demonstrating a key role for each enzyme in maintaining redox homeostasis. Despite their similarity in primary sequence and cofactor content, crystallographic, kinetic, and mass spectrometry analyses reveal that there are fundamental structural differences between the two enzymes, and NfnII does not catalyze the NfnI bifurcating reaction. Instead, it exhibits non-bifurcating ferredoxin NADP oxidoreductase-type activity. NfnII is therefore proposed to be a bifunctional enzyme and also to catalyze a bifurcating reaction, although its third substrate, in addition to ferredoxin and NADP(H), is as yet unknown. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Mutation in GNE Downregulates Peroxiredoxin IV Altering ER Redox Homeostasis.

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    Chanana, Pratibha; Padhy, Gayatri; Bhargava, Kalpana; Arya, Ranjana

    2017-12-01

    GNE myopathy is a rare neuromuscular genetic disorder characterized by early adult onset and muscle weakness due to mutation in sialic acid biosynthetic enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). More than 180 different GNE mutations are known all over the world with unclear pathomechanism. Although hyposialylation of glycoproteins is speculated to be the major cause, but cellular mechanism leading to loss of muscle mass has not yet been deciphered. Besides sialic acid biosynthesis, GNE affects other cellular functions such as cell adhesion and apoptosis. In order to understand the effect of mutant GNE protein on cellular functions, differential proteome profile of HEK293 cells overexpressing pathologically relevant recombinant mutant GNE protein (D207V and V603L) was analyzed. These cells, along with vector control and wild-type GNE-overexpressing cells, were subjected to two-dimensional gel electrophoresis coupled with mass spectrometry (MALDI-TOF/TOF MS/MS). In the study, 10 differentially expressed proteins were identified. Progenesis same spots software revealed downregulation of peroxiredoxin IV (PrdxIV), an ER-resident H 2 O 2 sensor that regulates neurogenesis. Significant reduction in mRNA and protein levels of PrdxIV was observed in GNE mutant cell lines compared with vector control. However, neither total reactive oxygen species was altered nor H 2 O 2 accumulation was observed in GNE mutant cell lines. Interestingly, ER redox state was significantly affected due to reduced normal GNE enzyme activity. Our study indicates that downregulation of PrdxIV affects ER redox state that may contribute to misfolding and aggregation of proteins in GNE myopathy.

  5. Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

    Science.gov (United States)

    Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

    2017-07-01

    The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The chemokine receptor CCR2 maintains plasmacytoid dendritic cell homeostasis

    DEFF Research Database (Denmark)

    Cédile, Oriane; Østerby Jørgensen, Line; Frank, Ida

    2017-01-01

    Thymic dendritic cells (DC) play a role in central tolerance. Three thymic DC subtypes have been described: plasmacytoid DC (pDC) and two conventional DC (cDC), CD8α+ Sirpα- DC and Sirpα+ CD8α- cDC. Both pDC and Sirpα+ cDC can take up antigen in periphery and migrate into the thymus in response t...... by CCL2 or CCR2 deficiency. Although some thymic progenitors expressed CCR2, this did not include those that give rise to pDC. Based on these results, we propose that CCR2 is involved in pDC homeostasis but its ligand CCL2 does not play a major role....

  7. Modulation of redox homeostasis under suboptimal conditions by Arabidopsis nudix hydrolase 7

    Directory of Open Access Journals (Sweden)

    Jambunathan Niranjani

    2010-08-01

    differences observed in growth phenotypes of the Atnudt7-1 knockout mutants can be due to differences in the nutrient composition of potting mix. Our data suggests AtNUDT7 plays an important role in maintaining redox homeostasis, particularly for maintaining NADH:NAD+ balance for normal growth and development. During stress conditions, rapid induction of AtNUDT7 is important for regulating the activation of stress/defense signaling and cell death pathways.

  8. Compromised redox homeostasis, altered nitroso-redox balance, and therapeutic possibilities in atrial fibrillation.

    Science.gov (United States)

    Simon, Jillian N; Ziberna, Klemen; Casadei, Barbara

    2016-04-01

    Although the initiation, development, and maintenance of atrial fibrillation (AF) have been linked to alterations in myocyte redox state, the field lacks a complete understanding of the impact these changes may have on cellular signalling, atrial electrophysiology, and disease progression. Recent studies demonstrate spatiotemporal changes in reactive oxygen species production shortly after the induction of AF in animal models with an uncoupling of nitric oxide synthase activity ensuing in the presence of long-standing persistent AF, ultimately leading to a major shift in nitroso-redox balance. However, it remains unclear which radical or non-radical species are primarily involved in the underlying mechanisms of AF or which proteins are targeted for redox modification. In most instances, only free radical oxygen species have been assessed; yet evidence from the redox signalling field suggests that non-radical species are more likely to regulate cellular processes. A wider appreciation for the distinction of these species and how both species may be involved in the development and maintenance of AF could impact treatment strategies. In this review, we summarize how redox second-messenger systems are regulated and discuss the recent evidence for alterations in redox regulation in the atrial myocardium in the presence of AF, while identifying some critical missing links. We also examine studies looking at antioxidants for the prevention and treatment of AF and propose alternative redox targets that may serve as superior therapeutic options for the treatment of AF. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

  9. A novel role of RASSF9 in maintaining epidermal homeostasis.

    Directory of Open Access Journals (Sweden)

    Chiou-Mei Lee

    Full Text Available The physiological role of RASSF9, a member of the Ras-association domain family (RASSF, is currently unclear. Here, we report a mouse line in which an Epstein-Barr virus Latent Membrane Protein 1 (LMP1 transgene insertion has created a 7.2-kb chromosomal deletion, which abolished RASSF9 gene expression. The RASSF9-null mice exhibited interesting phenotypes that resembled human ageing, including growth retardation, short lifespan, less subcutaneous adipose layer and alopecia. In the wild-type mice, RASSF9 is predominantly expressed in the epidermal keratinocytes of skin, as determined by quantitative reverse-transcription PCR, immunofluorescence and in situ hybridization. In contrast, RASSF9-/- mice presented a dramatic change in epithelial organization of skin with increased proliferation and aberrant differentiation as detected by bromodeoxyuridine incorporation assays and immunofluorescence analyses. Furthermore, characteristic functions of RASSF9-/- versus wild type (WT mouse primary keratinocytes showed significant proliferation linked to a reduction of p21Cip1 expression under growth or early differentiation conditions. Additionally, in RASSF9-/- keratinocytes there was a drastic down-modulation of terminal differentiation markers, which could be rescued by infection with a recombinant adenovirus, Adv/HA-RASSF9. Our results indicate a novel and significant role of RASSF9 in epidermal homeostasis.

  10. Mechanism for maintaining homeostasis in the immune system of the intestine.

    Science.gov (United States)

    Taniguchi, Yoshie; Yoshioka, Noriko; Nakata, Kazue; Nishizawa, Takashi; Inagawa, Hiroyuki; Kohchi, Chie; Soma, Gen-Ichiro

    2009-11-01

    Every organism possesses a mechanism for maintaining homeostasis. We have focused on the immune system as a system that helps maintain homeostasis of the body, and particularly on the intestine as the largest organ of immunity in the body. We have also focused our research on the mechanism that responds to foreign substances in the intestine, especially the toll-like receptors (TLR). The activation of myeloid differentiation primary response gene 88 (MyD88) signal transduction as a response to TLR in the intestine is believed to contribute to the maintenance of homeostasis of the body through the homeostasis of the intestine. Furthermore, significant findings were reported in which signal transduction from TLR4 was essential for the maintenance and regulation of the intestine. These results strongly suggest the possibility that homeostasis in the intestine is maintained by TLR4, and signaling by TLR4 after exposure to lipopolysaccharide (LPS) probably has a role in regulating homeostasis. It is expected that the prevention and treatment of various diseases using TLR4 will continue to develop. As LPS is a substance that enhances the activity of TLR4, it will also attract attention as a valuable substance in its own right.

  11. Cutting edge: CD95 maintains effector T cell homeostasis in chronic immune activation

    NARCIS (Netherlands)

    Arens, Ramon; Baars, Paul A.; Jak, Margot; Tesselaar, Kiki; van der Valk, Martin; van Oers, Marinus H. J.; van Lier, René A. W.

    2005-01-01

    The elimination of activated T cells is important to maintain homeostasis and avoid immunopathology. CD95 (Fas/APO-1) has been identified as a death mediator for activated T cells in vitro but the function of CD95 in death of mature T cells in vivo is still controversial. Here we show that

  12. NAC selectively inhibit cancer telomerase activity: A higher redox homeostasis threshold exists in cancer cells

    Directory of Open Access Journals (Sweden)

    Pengying Li

    2016-08-01

    Full Text Available Telomerase activity controls telomere length, and this plays an important role in stem cells, aging and tumors. Antioxidant was shown to protect telomerase activity in normal cells but inhibit that in cancer cells, but the underlying mechanism is elusive. Here we found that 7721 hepatoma cells held a higher redox homeostasis threshold than L02 normal liver cells which caused 7721 cells to have a higher demand for ROS; MnSOD over-expression in 7721 decreased endogenous reactive oxygen species (ROS and inhibited telomerase activity; Akt phosphorylation inhibitor and NAC both inhibited 7721 telomerase activity. The over-elimination of ROS by NAC resulted in the inhibition of Akt pathway. Our results suggest that ROS is involved in the regulation of cancer telomerase activity through Akt pathway. The different intracellular redox homeostasis and antioxidant system in normal cells and tumor cells may be the cause of the opposite effect on telomerase activity in response to NAC treatment. Our results provide a theoretical base of using antioxidants selectively inhibit cancer telomerase activity. Findings of the present study may provide insights into novel approaches for cancer treatment.

  13. Oncogenic IDH1 Mutations Promote Enhanced Proline Synthesis through PYCR1 to Support the Maintenance of Mitochondrial Redox Homeostasis

    Directory of Open Access Journals (Sweden)

    Kate E.R. Hollinshead

    2018-03-01

    Full Text Available Summary: Since the discovery of mutations in isocitrate dehydrogenase 1 (IDH1 in gliomas and other tumors, significant efforts have been made to gain a deeper understanding of the consequences of this oncogenic mutation. One aspect of the neomorphic function of the IDH1 R132H enzyme that has received less attention is the perturbation of cellular redox homeostasis. Here, we describe a biosynthetic pathway exhibited by cells expressing mutant IDH1. By virtue of a change in cellular redox homeostasis, IDH1-mutated cells synthesize excess glutamine-derived proline through enhanced activity of pyrroline 5-carboxylate reductase 1 (PYCR1, coupled to NADH oxidation. Enhanced proline biosynthesis partially uncouples the electron transport chain from tricarboxylic acid (TCA cycle activity through the maintenance of a lower NADH/NAD+ ratio and subsequent reduction in oxygen consumption. Thus, we have uncovered a mechanism by which tumor cell survival may be promoted in conditions associated with perturbed redox homeostasis, as occurs in IDH1-mutated glioma. : Hollinshead et al. demonstrate a role for PYCR1 in control of mitochondrial redox homeostasis. Expression of IDH1 R132H mutation leads to increased NADH-coupled proline biosynthesis, mediated by PYCR1. The resulting metabolic phenotype partially uncouples mitochondrial NADH oxidation from respiration, representing an oxygen-sparing metabolic phenotype. Keywords: glioma, IDH1, redox, metabolism, proline

  14. Role of redox homeostasis in thermo-tolerance under a climate change scenario

    Science.gov (United States)

    de Pinto, Maria Concetta; Locato, Vittoria; Paradiso, Annalisa; De Gara, Laura

    2015-01-01

    Background Climate change predictions indicate a progressive increase in average temperatures and an increase in the frequency of heatwaves, which will have a negative impact on crop productivity. Over the last decade, a number of studies have addressed the question of how model plants or specific crops modify their metabolism when exposed to heat stress. Scope This review provides an overview of the redox pathways that contribute to how plants cope with heat stress. The focus is on the role of reactive oxygen species (ROS), redox metabolites and enzymes in the signalling pathways leading to the activation of defence responses. Additional attention is paid to the regulating mechanisms that lead to an increase in specific ROS-scavenging systems during heat stress, which have been studied in different model systems. Finally, increasing thermo-tolerance in model and crop plants by exposing them to heat acclimation or to exogenous treatments is discussed. Conclusions Although there is clear evidence that several strategies are specifically activated according to the intensity and the duration of heat stress, as well as the capacity of the different species or genotypes to overcome stress, an alteration in redox homeostasis seems to be a common event. Different mechanisms that act to enhance redox systems enable crops to overcome heat stress more effectively. Knowledge of thermo-tolerance within agronomic biodiversity is thus of key importance to enable researchers to identify new strategies for overcoming the impacts of climate change, and for decision-makers in planning for an uncertain future with new choices and options open to them. PMID:26034009

  15. CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

    Science.gov (United States)

    Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

    2017-07-15

    Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

  16. Chromatin-Bound MDM2 Regulates Serine Metabolism and Redox Homeostasis Independently of p53.

    Science.gov (United States)

    Riscal, Romain; Schrepfer, Emilie; Arena, Giuseppe; Cissé, Madi Y; Bellvert, Floriant; Heuillet, Maud; Rambow, Florian; Bonneil, Eric; Sabourdy, Frédérique; Vincent, Charles; Ait-Arsa, Imade; Levade, Thierry; Thibaut, Pierre; Marine, Jean-Christophe; Portais, Jean-Charles; Sarry, Jean-Emmanuel; Le Cam, Laurent; Linares, Laetitia K

    2016-06-16

    The mouse double minute 2 (MDM2) oncoprotein is recognized as a major negative regulator of the p53 tumor suppressor, but growing evidence indicates that its oncogenic activities extend beyond p53. Here, we show that MDM2 is recruited to chromatin independently of p53 to regulate a transcriptional program implicated in amino acid metabolism and redox homeostasis. Identification of MDM2 target genes at the whole-genome level highlights an important role for ATF3/4 transcription factors in tethering MDM2 to chromatin. MDM2 recruitment to chromatin is a tightly regulated process that occurs during oxidative stress and serine/glycine deprivation and is modulated by the pyruvate kinase M2 (PKM2) metabolic enzyme. Depletion of endogenous MDM2 in p53-deficient cells impairs serine/glycine metabolism, the NAD(+)/NADH ratio, and glutathione (GSH) recycling, impacting their redox state and tumorigenic potential. Collectively, our data illustrate a previously unsuspected function of chromatin-bound MDM2 in cancer cell metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Redox homeostasis and age‐related deficits in neuromuscular integrity and function

    Science.gov (United States)

    Lightfoot, Adam P.; Earl, Kate E.; Stofanko, Martin; McDonagh, Brian

    2017-01-01

    Abstract Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness. PMID:28744984

  18. Neuronal redox imbalance results in altered energy homeostasis and early postnatal lethality.

    Science.gov (United States)

    Maity-Kumar, Gandhari; Thal, Dietmar R; Baumann, Bernd; Scharffetter-Kochanek, Karin; Wirth, Thomas

    2015-07-01

    Redox imbalance is believed to contribute to the development and progression of several neurodegenerative disorders. Our aim was to develop an animal model that exhibits neuron-specific oxidative stress in the CNS to study the consequences and eventually find clues regarding the pathomechanisms of oxidative insults in neuronal homeostasis. We therefore generated a novel neuron-specific superoxide dismutase 2 (SOD2)-deficient mouse by deleting exon 3 of the SOD2 gene using CamKIIα promoter-driven Cre expression. These neuron-specific SOD2 knockout (SOD2(nko)) mice, although born at normal frequencies, died at the age of 4 weeks with critical growth retardation, severe energy failure, and several neurologic phenotypes. In addition, SOD2(nko) mice exhibited severe neuronal alterations such as reactive astrogliosis, neuronal cell cycle inhibition, and induction of apoptosis. JNK activation and stabilization of p53, as a result of reactive oxygen species accumulation, are most likely the inducers of neuronal apoptosis in SOD2(nko) mice. It is remarkable that hypothalamic regulation of glucose metabolism was affected, which in turn induced necrotic brain lesions in SOD2(nko) mice. Taken together, our findings suggest that exclusive deficiency of SOD2 in neurons results in an impaired central regulation of energy homeostasis that leads to persistent hypoglycemia, hypoglycemia-related neuropathology, and an early lethality of the mutant mice. © FASEB.

  19. TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis.

    Science.gov (United States)

    Sun, Honghong; Gong, Shunyou; Carmody, Ruaidhri J; Hilliard, Anja; Li, Li; Sun, Jing; Kong, Li; Xu, Lingyun; Hilliard, Brendan; Hu, Shimin; Shen, Hao; Yang, Xiaolu; Chen, Youhai H

    2008-05-02

    Immune homeostasis is essential for the normal functioning of the immune system, and its breakdown leads to fatal inflammatory diseases. We report here the identification of a member of the tumor necrosis factor-alpha-induced protein-8 (TNFAIP8) family, designated TIPE2, that is required for maintaining immune homeostasis. TIPE2 is preferentially expressed in lymphoid tissues, and its deletion in mice leads to multiorgan inflammation, splenomegaly, and premature death. TIPE2-deficient animals are hypersensitive to septic shock, and TIPE2-deficient cells are hyper-responsive to Toll-like receptor (TLR) and T cell receptor (TCR) activation. Importantly, TIPE2 binds to caspase-8 and inhibits activating protein-1 and nuclear factor-kappaB activation while promoting Fas-induced apoptosis. Inhibiting caspase-8 significantly blocks the hyper-responsiveness of TIPE2-deficient cells. These results establish that TIPE2 is an essential negative regulator of TLR and TCR function, and its selective expression in the immune system prevents hyperresponsiveness and maintains immune homeostasis.

  20. Tongue and Taste Organ Biology and Function: Homeostasis Maintained by Hedgehog Signaling.

    Science.gov (United States)

    Mistretta, Charlotte M; Kumari, Archana

    2017-02-10

    The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Recently, the Hedgehog (Hh) pathway has emerged as an essential regulator that maintains lingual taste papillae, taste bud and progenitor cell proliferation and differentiation, and neurophysiological function. Activating or suppressing Hh signaling, with genetic models or pharmacological agents used in cancer treatments, disrupts taste papilla and taste bud integrity and can eliminate responses from taste nerves to chemical stimuli but not to touch or temperature. Understanding Hh regulation of taste organ homeostasis contributes knowledge about the basic biology underlying taste disruptions in patients treated with Hh pathway inhibitors.

  1. Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula

    2006-01-01

    Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was inves......Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis...... was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity...... significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx...

  2. The DNA Sensor AIM2 Maintains Intestinal Homeostasis via Regulation of Epithelial Antimicrobial Host Defense

    Directory of Open Access Journals (Sweden)

    Shuiqing Hu

    2015-12-01

    Full Text Available Microbial pattern molecules in the intestine play immunoregulatory roles via diverse pattern recognition receptors. However, the role of the cytosolic DNA sensor AIM2 in the maintenance of intestinal homeostasis is unknown. Here, we show that Aim2−/− mice are highly susceptible to dextran sodium sulfate-induced colitis that is associated with microbial dysbiosis as represented by higher colonic burden of commensal Escherichia coli. Colonization of germ-free mice with Aim2−/− mouse microbiota leads to higher colitis susceptibility. In-depth investigation of AIM2-mediated host defense responses reveals that caspase-1 activation and IL-1β and IL-18 production are compromised in Aim2−/− mouse colons, consistent with defective inflammasome function. Moreover, IL-18 infusion reduces E. coli burden as well as colitis susceptibility in Aim2−/− mice. Altered microbiota in inflammasome-defective mice correlate with reduced expression of several antimicrobial peptides in intestinal epithelial cells. Together, these findings implicate DNA sensing by AIM2 as a regulatory mechanism for maintaining intestinal homeostasis.

  3. Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons.

    Science.gov (United States)

    Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

    2006-10-01

    Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity including vesicular release. The incorporation of 13C label into intracellular lactate, alanine, succinate, glutamate, and aspartate was determined by mass spectrometry. The metabolism of [U-13C]lactate under non-depolarizing conditions was high compared with that of [U-13C]glucose; however, it decreased significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx and efflux of glutamate was examined using preloaded D-[3H]aspartate as a glutamate tracer and DL-threo-beta-benzyloxyaspartate to inhibit glutamate transporters. The results suggest that glucose is essential to prevent depolarization-induced reversal of the transporter (efflux), whereas vesicular release was unaffected by the choice of substrate. In conclusion, the present study shows that glucose is a necessary substrate to maintain neurotransmitter homeostasis during synaptic activity and that synaptic activity does not induce an upregulation of lactate metabolism in glutamatergic neurons.

  4. Novel roles of folic acid as redox regulator: Modulation of reactive oxygen species sinker protein expression and maintenance of mitochondrial redox homeostasis on hepatocellular carcinoma.

    Science.gov (United States)

    Lai, Kun-Goung; Chen, Chi-Fen; Ho, Chun-Te; Liu, Jun-Jen; Liu, Tsan-Zon; Chern, Chi-Liang

    2017-06-01

    We provide herein several lines of evidence to substantiate that folic acid (or folate) is a micronutrient capable of functioning as a novel redox regulator on hepatocellular carcinoma. First, we uncovered that folate deficiency could profoundly downregulate two prominent anti-apoptotic effectors including survivin and glucose-regulated protein-78. Silencing of either survivin or glucose-regulated protein-78 via small interfering RNA interfering technique established that both effectors could serve as reactive oxygen species sinker proteins. Second, folate deficiency-triggered oxidative-nitrosative stress could strongly induce endoplasmic reticulum stress that in turn could provoke cellular glutathione depletion through the modulation of the following two crucial events: (1) folate deficiency could strongly inhibit Bcl-2 expression leading to severe suppression of the mitochondrial glutathione pool and (2) folate deficiency could also profoundly inhibit two key enzymes that governing cellular glutathione redox regulation including γ-glutamylcysteinyl synthetase heavy chain, a catalytic enzyme for glutathione biosynthesis, and mitochondrial isocitrate dehydrogenase 2, an enzyme responsible for providing nicotinamide adenine dinucleotide phosphate necessary for regenerating oxidized glutathione disulfide back to glutathione via mitochondrial glutathione reductase. Collectively, we add to the literature new data to strengthen the notion that folate is an essential micronutrient that confers a novel role to combat reactive oxygen species insults and thus serves as a redox regulator via upregulating reactive oxygen species sinker proteins and averting mitochondrial glutathione depletion through proper maintenance of redox homeostasis via positively regulating glutathione biosynthesis, glutathione transporting system, and mitochondrial glutathione recycling process.

  5. Selenophosphate synthetase 1 and its role in redox homeostasis, defense and proliferation.

    Science.gov (United States)

    Na, Jiwoon; Jung, Jisu; Bang, Jeyoung; Lu, Qiao; Carlson, Bradley A; Guo, Xiong; Gladyshev, Vadim N; Kim, Jinhong; Hatfield, Dolph L; Lee, Byeong Jae

    2018-04-30

    inhibition of cell growth/proliferation, the accumulation of hydrogen peroxide in mammals and an unidentified reactive oxygen species (ROS) in Drosophila, and the activation of a defense system. Hydrogen peroxide accumulation in SEPHS1-deficient cells is mainly caused by the down-regulation of genes involved in ROS scavenging, and leads to the inhibition of cell proliferation and survival. However, the mechanisms underlying SEPHS1 regulation of redox homeostasis are still not understood. Copyright © 2018. Published by Elsevier Inc.

  6. Comparative analysis of two thioredoxin-like genes in black rockfish Sebastes schlegelii and their possible involvement in redox homeostasis and innate immune responses.

    Science.gov (United States)

    Kugapreethan, Roopasingam; Umasuthan, Navaneethaiyer; Wan, Qiang; Thulasitha, William Shanthakumar; Kim, Chul; Lee, Jehee

    2017-02-01

    Elevated levels of ROS can cause serious intracellular damages by reacting readily with nucleic acids, proteins and lipids, thus triggering tissue damage and cell death. Thioredoxin system is one of the principal factors that maintain the intracellular redox balance via its antioxidant property. In this study, we characterized two new thioredoxin isoforms (SsTXN-like 1 and SsMtTXN-like) from black rockfish, Sebastes schlegelii. The molecular and structural characteristics, as well as the evolutionary relationships of SsTXN-like 1 and SsMtTXN-like confirmed that they belong to the thioredoxin superfamily. A classical thioredoxin domain was found in both proteins with a conserved redox-active site CXYC, however, only the precursor of SsMtTXN-like protein possessed a mitochondrial targeting signal. The results from insulin disulfide reduction activity assay demonstrated that their recombinant proteins are capable of reducing the disulfide bonds of oxidatively damaged proteins via their oxidoreductase activities. The free radical scavenging activity assay revealed the prominent hydroxyl and DPPH scavenging activities of rSsTXN-like 1 and rSsMtTXN-like in a dose-dependent manner. Transcriptional studies showed a broad distribution of SsTXN-like 1 and SsMtTXN-like transcripts in all the examined tissues. Significant (p immune-related tissues after LPS, poly I:C and Streptococcus iniae challenges reflect their critical role in redox homeostasis in black rockfish. Taken together, SsTXN-like 1 and SsMtTXN-like, as two active members of thioredoxin superfamily, have significant antioxidant properties to housekeep the redox potential during various stress conditions and innate immune response of Sebastes schlegelii. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Polyethylenimine architecture-dependent metabolic imprints and perturbation of cellular redox homeostasis

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Parhamifar, Ladan; Lange, Marina Krarup

    2015-01-01

    oxygen species (ROS). The differences in metabolic and redox imprints were further reflected in the transfection performance of the polycations, but co-treatment with the GSH precursor N-acetyl-cysteine (NAC) counteracted redox dysregulation and increased the number of viable transfected cells...

  8. Redox and Ionic Homeostasis Regulations against Oxidative, Salinity and Drought Stress in Wheat (A Systems Biology Approach

    Directory of Open Access Journals (Sweden)

    Zahid Hussain Shah

    2017-10-01

    Full Text Available Systems biology and omics has provided a comprehensive understanding about the dynamics of the genome, metabolome, transcriptome, and proteome under stress. In wheat, abiotic stresses trigger specific networks of pathways involved in redox and ionic homeostasis as well as osmotic balance. These networks are considerably more complicated than those in model plants, and therefore, counter models are proposed by unifying the approaches of omics and stress systems biology. Furthermore, crosstalk among these pathways is monitored by the regulation and streaming of transcripts and genes. In this review, we discuss systems biology and omics as a promising tool to study responses to oxidative, salinity, and drought stress in wheat.

  9. Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus

    Science.gov (United States)

    Blossom, Sarah J.; Melnyk, Stepan; Cooney, Craig A.; Gilbert, Kathleen M.; James, S. Jill

    2012-01-01

    Previous studies have shown that continuous exposure throughout gestation until the juvenile period to environmentally-relevant doses of trichloroethylene (TCE) in the drinking water of MRL+/+ mice promoted adverse behavior associated with glutathione depletion in the cerebellum indicating increased sensitivity to oxidative stress. The purpose of this study was to extend our findings and further characterize the impact of TCE exposure on redox homeostasis and biomarkers of oxidative stress in the hippocampus, a brain region prone to oxidative stress. Instead of a continuous exposure, the mice were exposed to water only or two environmentally relevant doses of TCE in the drinking water postnatally from birth until 6 weeks of age. Biomarkers of plasma metabolites in the transsulfuration pathway and the transmethylation pathway of the methionine cycle were also examined. Gene expression of neurotrophins was examined to investigate a possible relationship between oxidative stress, redox imbalance and neurotrophic factor expression with TCE exposure. Our results show that hippocampi isolated from male mice exposed to TCE showed altered glutathione redox homeostasis indicating a more oxidized state. Also observed was a significant, dose dependent increase in glutathione precursors. Plasma from the TCE treated mice showed alterations in metabolites in the transsulfuration and transmethylation pathways indicating redox imbalance and altered methylation capacity. 3-Nitrotyrosine, a biomarker of protein oxidative stress, was also significantly higher in plasma and hippocampus of TCE-exposed mice compared to controls. In contrast, expression of key neurotrophic factors in the hippocampus (BDNF, NGF, and NT-3) was significantly reduced compared to controls. Our results demonstrate that low-level postnatal and early life TCE exposure modulates neurotrophin gene expression in the mouse hippocampus and may provide a mechanism for TCE-mediated neurotoxicity. PMID:22421312

  10. The role of shear stress and arteriogenesis in maintaining vascular homeostasis and preventing cerebral atherosclerosis

    Directory of Open Access Journals (Sweden)

    David Della-Morte

    2015-01-01

    Full Text Available Shear stress (SS is a biomechanical force that is determined by blood flow, vessel geometry, and fluid viscosity. Although a wide range of known vascular risk factors promote development of atherosclerosis, atherosclerotic changes occur predominately at specific sites within the arterial tree, suggesting a critical role for local factors within the vasculature. Atherosclerotic lesions develop predominantly at branches, bends, and bifurcations in the arterial tree because these sites are exposed to low or disturbed blood flow and low SS. Low SS predisposes arteries to atherosclerosis by causing endothelial dysfunction. A natural system of preexisting cerebral collateral arteries protects against ischemia by bypassing sites of arterial occlusion through a mechanism of arteriogenesis. The main trigger for arteriogenesis is impaired vascular homeostasis (VH in response to local changes in SS induced by ischemia. VH is a critical process for maintaining the physiological function of cerebral circulation. It is regulated through a complex biological system of blood flow hemodynamic and physiological responses to flow changes. Restoration of VH by increasing arteriogenesis and SS may provide a novel therapeutic target for stroke, especially in the elderly, who are more prone to VH impairment. In this review article, we discuss the mechanisms and structures necessary to maintain VH in brain circulation, the role of SS, and risk factors leading to atherosclerosis, including the effects of aging. We also discuss arteriogenesis as an adaptive and protective process in response to ischemic injury, the imaging techniques currently available to evaluate arterogenesis such as magnetic resonance imaging/positron emission tomography (MRI/PET, and the potential therapeutic approaches against ischemic injury that target arteriogenesis.

  11. Alternative Oxidase: A Mitochondrial Respiratory Pathway to Maintain Metabolic and Signaling Homeostasis during Abiotic and Biotic Stress in Plants

    Directory of Open Access Journals (Sweden)

    Greg C. Vanlerberghe

    2013-03-01

    Full Text Available Alternative oxidase (AOX is a non-energy conserving terminal oxidase in the plant mitochondrial electron transport chain. While respiratory carbon oxidation pathways, electron transport, and ATP turnover are tightly coupled processes, AOX provides a means to relax this coupling, thus providing a degree of metabolic homeostasis to carbon and energy metabolism. Beside their role in primary metabolism, plant mitochondria also act as “signaling organelles”, able to influence processes such as nuclear gene expression. AOX activity can control the level of potential mitochondrial signaling molecules such as superoxide, nitric oxide and important redox couples. In this way, AOX also provides a degree of signaling homeostasis to the organelle. Evidence suggests that AOX function in metabolic and signaling homeostasis is particularly important during stress. These include abiotic stresses such as low temperature, drought, and nutrient deficiency, as well as biotic stresses such as bacterial infection. This review provides an introduction to the genetic and biochemical control of AOX respiration, as well as providing generalized examples of how AOX activity can provide metabolic and signaling homeostasis. This review also examines abiotic and biotic stresses in which AOX respiration has been critically evaluated, and considers the overall role of AOX in growth and stress tolerance.

  12. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis: LAMP-2 deficient mice develop pancreatitis.

    Science.gov (United States)

    Mareninova, Olga A; Sendler, Matthias; Malla, Sudarshan Ravi; Yakubov, Iskandar; French, Samuel W; Tokhtaeva, Elmira; Vagin, Olga; Oorschot, Viola; Lüllmann-Rauch, Renate; Blanz, Judith; Dawson, David; Klumperman, Judith; Lerch, Markus M; Mayerle, Julia; Gukovsky, Ilya; Gukovskaya, Anna S

    2015-11-01

    The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated membrane proteins (LAMPs) in pancreatitis. We analyzed changes in LAMPs in experimental models and human pancreatitis, and the underlying mechanisms: LAMP de-glycosylation and degradation. LAMP cleavage by cathepsin B (CatB) was analyzed by mass spectrometry. We used mice deficient in LAMP-2 to assess its role in pancreatitis. Pancreatic levels of LAMP-1 and LAMP-2 greatly decrease across various pancreatitis models and in human disease. Pancreatitis does not trigger LAMPs' bulk de-glycosylation, but induces their degradation via CatB-mediated cleavage of LAMP molecule close to the boundary between luminal and transmembrane domains. LAMP-2 null mice spontaneously develop pancreatitis that begins with acinar cell vacuolization due to impaired autophagic flux, and progresses to severe pancreas damage characterized by trypsinogen activation, macrophage-driven inflammation, and acinar cell death. LAMP-2 deficiency causes a decrease in pancreatic digestive enzymes content, stimulates the basal and inhibits CCK-induced amylase secretion by acinar cells. The effects of LAMP-2 knockout and acute cerulein pancreatitis overlap, which corroborates the pathogenic role of LAMP decrease in experimental pancreatitis models. The results indicate a critical role for LAMPs, particularly LAMP-2, in maintaining pancreatic acinar cell homeostasis, and provide evidence that defective lysosomal function, resulting in impaired autophagy, leads to pancreatitis. Mice with LAMP-2 deficiency present a novel genetic model of human pancreatitis caused by lysosomal/autophagic dysfunction.

  13. Tissues Use Resident Dendritic Cells and Macrophages to Maintain Homeostasis and to Regain Homeostasis upon Tissue Injury: The Immunoregulatory Role of Changing Tissue Environments

    Science.gov (United States)

    Lech, Maciej; Gröbmayr, Regina; Weidenbusch, Marc; Anders, Hans-Joachim

    2012-01-01

    Most tissues harbor resident mononuclear phagocytes, that is, dendritic cells and macrophages. A classification that sufficiently covers their phenotypic heterogeneity and plasticity during homeostasis and disease does not yet exist because cell culture-based phenotypes often do not match those found in vivo. The plasticity of mononuclear phagocytes becomes obvious during dynamic or complex disease processes. Different data interpretation also originates from different conceptual perspectives. An immune-centric view assumes that a particular priming of phagocytes then causes a particular type of pathology in target tissues, conceptually similar to antigen-specific T-cell priming. A tissue-centric view assumes that changing tissue microenvironments shape the phenotypes of their resident and infiltrating mononuclear phagocytes to fulfill the tissue's need to maintain or regain homeostasis. Here we discuss the latter concept, for example, why different organs host different types of mononuclear phagocytes during homeostasis. We further discuss how injuries alter tissue environments and how this primes mononuclear phagocytes to enforce this particular environment, for example, to support host defense and pathogen clearance, to support the resolution of inflammation, to support epithelial and mesenchymal healing, and to support the resolution of fibrosis to the smallest possible scar. Thus, organ- and disease phase-specific microenvironments determine macrophage and dendritic cell heterogeneity in a temporal and spatial manner, which assures their support to maintain and regain homeostasis in whatever condition. Mononuclear phagocytes contributions to tissue pathologies relate to their central roles in orchestrating all stages of host defense and wound healing, which often become maladaptive processes, especially in sterile and/or diffuse tissue injuries. PMID:23251037

  14. Visualization of Nicotine Adenine Dinucleotide Redox Homeostasis with Genetically Encoded Fluorescent Sensors.

    Science.gov (United States)

    Zhao, Yuzheng; Zhang, Zhuo; Zou, Yejun; Yang, Yi

    2018-01-20

    Beyond their roles as redox currency in living organisms, pyridine dinucleotides (NAD + /NADH and NADP + /NADPH) are also precursors or cosubstrates of great significance in various physiologic and pathologic processes. Recent Advances: For many years, it was challenging to develop methodologies for monitoring pyridine dinucleotides in situ or in vivo. Recent advances in fluorescent protein-based sensors provide a rapid, sensitive, specific, and real-time readout of pyridine dinucleotide dynamics in single cells or in vivo, thereby opening a new era of pyridine dinucleotide bioimaging. In this article, we summarize the developments in genetically encoded fluorescent sensors for NAD + /NADH and NADP + /NADPH redox states, as well as their applications in life sciences and drug discovery. The strengths and weaknesses of individual sensors are also discussed. These sensors have the advantages of being specific and organelle targetable, enabling real-time monitoring and subcellular-level quantification of targeted molecules in living cells and in vivo. NAD + /NADH and NADP + /NADPH have distinct functions in metabolic and redox regulation, and thus, a comprehensive evaluation of metabolic and redox states must be multiplexed with a combination of various metabolite sensors in a single cell. Antioxid. Redox Signal. 28, 213-229.

  15. Changes in mitochondrial homeostasis and redox status in astronauts following long stays in space

    DEFF Research Database (Denmark)

    Indo, Hiroko P; Majima, Hideyuki J; Terada, Masahiro

    2016-01-01

    reductions in the mtRNA/nRNA ratios in both the Inflight and Postflight samples. The mtRNA/mtDNA ratios were relatively constant, except in the Postflight samples. Using the same samples, the expression of redox and signal transduction related genes, MnSOD, CuZnSOD, Nrf2, Keap1, GPx4 and Catalase was also...... examined. The results of the combined data from Preflight, Inflight and Postflight show a significant decrease in the expression of all of the redox-related genes in the samples collected Postflight, with the exception of Catalase, which show no change. This decreased expression may contribute to increased...

  16. Diglycosyl diselenides alter redox homeostasis and glucose consumption of infective African trypanosomes

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    Jaime Franco

    2017-12-01

    Full Text Available With the aim to develop compounds able to target multiple metabolic pathways and, thus, to lower the chances of drug resistance, we investigated the anti-trypanosomal activity and selectivity of a series of symmetric diglycosyl diselenides and disulfides. Of 18 compounds tested the fully acetylated forms of di-β-D-glucopyranosyl and di-β-D-galactopyranosyl diselenides (13 and 15, respectively displayed strong growth inhibition against the bloodstream stage of African trypanosomes (EC50 0.54 μM for 13 and 1.49 μM for 15 although with rather low selectivity (SI < 10 assayed with murine macrophages. Nonacetylated versions of the same sugar diselenides proved to be, however, much less efficient or completely inactive to suppress trypanosome growth. Significantly, the galactosyl (15, and to a minor extent the glucosyl (13, derivative inhibited glucose catabolism but not its uptake. Both compounds induced redox unbalance in the pathogen. In vitro NMR analysis indicated that diglycosyl diselenides react with glutathione, under physiological conditions, via formation of selenenylsulfide bonds. Our results suggest that non-specific cellular targets as well as actors of the glucose and the redox metabolism of the parasite may be affected. These molecules are therefore promising leads for the development of novel multitarget antitrypanosomal agents. Keywords: Glutathione, Redox biosensor, Selenosugar, Trypanosome inhibition, Selenium NMR

  17. Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance

    Science.gov (United States)

    Jin, Jianliang; Lv, Xianhui; Chen, Lulu; Zhang, Wei; Li, Jinbo; Wang, Qian; Wang, Rong; Lu, Xiang; Miao, Dengshun

    2014-01-01

    To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quinone (PQQ, 4 mg kg−1 diet) in their diet for 2 weeks, and their renal phenotypes were compared with vehicle-treated Bmi1-/- and wild-type mice. Bmi-1 was knocked down in human renal proximal tubular epithelial (HK2) cells which were treated with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control cells. Five-week-old vehicle-treated Bmi-1-/- mice displayed renal interstitial fibrosis, tubular atrophy, and severe renal function impairment with decreased renal cell proliferation, increased renal cell apoptosis and senescence, and inflammatory cell infiltration. Impaired mitochondrial structure, decreased mitochondrial numbers, and increased oxidative stress occurred in Bmi-1-/- mice; subsequently, this caused DNA damage, the activation of TGF-β1/Smad signaling, and the imbalance between extracellular matrix synthesis and degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant treatment. These findings indicate that Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance and will be a novel therapeutic target for preventing renal tubulointerstitial injury. PMID:24915841

  18. Studies on the effect of quercetin and nitrates on the redox homeostasis using in vitro model.

    Science.gov (United States)

    Kurzeja, Ewa; Stec, Małgorzata; Synowiec-Wojtarowicz, Agnieszka; Jowsa, Andrzej; Pawłowska-Góral, Katarzyna

    2014-07-01

    Antioxidants are widely considered to be a preventive measure for many diseases and beneficial for health. However, an increasing number of reports suggest a lack of any influence by antioxidants on health or even harmful pro-oxidative effects of antioxidants. In most cases, the research was conducted with respect to a chosen antioxidant, without considering the presence of other chemical substances present in food, with which these compounds may react. The aim of this work was to determine whether and to what extent the simultaneous presence of quercetin and sodium nitrate influences oxidative-reductive homeostasis in fibroblast cultures. Superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and nitric oxide synthase (NOS) activities were measured together with nitric oxide (NO) concentration and total antioxidant status (TAS). An increase in the activity of all the enzymes measured and in the NO concentration was determined compared with the control culture. The most prominent changes were observed at the highest quercetin concentration. These results indicate that the simultaneous presence of quercetin and sodium nitrate disrupts the oxidative-reductive homeostasis in fibroblasts. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Alpha-ketoglutarate stabilizes redox homeostasis and improves arterial elasticity in aged mice.

    Science.gov (United States)

    Niemiec, T; Sikorska, J; Harrison, A; Szmidt, M; Sawosz, E; Wirth-Dzieciolowska, E; Wilczak, J; Pierzynowski, S

    2011-02-01

    The objective of this study was to evaluate the effect of α-ketoglutarate on redox state parameters and arterial elasticity in elderly mice. Mice in the control group were fed with standard diet, while the experimental animals received the diet supplemented either with calcium (Ca-AKG) or sodium salt of α-ketoglutarate (Na-AKG). The experimental animals were divided into 4 groups with 10 individuals in each: control I (12 months old), control II (2 months old), experimental group I fed with Ca-AKG (12 months old) and experimental group II fed with Na-AKG (12 months old). Mice treated with Ca-AKG as well as the control II animals demonstrated significantly higher level of total antioxidant status (TAS), comparing to the control I animals and those treated with Ca-AKG. Thiobarbituric acid reactive substances (TBARS) level in blood plasma was found significantly lower in young and Ca-AKG treated mice. TBARS liver concentration was significantly different in each examined group. The study also demonstrates the decrease in TBARS level in Ca-AKG treated animals. Treatment with Na-AKG significantly increased glutathione peroxidase activity and decreased the activity of superoxide dismutase. The presented results suggest that Ca-AKG protects the organism against the free radicals related elderly processes. The study presents also the effect of Ca-AKG treatment on arterial elastic characteristics in elderly mice. The beneficial effect of Ca-AKG on ageing organisms was confirmed via redox state stabilization and blood vessel elasticity improvement.

  20. Obesity induced alterations in redox homeostasis and oxidative stress are present from an early age.

    Science.gov (United States)

    Lechuga-Sancho, Alfonso M; Gallego-Andujar, David; Ruiz-Ocaña, Pablo; Visiedo, Francisco M; Saez-Benito, Ana; Schwarz, Mónica; Segundo, Carmen; Mateos, Rosa M

    2018-01-01

    Oxidative stress and inflammation have been postulated as underlying mechanisms for the development of obesity-related insulin resistance. This association however, remains elusive especially in childhood. We sought to investigate this relation by measuring oxidative stress and antioxidant response biomarkers, before and during an oral glucose tolerance test (OGTT), in different biological samples from obese children. 24 children were recruited for the study, (18 obese and 6 controls). After OGTT, the obese group was subdivided in two, according to whether or not carbohydrate metabolic impairment (Ob.IR+, Ob.IR-; respectively) was found. Different biomarkers were analyzed after fasting (T = 0) and during an OGTT (T = 60 and 120 min). Lipoperoxides were measured in plasma, erythrocytes, and urine; while advanced glycation end products were determined in plasma, and redox status (GSH/GSSG ratio) in erythrocytes. We found marked differences in the characterization of the oxidative status in urine and erythrocytes, and in the dynamics of the antioxidant response during OGTT. Specifically, Ob.IR+ children show increased oxidative stress, deficient antioxidant response and a significant imbalance in redox status, in comparison to controls and Ob.IR- children. Obese children with insulin resistance show increased levels of oxidative stress biomarkers, and a stunted antioxidant response to an OGTT leading to increased oxidative stress after a single glucose load, as detected in erythrocytes, but not in plasma. We propose erythrocytes as sensors of early and acute changes in oxidative stress associated with insulin resistance in childhood obesity. This is a pilot study, performed with a limited sample size, so data should be interpreted with caution until reproduced.

  1. The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2/ARE Pathway

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2012-01-01

    Full Text Available Among various cancer cell lines, the leukemia cell line HL-60 was most sensitive to Shikonin, with evidence showing both the prooxidative activities and proapoptotic effects of micromolar concentrations of Shikonin. However, the mechanism involved in the cytotoxicity of Shikonin in the submicromolar range has not been fully characterized. Using biochemical and free radical biological experiments in vitro, we identified the prodifferentiated profiles of Shikonin and evaluated the redox homeostasis during HL-60 differentiation. The data showed a strong dose-response relationship between Shikonin exposure and the characteristics of HL-60 differentiation in terms of morphology changes, nitroblue tetrazolium (NBT reductive activity, and the expression level of surface antigens CD11b/CD14. During drug exposure, intercellular redox homeostasis changes towards oxidation are necessary to support Shikonin-induced differentiation, which was proven by additional enzymatic and non-enzymatic redox modulators. A statistically significant and dose-dependent increase (P<0.05 was recorded with regard to the unique expression levels of the Nrf2/ARE downstream target genes in HL-60 cells undergoing late differentiation, which were restored with further antioxidants employed with the Shikonin treatment. Our research demonstrated that Shikonin is a differentiation-inducing agent, and its mechanisms involve the Nrf2/ARE pathway to modulate the intercellular redox homeostasis, thus facilitating differentiation.

  2. Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

    Science.gov (United States)

    Tran, Khiem A; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F; Göthert, Joachim R; Malik, Asrar B; Valyi-Nagy, Tibor; Zhao, You-Yang

    2016-01-12

    The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation. © 2015 American Heart Association, Inc.

  3. A whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Xu

    2011-12-01

    Full Text Available Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into "whole-body" contextual models that mimic in vivo conditions.

  4. Genetic regulation by NLA and microRNA827 for maintaining nitrate-dependent phosphate homeostasis in arabidopsis.

    Science.gov (United States)

    Kant, Surya; Peng, Mingsheng; Rothstein, Steven J

    2011-03-01

    Plants need abundant nitrogen and phosphorus for higher yield. Improving plant genetics for higher nitrogen and phosphorus use efficiency would save potentially billions of dollars annually on fertilizers and reduce global environmental pollution. This will require knowledge of molecular regulators for maintaining homeostasis of these nutrients in plants. Previously, we reported that the NITROGEN LIMITATION ADAPTATION (NLA) gene is involved in adaptive responses to low-nitrogen conditions in Arabidopsis, where nla mutant plants display abrupt early senescence. To understand the molecular mechanisms underlying NLA function, two suppressors of the nla mutation were isolated that recover the nla mutant phenotype to wild type. Map-based cloning identified these suppressors as the phosphate (Pi) transport-related genes PHF1 and PHT1.1. In addition, NLA expression is shown to be regulated by the low-Pi induced microRNA miR827. Pi analysis revealed that the early senescence in nla mutant plants was due to Pi toxicity. These plants accumulated over five times the normal Pi content in shoots specifically under low nitrate and high Pi but not under high nitrate conditions. Also the Pi overaccumulator pho2 mutant shows Pi toxicity in a nitrate-dependent manner similar to the nla mutant. Further, the nitrate and Pi levels are shown to have an antagonistic crosstalk as displayed by their differential effects on flowering time. The results demonstrate that NLA and miR827 have pivotal roles in regulating Pi homeostasis in plants in a nitrate-dependent fashion.

  5. Ocean acidification affects redox-balance and ion-homeostasis in the life-cycle stages of Emiliania huxleyi.

    Directory of Open Access Journals (Sweden)

    Sebastian D Rokitta

    Full Text Available Ocean Acidification (OA has been shown to affect photosynthesis and calcification in the coccolithophore Emiliania huxleyi, a cosmopolitan calcifier that significantly contributes to the regulation of the biological carbon pumps. Its non-calcifying, haploid life-cycle stage was found to be relatively unaffected by OA with respect to biomass production. Deeper insights into physiological key processes and their dependence on environmental factors are lacking, but are required to understand and possibly estimate the dynamics of carbon cycling in present and future oceans. Therefore, calcifying diploid and non-calcifying haploid cells were acclimated to present and future CO(2 partial pressures (pCO(2; 38.5 Pa vs. 101.3 Pa CO(2 under low and high light (50 vs. 300 µmol photons m(-2 s(-1. Comparative microarray-based transcriptome profiling was used to screen for the underlying cellular processes and allowed to follow up interpretations derived from physiological data. In the diplont, the observed increases in biomass production under OA are likely caused by stimulated production of glycoconjugates and lipids. The observed lowered calcification under OA can be attributed to impaired signal-transduction and ion-transport. The haplont utilizes distinct genes and metabolic pathways, reflecting the stage-specific usage of certain portions of the genome. With respect to functionality and energy-dependence, however, the transcriptomic OA-responses resemble those of the diplont. In both life-cycle stages, OA affects the cellular redox-state as a master regulator and thereby causes a metabolic shift from oxidative towards reductive pathways, which involves a reconstellation of carbon flux networks within and across compartments. Whereas signal transduction and ion-homeostasis appear equally OA-sensitive under both light intensities, the effects on carbon metabolism and light physiology are clearly modulated by light availability. These interactive effects

  6. Ocean acidification affects redox-balance and ion-homeostasis in the life-cycle stages of Emiliania huxleyi.

    Science.gov (United States)

    Rokitta, Sebastian D; John, Uwe; Rost, Björn

    2012-01-01

    Ocean Acidification (OA) has been shown to affect photosynthesis and calcification in the coccolithophore Emiliania huxleyi, a cosmopolitan calcifier that significantly contributes to the regulation of the biological carbon pumps. Its non-calcifying, haploid life-cycle stage was found to be relatively unaffected by OA with respect to biomass production. Deeper insights into physiological key processes and their dependence on environmental factors are lacking, but are required to understand and possibly estimate the dynamics of carbon cycling in present and future oceans. Therefore, calcifying diploid and non-calcifying haploid cells were acclimated to present and future CO(2) partial pressures (pCO(2); 38.5 Pa vs. 101.3 Pa CO(2)) under low and high light (50 vs. 300 µmol photons m(-2) s(-1)). Comparative microarray-based transcriptome profiling was used to screen for the underlying cellular processes and allowed to follow up interpretations derived from physiological data. In the diplont, the observed increases in biomass production under OA are likely caused by stimulated production of glycoconjugates and lipids. The observed lowered calcification under OA can be attributed to impaired signal-transduction and ion-transport. The haplont utilizes distinct genes and metabolic pathways, reflecting the stage-specific usage of certain portions of the genome. With respect to functionality and energy-dependence, however, the transcriptomic OA-responses resemble those of the diplont. In both life-cycle stages, OA affects the cellular redox-state as a master regulator and thereby causes a metabolic shift from oxidative towards reductive pathways, which involves a reconstellation of carbon flux networks within and across compartments. Whereas signal transduction and ion-homeostasis appear equally OA-sensitive under both light intensities, the effects on carbon metabolism and light physiology are clearly modulated by light availability. These interactive effects can be

  7. CD 4 + CD 25 + T cells maintain homeostasis by promoting TER - 119 cell development and inhibiting T cell activation

    Directory of Open Access Journals (Sweden)

    Muhaimin Rifa’i

    2014-05-01

    Full Text Available CD4+ CD25+ regulatory T cells involved in the regulation of self- tolerance and normality of homeostasis. CD122 deficient mice are model animals that have an abnormal immune system characteristically have a high number of activated T cells and TER-119 cell decreased. Here we showed evidence that the transfer of CD4+ CD25+ regulatory T cells derived from normal mice to CD122- defficient neonates prevent the development of activated memory T cells and elicit TER-119 differentiation. Bone marrow reconstitution derived from CD122-/- mice to normal mice resulting tolerance to individual that genetically different. Importantly, CD4+ CD25+ regulatory T cells derived from normal mice can replace CD4+ CD25+ cells derived from CD122-/- mice. The results of this experiment suggest that regulatory T cells from normal mice exert a critical role in maintaining peripheral tolerance and controlling hematopoietic disorder.

  8. TOR Complex 2-Ypk1 Signaling Maintains Sphingolipid Homeostasis by Sensing and Regulating ROS Accumulation

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    Brad J. Niles

    2014-02-01

    Full Text Available Reactive oxygen species (ROS are produced during normal metabolism and can function as signaling molecules. However, ROS at elevated levels can damage cells. Here, we identify the conserved target of rapamycin complex 2 (TORC2/Ypk1 signaling module as an important regulator of ROS in the model eukaryotic organism, S. cerevisiae. We show that TORC2/Ypk1 suppresses ROS produced both by mitochondria as well as by nonmitochondrial sources, including changes in acidification of the vacuole. Furthermore, we link vacuole-related ROS to sphingolipids, essential components of cellular membranes, whose synthesis is also controlled by TORC2/Ypk1 signaling. In total, our data reveal that TORC2/Ypk1 act within a homeostatic feedback loop to maintain sphingolipid levels and that ROS are a critical regulatory signal within this system. Thus, ROS sensing and signaling by TORC2/Ypk1 play a central physiological role in sphingolipid biosynthesis and in the maintenance of cell growth and viability.

  9. Radiation-induced disruption of hippocampal redox homeostasis, neurogenesis and cognitive function: protective role of melatonin and its metabolites

    International Nuclear Information System (INIS)

    Manda, Kailash

    2012-01-01

    The sensitivity of neuronal tissues to ionizing radiation depends on the rate of differentiation and accompanying factors of the tissues as well as on the efficiency of the intrinsic antioxidative defense systems. Neurogenic area in the adult brain are reported be highly sensitive to ionizing radiation. While the pathogenesis of radiation induced cognitive impairment is not well understood, recent studies indicated that neuronal precursor cells in the hippocampus may be involved. The dentate gyrus of the hippocampus is unique in that it is one of two regions in the mammalian brain that continues to produce new neurons in adulthood. Moreover, brain is considered abnormally sensitive to oxidative damage and in fact early studies demonstrating the ease of peroxidation of brain membranes supported this notion. Brain is enriched in the more easily peroxidizable fatty acids, consumes an inordinate fraction (20%) of the total oxygen consumption for its relatively small weight (2%), and is not particularly enriched in antioxidant defenses. Our recent findings showed an inverse relationship between mice cognitive performance and cellular indicators of oxidative stress or redox status which was reported in the term glutathione homeostasis (GSH/GSSG), DNA damage, protein oxidation and lipid peroxidation. Radiation exposure severely impaired the hipocampal neurogenesis as measure in the terms of immunoreactivity of immature and proliferating neurons in dentate gyrus, the doublecortin (Dcx) and Ki-67 positive cells respectively. Our results showed a significant implication of hippocampus neurogenesis in cognitive functions and pre-treatment of melatonin and its metabolites significantly protected the neurogenic potential of brain and thereby the cognitive functions. (author)

  10. Comparison of Selected Parameters of Redox Homeostasis in Patients with Ataxia-Telangiectasia and Nijmegen Breakage Syndrome

    Directory of Open Access Journals (Sweden)

    Barbara Pietrucha

    2017-01-01

    Full Text Available This study compared the antioxidant status and major lipophilic antioxidants in patients with ataxia-telangiectasia (AT and Nijmegen breakage syndrome (NBS. Total antioxidant status (TAS, total oxidant status (TOS, oxidative stress index (OSI, and concentrations of coenzyme Q10 (CoQ10 and vitamins A and E were estimated in the plasma of 22 patients with AT, 12 children with NBS, and the healthy controls. In AT patients, TAS (median 261.7 μmol/L was statistically lower but TOS (496.8 μmol/L was significantly elevated in comparison with the healthy group (312.7 μmol/L and 311.2 μmol/L, resp.. Tocopherol (0.8 μg/mL and CoQ10 (0.1 μg/mL were reduced in AT patients versus control (1.4 μg/mL and 0.3 μg/mL, resp.. NBS patients also displayed statistically lower TAS levels (290.3 μmol/L, while TOS (404.8 μmol/L was comparable to the controls. We found that in NBS patients retinol concentration (0.1 μg/mL was highly elevated and CoQ10 (0.1 μg/mL was significantly lower in comparison with those in the healthy group. Our study confirms disturbances in redox homeostasis in AT and NBS patients and indicates a need for diagnosing oxidative stress in those cases as a potential disease biomarker. Decreased CoQ10 concentration found in NBS and AT indicates a need for possible supplementation.

  11. STAT3-RXR-Nrf2 activates systemic redox and energy homeostasis upon steep decline in pO2 gradient

    Directory of Open Access Journals (Sweden)

    Subhojit Paul

    2018-04-01

    Full Text Available Hypobaric hypoxia elicits several patho-physiological manifestations, some of which are known to be lethal. Among various molecular mechanisms proposed so far, perturbation in redox state due to imbalance between radical generation and antioxidant defence is promising. These molecular events are also related to hypoxic status of cancer cells and therefore its understanding has extended clinical advantage beyond high altitude hypoxia. In present study, however, the focus was to understand and propose a model for rapid acclimatization of high altitude visitors to enhance their performance based on molecular changes. We considered using simulated hypobaric hypoxia at some established thresholds of high altitude stratification based on known physiological effects. Previous studies have focused on the temporal aspect while overlooking the effects of varying pO2 levels during exposure to hypobaric hypoxia. The pO2 levels, indicative of altitude, are crucial to redox homeostasis and can be the limiting factor during acclimatization to hypobaric hypoxia. In this study we present the effects of acute (24 h exposure to high (3049 m; pO2: 71 kPa, very high (4573 m; pO2: 59 kPa and extreme altitude (7620 m; pO2: 40 kPa zones on lung and plasma using semi-quantitative redox specific transcripts and quantitative proteo-bioinformatics workflow in conjunction with redox stress assays. It was observed that direct exposure to extreme altitude caused 100% mortality, which turned into high survival rate after pre-exposure to 59 kPa, for which molecular explanation were also found. The pO2 of 59 kPa (very high altitude zone elicits systemic energy and redox homeostatic processes by modulating the STAT3-RXR-Nrf2 trio. Finally we posit the various processes downstream of STAT3-RXR-Nrf2 and the plasma proteins that can be used to ascertain the redox status of an individual. Keywords: STAT3, RXR, Nrf2, Network biology, Cytoskeleton, Redox homeostasis, Energy

  12. Endogenous Vascular Endothelial Growth Factor-A (VEGF-A) Maintains Endothelial Cell Homeostasis by Regulating VEGF Receptor-2 Transcription*

    Science.gov (United States)

    E, Guangqi; Cao, Ying; Bhattacharya, Santanu; Dutta, Shamit; Wang, Enfeng; Mukhopadhyay, Debabrata

    2012-01-01

    Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis. PMID:22167188

  13. Probiotic-derived polyphosphate enhances the epithelial barrier function and maintains intestinal homeostasis through integrin-p38 MAPK pathway.

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    Shuichi Segawa

    Full Text Available Probiotics exhibit beneficial effects on human health, particularly in the maintenance of intestinal homeostasis in a complex manner notwithstanding the diversity of an intestinal flora between individuals. Thus, it is highly probable that some common molecules secreted by probiotic and/or commensal bacteria contribute to the maintenance of intestinal homeostasis and protect the intestinal epithelium from injurious stimuli. To address this question, we aimed to isolate the cytoprotective compound from a lactobacillus strain, Lactobacillus brevis SBC8803 which possess the ability to induce cytoprotective heat shock proteins in mouse small intestine. L. brevis was incubated in MRS broth and the supernatant was passed through with a 0.2-µm filter. Caco2/bbe cells were treated with the culture supernatant, and HSP27 expression was evaluated by Western blotting. HSP27-inducible components were separated by ammonium sulfate precipitation, DEAE anion exchange chromatography, gel filtration, and HPLC. Finally, we identified that the HSP27-inducible fraction was polyphosphate (poly P, a simple repeated structure of phosphates, which is a common product of lactobacilli and other bacteria associated with intestinal microflora without any definitive physiological functions. Then, poly P was synthesized by poly P-synthesizing enzyme polyphosphate kinase. The synthesized poly P significantly induced HSP27 from Caco2/BBE cells. In addition, Poly P suppressed the oxidant-induced intestinal permeability in the mouse small intestine and pharmacological inhibitors of p38 MAPK and integrins counteract its protective effect. Daily intrarectal administration of poly P (10 µg improved the inflammation grade and survival rate in 4% sodium dextran sulfate-administered mice. This study, for the first time, demonstrated that poly P is the molecule responsible for maintaining intestinal barrier actions which are mediated through the intestinal integrin β1-p38 MAPK.

  14. Genetic regulation by NLA and microRNA827 for maintaining nitrate-dependent phosphate homeostasis in arabidopsis.

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    Surya Kant

    2011-03-01

    Full Text Available Plants need abundant nitrogen and phosphorus for higher yield. Improving plant genetics for higher nitrogen and phosphorus use efficiency would save potentially billions of dollars annually on fertilizers and reduce global environmental pollution. This will require knowledge of molecular regulators for maintaining homeostasis of these nutrients in plants. Previously, we reported that the NITROGEN LIMITATION ADAPTATION (NLA gene is involved in adaptive responses to low-nitrogen conditions in Arabidopsis, where nla mutant plants display abrupt early senescence. To understand the molecular mechanisms underlying NLA function, two suppressors of the nla mutation were isolated that recover the nla mutant phenotype to wild type. Map-based cloning identified these suppressors as the phosphate (Pi transport-related genes PHF1 and PHT1.1. In addition, NLA expression is shown to be regulated by the low-Pi induced microRNA miR827. Pi analysis revealed that the early senescence in nla mutant plants was due to Pi toxicity. These plants accumulated over five times the normal Pi content in shoots specifically under low nitrate and high Pi but not under high nitrate conditions. Also the Pi overaccumulator pho2 mutant shows Pi toxicity in a nitrate-dependent manner similar to the nla mutant. Further, the nitrate and Pi levels are shown to have an antagonistic crosstalk as displayed by their differential effects on flowering time. The results demonstrate that NLA and miR827 have pivotal roles in regulating Pi homeostasis in plants in a nitrate-dependent fashion.

  15. Asada-Halliwell pathway maintains redox status in Dioscorea alata tuber which helps in germination.

    Science.gov (United States)

    Sharma, Shruti; Sehrawat, Ankita; Deswal, Renu

    2016-09-01

    Reactive Oxygen Species (ROS) are important regulatory molecules governing physiological processes. In the present study a biochemical and proteome level comparison of two contrasting growth stages of Dioscorea alata tuber namely germinating and mature tuber was performed in order to understand the tuber physiology and biochemistry. Existence of all the component enzymes [APx (ascorbate peroxidase), GR (glutathione reductase), DHAR (dehydroascorbate reductase), MDHAR (mono-dehydroascorbate reductase)] and major products [ascorbate (ASC) and glutathione (GSH)] of the cycle showed an operational Asada-Halliwell cycle in the tuber. A 2.65 fold increase in ASC content & a 3.8 fold increase in GR activity fortified the redox milieu during germination. In contrast a 5 fold higher H2O2 content (due to 3.08 fold lower APx activity) and accumulation of reactive nitrogen species (RNS) such as nitric oxide (NO, 2.4-fold) and S-nitrosothiol (SNO, 2.08 fold) contributed to overall oxidative conditions in the mature tuber. The carbonic anhydrase (CA, 7.5 fold), DHAR (5.31 fold) and MDHAR (7 fold) activities were higher in the germinating tuber in comparison with the mature tuber. GSNO negatively regulated the CA (3.6 & 3.95 fold), MDHAR (7.5 & 1.5 fold) and APx (2.3 & 1.81 fold) while another NO donor, CysNO negatively regulated the DHAR (2.24 & 1.32 fold) activity in the mature and germinating stages respectively indicating again that the lesser inhibition by NO (via nitrosylation) may be because of overall reducing environment in the germinating tuber. Increased SNO leading to S-nitrosylation of dioscorin was confirmed by Biotin switch assay. This is the first report showing dioscorin nitrosylation. The present analysis showed differential redox regulation and also suggests the physiological relevance of CA, DHAR, MDHAR, APx & GR in tuber germination for the first time. These enzymes may be used as potential markers of tuber germination in future. Copyright © 2016 Elsevier

  16. Microorganisms maintain crowding homeostasis

    NARCIS (Netherlands)

    van den Berg, Jonas; Boersma, Arnold J; Poolman, Bert

    2017-01-01

    Macromolecular crowding affects the mobility of biomolecules, protein folding and stability, and the association of macromolecules with each other. Local differences in crowding that arise as a result of subcellular components and supramolecular assemblies contribute to the structural organization

  17. Influence of exogenous leptin on redox homeostasis in neutrophils and lymphocytes cultured in synovial fluid isolated from patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Michał Gajewski

    2016-07-01

    Full Text Available Objectives : Leptin is an adipose cells derived hormone that regulates energy homeostasis within the body. Energy metabolism of immune cells influences their activity within numerous pathological states, but the effect of leptin on these cells in unclear. On the one hand, it was observed that leptin induces neutrophils chemotaxis and modulates phagocytosis. On the other hand, neutrophils exposed to leptin did not display detectable Ca 2+ ions mobilization or β 2 -integrin upregulation. In this study, we investigated the effect of leptin on the redox homeostasis in lymphocytes and neutrophils. Material and methods : Neutrophils and lymphocytes were isolated by density-gradient centrifugation of blood from healthy volunteers. Cells were cultured with or without leptin (100 ng/ml for lymphocytes and 500 ng/ml for neutrophils or with or without synovial fluid (85% for 0–72 h. Culture media were not changed during incubation. Cells were homogenized and homogenate was frozen until laboratory measurements. Redox homeostasis was assessed by the reduced glutathione (GSH vs. oxidized glutathione (GSSG ratio and membrane lipid peroxidation evaluation. Results : Lymphocytes cultured with leptin and synovial fluid showed a significant increase of the GSSG level. The GSSG/GSH ratio increased by 184 ±37%. In neutrophils incubated in a similar environment, the GSSG/GSH ratio increased by just 21 ±7%, and the effect was observed irrespectively of whether they were exposed to leptin or synovial fluid or both together. Neither leptin nor synovial fluid influenced lipid peroxidation in neutrophils, but in lymphocytes leptin intensified lipid peroxidation. Conclusions : Leptin altered the lymphocytes, but not neutrophils redox state. Because firstly neutrophils are anaerobic cells and have just a few mitochondria and secondly lymphocytes have typical aerobic metabolism, the divergence of our data supports the hypothesis that leptin induces oxidative stress by

  18. High salinity helps the halophyte Sesuvium portulacastrum in defense against Cd toxicity by maintaining redox balance and photosynthesis.

    Science.gov (United States)

    Wali, Mariem; Gunsè, Benet; Llugany, Mercè; Corrales, Isabel; Abdelly, Chedly; Poschenrieder, Charlotte; Ghnaya, Tahar

    2016-08-01

    NaCl alleviates Cd toxicity in Sesvium portulacastrum by maintaining plant water status and redox balance, protecting chloroplasts structure and inducing some potential Cd (2+) chelators as GSH and proline. It has been demonstrated that NaCl alleviates Cd-induced growth inhibition in the halophyte Sesuvium portulacastrum. However, the processes that mediate this effect are still unclear. In this work we combined physiological, biochemical and ultrastructural studies to highlight the effects of salt on the redox balance and photosynthesis in Cd-stressed plants. Seedlings were exposed to different Cd concentrations (0, 25 and 50 µM Cd) combined with low (0.09 mM) (LS), or high (200 mM) NaCl (HS) in hydroponic culture. Plant-water relations, photosynthesis rate, leaf gas exchange, chlorophyll fluorescence, chloroplast ultrastructure, and proline and glutathione concentrations were analyzed after 1 month of treatment. In addition, the endogenous levels of stress-related hormones were determined in plants subjected to 25 µM Cd combined with both NaCl concentrations. In plants with low salt supply (LS), Cd reduced growth, induced plant dehydration, disrupted chloroplast structure and functioning, decreased net CO2 assimilation rate (A) and transpiration rate (E), inhibited the maximum potential quantum efficiency (Fv/Fm) and the quantum yield efficiency (Φ PSII) of PSII, and enhanced the non-photochemical quenching (NPQ). The addition of 200 mM NaCl (HS) to the Cd-containing medium culture significantly mitigated Cd phytotoxicity. Hence, even at similar internal Cd concentrations, HS-Cd plants were less affected by Cd than LS-Cd ones. Hence, 200 mM NaCl significantly alleviates Cd-induced toxicity symptoms, growth inhibition, and photosynthesis disturbances. The cell ultrastructure was better preserved in HS-Cd plants but affected in LS-Cd plants. The HS-Cd plants showed also higher concentrations of reduced glutathione (GSH), proline and jasmonic acid (JA

  19. FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting.

    Science.gov (United States)

    Liang, Qingning; Zhong, Ling; Zhang, Jialiang; Wang, Yu; Bornstein, Stefan R; Triggle, Chris R; Ding, Hong; Lam, Karen S L; Xu, Aimin

    2014-12-01

    Hepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. STAT3-RXR-Nrf2 activates systemic redox and energy homeostasis upon steep decline in pO2 gradient.

    Science.gov (United States)

    Paul, Subhojit; Gangwar, Anamika; Bhargava, Kalpana; Ahmad, Yasmin

    2018-04-01

    Hypobaric hypoxia elicits several patho-physiological manifestations, some of which are known to be lethal. Among various molecular mechanisms proposed so far, perturbation in redox state due to imbalance between radical generation and antioxidant defence is promising. These molecular events are also related to hypoxic status of cancer cells and therefore its understanding has extended clinical advantage beyond high altitude hypoxia. In present study, however, the focus was to understand and propose a model for rapid acclimatization of high altitude visitors to enhance their performance based on molecular changes. We considered using simulated hypobaric hypoxia at some established thresholds of high altitude stratification based on known physiological effects. Previous studies have focused on the temporal aspect while overlooking the effects of varying pO 2 levels during exposure to hypobaric hypoxia. The pO 2 levels, indicative of altitude, are crucial to redox homeostasis and can be the limiting factor during acclimatization to hypobaric hypoxia. In this study we present the effects of acute (24h) exposure to high (3049m; pO 2 : 71kPa), very high (4573m; pO 2 : 59kPa) and extreme altitude (7620m; pO 2 : 40kPa) zones on lung and plasma using semi-quantitative redox specific transcripts and quantitative proteo-bioinformatics workflow in conjunction with redox stress assays. It was observed that direct exposure to extreme altitude caused 100% mortality, which turned into high survival rate after pre-exposure to 59kPa, for which molecular explanation were also found. The pO 2 of 59kPa (very high altitude zone) elicits systemic energy and redox homeostatic processes by modulating the STAT3-RXR-Nrf2 trio. Finally we posit the various processes downstream of STAT3-RXR-Nrf2 and the plasma proteins that can be used to ascertain the redox status of an individual. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Engineering redox balance through cofactor systems.

    Science.gov (United States)

    Chen, Xiulai; Li, Shubo; Liu, Liming

    2014-06-01

    Redox balance plays an important role in the production of enzymes, pharmaceuticals, and chemicals. To meet the demands of industrial production, it is desirable that microbes maintain a maximal carbon flux towards target metabolites with no fluctuations in redox. This requires functional cofactor systems that support dynamic homeostasis between different redox states or functional stability in a given redox state. Redox balance can be achieved by improving the self-balance of a cofactor system, regulating the substrate balance of a cofactor system, and engineering the synthetic balance of a cofactor system. This review summarizes how cofactor systems can be manipulated to improve redox balance in microbes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. An appraisal of how the vitamin A-redox hypothesis can maintain honesty of carotenoid-dependent signals

    NARCIS (Netherlands)

    Simons, Mirre J. P.; Groothuis, Ton G. G.; Verhulst, Simon

    The vitamin A-redox hypothesis provides an explanation for honest signaling of phenotypic quality by carotenoid-dependent traits. A key aspect of the vitamin A-redox hypothesis, applicable to both yellow and red coloration, is the hypothesized negative feedback of tightly regulated Vitamin A plasma

  3. Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs.

    Science.gov (United States)

    Leoncini, Silvia; De Felice, Claudio; Signorini, Cinzia; Zollo, Gloria; Cortelazzo, Alessio; Durand, Thierry; Galano, Jean-Marie; Guerranti, Roberto; Rossi, Marcello; Ciccoli, Lucia; Hayek, Joussef

    2015-01-01

    An involvement of the immune system has been suggested in Rett syndrome (RTT), a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene (MECP2) or, more rarely, cyclin-dependent kinase-like 5 (CDKL5). To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg) response, as well as chemokines, were investigated in MECP2- (MECP2-RTT) (n = 16) and CDKL5-Rett syndrome (CDKL5-RTT) (n = 8), before and after ω-3 polyunsaturated fatty acids (PUFAs) supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2-RTT, a Th2-shifted balance was evidenced, whereas in CDKL5-RTT both Th1- and Th2-related cytokines (except for IL-4) were upregulated. In MECP2-RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5-RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system.

  4. Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs

    Directory of Open Access Journals (Sweden)

    Silvia Leoncini

    2015-01-01

    Full Text Available An involvement of the immune system has been suggested in Rett syndrome (RTT, a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene (MECP2 or, more rarely, cyclin-dependent kinase-like 5 (CDKL5. To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg response, as well as chemokines, were investigated in MECP2- (MECP2-RTT (n=16 and CDKL5-Rett syndrome (CDKL5-RTT (n=8, before and after ω-3 polyunsaturated fatty acids (PUFAs supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2-RTT, a Th2-shifted balance was evidenced, whereas in CDKL5-RTT both Th1- and Th2-related cytokines (except for IL-4 were upregulated. In MECP2-RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5-RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system.

  5. Melatonin confers plant tolerance against cadmium stress via the decrease of cadmium accumulation and reestablishment of microRNA-mediated redox homeostasis.

    Science.gov (United States)

    Gu, Quan; Chen, Ziping; Yu, Xiuli; Cui, Weiti; Pan, Jincheng; Zhao, Gan; Xu, Sheng; Wang, Ren; Shen, Wenbiao

    2017-08-01

    Although melatonin-alleviated cadmium (Cd) toxicity both in animals and plants have been well studied, little is known about its regulatory mechanisms in plants. Here, we discovered that Cd stress stimulated the production of endogenous melatonin in alfalfa seedling root tissues. The pretreatment with exogenous melatonin not only increased melatonin content, but also alleviated Cd-induced seedling growth inhibition. The melatonin-rich transgenic Arabidopsis plants overexpressing alfalfa SNAT (a melatonin synthetic gene) exhibited more tolerance than wild-type plants under Cd conditions. Cd content was also reduced in root tissues. In comparison with Cd stress alone, ABC transporter and PCR2 transcripts in alfalfa seedlings, PDR8 and HMA4 in Arabidopsis, were up-regulated by melatonin. By contrast, Nramp6 transcripts were down-regulated. Changes in above transporters were correlated with the less accumulation of Cd. Additionally Cd-triggered redox imbalance was improved by melatonin. These could be supported by the changes of the Cu/Zn Superoxide Dismutase gene regulated by miR398a and miR398b. Histochemical staining, laser scanning confocal microscope, and H 2 O 2 contents analyses showed the similar tendencies. Taking together, we clearly suggested that melatonin enhanced Cd tolerance via decreasing cadmium accumulation and reestablishing the microRNAs-mediated redox homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Recruitment of glutathione into the nucleus during cell proliferation adjusts whole-cell redox homeostasis in Arabidopsis thaliana and lowers the oxidative defence shield.

    Science.gov (United States)

    Vivancos, Pedro Diaz; Dong, Yingping; Ziegler, Kerstin; Markovic, Jelena; Pallardó, Federico V; Pellny, Till K; Verrier, Paul J; Foyer, Christine H

    2010-12-01

    Cellular redox homeostasis and signalling are important in progression of the eukaryotic cell cycle. In animals, the low-molecular-weight thiol tripeptide glutathione (GSH) is recruited into the nucleus early in the cell proliferation cycle. To determine whether a similar process occurs in plants, we studied cell proliferation in Arabidopsis thaliana. We show that GSH co-localizes with nuclear DNA during the proliferation of A. thaliana cells in culture. Moreover, GSH localization in the nucleus was observed in dividing pericycle cells of the lateral root meristem. There was pronounced accumulation of GSH in the nucleus at points in the growth cycle at which a high percentage of the cells were in G(1) phase, as identified by flow cytometry and marker transcripts. Recruitment of GSH into the nucleus led to a high abundance of GSH in the nucleus (GSHn) and severe depletion of the cytoplasmic GSH pool (GSHc). Sequestration of GSH in the nucleus was accompanied by significant decreases in transcripts associated with oxidative signalling and stress tolerance, and an increase in the abundance of hydrogen peroxide, an effect that was enhanced when the dividing cells were treated with salicylic acid. Total cellular GSH and the abundance of GSH1 and GSH2 transcripts increased after the initial recruitment of GSH into the nucleus. We conclude that GSH recruitment into the nucleus during cell proliferation has a profound effect on the whole-cell redox state. High GSHn levels trigger redox adjustments in the cytoplasm, favouring decreased oxidative signalling and enhanced GSH synthesis. © 2010 The Authors. The Plant Journal © 2010 Blackwell Publishing Ltd.

  7. All-oxide Raman-active traps for light and matter: probing redox homeostasis model reactions in aqueous environment.

    Science.gov (United States)

    Alessandri, Ivano; Depero, L E

    2014-04-09

    Core-shell colloidal crystals can act as very efficient traps for light and analytes. Here it is shown that Raman-active probes can be achieved using SiO2-TiO2 core-shell beads. These systems are successfully tested in monitoring of glutathione redox cycle at physiological concentration in aqueous environment, without need of any interfering enhancers. These materials represent a promising alternative to conventional, metal-based SERS probes for investigating chemical and biochemical reactions under real working conditions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Nitric oxide-mediated maintenance of redox homeostasis contributes to NPR1-dependent plant innate immunity triggered by lipopolysaccharides.

    Science.gov (United States)

    Sun, Aizhen; Nie, Shengjun; Xing, Da

    2012-10-01

    The perception of lipopolysaccharides (LPS) by plant cells can lead to nitric oxide (NO) production and defense gene induction. However, the signaling cascades underlying these cellular responses have not yet been resolved. This work investigated the biosynthetic origin of NO and the role of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) to gain insight into the mechanism involved in LPS-induced resistance of Arabidopsis (Arabidopsis thaliana). Analysis of inhibitors and mutants showed that LPS-induced NO synthesis was mainly mediated by an arginine-utilizing source of NO generation. Furthermore, LPS-induced NO caused transcript accumulation of alternative oxidase genes and increased antioxidant enzyme activity, which enhanced antioxidant capacity and modulated redox state. We also analyzed the subcellular localization of NPR1 to identify the mechanism for protein-modulated plant innate immunity triggered by LPS. LPS-activated defense responses, including callose deposition and defense-related gene expression, were found to be regulated through an NPR1-dependent pathway. In summary, a significant NO synthesis induced by LPS contributes to the LPS-induced defense responses by up-regulation of defense genes and modulation of cellular redox state. Moreover, NPR1 plays an important role in LPS-triggered plant innate immunity.

  9. A reason to eat healthy: The role of meaning in life in maintaining homeostasis in modern society

    Directory of Open Access Journals (Sweden)

    Bettina F Piko

    2016-02-01

    Full Text Available Health is a state of homeostasis of four principle kinds, namely, biochemical, physiological, psychological, and social. In this article, we complete this theory with a fifth element, namely, spiritual balance. Existential attitudes have been found to be closely related to identity formation, moral development, value-related attitudes, personal goals, and lifestyle choices. Meaning in life and searching for meaning serve better health since they may encourage people to engage in health-promoting behaviors and avoid health-risking behaviors, such as obesity and eating disorders. The meaning-making model proposes that people’s perceptions may contribute to content/discontent with life, body, and the world.

  10. Presenilin 1 Maintains Lysosomal Ca(2+) Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification.

    Science.gov (United States)

    Lee, Ju-Hyun; McBrayer, Mary Kate; Wolfe, Devin M; Haslett, Luke J; Kumar, Asok; Sato, Yutaka; Lie, Pearl P Y; Mohan, Panaiyur; Coffey, Erin E; Kompella, Uday; Mitchell, Claire H; Lloyd-Evans, Emyr; Nixon, Ralph A

    2015-09-01

    Presenilin 1 (PS1) deletion or Alzheimer's disease (AD)-linked mutations disrupt lysosomal acidification and proteolysis, which inhibits autophagy. Here, we establish that this phenotype stems from impaired glycosylation and instability of vATPase V0a1 subunit, causing deficient lysosomal vATPase assembly and function. We further demonstrate that elevated lysosomal pH in Presenilin 1 knockout (PS1KO) cells induces abnormal Ca(2+) efflux from lysosomes mediated by TRPML1 and elevates cytosolic Ca(2+). In WT cells, blocking vATPase activity or knockdown of either PS1 or the V0a1 subunit of vATPase reproduces all of these abnormalities. Normalizing lysosomal pH in PS1KO cells using acidic nanoparticles restores normal lysosomal proteolysis, autophagy, and Ca(2+) homeostasis, but correcting lysosomal Ca(2+) deficits alone neither re-acidifies lysosomes nor reverses proteolytic and autophagic deficits. Our results indicate that vATPase deficiency in PS1 loss-of-function states causes lysosomal/autophagy deficits and contributes to abnormal cellular Ca(2+) homeostasis, thus linking two AD-related pathogenic processes through a common molecular mechanism. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Presenilin 1 Maintains Lysosomal Ca2+ Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification

    Directory of Open Access Journals (Sweden)

    Ju-Hyun Lee

    2015-09-01

    Full Text Available Presenilin 1 (PS1 deletion or Alzheimer’s disease (AD-linked mutations disrupt lysosomal acidification and proteolysis, which inhibits autophagy. Here, we establish that this phenotype stems from impaired glycosylation and instability of vATPase V0a1 subunit, causing deficient lysosomal vATPase assembly and function. We further demonstrate that elevated lysosomal pH in Presenilin 1 knockout (PS1KO cells induces abnormal Ca2+ efflux from lysosomes mediated by TRPML1 and elevates cytosolic Ca2+. In WT cells, blocking vATPase activity or knockdown of either PS1 or the V0a1 subunit of vATPase reproduces all of these abnormalities. Normalizing lysosomal pH in PS1KO cells using acidic nanoparticles restores normal lysosomal proteolysis, autophagy, and Ca2+ homeostasis, but correcting lysosomal Ca2+ deficits alone neither re-acidifies lysosomes nor reverses proteolytic and autophagic deficits. Our results indicate that vATPase deficiency in PS1 loss-of-function states causes lysosomal/autophagy deficits and contributes to abnormal cellular Ca2+ homeostasis, thus linking two AD-related pathogenic processes through a common molecular mechanism.

  12. Chloroplastic thioredoxin-f and thioredoxin-m1/4 play important roles in brassinosteroids-induced changes in CO2 assimilation and cellular redox homeostasis in tomato

    OpenAIRE

    Cheng, Fei; Zhou, Yan-Hong; Xia, Xiao-Jian; Shi, Kai; Zhou, Jie; Yu, Jing-Quan

    2014-01-01

    Chloroplast thioredoxins (TRXs) and glutathione function as redox messengers in the regulation of photosynthesis. In this work, the roles of chloroplast TRXs in brassinosteroids (BRs)-induced changes in cellular redox homeostasis and CO2 assimilation were studied in the leaves of tomato plants. BRs-deficient d ^im plants showed decreased transcripts of TRX-f, TRX-m2, TRX-m1/4, and TRX-x, while exogenous BRs significantly induced CO2 assimilation and the expression of TRX-f, TRX-m2, TRX-m1/4, ...

  13. Wolfram Syndrome protein, Miner1, regulates sulphydryl redox status, the unfolded protein response, and Ca2+ homeostasis.

    Science.gov (United States)

    Wiley, Sandra E; Andreyev, Alexander Y; Divakaruni, Ajit S; Karisch, Robert; Perkins, Guy; Wall, Estelle A; van der Geer, Peter; Chen, Yi-Fan; Tsai, Ting-Fen; Simon, Melvin I; Neel, Benjamin G; Dixon, Jack E; Murphy, Anne N

    2013-06-01

    Miner1 is a redox-active 2Fe2S cluster protein. Mutations in Miner1 result in Wolfram Syndrome, a metabolic disease associated with diabetes, blindness, deafness, and a shortened lifespan. Embryonic fibroblasts from Miner1(-/-) mice displayed ER stress and showed hallmarks of the unfolded protein response. In addition, loss of Miner1 caused a depletion of ER Ca(2+) stores, a dramatic increase in mitochondrial Ca(2+) load, increased reactive oxygen and nitrogen species, an increase in the GSSG/GSH and NAD(+)/NADH ratios, and an increase in the ADP/ATP ratio consistent with enhanced ATP utilization. Furthermore, mitochondria in fibroblasts lacking Miner1 displayed ultrastructural alterations, such as increased cristae density and punctate morphology, and an increase in O2 consumption. Treatment with the sulphydryl anti-oxidant N-acetylcysteine reversed the abnormalities in the Miner1 deficient cells, suggesting that sulphydryl reducing agents should be explored as a treatment for this rare genetic disease. Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  14. Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution.

    Science.gov (United States)

    Zeng, Ming; Paiardini, Mirko; Engram, Jessica C; Beilman, Greg J; Chipman, Jeffrey G; Schacker, Timothy W; Silvestri, Guido; Haase, Ashley T

    2012-08-30

    Loss of the fibroblastic reticular cell (FRC) network in lymphoid tissues during HIV-1 infection has been shown to impair the survival of naive T cells and limit immune reconstitution after antiretroviral therapy. What causes this FRC loss is unknown. Because FRC loss correlates with loss of both naive CD4 and CD8 T-cell subsets and decreased lymphotoxin-β, a key factor for maintenance of FRC network, we hypothesized that loss of naive T cells is responsible for loss of the FRC network. To test this hypothesis, we assessed the consequences of antibody-mediated depletion of CD4 and CD8 T cells in rhesus macaques and sooty mangabeys. We found that only CD4 T-cell depletion resulted in FRC loss in both species and that this loss was caused by decreased lymphotoxin-β mainly produced by the CD4 T cells. We further found the same dependence of the FRC network on CD4 T cells in HIV-1-infected patients before and after antiretroviral therapy and in other immunodeficiency conditions, such as CD4 depletion in cancer patients induced by chemotherapy and irradiation. CD4 T cells thus play a central role in the maintenance of lymphoid tissue structure necessary for their own homeostasis and reconstitution.

  15. Effects of 12-Week Endurance Training at Natural Low Altitude on the Blood Redox Homeostasis of Professional Adolescent Athletes: A Quasi-Experimental Field Trial

    Directory of Open Access Journals (Sweden)

    Tomas K. Tong

    2016-01-01

    Full Text Available This field study investigated the influences of exposure to natural low altitude on endurance training-induced alterations of redox homeostasis in professional adolescent runners undergoing 12-week off-season conditioning program at an altitude of 1700 m (Alt, by comparison with that of their counterparts completing the program at sea-level (SL. For age-, gender-, and Tanner-stage-matched comparison, 26 runners (n=13 in each group were selected and studied. Following the conditioning program, unaltered serum levels of thiobarbituric acid reactive substances (TBARS, total antioxidant capacity (T-AOC, and superoxide dismutase accompanied with an increase in oxidized glutathione (GSSG and decreases of xanthine oxidase, reduced glutathione (GSH, and GSH/GSSG ratio were observed in both Alt and SL groups. Serum glutathione peroxidase and catalase did not change in SL, whereas these enzymes, respectively, decreased and increased in Alt. Uric acid (UA decreased in SL and increased in Alt. Moreover, the decreases in GSH and GSH/GSSG ratio in Alt were relatively lower compared to those in SL. Further, significant interindividual correlations were found between changes in catalase and TBARS, as well as between UA and T-AOC. These findings suggest that long-term training at natural low altitude is unlikely to cause retained oxidative stress in professional adolescent runners.

  16. Effects of 12-Week Endurance Training at Natural Low Altitude on the Blood Redox Homeostasis of Professional Adolescent Athletes: A Quasi-Experimental Field Trial.

    Science.gov (United States)

    Tong, Tomas K; Kong, Zhaowei; Lin, Hua; He, Yeheng; Lippi, Giuseppe; Shi, Qingde; Zhang, Haifeng; Nie, Jinlei

    2016-01-01

    This field study investigated the influences of exposure to natural low altitude on endurance training-induced alterations of redox homeostasis in professional adolescent runners undergoing 12-week off-season conditioning program at an altitude of 1700 m (Alt), by comparison with that of their counterparts completing the program at sea-level (SL). For age-, gender-, and Tanner-stage-matched comparison, 26 runners (n = 13 in each group) were selected and studied. Following the conditioning program, unaltered serum levels of thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (T-AOC), and superoxide dismutase accompanied with an increase in oxidized glutathione (GSSG) and decreases of xanthine oxidase, reduced glutathione (GSH), and GSH/GSSG ratio were observed in both Alt and SL groups. Serum glutathione peroxidase and catalase did not change in SL, whereas these enzymes, respectively, decreased and increased in Alt. Uric acid (UA) decreased in SL and increased in Alt. Moreover, the decreases in GSH and GSH/GSSG ratio in Alt were relatively lower compared to those in SL. Further, significant interindividual correlations were found between changes in catalase and TBARS, as well as between UA and T-AOC. These findings suggest that long-term training at natural low altitude is unlikely to cause retained oxidative stress in professional adolescent runners.

  17. Obesity Management: What Should We Do If Fat Gain Is Necessary to Maintain Body Homeostasis in a Modern World?

    Directory of Open Access Journals (Sweden)

    Angelo Tremblay

    2018-06-01

    Full Text Available The prevalence of overweight has substantially increased over the last decades despite the intent of health professionals and the general population to prevent this trend. Traditionally, this phenomenon has been attributed to unhealthy dietary macronutrient composition and/or to the decrease in physical activity participation. Beyond the influence of these factors, it is more than likely that other factors have influenced energy balance in a context of modernity. These include inadequate sleep, demanding cognitive effort, chemical pollution, and probably others which also have the potential to promote a positive energy balance but which are also part of the reality of success and productivity in a globalized world. As discussed in this paper, many individuals may become conflicted with themselves if they wish to prevent weight gain while influencing factors which are determinants of their socioeconomic success. In this regard, this paper reminds us of the contribution of adipose tissue gain in body homeostasis which is essential to permit energy balance, especially under lifestyle conditions promoting overfeeding. From a clinical standpoint, this imposes the consideration of a weight loss program as a search for compromise between what can be changed to promote a negative energy balance and what can be tolerated by the body in terms of fat loss. Furthermore, if we also consider the impact of pollution on energy balance for which we currently do not hold solutions of reversibility, we probably must accept that the mankind of today will have to be more corpulent than its ancestors. In this pessimistic environment, there are still possibilities to do better; however, this will probably require the revisiting of lifestyle practices according to what the human body and planet can tolerate as deviation from optimal functioning.

  18. Obesity Management: What Should We Do If Fat Gain Is Necessary to Maintain Body Homeostasis in a Modern World?

    Science.gov (United States)

    Tremblay, Angelo

    2018-01-01

    The prevalence of overweight has substantially increased over the last decades despite the intent of health professionals and the general population to prevent this trend. Traditionally, this phenomenon has been attributed to unhealthy dietary macronutrient composition and/or to the decrease in physical activity participation. Beyond the influence of these factors, it is more than likely that other factors have influenced energy balance in a context of modernity. These include inadequate sleep, demanding cognitive effort, chemical pollution, and probably others which also have the potential to promote a positive energy balance but which are also part of the reality of success and productivity in a globalized world. As discussed in this paper, many individuals may become conflicted with themselves if they wish to prevent weight gain while influencing factors which are determinants of their socioeconomic success. In this regard, this paper reminds us of the contribution of adipose tissue gain in body homeostasis which is essential to permit energy balance, especially under lifestyle conditions promoting overfeeding. From a clinical standpoint, this imposes the consideration of a weight loss program as a search for compromise between what can be changed to promote a negative energy balance and what can be tolerated by the body in terms of fat loss. Furthermore, if we also consider the impact of pollution on energy balance for which we currently do not hold solutions of reversibility, we probably must accept that the mankind of today will have to be more corpulent than its ancestors. In this pessimistic environment, there are still possibilities to do better; however, this will probably require the revisiting of lifestyle practices according to what the human body and planet can tolerate as deviation from optimal functioning.

  19. Critical role of RanBP2-mediated SUMOylation of Small Heterodimer Partner in maintaining bile acid homeostasis

    Science.gov (United States)

    Kim, Dong-Hyun; Kwon, Sanghoon; Byun, Sangwon; Xiao, Zhen; Park, Sean; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Kemper, Byron; Kemper, Jongsook Kim

    2016-01-01

    Bile acids (BAs) are recently recognized signalling molecules that profoundly affect metabolism. Because of detergent-like toxicity, BA levels must be tightly regulated. An orphan nuclear receptor, Small Heterodimer Partner (SHP), plays a key role in this regulation, but how SHP senses the BA signal for feedback transcriptional responses is not clearly understood. We show an unexpected function of a nucleoporin, RanBP2, in maintaining BA homoeostasis through SUMOylation of SHP. Upon BA signalling, RanBP2 co-localizes with SHP at the nuclear envelope region and mediates SUMO2 modification at K68, which facilitates nuclear transport of SHP and its interaction with repressive histone modifiers to inhibit BA synthetic genes. Mice expressing a SUMO-defective K68R SHP mutant have increased liver BA levels, and upon BA- or drug-induced biliary insults, these mice exhibit exacerbated cholestatic pathologies. These results demonstrate a function of RanBP2-mediated SUMOylation of SHP in maintaining BA homoeostasis and protecting from the BA hepatotoxicity. PMID:27412403

  20. Identification of novel microRNAs in post-transcriptional control of Nrf2 expression and redox homeostasis in neuronal, SH-SY5Y cells.

    Directory of Open Access Journals (Sweden)

    Madhusudhanan Narasimhan

    Full Text Available Nuclear factor-erythroid 2-related factor 2 (Nrf2/NFE2L2, a redox-sensitive transcription factor plays a critical role in adaptation to cellular stress and affords cellular defense by initiating transcription of antioxidative and detoxification genes. While a protein can be regulated at multiple levels, control of Nrf2 has been largely studied at post-translational regulation points by Keap1. Importantly, post-transcriptional/translational based regulation of Nrf2 is less understood and to date there are no reports on such mechanisms in neuronal systems. In this context, studies involving the role of microRNAs (miRs which are normally considered as fine tuning regulators of protein production through translation repression and/or post-transcriptional alterations, are in place. In the current study, based on in-silico analysis followed by immunoblotting and real time analysis, we have identified and validated for the first time that human NFE2L2 could be targeted by miR153/miR27a/miR142-5p/miR144 in neuronal, SH-SY5Y cells. Co-transfection studies with individual miR mimics along with either WT 3' UTR of human Nrf2 or mutated miRNA targeting seed sequence within Nrf2 3' UTR, demonstrated that Nrf2 is a direct regulatory target of these miRs. In addition, ectopic expression of miR153/miR27a/miR142-5p/miR144 affected Nrf2 mRNA abundance and nucleo-cytoplasmic concentration of Nrf2 in a Keap1 independent manner resulting in inefficient transactivating ability of Nrf2. Furthermore, forced expression of miRs diminished GCLC and GSR expression resulting in alteration of Nrf2 dependent redox homeostasis. Finally, bioinformatics based miRNA-disease network analysis (MDN along with extended computational network analysis of Nrf2 associated pathologic processes suggests that if in a particular cellular scenario where any of these miR153/miR27a/miR142-5p/miR144 either individually or as a group is altered, it could affect Nrf2 thus triggering and

  1. Novel insights in preventing Gram-negative bacterial infection in cirrhotic patients: review on the effects of GM-CSF in maintaining homeostasis of the immune system.

    Science.gov (United States)

    Xu, Dong; Zhao, Manzhi; Song, Yuhu; Song, Jianxin; Huang, Yuancheng; Wang, Junshuai

    2015-01-01

    Cirrhotic patients with dysfunctional and/or low numbers of leukocytes are often infected with bacteria, especially Gram-negative bacteria, which is characterized by producing lipopolysaccharide (LPS). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that influences the production, maturation, function, and survival of various immune cells. In this paper, we reviewed not only Toll-like receptors 4 (TLR4) signaling pathway and its immunological effect, but also the specific stimulating function and autocrine performance of GM-CSF on hematopoietic cells, as well as the recent discovery of innate response activator-B cells in protection against microbial sepsis and the direct LPS-TLR4 signaling on hematopoiesis. Thus we concluded that GM-CSF might play important roles in preventing Gram-negative bacterial infections in cirrhotic patients through maintaining immune system functions and homeostasis.

  2. Four weeks of normobaric "live high-train low" do not alter muscular or systemic capacity for maintaining pH and K+ homeostasis during intense exercise

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai B; Siebenmann, C; Jacobs, R A

    2012-01-01

    was double-blind and placebo controlled. Mean power during 30-s all-out cycling was similar before and immediately after LHTL (650 ± 31 vs. 628 ± 32 W; n = 10) and placebo exposure (658 ± 22 vs. 660 ± 23 W; n = 6). Supporting the performance data, arterial plasma pH, lactate, and K(+) during submaximal......It was investigated if athletes subjected to 4 wk of living in normobaric hypoxia (3,000 m; 16 h/day) while training at 800-1,300 m ["live high-train low" (LHTL)] increase muscular and systemic capacity for maintaining pH and K(+) homeostasis as well as intense exercise performance. The design...... before and after 4 wk of placebo-controlled normobaric LHTL. In accordance, 30-s all-out sprint ability was similar before and after LHTL....

  3. The actin-binding protein capulet genetically interacts with the microtubule motor kinesin to maintain neuronal dendrite homeostasis.

    Directory of Open Access Journals (Sweden)

    Paul M B Medina

    Full Text Available BACKGROUND: Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other. CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease.

  4. NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism.

    Science.gov (United States)

    Xiao, Wusheng; Wang, Rui-Sheng; Handy, Diane E; Loscalzo, Joseph

    2018-01-20

    The nicotinamide adenine dinucleotide (NAD + )/reduced NAD + (NADH) and NADP + /reduced NADP + (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD + -consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD + precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.

  5. Perturbations of Amino Acid Metabolism Associated with Glyphosate-Dependent Inhibition of Shikimic Acid Metabolism Affect Cellular Redox Homeostasis and Alter the Abundance of Proteins Involved in Photosynthesis and Photorespiration1[W][OA

    Science.gov (United States)

    Vivancos, Pedro Diaz; Driscoll, Simon P.; Bulman, Christopher A.; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H.

    2011-01-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway. PMID:21757634

  6. Perturbations of amino acid metabolism associated with glyphosate-dependent inhibition of shikimic acid metabolism affect cellular redox homeostasis and alter the abundance of proteins involved in photosynthesis and photorespiration.

    Science.gov (United States)

    Vivancos, Pedro Diaz; Driscoll, Simon P; Bulman, Christopher A; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H

    2011-09-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway.

  7. A novel differentiation pathway from CD4⁺ T cells to CD4⁻ T cells for maintaining immune system homeostasis.

    Science.gov (United States)

    Zhao, X; Sun, G; Sun, X; Tian, D; Liu, K; Liu, T; Cong, M; Xu, H; Li, X; Shi, W; Tian, Y; Yao, J; Guo, H; Zhang, D

    2016-04-14

    CD4(+) T lymphocytes are key players in the adaptive immune system and can differentiate into a variety of effector and regulatory T cells. Here, we provide evidence that a novel differentiation pathway of CD4(+) T cells shifts the balance from a destructive T-cell response to one that favors regulation in an immune-mediated liver injury model. Peripheral CD4(-)CD8(-)NK1.1(-) double-negative T cells (DNT) was increased following Concanavalin A administration in mice. Adoptive transfer of DNT led to significant protection from hepatocyte necrosis by direct inhibition on the activation of lymphocytes, a process that occurred primarily through the perforin-granzyme B route. These DNT converted from CD4(+) rather than CD8(+) T cells, a process primarily regulated by OX40. DNT migrated to the liver through the CXCR3-CXCL9/CXCL10 interaction. In conclusion, we elucidated a novel differentiation pathway from activated CD4(+) T cells to regulatory DNT cells for maintaining homeostasis of the immune system in vivo, and provided key evidence that utilizing this novel differentiation pathway has potential application in the prevention and treatment of autoimmune diseases.

  8. Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter.

    Science.gov (United States)

    Yang, Ruili; Yu, Tingting; Kou, Xiaoxing; Gao, Xiang; Chen, Chider; Liu, Dawei; Zhou, Yanheng; Shi, Songtao

    2018-06-01

    Ten-eleven translocation (Tet) family-mediated DNA oxidation represents an epigenetic modification capable of converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), which regulates various biological processes. However, it is unknown whether Tet family affects mesenchymal stem cells (MSCs) or the skeletal system. Here we show that depletion of Tet1 and Tet2 results in impaired self-renewal and differentiation of bone marrow MSCs (BMMSCs) and a significant osteopenia phenotype. Tet1 and Tet2 deficiency reduces demethylation of the P2rX7 promoter and downregulates exosome release, leading to intracellular accumulation of miR-297a-5p, miR-297b-5p, and miR-297c-5p. These miRNAs inhibit Runx2 signaling to impair BMMSC function. We show that overexpression of P2rX7 rescues the impaired BMMSCs and osteoporotic phenotype in Tet1 and Tet2 double knockout mice. These results indicate that Tet1 and Tet2 play a critical role in maintaining BMMSC and bone homeostasis through demethylation of P2rX7 to control exosome and miRNA release. This Tet/P2rX7/Runx2 cascade may serve as a target for the development of novel therapies for osteopenia disorders.

  9. Pak3 promotes cell cycle exit and differentiation of β-cells in the embryonic pancreas and is necessary to maintain glucose homeostasis in adult mice.

    Science.gov (United States)

    Piccand, Julie; Meunier, Aline; Merle, Carole; Jia, Zhengping; Barnier, Jean-Vianney; Gradwohl, Gérard

    2014-01-01

    The transcription factor neurogenin3 (Ngn3) triggers islet cell differentiation in the developing pancreas. However, little is known about the molecular mechanisms coupling cell cycle exit and differentiation in Ngn3(+) islet progenitors. We identified a novel effector of Ngn3 endocrinogenic function, the p21 protein-activated kinase Pak3, known to control neuronal differentiation and implicated in X-linked intellectual disability in humans. We show that Pak3 expression is initiated in Ngn3(+) endocrine progenitor cells and next maintained in maturing hormone-expressing cells during pancreas development as well as in adult islet cells. In Pak3-deficient embryos, the proliferation of Ngn3(+) progenitors and β-cells is transiently increased concomitantly with an upregulation of Ccnd1. β-Cell differentiation is impaired at E15.5 but resumes at later stages. Pak3-deficient mice do not develop overt diabetes but are glucose intolerant under high-fat diet (HFD). In the intestine, Pak3 is expressed in enteroendocrine cells but is not necessary for their differentiation. Our results indicate that Pak3 is a novel regulator of β-cell differentiation and function. Pak3 acts downstream of Ngn3 to promote cell cycle exit and differentiation in the embryo by a mechanism that might involve repression of Ccnd1. In the adult, Pak3 is required for the proper control of glucose homeostasis under challenging HFD.

  10. CD8+CD122+CD49dlow regulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity.

    Science.gov (United States)

    Akane, Kazuyuki; Kojima, Seiji; Mak, Tak W; Shiku, Hiroshi; Suzuki, Haruhiko

    2016-03-01

    The Fas/FasL (CD95/CD178) system is required for immune regulation; however, it is unclear in which cells, when, and where Fas/FasL molecules act in the immune system. We found that CD8(+)CD122(+) cells, which are mostly composed of memory T cells in comparison with naïve cells in the CD8(+)CD122(-) population, were previously shown to include cells with regulatory activity and could be separated into CD49d(low) cells and CD49d(high) cells. We established in vitro and in vivo experimental systems to evaluate the regulatory activity of CD122(+) cells. Regulatory activity was observed in CD8(+)CD122(+)CD49d(low) but not in CD8(+)CD122(+)CD49d(high) cells, indicating that the regulatory cells in the CD8(+)CD122(+) population could be narrowed down to CD49d(low) cells. CD8(+)CD122(-) cells taken from lymphoproliferation (lpr) mice were resistant to regulation by normal CD122(+) Tregs. CD122(+) Tregs taken from generalized lymphoproliferative disease (gld) mice did not regulate wild-type CD8(+)CD122(-) cells, indicating that the regulation by CD122(+) Tregs is Fas/FasL-dependent. CD122(+) Tregs taken from IL-10-deficient mice could regulate CD8(+)CD122(-) cells as equally as wild-type CD122(+) Tregs both in vitro and in vivo. MHC class I-missing T cells were not regulated by CD122(+) Tregs in vitro. CD122(+) Tregs also regulated CD4(+) cells in a Fas/FasL-dependent manner in vitro. These results suggest an essential role of Fas/FasL as a terminal effector of the CD122(+) Tregs that kill activated T cells to maintain immune homeostasis.

  11. Lysosome-Associated Membrane Proteins (LAMP Maintain Pancreatic Acinar Cell Homeostasis: LAMP-2–Deficient Mice Develop PancreatitisSummary

    Directory of Open Access Journals (Sweden)

    Olga A. Mareninova

    2015-11-01

    Full Text Available Background & Aims: The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated membrane proteins (LAMPs in pancreatitis. Methods: We analyzed changes in LAMPs in experimental models and human pancreatitis, and the underlying mechanisms: LAMP deglycosylation and degradation. LAMP cleavage by cathepsin B (CatB was analyzed by mass spectrometry. We used mice deficient in LAMP-2 to assess its role in pancreatitis. Results: Pancreatic levels of LAMP-1 and LAMP-2 greatly decrease across various pancreatitis models and in human disease. Pancreatitis does not trigger the LAMPs’ bulk deglycosylation but induces their degradation via CatB-mediated cleavage of the LAMP molecule close to the boundary between luminal and transmembrane domains. LAMP-2 null mice spontaneously develop pancreatitis that begins with acinar cell vacuolization due to impaired autophagic flux, and progresses to severe pancreas damage characterized by trypsinogen activation, macrophage-driven inflammation, and acinar cell death. LAMP-2 deficiency causes a decrease in pancreatic digestive enzymes content, and stimulates the basal and inhibits cholecystokinin-induced amylase secretion by acinar cells. The effects of LAMP-2 knockout and acute cerulein pancreatitis overlap, which corroborates the pathogenic role of LAMP decrease in experimental pancreatitis models. Conclusions: The results indicate a critical role for LAMPs, particularly LAMP-2, in maintaining pancreatic acinar cell homeostasis and provide evidence that defective lysosomal function, resulting in impaired autophagy, leads to pancreatitis. Mice with LAMP-2 deficiency present a novel genetic model of human pancreatitis caused by lysosomal/autophagic dysfunction. Keywords: Amylase Secretion, Autophagy

  12. Chloroplastic thioredoxin-f and thioredoxin-m1/4 play important roles in brassinosteroids-induced changes in CO2 assimilation and cellular redox homeostasis in tomato

    Science.gov (United States)

    Cheng, Fei; Zhou, Yan-Hong; Xia, Xiao-Jian; Shi, Kai; Zhou, Jie; Yu, Jing-Quan

    2014-01-01

    Chloroplast thioredoxins (TRXs) and glutathione function as redox messengers in the regulation of photosynthesis. In this work, the roles of chloroplast TRXs in brassinosteroids (BRs)-induced changes in cellular redox homeostasis and CO2 assimilation were studied in the leaves of tomato plants. BRs-deficient d ^im plants showed decreased transcripts of TRX-f, TRX-m2, TRX-m1/4, and TRX-x, while exogenous BRs significantly induced CO2 assimilation and the expression of TRX-f, TRX-m2, TRX-m1/4, and TRX-x. Virus-induced gene silencing (VIGS) of the chloroplast TRX-f, TRX-m2, TRX-m1/4, and TRX-y genes individually increased membrane lipid peroxidation and accumulation of 2-Cys peroxiredoxin dimers, and decreased the activities of the ascorbate–glutathione cycle enzymes and the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in the leaves. Furthermore, partial silencing of TRX-f, TRX-m2, TRX-m1/4, and TRX-y resulted in decreased expression of genes involved in the Benson–Calvin cycle and decreased activity of the associated enzymes. Importantly, the BRs-induced increase in CO2 assimilation and the increased expression and activities of antioxidant- and photosynthesis-related genes and enzymes were compromised in the partially TRX-f- and TRX-m1/4-silenced plants. All of these results suggest that TRX-f and TRX-m1/4 are involved in the BRs-induced changes in CO2 assimilation and cellular redox homeostasis in tomato. PMID:24847092

  13. STAT3-RXR-Nrf2 activates systemic redox and energy homeostasis upon steep decline in pO2 gradient

    OpenAIRE

    Subhojit Paul; Anamika Gangwar; Kalpana Bhargava; Yasmin Ahmad

    2018-01-01

    Hypobaric hypoxia elicits several patho-physiological manifestations, some of which are known to be lethal. Among various molecular mechanisms proposed so far, perturbation in redox state due to imbalance between radical generation and antioxidant defence is promising. These molecular events are also related to hypoxic status of cancer cells and therefore its understanding has extended clinical advantage beyond high altitude hypoxia. In present study, however, the focus was to understand and ...

  14. Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T-cell Effector Function in Mice: Implications for Combination with Immunotherapy.

    Science.gov (United States)

    Tyler, Paul M; Servos, Mariah M; de Vries, Romy C; Klebanov, Boris; Kashyap, Trinayan; Sacham, Sharon; Landesman, Yosef; Dougan, Michael; Dougan, Stephanie K

    2017-03-01

    Selinexor (KPT-330) is a first-in-class nuclear transport inhibitor currently in clinical trials as an anticancer agent. To determine how selinexor might affect antitumor immunity, we analyzed immune homeostasis in mice treated with selinexor and found disruptions in T-cell development, a progressive loss of CD8 T cells, and increases in inflammatory monocytes. Antibody production in response to immunization was mostly normal. Precursor populations in bone marrow and thymus were unaffected by selinexor, suggesting that normal immune homeostasis could recover. We found that a high dose of selinexor given once per week preserved nearly normal immune functioning, whereas a lower dose given 3 times per week did not restore immune homeostasis. Both naïve and effector CD8 T cells cultured in vitro showed impaired activation in the presence of selinexor. These experiments suggest that nuclear exportins are required for T-cell development and function. We determined the minimum concentration of selinexor required to block T-cell activation and showed that T-cell-inhibitory effects of selinexor occur at levels above 100 nmol/L, corresponding to the first 24 hours post-oral dosing. In a model of implantable melanoma, selinexor treatment at 10 mg/kg with a 4-day drug holiday led to intratumoral IFNγ + , granzyme B + cytotoxic CD8 T cells that were comparable with vehicle-treated mice. Overall, selinexor treatment leads to transient inhibition of T-cell activation, but clinically relevant once and twice weekly dosing schedules that incorporate sufficient drug holidays allow for normal CD8 T-cell functioning and development of antitumor immunity. Mol Cancer Ther; 16(3); 428-39. ©2017 AACR See related article by Farren et al., p. 417 . ©2017 American Association for Cancer Research.

  15. Clinical dosing regimen of selinexor maintains normal immune homeostasis and T cell effector function in mice: implications for combination with immunotherapy

    Science.gov (United States)

    Tyler, Paul M.; Servos, Mariah M.; de Vries, Romy C.; Klebanov, Boris; Kashyap, Trinayan; Sacham, Sharon; Landesman, Yosef; Dougan, Michael; Dougan, Stephanie K.

    2017-01-01

    Selinexor (KPT-330) is a first in class nuclear transport inhibitor currently in clinical trials as an anti-cancer agent. To determine how selinexor might impact anti-tumor immunity, we analyzed immune homeostasis in mice treated with selinexor and found disruptions in T cell development, a progressive loss of CD8 T cells and increases in inflammatory monocytes. Antibody production in response to immunization was mostly normal. Precursor populations in bone marrow and thymus were unaffected by selinexor, suggesting that normal immune homeostasis could recover. We found that a high dose of selinexor given once per week preserved nearly normal immune functioning, whereas a lower dose given 3 times per week did not restore immune homeostasis. Both naïve and effector CD8 T cells cultured in vitro showed impaired activation in the presence of selinexor. These experiments suggest that nuclear exportins are required for T cell development and function. We determined the minimum concentration of selinexor required to block T cell activation, and showed that T cell inhibitory effects of selinexor occur at levels above 100nM, corresponding to the first 24 hours post-oral dosing. In a model of implantable melanoma, selinexor treatment at 10 mg/kg with a 5 day drug holiday led to intratumoral IFNγ+, granzyme B+ cytotoxic CD8 T cells that were comparable to vehicle treated mice. Overall, selinexor treatment leads to transient inhibition of T cell activation but clinically relevant once and twice weekly dosing schedules that incorporate sufficient drug holidays allow for normal CD8 T cell functioning and development of anti-tumor immunity. PMID:28148714

  16. Plant redox proteomics

    DEFF Research Database (Denmark)

    Navrot, Nicolas; Finnie, Christine; Svensson, Birte

    2011-01-01

    PTMs in regulating enzymatic activities and controlling biological processes in plants. Notably, proteins controlling the cellular redox state, e.g. thioredoxin and glutaredoxin, appear to play dual roles to maintain oxidative stress resistance and regulate signal transduction pathways via redox PTMs......In common with other aerobic organisms, plants are exposed to reactive oxygen species resulting in formation of post-translational modifications related to protein oxidoreduction (redox PTMs) that may inflict oxidative protein damage. Accumulating evidence also underscores the importance of redox....... To get a comprehensive overview of these types of redox-regulated pathways there is therefore an emerging interest to monitor changes in redox PTMs on a proteome scale. Compared to some other PTMs, e.g. protein phosphorylation, redox PTMs have received less attention in plant proteome analysis, possibly...

  17. Short-Term Effects of Nose-Only Cigarette Smoke Exposure on Glutathione Redox Homeostasis, Cytochrome P450 1A1/2 and Respiratory Enzyme Activities in Mice Tissues

    Directory of Open Access Journals (Sweden)

    Haider Raza

    2013-05-01

    Full Text Available Background/Aims: The components of cigarette smoke (CS have been implicated in the development of cancer as well as in cardiopulmonary diseases. We have previously reported increased oxidative stress in rat tissues induced by tobacco-specific toxins nicotine and 4-(N-methyl-N-nitrosamino-1-(3-pyridyl-1-butanone (NNK. Recently, we have also shown increased oxidative stress and associated inflammatory responses in various tissues after exposure to cigarette smoke. Methods: In this study, we have further investigated the effects of nose-only cigarette smoke exposure on mitochondrial functions and glutathione-dependent redox metabolism in tissues of BALB/C mice. Liver, kidney, heart and lung tissues were analyzed for oxidative stress, glutathione (GSH and cytochrome P450 dependent enzyme activities and mitochondrial functions after exposure to smoke generated by 9 cigarettes/day for 4 days. Control mice were exposed to air only. Results: An increase in oxidative stress as observed by increased production of reactive oxygen species (ROS and altered GSH metabolism was apparent in all the tissues, but lung and heart appeared to be the main targets. Increased expression and activity of CYP450 1A1 and 1A2 were also observed in the tissues after exposure to cigarette smoke. Mitochondrial respiratory dysfunction in the tissues, as observed by alterations in the activities of Complex I and IV enzymes, was also observed after exposure to cigarette smoke. SDS-PAGE and Western blot results also indicate that alterations in the expression of enzyme proteins were in accordance with the changes in their catalytic functions. Conclusion: These results suggest that even short term exposure of cigarette smoke have adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking.

  18. Chloroplast Redox Poise

    DEFF Research Database (Denmark)

    Steccanella, Verdiana

    the redox status of the plastoquinone pool and chlorophyll biosynthesis. Furthermore, in the plant cell, the equilibrium between redox reactions and ROS signals is also maintained by various balancing mechanisms among which the thioredoxin reductase-thioredoxin system (TR-Trx) stands out as a mediator......The redox state of the chloroplast is maintained by a delicate balance between energy production and consumption and is affected by the need to avoid increased production of reactive oxygen species (ROS). Redox power and ROS generated in the chloroplast are essential for maintaining physiological...... metabolic pathways and for optimizing chloroplast functions. The redox poise of photosynthetic electron transport components like plastoquinone is crucial to initiate signaling cascades and might also be involved in key biosynthetic pathways such as chlorophyll biosynthesis. We, therefore, explored...

  19. Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs

    Directory of Open Access Journals (Sweden)

    Masanori Yoshinaga

    2017-05-01

    Full Text Available Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1, has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1−/− mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis.

  20. Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs.

    Science.gov (United States)

    Yoshinaga, Masanori; Nakatsuka, Yoshinari; Vandenbon, Alexis; Ori, Daisuke; Uehata, Takuya; Tsujimura, Tohru; Suzuki, Yutaka; Mino, Takashi; Takeuchi, Osamu

    2017-05-23

    Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1), has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1 -/- mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Jicheng; Gaffrey, Matthew J.; Qian, Wei-Jun

    2017-01-01

    Protein cysteine thiols play a crucial role in redox signaling, regulation of enzymatic activity and protein function, and maintaining redox homeostasis in living systems. The unique chemical reactivity of thiol groups makes cysteine susceptible to oxidative modifications by reactive oxygen and nitrogen species to form a broad array of reversible and irreversible protein post-translational modifications (PTMs). The reversible modifications in particular are one of the major components of redox signaling and are involved in regulation of various cellular processes under physiological and pathological conditions. The biological significance of these redox PTMs in health and diseases has been increasingly recognized. Herein, we review the recent advances of quantitative proteomic approaches for investigating redox PTMs in complex biological systems, including the general considerations of sample processing, various chemical or affinity enrichment strategies, and quantitative approaches. We also highlight a number of redox proteomic approaches that enable effective profiling of redox PTMs for addressing specific biological questions. Although some technological limitations remain, redox proteomics is paving the way towards a better understanding of redox signaling and regulation in human health and diseases.

  2. Anion exchanger 2 is critical for CD8(+) T cells to maintain pHi homeostasis and modulate immune responses.

    Science.gov (United States)

    Concepcion, Axel R; Salas, January T; Sarvide, Sarai; Sáez, Elena; Ferrer, Alex; López, María; Portu, Ainhoa; Banales, Jesús M; Hervás-Stubbs, Sandra; Oude Elferink, Ronald P J; Prieto, Jesús; Medina, Juan F

    2014-05-01

    Mitogenic stimulation of lymphocytes involves alkalinization of intracellular pH (pHi ). Subsequent pHi regulation may involve HCO3 (-) extrusion through Cl(-) /HCO3 (-) exchangers and/or Na(+) -HCO3 (-) co-transporters with acid-loading capability. Abnormalities in these mechanisms could result in immune dysfunctions, as suggested by the CD8(+) T-cell expansion encountered in mice lacking Ae2 (a widely expressed acid loader with electroneutral and Na(+) -independent Cl(-) /HCO3 (-) anion-exchange activity). Here we report that CD8(+) T cells but not CD4(+) T cells or other lymphocyte populations, are crucially dependent on Ae2 for pHi regulation. While total lymphocytes (including isolated CD4(+) T cells) exhibit Ae1 expression and Na(+) -HCO3 (-) co-transport with acidifying potential, CD8(+) T cells lack these acid-loading mechanisms. In Ae2-KO mice, CD4(+) but not CD8(+) T cells upregulate these potential Ae2 surrogates. As a consequence, Ae2-KO CD8(+) T cells exhibit alkalinized pHi , and dramatically increase their pHi upon CD3 stimulation. Moreover, stimulated Ae2-deficient CD8(+) T cells show enhanced intracellular production of IL-2 and membrane expression of its receptor IL-2Rα, together with increased cell proliferation and activation. These findings demonstrate that CD8(+) T cells are critically dependent on Ae2 for pHi homeostasis and tuning of cell proliferation and activation. Ae2 thus constitutes a novel target to modulate CD8(+) T-cell responses. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Mitochondrial Energy and Redox Signaling in Plants

    Science.gov (United States)

    Schwarzländer, Markus

    2013-01-01

    Abstract Significance: For a plant to grow and develop, energy and appropriate building blocks are a fundamental requirement. Mitochondrial respiration is a vital source for both. The delicate redox processes that make up respiration are affected by the plant's changing environment. Therefore, mitochondrial regulation is critically important to maintain cellular homeostasis. This involves sensing signals from changes in mitochondrial physiology, transducing this information, and mounting tailored responses, by either adjusting mitochondrial and cellular functions directly or reprogramming gene expression. Recent Advances: Retrograde (RTG) signaling, by which mitochondrial signals control nuclear gene expression, has been a field of very active research in recent years. Nevertheless, no mitochondrial RTG-signaling pathway is yet understood in plants. This review summarizes recent advances toward elucidating redox processes and other bioenergetic factors as a part of RTG signaling of plant mitochondria. Critical Issues: Novel insights into mitochondrial physiology and redox-regulation provide a framework of upstream signaling. On the other end, downstream responses to modified mitochondrial function have become available, including transcriptomic data and mitochondrial phenotypes, revealing processes in the plant that are under mitochondrial control. Future Directions: Drawing parallels to chloroplast signaling and mitochondrial signaling in animal systems allows to bridge gaps in the current understanding and to deduce promising directions for future research. It is proposed that targeted usage of new technical approaches, such as quantitative in vivo imaging, will provide novel leverage to the dissection of plant mitochondrial signaling. Antioxid. Redox Signal. 18, 2122–2144. PMID:23234467

  4. TmpL, a transmembrane protein required for intracellular redox homeostasis and virulence in a plant and an animal fungal pathogen.

    Directory of Open Access Journals (Sweden)

    Kwang-Hyung Kim

    2009-11-01

    have discovered a novel protein involved in the virulence of both plant and animal fungal pathogens. Our results strongly suggest that dysregulation of oxidative stress homeostasis in the absence of TmpL is the underpinning cause of the developmental and virulence defects observed in these studies.

  5. Mycobacterium tuberculosis has diminished capacity to counteract redox stress induced by elevated levels of endogenous superoxide.

    Science.gov (United States)

    Tyagi, Priyanka; Dharmaraja, Allimuthu T; Bhaskar, Ashima; Chakrapani, Harinath; Singh, Amit

    2015-07-01

    Mycobacterium tuberculosis (Mtb) has evolved protective and detoxification mechanisms to maintain cytoplasmic redox balance in response to exogenous oxidative stress encountered inside host phagocytes. In contrast, little is known about the dynamic response of this pathogen to endogenous oxidative stress generated within Mtb. Using a noninvasive and specific biosensor of cytoplasmic redox state of Mtb, we for first time discovered a surprisingly high sensitivity of this pathogen to perturbation in redox homeostasis induced by elevated endogenous reactive oxygen species (ROS). We synthesized a series of hydroquinone-based small molecule ROS generators and found that ATD-3169 permeated mycobacteria to reliably enhance endogenous ROS including superoxide radicals. When Mtb strains including multidrug-resistant (MDR) and extensively drug-resistant (XDR) patient isolates were exposed to this compound, a dose-dependent, long-lasting, and irreversible oxidative shift in intramycobacterial redox potential was detected. Dynamic redox potential measurements revealed that Mtb had diminished capacity to restore cytoplasmic redox balance in comparison with Mycobacterium smegmatis (Msm), a fast growing nonpathogenic mycobacterial species. Accordingly, Mtb strains were extremely susceptible to inhibition by ATD-3169 but not Msm, suggesting a functional linkage between dynamic redox changes and survival. Microarray analysis showed major realignment of pathways involved in redox homeostasis, central metabolism, DNA repair, and cell wall lipid biosynthesis in response to ATD-3169, all consistent with enhanced endogenous ROS contributing to lethality induced by this compound. This work provides empirical evidence that the cytoplasmic redox poise of Mtb is uniquely sensitive to manipulation in steady-state endogenous ROS levels, thus revealing the importance of targeting intramycobacterial redox metabolism for controlling TB infection. Copyright © 2015 The Authors. Published by

  6. Redox cofactor engineering in industrial microorganisms: strategies, recent applications and future directions.

    Science.gov (United States)

    Liu, Jiaheng; Li, Huiling; Zhao, Guangrong; Caiyin, Qinggele; Qiao, Jianjun

    2018-05-01

    NAD and NADP, a pivotal class of cofactors, which function as essential electron donors or acceptors in all biological organisms, drive considerable catabolic and anabolic reactions. Furthermore, they play critical roles in maintaining intracellular redox homeostasis. However, many metabolic engineering efforts in industrial microorganisms towards modification or introduction of metabolic pathways, especially those involving consumption, generation or transformation of NAD/NADP, often induce fluctuations in redox state, which dramatically impede cellular metabolism, resulting in decreased growth performance and biosynthetic capacity. Here, we comprehensively review the cofactor engineering strategies for solving the problematic redox imbalance in metabolism modification, as well as their features, suitabilities and recent applications. Some representative examples of in vitro biocatalysis are also described. In addition, we briefly discuss how tools and methods from the field of synthetic biology can be applied for cofactor engineering. Finally, future directions and challenges for development of cofactor redox engineering are presented.

  7. Ets transcription factor GABP controls T cell homeostasis and immunity.

    Science.gov (United States)

    Luo, Chong T; Osmanbeyoglu, Hatice U; Do, Mytrang H; Bivona, Michael R; Toure, Ahmed; Kang, Davina; Xie, Yuchen; Leslie, Christina S; Li, Ming O

    2017-10-20

    Peripheral T cells are maintained in the absence of vigorous stimuli, and respond to antigenic stimulation by initiating cell cycle progression and functional differentiation. Here we show that depletion of the Ets family transcription factor GA-binding protein (GABP) in T cells impairs T-cell homeostasis. In addition, GABP is critically required for antigen-stimulated T-cell responses in vitro and in vivo. Transcriptome and genome-wide GABP-binding site analyses identify GABP direct targets encoding proteins involved in cellular redox balance and DNA replication, including the Mcm replicative helicases. These findings show that GABP has a nonredundant role in the control of T-cell homeostasis and immunity.

  8. Proteostasis and REDOX state in the heart

    Science.gov (United States)

    Christians, Elisabeth S.

    2012-01-01

    Force-generating contractile cells of the myocardium must achieve and maintain their primary function as an efficient mechanical pump over the life span of the organism. Because only half of the cardiomyocytes can be replaced during the entire human life span, the maintenance strategy elicited by cardiac cells relies on uninterrupted renewal of their components, including proteins whose specialized functions constitute this complex and sophisticated contractile apparatus. Thus cardiac proteins are continuously synthesized and degraded to ensure proteome homeostasis, also termed “proteostasis.” Once synthesized, proteins undergo additional folding, posttranslational modifications, and trafficking and/or become involved in protein-protein or protein-DNA interactions to exert their functions. This includes key transient interactions of cardiac proteins with molecular chaperones, which assist with quality control at multiple levels to prevent misfolding or to facilitate degradation. Importantly, cardiac proteome maintenance depends on the cellular environment and, in particular, the reduction-oxidation (REDOX) state, which is significantly different among cardiac organelles (e.g., mitochondria and endoplasmic reticulum). Taking into account the high metabolic activity for oxygen consumption and ATP production by mitochondria, it is a challenge for cardiac cells to maintain the REDOX state while preventing either excessive oxidative or reductive stress. A perturbed REDOX environment can affect protein handling and conformation (e.g., disulfide bonds), disrupt key structure-function relationships, and trigger a pathogenic cascade of protein aggregation, decreased cell survival, and increased organ dysfunction. This review covers current knowledge regarding the general domain of REDOX state and protein folding, specifically in cardiomyocytes under normal-healthy conditions and during disease states associated with morbidity and mortality in humans. PMID:22003057

  9. Wine consumption and intestinal redox homeostasis

    Directory of Open Access Journals (Sweden)

    Fiorella Biasi

    2014-01-01

    Wine components have been proposed as an alternative natural approach to prevent or treat inflammatory bowel diseases. The difficulty remains to distinguish whether these positive properties are due only to polyphenols in wine or also to the alcohol intake, since many studies have reported ethanol to possess various beneficial effects. Our knowledge of the use of wine components in managing human intestinal inflammatory diseases is still quite limited, and further clinical studies may afford more solid evidence of their beneficial effects.

  10. Redox Signaling Mediated by Thioredoxin and Glutathione Systems in the Central Nervous System.

    Science.gov (United States)

    Ren, Xiaoyuan; Zou, Lili; Zhang, Xu; Branco, Vasco; Wang, Jun; Carvalho, Cristina; Holmgren, Arne; Lu, Jun

    2017-11-01

    The thioredoxin (Trx) and glutathione (GSH) systems play important roles in maintaining the redox balance in the brain, a tissue that is prone to oxidative stress due to its high-energy demand. These two disulfide reductase systems are active in various areas of the brain and are considered to be critical antioxidant systems in the central nervous system (CNS). Various neuronal disorders have been characterized to have imbalanced redox homeostasis. Recent Advances: In addition to their detrimental effects, recent studies have highlighted that reactive oxygen species/reactive nitrogen species (ROS/RNS) act as critical signaling molecules by modifying thiols in proteins. The Trx and GSH systems, which reversibly regulate thiol modifications, regulate redox signaling involved in various biological events in the CNS. In this review, we focus on the following: (i) how ROS/RNS are produced and mediate signaling in CNS; (ii) how Trx and GSH systems regulate redox signaling by catalyzing reversible thiol modifications; (iii) how dysfunction of the Trx and GSH systems causes alterations of cellular redox signaling in human neuronal diseases; and (iv) the effects of certain small molecules that target thiol-based signaling pathways in the CNS. Further study on the roles of thiol-dependent redox systems in the CNS will improve our understanding of the pathogenesis of many human neuronal disorders and also help to develop novel protective and therapeutic strategies against neuronal diseases. Antioxid. Redox Signal. 27, 989-1010.

  11. Protosappanin B protects PC12 cells against oxygen-glucose deprivation-induced neuronal death by maintaining mitochondrial homeostasis via induction of ubiquitin-dependent p53 protein degradation.

    Science.gov (United States)

    Zeng, Ke-Wu; Liao, Li-Xi; Zhao, Ming-Bo; Song, Fang-Jiao; Yu, Qian; Jiang, Yong; Tu, Peng-Fei

    2015-03-15

    Protosappanin B (PTB) is a bioactive dibenzoxocin derivative isolated from Caesalpinia sappan L. Here, we investigated the neuroprotective effects and the potential mechanisms of PTB on oxygen-glucose deprivation (OGD)-injured PC12 cells. Results showed that PTB significantly increased cell viability, inhibited cell apoptosis and up-regulated the expression of growth-associated protein 43 (a marker of neural outgrowth). Moreover, our study revealed that PTB effectively maintained mitochondrial homeostasis by up-regulation of mitochondrial membrane potential (MMP), inhibition of cytochrome c release from mitochondria and inactivation of mitochondrial caspase-9/3 apoptosis pathway. Further study showed that PTB significantly promoted cytoplasmic component degradation of p53 protein, a key negative regulator for mitochondrial function, resulting in a release of Bcl-2 from p53-Bcl-2 complex and an enhancing translocation of Bcl-2 to mitochondrial outer membrane. Finally, we found the degradation of p53 protein was induced by PTB via activation of a MDM2-dependent ubiquitination process. Taken together, our findings provided a new viewpoint of neuronal protection strategy for anoxia and ischemic injury with natural small molecular dibenzoxocin derivative by activating ubiquitin-dependent p53 protein degradation as well as increasing mitochondrial function. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Redox fronts

    International Nuclear Information System (INIS)

    Chapman, N.; McKinley, I.; Shea, M.; Smellie, J.

    1993-01-01

    This article describes the investigations of redox fronts performed at the Osamu Utsumi mine. Results obtained by modelling groups on the rate of movement of the redox fronts and on the chemical reactions involved are discussed. Some of the most important rockwater interactions which occur at redox fronts can be modelled reasonably well but the complex redox chemistry of elements like sulphur is poorly simulated. The observed enrichment of many trace elements close to the redox fronts could be of significance for high-level waste repositories, but cannot be quantified by existing models. (author) 6 figs., 1 tab

  13. The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

    Directory of Open Access Journals (Sweden)

    Stéphanie Anaís Castaldo

    2016-01-01

    Full Text Available The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy.

  14. Metal ion transporters and homeostasis.

    OpenAIRE

    Nelson, N

    1999-01-01

    Transition metals are essential for many metabolic processes and their homeostasis is crucial for life. Aberrations in the cellular metal ion concentrations may lead to cell death and severe diseases. Metal ion transporters play a major role in maintaining the correct concentrations of the various metal ions in the different cellular compartments. Recent studies of yeast mutants revealed key elements in metal ion homeostasis, including novel transport systems. Several of the proteins discover...

  15. Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

    Science.gov (United States)

    Taveggia, Carla

    2014-01-01

    Abstract Significance: Iron is the most abundant transition metal in biology and an essential cofactor for many cellular enzymes. Iron homeostasis impairment is also a component of peripheral neuropathies. Recent Advances: During the past years, much effort has been paid to understand the molecular mechanism involved in maintaining systemic iron homeostasis in mammals. This has been stimulated by the evidence that iron dyshomeostasis is an initial cause of several disorders, including genetic and sporadic neurodegenerative disorders. Critical Issues: However, very little has been done to investigate the physiological role of iron in peripheral nervous system (PNS), despite the development of suitable cellular and animal models. Future Directions: To stimulate research on iron metabolism and peripheral neuropathy, we provide a summary of the knowledge on iron homeostasis in the PNS, on its transport across the blood–nerve barrier, its involvement in myelination, and we identify unresolved questions. Furthermore, we comment on the role of iron in iron-related disorder with peripheral component, in demyelinating and metabolic peripheral neuropathies. Antioxid. Redox Signal. 21, 634–648. PMID:24409826

  16. Redox Biology in Neurological Function, Dysfunction, and Aging.

    Science.gov (United States)

    Franco, Rodrigo; Vargas, Marcelo R

    2018-04-23

    Reduction oxidation (redox) reactions are central to life and when altered, they can promote disease progression. In the brain, redox homeostasis is recognized to be involved in all aspects of central nervous system (CNS) development, function, aging, and disease. Recent studies have uncovered the diverse nature by which redox reactions and homeostasis contribute to brain physiology, and when dysregulated to pathological consequences. Redox reactions go beyond what is commonly described as oxidative stress and involve redox mechanisms linked to signaling and metabolism. In contrast to the nonspecific nature of oxidative damage, redox signaling involves specific oxidation/reduction reactions that regulate a myriad of neurological processes such as neurotransmission, homeostasis, and degeneration. This Forum is focused on the role of redox metabolism and signaling in the brain. Six review articles from leading scientists in the field that appraise the role of redox metabolism and signaling in different aspects of brain biology including neurodevelopment, neurotransmission, aging, neuroinflammation, neurodegeneration, and neurotoxicity are included. An original research article exemplifying these concepts uncovers a novel link between oxidative modifications, redox signaling, and neurodegeneration. This Forum highlights the recent advances in the field and we hope it encourages future research aimed to understand the mechanisms by which redox metabolism and signaling regulate CNS physiology and pathophysiology. Antioxid. Redox Signal. 00, 000-000.

  17. Monitoring thioredoxin redox with a genetically encoded red fluorescent biosensor.

    Science.gov (United States)

    Fan, Yichong; Makar, Merna; Wang, Michael X; Ai, Hui-Wang

    2017-09-01

    Thioredoxin (Trx) is one of the two major thiol antioxidants, playing essential roles in redox homeostasis and signaling. Despite its importance, there is a lack of methods for monitoring Trx redox dynamics in live cells, hindering a better understanding of physiological and pathological roles of the Trx redox system. In this work, we developed the first genetically encoded fluorescent biosensor for Trx redox by engineering a redox relay between the active-site cysteines of human Trx1 and rxRFP1, a redox-sensitive red fluorescent protein. We used the resultant biosensor-TrxRFP1-to selectively monitor perturbations of Trx redox in various mammalian cell lines. We subcellularly localized TrxRFP1 to image compartmentalized Trx redox changes. We further combined TrxRFP1 with a green fluorescent Grx1-roGFP2 biosensor to simultaneously monitor Trx and glutathione redox dynamics in live cells in response to chemical and physiologically relevant stimuli.

  18. Redox Buffer Strength

    Science.gov (United States)

    de Levie, Robert

    1999-04-01

    The proper functioning of enzymes in bodily fluids requires that the pH be maintained within rather narrow limits. The first line of defense against large pH fluctuations in such fluids is the passive control provided by the presence of pH buffers. The ability of pH buffers to stabilize the pH is indicated by the buffer value b introduced in 1922 by van Slyke. It is equally important for many enzymes that the redox potential is kept within a narrow range. In that case, stability of the potential is most readily achieved with a redox buffer. In this communication we define the redox buffer strength by analogy with acid-base buffer strength.

  19. Glutathione Redox System in β-Thalassemia/Hb E Patients

    Directory of Open Access Journals (Sweden)

    Ruchaneekorn W. Kalpravidh

    2013-01-01

    Full Text Available β-thalassemia/Hb E is known to cause oxidative stress induced by iron overload. The glutathione system is the major endogenous antioxidant that protects animal cells from oxidative damage. This study aimed to determine the effect of disease state and splenectomy on redox status expressed by whole blood glutathione (GSH/glutathione disulfide (GSSG and also to evaluate glutathione-related responses to oxidation in β-thalassemia/Hb E patients. Twenty-seven normal subjects and 25 β-thalassemia/Hb E patients were recruited and blood was collected. The GSH/GSSG ratio, activities of glutathione-related enzymes, hematological parameters, and serum ferritin levels were determined in individuals. Patients had high iron-induced oxidative stress, shown as significantly increased serum ferritin, a decreased GSH/GSSG ratio, and increased activities of glutathione-related enzymes. Splenectomy increased serum ferritin levels and decreased GSH levels concomitant with unchanged glutathione-related enzyme activities. The redox ratio had a positive correlation with hemoglobin levels and negative correlation with levels of serum ferritin. The glutathione system may be the body’s first-line defense used against oxidative stress and to maintain redox homeostasis in thalassemic patients based on the significant correlations between the GSH/GSSH ratio and degree of anemia or body iron stores.

  20. Persistent hepatitis virus infection and immune homeostasis

    OpenAIRE

    ZHOU Yun

    2014-01-01

    Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

  1. Amyloid and immune homeostasis.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2018-03-01

    Extracellular amyloid deposition defines a range of amyloidosis and amyloid-related disease. Addition to primary and secondary amyloidosis, amyloid-related disease can be observed in different tissue/organ that sharing the common pathogenesis based on the formation of amyloid deposition. Currently, both Alzheimer's disease and type 2 diabetes can be diagnosed with certainly only based on the autopsy results, by which amyloidosis of the associative tissue/organ is observed. Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. Furthermore, attempts for preventing amyloid formation and/or removing amyloid deposits from the brain have caused meningoencephalitis and consequent deaths among the subjects. Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Pain emotion and homeostasis.

    Science.gov (United States)

    Panerai, Alberto E

    2011-05-01

    Pain has always been considered as part of a defensive strategy, whose specific role is to signal an immediate, active danger. This definition partially fits acute pain, but certainly not chronic pain, that is maintained also in the absence of an active noxa or danger and that nowadays is considered a disease by itself. Moreover, acute pain is not only an automatic alerting system, but its severity and characteristics can change depending on the surrounding environment. The affective, emotional components of pain have been and are the object of extensive attention and research by psychologists, philosophers, physiologists and also pharmacologists. Pain itself can be considered to share the same genesis as emotions and as a specific emotion in contributing to the maintenance of the homeostasis of each unique subject. Interestingly, this role of pain reaches its maximal development in the human; some even argue that it is specific for the human primate.

  3. Gut Homeostasis, Microbial Dysbiosis, and Opioids.

    Science.gov (United States)

    Wang, Fuyuan; Roy, Sabita

    2017-01-01

    Gut homeostasis plays an important role in maintaining animal and human health. The disruption of gut homeostasis has been shown to be associated with multiple diseases. The mutually beneficial relationship between the gut microbiota and the host has been demonstrated to maintain homeostasis of the mucosal immunity and preserve the integrity of the gut epithelial barrier. Currently, rapid progress in the understanding of the host-microbial interaction has redefined toxicological pathology of opioids and their pharmacokinetics. However, it is unclear how opioids modulate the gut microbiome and metabolome. Our study, showing opioid modulation of gut homeostasis in mice, suggests that medical interventions to ameliorate the consequences of drug use/abuse will provide potential therapeutic and diagnostic strategies for opioid-modulated intestinal infections. The study of morphine's modulation of the gut microbiome and metabolome will shed light on the toxicological pathology of opioids and its role in the susceptibility to infectious diseases.

  4. Maintainability allocation

    International Nuclear Information System (INIS)

    Guyot, Christian.

    1980-06-01

    The author gives the general lines of a method for the allocation and for the evaluation of maintainability of complex systems which is to be developed during the conference. The maintainability objective is supposed to be formulated under the form of a mean time to repair (M.T.T.R.) [fr

  5. Three-component homeostasis control

    Science.gov (United States)

    Xu, Jin; Hong, Hyunsuk; Jo, Junghyo

    2014-03-01

    Two reciprocal components seem to be sufficient to maintain a control variable constant. However, pancreatic islets adapt three components to control glucose homeostasis. They are α (secreting glucagon), β (insulin), and δ (somatostatin) cells. Glucagon and insulin are the reciprocal hormones for increasing and decreasing blood glucose levels, while the role of somatostatin is unknown. However, it has been known how each hormone affects other cell types. Based on the pulsatile hormone secretion and the cellular interactions, this system can be described as coupled oscillators. In particular, we used the Landau-Stuart model to consider both amplitudes and phases of hormone oscillations. We found that the presence of the third component, δ cell, was effective to resist under glucose perturbations, and to quickly return to the normal glucose level once perturbed. Our analysis suggested that three components are necessary for advanced homeostasis control.

  6. Telomere Homeostasis: Interplay with Magnesium

    Directory of Open Access Journals (Sweden)

    Donogh Maguire

    2018-01-01

    Full Text Available Telomere biology, a key component of the hallmarks of ageing, offers insight into dysregulation of normative ageing processes that accompany age-related diseases such as cancer. Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also diminished during cellular senescence and normative physiological ageing. Inherent in the biochemistry of these processes is the role of magnesium, one of the main cellular ions and an essential cofactor in all reactions that use ATP. Magnesium plays an important role in many of the processes involved in regulating telomere structure, integrity and function. This review explores the mechanisms that maintain telomere structure and function, their influence on circadian rhythms and their impact on health and age-related disease. The pervasive role of magnesium in telomere homeostasis is also highlighted.

  7. Mechanisms of redox metabolism and cancer cell survival during extracellular matrix detachment.

    Science.gov (United States)

    Hawk, Mark A; Schafer, Zachary T

    2018-01-16

    Non-transformed cells that become detached from the extracellular matrix (ECM) undergo dysregulation of redox homeostasis and cell death. In contrast, cancer cells often acquire the ability to mitigate programmed cell death pathways and recalibrate the redox balance to survive after ECM detachment, facilitating metastatic dissemination. Accordingly, recent studies of the mechanisms by which cancer cells overcome ECM detachment-induced metabolic alterations have focused on mechanisms in redox homeostasis. The insights into these mechanisms may inform the development of therapeutics that manipulate redox homeostasis to eliminate ECM-detached cancer cells. Here, we review how ECM-detached cancer cells balance redox metabolism for survival. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Arabidopsis Glutaredoxin S17 Contributes to Vegetative Growth, Mineral Accumulation, and Redox Balance during Iron Deficiency

    Directory of Open Access Journals (Sweden)

    Han Yu

    2017-06-01

    Full Text Available Iron (Fe is an essential mineral nutrient and a metal cofactor required for many proteins and enzymes involved in the processes of DNA synthesis, respiration, and photosynthesis. Iron limitation can have detrimental effects on plant growth and development. Such effects are mediated, at least in part, through the generation of reactive oxygen species (ROS. Thus, plants have evolved a complex regulatory network to respond to conditions of iron limitations. However, the mechanisms that couple iron deficiency and oxidative stress responses are not fully understood. Here, we report the discovery that an Arabidopsis thaliana monothiol glutaredoxin S17 (AtGRXS17 plays a critical role in the plants ability to respond to iron deficiency stress and maintain redox homeostasis. In a yeast expression assay, AtGRXS17 was able to suppress the iron accumulation in yeast ScGrx3/ScGrx4 mutant cells. Genetic analysis indicated that plants with reduced AtGRXS17 expression were hypersensitive to iron deficiency and showed increased iron concentrations in mature seeds. Disruption of AtGRXS17 caused plant sensitivity to exogenous oxidants and increased ROS production under iron deficiency. Addition of reduced glutathione rescued the growth and alleviates the sensitivity of atgrxs17 mutants to iron deficiency. These findings suggest AtGRXS17 helps integrate redox homeostasis and iron deficiency responses.

  9. Neuronal regulation of homeostasis by nutrient sensing.

    Science.gov (United States)

    Lam, Tony K T

    2010-04-01

    In type 2 diabetes and obesity, the homeostatic control of glucose and energy balance is impaired, leading to hyperglycemia and hyperphagia. Recent studies indicate that nutrient-sensing mechanisms in the body activate negative-feedback systems to regulate energy and glucose homeostasis through a neuronal network. Direct metabolic signaling within the intestine activates gut-brain and gut-brain-liver axes to regulate energy and glucose homeostasis, respectively. In parallel, direct metabolism of nutrients within the hypothalamus regulates food intake and blood glucose levels. These findings highlight the importance of the central nervous system in mediating the ability of nutrient sensing to maintain homeostasis. Futhermore, they provide a physiological and neuronal framework by which enhancing or restoring nutrient sensing in the intestine and the brain could normalize energy and glucose homeostasis in diabetes and obesity.

  10. Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance

    Directory of Open Access Journals (Sweden)

    Anna E. Maciag

    2013-01-01

    Full Text Available JS-K is a nitric oxide (NO-releasing prodrug of the O2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the dearylation of the diazeniumdiolate by glutathione (GSH via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion spontaneously hydrolyzes, releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action.

  11. The homeostasis solution – Mechanical homeostasis in architecturally homeostatic buildings

    International Nuclear Information System (INIS)

    Wang, Lin-Shu; Ma, Peizheng

    2016-01-01

    Highlights: • Architectural homeostatic buildings (AHBs) make sense because of the laws of physics. • However, high efficiency can be obtained only with AHBs and equipment considered as systems. • Mechanical homeostasis facilitates AHB-equipment system synergy with heat extraction. • Entropically speaking a building needs neither energy nor a fixed amount of heat, but its homeostatic existence. • Homeostatic buildings can reduce building energy consumption from 80% to 90%. - Abstract: We already know, for energy-saving potential, the necessary architectural features in well-designed buildings: high performance building envelope, sufficient interior thermal mass, and hydronic-network activated radiant surfaces for cooling and heating. Buildings with these features may be referred to as architecturally homeostatic buildings (AHBs); such a building-system is thermally semi-autonomous in the sense that its temperature variation stays within a certain range even without conditioning equipment, and, with conditioning equipment in operation, its thermal regulation is handled by its hydronic heat-distribution-network for controlling the temperature level of the building. At the present time conventional HVAC equipment is used for maintaining the heat-distribution-network: this arrangement, however, has resulted in great energy saving only for AHBs with accessible natural water bodies. In operation of general AHBs, a case is made here for a new kind of mechanical equipment having the attribute of mechanical homeostasis (MH). MH is a new energy transformation concept in a triadic framework. Superlative energy efficiency is predicted as a result of combined improvements in higher triadCOPs and lower total (inducted + removed) heat rates—evincing existence of synergy in architectural and mechanical homeostasis, which together will be referred to as the homeostasis solution.

  12. Iron Supplementation Effects on Redox Status following Aseptic Skeletal Muscle Trauma in Adults and Children

    Directory of Open Access Journals (Sweden)

    Chariklia K. Deli

    2017-01-01

    Full Text Available Exercise-induced skeletal muscle microtrauma is characterized by loss of muscle cell integrity, marked aseptic inflammatory response, and oxidative stress. We examined if iron supplementation would alter redox status after eccentric exercise. In a randomized, double blind crossover study, that was conducted in two cycles, healthy adults (n=14 and children (n=11 received daily either 37 mg of elemental iron or placebo for 3 weeks prior to and up to 72 h after an acute eccentric exercise bout. Blood was drawn at baseline, before exercise, and 72 h after exercise for the assessment of iron status, creatine kinase activity (CK, and redox status. Iron supplementation at rest increased iron concentration and transferrin saturation (p<0.01. In adults, CK activity increased at 72 h after exercise, while no changes occurred in children. Iron supplementation increased TBARS at 72 h after exercise in both adults and children; no changes occurred under placebo condition. Eccentric exercise decreased bilirubin concentration at 72 h in all groups. Iron supplementation can alter redox responses after muscle-damaging exercise in both adults and children. This could be of great importance not only for healthy exercising individuals, but also in clinical conditions which are characterized by skeletal muscle injury and inflammation, yet iron supplementation is crucial for maintaining iron homeostasis. This study was registered at Clinicaltrials.gov Identifier: NCT02374619.

  13. Iron Supplementation Effects on Redox Status following Aseptic Skeletal Muscle Trauma in Adults and Children.

    Science.gov (United States)

    Deli, Chariklia K; Fatouros, Ioannis G; Paschalis, Vassilis; Tsiokanos, Athanasios; Georgakouli, Kalliopi; Zalavras, Athanasios; Avloniti, Alexandra; Koutedakis, Yiannis; Jamurtas, Athanasios Z

    2017-01-01

    Exercise-induced skeletal muscle microtrauma is characterized by loss of muscle cell integrity, marked aseptic inflammatory response, and oxidative stress. We examined if iron supplementation would alter redox status after eccentric exercise. In a randomized, double blind crossover study, that was conducted in two cycles, healthy adults ( n = 14) and children ( n = 11) received daily either 37 mg of elemental iron or placebo for 3 weeks prior to and up to 72 h after an acute eccentric exercise bout. Blood was drawn at baseline, before exercise, and 72 h after exercise for the assessment of iron status, creatine kinase activity (CK), and redox status. Iron supplementation at rest increased iron concentration and transferrin saturation ( p exercise, while no changes occurred in children. Iron supplementation increased TBARS at 72 h after exercise in both adults and children; no changes occurred under placebo condition. Eccentric exercise decreased bilirubin concentration at 72 h in all groups. Iron supplementation can alter redox responses after muscle-damaging exercise in both adults and children. This could be of great importance not only for healthy exercising individuals, but also in clinical conditions which are characterized by skeletal muscle injury and inflammation, yet iron supplementation is crucial for maintaining iron homeostasis. This study was registered at Clinicaltrials.gov Identifier: NCT02374619.

  14. Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

    KAUST Repository

    Liu, Peng; Zhang, Huoming; Yu, Boying; Xiong, Liming; Xia, Yiji

    2015-01-01

    in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional

  15. Maintaining positive

    OpenAIRE

    Gheorghe Gh. IONESCU; Adina Letitia NEGRUSA

    2004-01-01

    Maintaining positive work-force relationships includes in effective labor-management relations and making appropriate responses to current employee issues. Among the major current employee issues are protection from arbitrary dismissal, drug and alcohol abuse, privacy rights and family maters and they impact work. In our paper we discus two problems: first, the meanings of industrial democracy; second, the three principal operational concepts of industrial democracy (1) industrial democracy t...

  16. Kynurenine pathway metabolites and enzymes involved in redox reactions.

    Science.gov (United States)

    González Esquivel, D; Ramírez-Ortega, D; Pineda, B; Castro, N; Ríos, C; Pérez de la Cruz, V

    2017-01-01

    Oxido-reduction reactions are a fundamental part of the life due to support many vital biological processes as cellular respiration and glucose oxidation. In the redox reactions, one substance transfers one or more electrons to another substance. An important electron carrier is the coenzyme NAD + , which is involved in many metabolic pathways. De novo biosynthesis of NAD + is through the kynurenine pathway, the major route of tryptophan catabolism, which is sensitive to redox environment and produces metabolites with redox capacity, able to alter biological functions that are controlled by redox-responsive signaling pathways. Kynurenine pathway metabolites have been implicated in the physiology process and in the physiopathology of many diseases; processes that also share others factors as dysregulation of calcium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation and cell death, which impact the redox environment. This review examines in detail the available evidence in which kynurenine pathway metabolites participate in redox reactions and their effect on cellular redox homeostasis, since the knowledge of the main factors and mechanisms that lead to cell death in many neurodegenative disorders and other pathologies, such as mitochondrial dysfunction, oxidative stress and kynurenines imbalance, will allow to develop therapies using them as targets. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Gut commensal flora: tolerance and homeostasis

    OpenAIRE

    Rescigno, Maria

    2009-01-01

    Commensal microorganisms are not ignored by the intestinal immune system. Recent evidence shows that commensals actively participate in maintaining intestinal immune homeostasis by interacting with intestinal epithelial cells and delivering tolerogenic signals that are transmitted to the underlying cells of the immune system.

  18. Exercise redox biochemistry: Conceptual, methodological and technical recommendations

    Directory of Open Access Journals (Sweden)

    James N. Cobley

    2017-08-01

    Full Text Available Exercise redox biochemistry is of considerable interest owing to its translational value in health and disease. However, unaddressed conceptual, methodological and technical issues complicate attempts to unravel how exercise alters redox homeostasis in health and disease. Conceptual issues relate to misunderstandings that arise when the chemical heterogeneity of redox biology is disregarded: which often complicates attempts to use redox-active compounds and assess redox signalling. Further, that oxidised macromolecule adduct levels reflect formation and repair is seldom considered. Methodological and technical issues relate to the use of out-dated assays and/or inappropriate sample preparation techniques that confound biochemical redox analysis. After considering each of the aforementioned issues, we outline how each issue can be resolved and provide a unifying set of recommendations. We specifically recommend that investigators: consider chemical heterogeneity, use redox-active compounds judiciously, abandon flawed assays, carefully prepare samples and assay buffers, consider repair/metabolism, use multiple biomarkers to assess oxidative damage and redox signalling. Keywords: Exercise, Oxidative stress, Free radical, Antioxidants, Redox signalling

  19. Redox proteomics of tomato in response to Pseudomonas syringae infection

    Science.gov (United States)

    Balmant, Kelly Mayrink; Parker, Jennifer; Yoo, Mi-Jeong; Zhu, Ning; Dufresne, Craig; Chen, Sixue

    2015-01-01

    Unlike mammals with adaptive immunity, plants rely on their innate immunity based on pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) for pathogen defense. Reactive oxygen species, known to play crucial roles in PTI and ETI, can perturb cellular redox homeostasis and lead to changes of redox-sensitive proteins through modification of cysteine sulfhydryl groups. Although redox regulation of protein functions has emerged as an important mechanism in several biological processes, little is known about redox proteins and how they function in PTI and ETI. In this study, cysTMT proteomics technology was used to identify similarities and differences of protein redox modifications in tomato resistant (PtoR) and susceptible (prf3) genotypes in response to Pseudomonas syringae pv tomato (Pst) infection. In addition, the results of the redox changes were compared and corrected with the protein level changes. A total of 90 potential redox-regulated proteins were identified with functions in carbohydrate and energy metabolism, biosynthesis of cysteine, sucrose and brassinosteroid, cell wall biogenesis, polysaccharide/starch biosynthesis, cuticle development, lipid metabolism, proteolysis, tricarboxylic acid cycle, protein targeting to vacuole, and oxidation–reduction. This inventory of previously unknown protein redox switches in tomato pathogen defense lays a foundation for future research toward understanding the biological significance of protein redox modifications in plant defense responses. PMID:26504582

  20. Maintaining system homeostasis: the third law of Newtonian immunology.

    Science.gov (United States)

    Germain, Ronald N

    2012-10-01

    Because of the potent effector mechanisms of the immune system, the potential for self-destructive immune responses is especially high and many negative regulatory modalities exist to prevent excessive tissue damage. This Commentary places such regulatory mechanisms in the larger context of system organization on many scales. The sometimes counterintuitive nature of feedback control is discussed and a case is made for greater attention to quantitative spatiotemporal aspects of regulation, rather than limiting the discussion to the qualitative descriptions of pathways that dominate at present.

  1. The Redox Code.

    Science.gov (United States)

    Jones, Dean P; Sies, Helmut

    2015-09-20

    The redox code is a set of principles that defines the positioning of the nicotinamide adenine dinucleotide (NAD, NADP) and thiol/disulfide and other redox systems as well as the thiol redox proteome in space and time in biological systems. The code is richly elaborated in an oxygen-dependent life, where activation/deactivation cycles involving O₂ and H₂O₂ contribute to spatiotemporal organization for differentiation, development, and adaptation to the environment. Disruption of this organizational structure during oxidative stress represents a fundamental mechanism in system failure and disease. Methodology in assessing components of the redox code under physiological conditions has progressed, permitting insight into spatiotemporal organization and allowing for identification of redox partners in redox proteomics and redox metabolomics. Complexity of redox networks and redox regulation is being revealed step by step, yet much still needs to be learned. Detailed knowledge of the molecular patterns generated from the principles of the redox code under defined physiological or pathological conditions in cells and organs will contribute to understanding the redox component in health and disease. Ultimately, there will be a scientific basis to a modern redox medicine.

  2. Reactive Oxygen Species and Mitochondrial Homeostasis as Regulators of Stem Cell Fate and Function.

    Science.gov (United States)

    Tan, Darren Q; Suda, Toshio

    2018-07-10

    The precise role and impact of reactive oxygen species (ROS) in stem cells, which are essential for lifelong tissue homeostasis and regeneration, remain of significant interest to the field. The long-term regenerative potential of a stem cell compartment is determined by the delicate balance between quiescence, self-renewal, and differentiation, all of which can be influenced by ROS levels. Recent Advances: The past decade has seen a growing appreciation for the importance of ROS and redox homeostasis in various stem cell compartments, particularly those of hematopoietic, neural, and muscle tissues. In recent years, the importance of proteostasis and mitochondria in relation to stem cell biology and redox homeostasis has garnered considerable interest. Here, we explore the reciprocal relationship between ROS and stem cells, with significant emphasis on mitochondria as a core component of redox homeostasis. We discuss how redox signaling, involving cell-fate determining protein kinases and transcription factors, can control stem cell function and fate. We also address the impact of oxidative stress on stem cells, especially oxidative damage of lipids, proteins, and nucleic acids. We further discuss ROS management in stem cells, and present recent evidence supporting the importance of mitochondrial activity and its modulation (via mitochondrial clearance, biogenesis, dynamics, and distribution [i.e., segregation and transfer]) in stem cell redox homeostasis. Therefore, elucidating the intricate links between mitochondria, cellular metabolism, and redox homeostasis is envisioned to be critical for our understanding of ROS in stem cell biology and its therapeutic relevance in regenerative medicine. Antioxid. Redox Signal. 00, 000-000.

  3. Anticancer Activity of Metal Complexes: Involvement of Redox Processes

    Science.gov (United States)

    Jungwirth, Ute; Kowol, Christian R.; Keppler, Bernhard K.; Hartinger, Christian G.; Berger, Walter; Heffeter, Petra

    2012-01-01

    Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e.g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of “activation by reduction” as well as the “hard and soft acids and bases” theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology. PMID:21275772

  4. Improving the hydrogen production capacity of Rhodobacter capsulatus by genetically modifying redox balancing pathways

    Energy Technology Data Exchange (ETDEWEB)

    Oeztuerk, Yavuz [TUEBITAK Research Institute for Genetic Engineering and Biotechnology, Gebze Kocaeli (Turkey); Goekce, Abdulmecit [Istanbul Technical Univ. (Turkey). Dept. of Molecular Biology and Genetics; Guergan, Muazzez; Yuecel, Meral [Middle East Technical Univ., Ankara (Turkey). Dept. of Biology

    2010-07-01

    In Rhodobacter capsulatus, balancing the oxidation-reduction potential (redox-balance) is maintained via a number of inter-dependent regulatory mechanisms that enable these organisms to accommodate divergent growth modes. In order to maintain redox homeostasis, this bacterium possesses regulatory mechanisms functioning as electron sinks affecting the oxidation-reduction state of the ubiquinone pool. Under the photoheterotrophic growth conditions with reduced carbon sources, the excess reducing equivalents are primarily consumed via the reduction of CO{sub 2} through the Calvin-Benson-Bassham (CBB) pathway or by the reduction of protons into hydrogen with the use of dinitrogenase enzyme system. In this study, our aim was to develop strategies to funnel the excess reducing equivalents to nitrogenase-dependent hydrogen production by blocking the carbon-fixation pathway. To realize this purpose, CO{sub 2} fixation was blocked by inactivating the Phosphoribulokinase (PRK) of CBB pathway in wild type (MT1131), uptake-hydrogenase (YO3) and cyt cbb{sub 3} oxidase deficient (YO4) strains. The hydrogen production capacity of newly generated strains deficient in the Calvin-Benson-Bassham pathway were analyzed and compared with wild type strains. The results indicated that, the hydrogen production efficiency and capacity of R. capsulatus was further improved by directing the excess reducing equivalents to dinitrogenase-dependent hydrogen production. (orig.)

  5. Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism

    DEFF Research Database (Denmark)

    Olsen, Rikke K J; Cornelius, Nanna; Gregersen, Niels

    2015-01-01

    Mitochondria play a key role in overall cell physiology and health by integrating cellular metabolism with cellular defense and repair mechanisms in response to physiological or environmental changes or stresses. In fact, dysregulation of mitochondrial stress responses and its consequences...... in the form of oxidative stress, has been linked to a wide variety of diseases including inborn errors of metabolism. In this review we will summarize how the functional state of mitochondria -- and especially the concentration of reactive oxygen species (ROS), produced in connection with the respiratory...... chain -- regulates cellular stress responses by redox regulation of nuclear gene networks involved in repair systems to maintain cellular homeostasis and health. Based on our own and other's studies we re-introduce the ROS triangle model and discuss how inborn errors of mitochondrial metabolism...

  6. Redox characteristics of the eukaryotic cytosol

    DEFF Research Database (Denmark)

    López-Mirabal, H Reynaldo; Winther, Jakob R

    2007-01-01

    The eukaryotic cytoplasm has long been regarded as a cellular compartment in which the reduced state of protein cysteines is largely favored. Under normal conditions, the cytosolic low-molecular weight redox buffer, comprising primarily of glutathione, is highly reducing and reactive oxygen species...... (ROS) and glutathionylated proteins are maintained at very low levels. In the present review, recent progress in the understanding of the cytosolic thiol-disulfide redox metabolism and novel analytical approaches to studying cytosolic redox properties are discussed. We will focus on the yeast model...... organism, Saccharomyces cerevisiae, where the combination of genetic and biochemical approaches has brought us furthest in understanding the mechanisms underlying cellular redox regulation. It has been shown in yeast that, in addition to the enzyme glutathione reductase, other mechanisms may exist...

  7. Exercise redox biochemistry: Conceptual, methodological and technical recommendations.

    Science.gov (United States)

    Cobley, James N; Close, Graeme L; Bailey, Damian M; Davison, Gareth W

    2017-08-01

    Exercise redox biochemistry is of considerable interest owing to its translational value in health and disease. However, unaddressed conceptual, methodological and technical issues complicate attempts to unravel how exercise alters redox homeostasis in health and disease. Conceptual issues relate to misunderstandings that arise when the chemical heterogeneity of redox biology is disregarded: which often complicates attempts to use redox-active compounds and assess redox signalling. Further, that oxidised macromolecule adduct levels reflect formation and repair is seldom considered. Methodological and technical issues relate to the use of out-dated assays and/or inappropriate sample preparation techniques that confound biochemical redox analysis. After considering each of the aforementioned issues, we outline how each issue can be resolved and provide a unifying set of recommendations. We specifically recommend that investigators: consider chemical heterogeneity, use redox-active compounds judiciously, abandon flawed assays, carefully prepare samples and assay buffers, consider repair/metabolism, use multiple biomarkers to assess oxidative damage and redox signalling. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Maintaining evolvability.

    Science.gov (United States)

    Crow, James F

    2008-12-01

    Although molecular methods, such as QTL mapping, have revealed a number of loci with large effects, it is still likely that the bulk of quantitative variability is due to multiple factors, each with small effect. Typically, these have a large additive component. Conventional wisdom argues that selection, natural or artificial, uses up additive variance and thus depletes its supply. Over time, the variance should be reduced, and at equilibrium be near zero. This is especially expected for fitness and traits highly correlated with it. Yet, populations typically have a great deal of additive variance, and do not seem to run out of genetic variability even after many generations of directional selection. Long-term selection experiments show that populations continue to retain seemingly undiminished additive variance despite large changes in the mean value. I propose that there are several reasons for this. (i) The environment is continually changing so that what was formerly most fit no longer is. (ii) There is an input of genetic variance from mutation, and sometimes from migration. (iii) As intermediate-frequency alleles increase in frequency towards one, producing less variance (as p --> 1, p(1 - p) --> 0), others that were originally near zero become more common and increase the variance. Thus, a roughly constant variance is maintained. (iv) There is always selection for fitness and for characters closely related to it. To the extent that the trait is heritable, later generations inherit a disproportionate number of genes acting additively on the trait, thus increasing genetic variance. For these reasons a selected population retains its ability to evolve. Of course, genes with large effect are also important. Conspicuous examples are the small number of loci that changed teosinte to maize, and major phylogenetic changes in the animal kingdom. The relative importance of these along with duplications, chromosome rearrangements, horizontal transmission and polyploidy

  9. Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation.

    Science.gov (United States)

    Tanaka, Leonardo Y; Laurindo, Francisco R M

    2017-08-01

    Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases. Copyright © 2017 Elsevier Inc. All

  10. [Bone homeostasis and Mechano biology.

    Science.gov (United States)

    Nakashima, Tomoki

    The weight-bearing exercises help to build bones and to maintain them strength. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. During bone remodeling, resorption by osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the regulation of bone remodeling in response to mechanical and endocrine stimuli.

  11. The Redox Proteome*

    Science.gov (United States)

    Go, Young-Mi; Jones, Dean P.

    2013-01-01

    The redox proteome consists of reversible and irreversible covalent modifications that link redox metabolism to biologic structure and function. These modifications, especially of Cys, function at the molecular level in protein folding and maturation, catalytic activity, signaling, and macromolecular interactions and at the macroscopic level in control of secretion and cell shape. Interaction of the redox proteome with redox-active chemicals is central to macromolecular structure, regulation, and signaling during the life cycle and has a central role in the tolerance and adaptability to diet and environmental challenges. PMID:23861437

  12. Baseline and post-stress seasonal changes in immunocompetence and redox state maintenance in the fishing bat Myotis vivesi

    Science.gov (United States)

    Ibáñez-Contreras, Alejandra; Miranda-Labra, Roxana U.; Flores-Martínez, José Juan

    2018-01-01

    Little is known of how the stress response varies when animals confront seasonal life-history processes. Antioxidant defenses and damage caused by oxidative stress and their link with immunocompetence are powerful biomarkers to assess animal´s physiological stress response. The aim of this study was A) to determine redox state and variation in basal (pre-acute stress) immune function during summer, autumn and winter (spring was not assessed due to restrictions in collecting permit) in the fish-eating Myotis (Myotis vivesi; Chiroptera), and B) to determine the effect of acute stress on immunocompetence and redox state during each season. Acute stress was stimulated by restricting animal movement for 6 and 12 h. The magnitude of the cellular immune response was higher during winter whilst that of the humoral response was at its highest during summer. Humoral response increased after 6 h of movement restriction stress and returned to baseline levels after 12 h. Basal redox state was maintained throughout the year, with no significant changes in protein damage, and antioxidant activity was modulated mainly in relation to variation to environment cues, increasing during high temperatures and decreasing during windy nights. Antioxidant activity increased after the 6 h of stressful stimuli especially during summer and autumn, and to a lesser extent in early winter, but redox state did not vary. However, protein damage increased after 12 h of stress during summer. Prolonged stress when the bat is engaged in activities of high energy demand overcame its capacity to maintain homeostasis resulting in oxidative damage. PMID:29293551

  13. New tools for redox biology: From imaging to manipulation.

    Science.gov (United States)

    Bilan, Dmitry S; Belousov, Vsevolod V

    2017-08-01

    Redox reactions play a key role in maintaining essential biological processes. Deviations in redox pathways result in the development of various pathologies at cellular and organismal levels. Until recently, studies on transformations in the intracellular redox state have been significantly hampered in living systems. The genetically encoded indicators, based on fluorescent proteins, have provided new opportunities in biomedical research. The existing indicators already enable monitoring of cellular redox parameters in different processes including embryogenesis, aging, inflammation, tissue regeneration, and pathogenesis of various diseases. In this review, we summarize information about all genetically encoded redox indicators developed to date. We provide the description of each indicator and discuss its advantages and limitations, as well as points that need to be considered when choosing an indicator for a particular experiment. One chapter is devoted to the important discoveries that have been made by using genetically encoded redox indicators. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Pathophysiology of neutrophil-mediated extracellular redox reactions.

    Science.gov (United States)

    Jaganjac, Morana; Cipak, Ana; Schaur, Rudolf Joerg; Zarkovic, Neven

    2016-01-01

    Neutrophil granulocyte leukocytes (neutrophils) play fundamental role in the innate immune response. In the presence of adequate stimuli, neutrophils release excessive amount of reactive oxygen species (ROS) that may induce cell and tissue injury. Oxidative burst of neutrophils acts as a double-edged sword. It may contribute to the pathology of atherosclerosis and brain injury but is also necessary in resolving infections. Moreover, neutrophil-derived ROS may also have both a tumor promoting and tumor suppressing role. ROS have a specific activities and diffusion distance, which is related to their short lifetime. Therefore, the manner in which ROS will act depends on the cells targeted and the intra- and extracellular levels of individual ROS, which can further cause production of reactive aldehydes like 4-hydroxynonenal (HNE) that act as a second messengers of ROS. In this review we discuss the influence of neutrophil mediated extracellular redox reactions in ischemia reperfusion injury, transplant rejection and chronic diseases (atherosclerosis, inflammatory bowel diseases and cancer). At the end a brief overview of cellular mechanisms to maintain ROS homeostasis is given.

  15. The interplay between mitochondrial protein and iron homeostasis and its possible role in ageing.

    Science.gov (United States)

    Mallikarjun, Venkatesh; Sriram, Ashwin; Scialo, Filippo; Sanz, Alberto

    2014-08-01

    Free (labile or chelatable) iron is extremely redox-active and only represents a small fraction of the total mitochondrial iron population. Several studies have shown that the proportion of free iron increases with age, leading to increased Fenton chemistry in later life. It is not clear why free iron accumulates in mitochondria, but it does so in parallel with an inability to degrade and recycle damaged proteins that causes loss of mitochondrial protein homeostasis (proteostasis). The increase in oxidative damage that has been shown to occur with age might be explained by these two processes. While this accumulation of oxidative damage has often been cited as causative to ageing there are examples of model organisms that possess high levels of oxidative damage throughout their lives with no effect on lifespan. Interestingly, these same animals are characterised by an outstanding ability to maintain correct proteostasis during their entire life. ROS can damage critical components of the iron homeostasis machinery, while the efficacy of mitochondrial quality control mechanisms will determine how detrimental that damage is. Here we review the interplay between iron and organellar quality control in mitochondrial dysfunction and we suggest that a decline in mitochondrial proteostasis with age leaves iron homeostasis (where several key stages are thought to be dependent on proteostasis machinery) vulnerable to oxidative damage and other age-related stress factors. This will have severe consequences for the electron transport chain and TCA cycle (among other processes) where several components are acutely dependent on correct assembly, insertion and maintenance of iron-sulphur clusters, leading to energetic crisis and death. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Thiol/disulfide redox states in signaling and sensing

    Science.gov (United States)

    Go, Young-Mi; Jones, Dean P.

    2015-01-01

    Rapid advances in redox systems biology are creating new opportunities to understand complexities of human disease and contributions of environmental exposures. New understanding of thiol-disulfide systems have occurred during the past decade as a consequence of the discoveries that thiol and disulfide systems are maintained in kinetically controlled steady-states displaced from thermodynamic equilibrium, that a widely distributed family of NADPH oxidases produces oxidants that function in cell signaling, and that a family of peroxiredoxins utilize thioredoxin as a reductant to complement the well-studied glutathione antioxidant system for peroxide elimination and redox regulation. This review focuses on thiol/disulfide redox state in biologic systems and the knowledge base available to support development of integrated redox systems biology models to better understand the function and dysfunction of thiol-disulfide redox systems. In particular, central principles have emerged concerning redox compartmentalization and utility of thiol/disulfide redox measures as indicators of physiologic function. Advances in redox proteomics show that, in addition to functioning in protein active sites and cell signaling, cysteine residues also serve as redox sensors to integrate biologic functions. These advances provide a framework for translation of redox systems biology concepts to practical use in understanding and treating human disease. Biological responses to cadmium, a widespread environmental agent, are used to illustrate the utility of these advances to the understanding of complex pleiotropic toxicities. PMID:23356510

  17. Molecular monitoring of equine joint homeostasis

    OpenAIRE

    de Grauw, J.C.

    2010-01-01

    Chronic joint disorders are a major cause of impaired mobility and loss of quality of life in both humans and horses. Regardless of the primary insult, any joint disorder is characterized by an upset in normal joint homeostasis, the balance between tissue anabolism and catabolism that is normally maintained by resident articular cells. This upset is often fuelled by a local inflammatory response in the synovial membrane and the articular cartilage. Our current understanding of the pathogenesi...

  18. Unusual thiol-based redox metabolism of parasitic flukes.

    Science.gov (United States)

    Tripathi, Timir; Suttiprapa, Sutas; Sripa, Banchob

    2017-08-01

    Parasitic flukes are exposed to free radicals and, to a greater extent, reactive oxygen species (ROS) during their life cycle. Despite being relentlessly exposed to ROS released by activated immune cells, these parasites can survive for many years in the host. Cellular thiol-based redox metabolism plays a crucial role in parasite survival within their hosts. Evidence shows that oxidative stress and redox homeostasis maintenance are important clinical and pathobiochemical as well as effective therapeutic principles in various diseases. The characterization of redox and antioxidant enzymes is likely to yield good target candidates for novel drugs and vaccines. The absence of active catalase in fluke parasites offers great potential for the development of chemotherapeutic agents that act by perturbing the redox equilibrium of the cell. One of the redox-sensitive enzymes, thioredoxin glutathione reductase (TGR), has been accepted as a drug target against blood fluke infections, and related clinical trials are in progress. TGR is the sole enzyme responsible for Trx and GSH reduction in parasitic flukes. The availability of helminth genomes has accelerated the research on redox metabolism of flukes; however, significant achievements have yet to be attained. The present review summarizes current knowledge on the redox and antioxidant system of the parasitic flukes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Effect of long-term fertilization on humic redox mediators in multiple microbial redox reactions.

    Science.gov (United States)

    Guo, Peng; Zhang, Chunfang; Wang, Yi; Yu, Xinwei; Zhang, Zhichao; Zhang, Dongdong

    2018-03-01

    This study investigated the effects of different long-term fertilizations on humic substances (HSs), humic acids (HAs) and humins, functioning as redox mediators for various microbial redox biotransformations, including 2,2',4,4',5,5'- hexachlorobiphenyl (PCB 153 ) dechlorination, dissimilatory iron reduction, and nitrate reduction, and their electron-mediating natures. The redox activity of HSs for various microbial redox metabolisms was substantially enhanced by long-term application of organic fertilizer (pig manure). As a redox mediator, only humin extracted from soils with organic fertilizer amendment (OF-HM) maintained microbial PCB 153 dechlorination activity (1.03 μM PCB 153 removal), and corresponding HA (OF-HA) most effectively enhanced iron reduction and nitrate reduction by Shewanella putrefaciens. Electrochemical analysis confirmed the enhancement of their electron transfer capacity and redox properties. Fourier transform infrared analysis showed that C=C and C=O bonds, and carboxylic or phenolic groups in HSs might be the redox functional groups affected by fertilization. This research enhances our understanding of the influence of anthropogenic fertility on the biogeochemical cycling of elements and in situ remediation ability in agroecosystems through microorganisms' metabolisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Redox signaling in plants.

    Science.gov (United States)

    Foyer, Christine H; Noctor, Graham

    2013-06-01

    Our aim is to deliver an authoritative and challenging perspective of current concepts in plant redox signaling, focusing particularly on the complex interface between the redox and hormone-signaling pathways that allow precise control of plant growth and defense in response to metabolic triggers and environmental constraints and cues. Plants produce significant amounts of singlet oxygen and other reactive oxygen species (ROS) as a result of photosynthetic electron transport and metabolism. Such pathways contribute to the compartment-specific redox-regulated signaling systems in plant cells that convey information to the nucleus to regulate gene expression. Like the chloroplasts and mitochondria, the apoplast-cell wall compartment makes a significant contribution to the redox signaling network, but unlike these organelles, the apoplast has a low antioxidant-buffering capacity. The respective roles of ROS, low-molecular antioxidants, redox-active proteins, and antioxidant enzymes are considered in relation to the functions of plant hormones such as salicylic acid, jasmonic acid, and auxin, in the composite control of plant growth and defense. Regulation of redox gradients between key compartments in plant cells such as those across the plasma membrane facilitates flexible and multiple faceted opportunities for redox signaling that spans the intracellular and extracellular environments. In conclusion, plants are recognized as masters of the art of redox regulation that use oxidants and antioxidants as flexible integrators of signals from metabolism and the environment.

  1. Compartmentation of redox metabolism in malaria parasites.

    Directory of Open Access Journals (Sweden)

    Sebastian Kehr

    Full Text Available Malaria, caused by the apicomplexan parasite Plasmodium, still represents a major threat to human health and welfare and leads to about one million human deaths annually. Plasmodium is a rapidly multiplying unicellular organism undergoing a complex developmental cycle in man and mosquito - a life style that requires rapid adaptation to various environments. In order to deal with high fluxes of reactive oxygen species and maintain redox regulatory processes and pathogenicity, Plasmodium depends upon an adequate redox balance. By systematically studying the subcellular localization of the major antioxidant and redox regulatory proteins, we obtained the first complete map of redox compartmentation in Plasmodium falciparum. We demonstrate the targeting of two plasmodial peroxiredoxins and a putative glyoxalase system to the apicoplast, a non-photosynthetic plastid. We furthermore obtained a complete picture of the compartmentation of thioredoxin- and glutaredoxin-like proteins. Notably, for the two major antioxidant redox-enzymes--glutathione reductase and thioredoxin reductase--Plasmodium makes use of alternative-translation-initiation (ATI to achieve differential targeting. Dual localization of proteins effected by ATI is likely to occur also in other Apicomplexa and might open new avenues for therapeutic intervention.

  2. Homeostasis as the Mechanism of Evolution

    Directory of Open Access Journals (Sweden)

    John S. Torday

    2015-09-01

    Full Text Available Homeostasis is conventionally thought of merely as a synchronic (same time servo-mechanism that maintains the status quo for organismal physiology. However, when seen from the perspective of developmental physiology, homeostasis is a robust, dynamic, intergenerational, diachronic (across-time mechanism for the maintenance, perpetuation and modification of physiologic structure and function. The integral relationships generated by cell-cell signaling for the mechanisms of embryogenesis, physiology and repair provide the needed insight to the scale-free universality of the homeostatic principle, offering a novel opportunity for a Systems approach to Biology. Starting with the inception of life itself, with the advent of reproduction during meiosis and mitosis, moving forward both ontogenetically and phylogenetically through the evolutionary steps involved in adaptation to an ever-changing environment, Biology and Evolution Theory need no longer default to teleology.

  3. Osteoclasts and CD8 T cells form a negative feedback loop that contributes to homeostasis of both the skeletal and immune systems.

    Science.gov (United States)

    Buchwald, Zachary S; Aurora, Rajeev

    2013-01-01

    There are a number of dynamic regulatory loops that maintain homeostasis of the immune and skeletal systems. In this review, we highlight a number of these regulatory interactions that contribute to maintaining homeostasis. In addition, we review data on a negative regulatory feedback loop between osteoclasts and CD8 T cells that contributes to homeostasis of both the skeletal and immune systems.

  4. Ageing and water homeostasis

    Science.gov (United States)

    Robertson, David; Jordan, Jens; Jacob, Giris; Ketch, Terry; Shannon, John R.; Biaggioni, Italo

    2002-01-01

    This review outlines current knowledge concerning fluid intake and volume homeostasis in ageing. The physiology of vasopressin is summarized. Studies have been carried out to determine orthostatic changes in plasma volume and to assess the effect of water ingestion in normal subjects, elderly subjects, and patients with dysautonomias. About 14% of plasma volume shifts out of the vasculature within 30 minutes of upright posture. Oral ingestion of water raises blood pressure in individuals with impaired autonomic reflexes and is an important source of noise in blood pressure trials in the elderly. On the average, oral ingestion of 16 ounces (473ml) of water raises blood pressure 11 mmHg in elderly normal subjects. In patients with autonomic impairment, such as multiple system atrophy, strikingly exaggerated pressor effects of water have been seen with blood pressure elevations greater than 75 mmHg not at all uncommon. Ingestion of water is a major determinant of blood pressure in the elderly population. Volume homeostasis is importantly affected by posture and large changes in plasma volume may occur within 30 minutes when upright posture is assumed.

  5. Redox Species of Redox Flow Batteries: A Review.

    Science.gov (United States)

    Pan, Feng; Wang, Qing

    2015-11-18

    Due to the capricious nature of renewable energy resources, such as wind and solar, large-scale energy storage devices are increasingly required to make the best use of the renewable power. The redox flow battery is considered suitable for large-scale applications due to its modular design, good scalability and flexible operation. The biggest challenge of the redox flow battery is the low energy density. The redox active species is the most important component in redox flow batteries, and the redox potential and solubility of redox species dictate the system energy density. This review is focused on the recent development of redox species. Different categories of redox species, including simple inorganic ions, metal complexes, metal-free organic compounds, polysulfide/sulfur and lithium storage active materials, are reviewed. The future development of redox species towards higher energy density is also suggested.

  6. Redox Species of Redox Flow Batteries: A Review

    Directory of Open Access Journals (Sweden)

    Feng Pan

    2015-11-01

    Full Text Available Due to the capricious nature of renewable energy resources, such as wind and solar, large-scale energy storage devices are increasingly required to make the best use of the renewable power. The redox flow battery is considered suitable for large-scale applications due to its modular design, good scalability and flexible operation. The biggest challenge of the redox flow battery is the low energy density. The redox active species is the most important component in redox flow batteries, and the redox potential and solubility of redox species dictate the system energy density. This review is focused on the recent development of redox species. Different categories of redox species, including simple inorganic ions, metal complexes, metal-free organic compounds, polysulfide/sulfur and lithium storage active materials, are reviewed. The future development of redox species towards higher energy density is also suggested.

  7. Two NAD-linked redox shuttles maintain the peroxisomal redox balance in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Al-Saryi, Nadal A.; Al-Hejjaj, Murtakab Y.; van Roermund, Carlo W. T.; Hulmes, Georgia E.; Ekal, Lakhan; Payton, Chantell; Wanders, Ronald J. A.; Hettema, Ewald H.

    2017-01-01

    In Saccharomyces cerevisiae, peroxisomes are the sole site of fatty acid beta-oxidation. During this process, NAD(+) is reduced to NADH. When cells are grown on oleate medium, peroxisomal NADH is reoxidised to NAD(+) by malate dehydrogenase (Mdh3p) and reduction equivalents are transferred to the

  8. A novel mitochondria-targeted two-photon fluorescent probe for dynamic and reversible detection of the redox cycles between peroxynitrite and glutathione.

    Science.gov (United States)

    Sun, Chunlong; Du, Wen; Wang, Peng; Wu, Yang; Wang, Baoqin; Wang, Jun; Xie, Wenjun

    2017-12-16

    Redox homeostasis is important for maintenance of normal physiological functions within cells. Redox state of cells is primarily a consequence of precise balance between levels of reducing equivalents and reactive oxygen species. Redox homeostasis between peroxynitrite (ONOO - ) and glutathione (GSH) is closely associated with physiological and pathological processes, such as prolonged relaxation in vascular tissues and smooth muscle preparations, attenuation of hepatic necrosis, and activation of matrix metalloproteinase-2. We report a two-photon fluorescent probe (TP-Se) based on water-soluble carbazole-based compound, which integrates with organic selenium, to monitor changes in ONOO - /GSH levels in cells. This probe can reversibly respond to ONOO - and GSH and exhibits high selectivity, sensitivity, and mitochondrial targeting. The probe was successfully applied to visualize changes in redox cycles during ONOO - outbreak and antioxidant GSH repair in cells. The probe will lead to significant development on redox events involved in cellular redox regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Hexose-6-phosphate dehydrogenase contributes to skeletal muscle homeostasis independent of 11β-hydroxysteroid dehydrogenase type 1.

    LENUS (Irish Health Repository)

    Semjonous, Nina M

    2011-01-01

    Glucose-6-phosphate (G6P) metabolism by the enzyme hexose-6-phosphate dehydrogenase (H6PDH) within the sarcoplasmic reticulum lumen generates nicotinamide adenine dinucleotide phosphate (reduced) to provide the redox potential for the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to activate glucocorticoid (GC). H6PDH knockout (KO) mice have a switch in 11β-HSD1 activity, resulting in GC inactivation and hypothalamic-pituitary-adrenal axis activation. Importantly, H6PDHKO mice develop a type II fiber myopathy with abnormalities in glucose metabolism and activation of the unfolded protein response (UPR). GCs play important roles in muscle physiology, and therefore, we have examined the importance of 11β-HSD1 and GC metabolism in mediating aspects of the H6PDHKO myopathy. To achieve this, we examined 11β-HSD1\\/H6PDH double-KO (DKO) mice, in which 11β-HSD1 mediated GC inactivation is negated. In contrast to H6PDHKO mice, DKO mice GC metabolism and hypothalamic-pituitary-adrenal axis set point is similar to that observed in 11β-HSD1KO mice. Critically, in contrast to 11β-HSD1KO mice, DKO mice phenocopy the salient features of the H6PDHKO, displaying reduced body mass, muscle atrophy, and vacuolation of type II fiber-rich muscle, fasting hypoglycemia, increased muscle glycogen deposition, and elevated expression of UPR genes. We propose that muscle G6P metabolism through H6PDH may be as important as changes in the redox environment when considering the mechanism underlying the activation of the UPR and the ensuing myopathy in H6PDHKO and DKO mice. These data are consistent with an 11β-HSD1-independent function for H6PDH in which sarcoplasmic reticulum G6P metabolism and nicotinamide adenine dinucleotide phosphate-(oxidized)\\/nicotinamide adenine dinucleotide phosphate (reduced) redox status are important for maintaining muscle homeostasis.

  10. Exercise-intensity dependent alterations in plasma redox status do not reflect skeletal muscle redox-sensitive protein signaling.

    Science.gov (United States)

    Parker, Lewan; Trewin, Adam; Levinger, Itamar; Shaw, Christopher S; Stepto, Nigel K

    2018-04-01

    Redox homeostasis and redox-sensitive protein signaling play a role in exercise-induced adaptation. The effects of sprint-interval exercise (SIE), high-intensity interval exercise (HIIE) and continuous moderate-intensity exercise (CMIE), on post-exercise plasma redox status are unclear. Furthermore, whether post-exercise plasma redox status reflects skeletal muscle redox-sensitive protein signaling is unknown. In a randomized crossover design, eight healthy adults performed a cycling session of HIIE (5×4min at 75% W max ), SIE (4×30s Wingate's), and CMIE work-matched to HIIE (30min at 50% of W max ). Plasma hydrogen peroxide (H 2 O 2 ), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) activity, and catalase activity were measured immediately post, 1h, 2h and 3h post-exercise. Plasma redox status biomarkers were correlated with phosphorylation of skeletal muscle p38-MAPK, JNK, NF-κB, and IκBα protein content immediately and 3h post-exercise. Plasma catalase activity was greater with SIE (56.6±3.8Uml -1 ) compared to CMIE (42.7±3.2, pexercise plasma TBARS and SOD activity significantly (pexercise protocol. A significant positive correlation was detected between plasma catalase activity and skeletal muscle p38-MAPK phosphorylation 3h post-exercise (r=0.40, p=0.04). No other correlations were detected (all p>0.05). Low-volume SIE elicited greater post-exercise plasma catalase activity compared to HIIE and CMIE, and greater H 2 O 2 compared to CMIE. Plasma redox status did not, however, adequately reflect skeletal muscle redox-sensitive protein signaling. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  11. A Physiologist's View of Homeostasis

    Science.gov (United States)

    Modell, Harold; Cliff, William; Michael, Joel; McFarland, Jenny; Wenderoth, Mary Pat; Wright, Ann

    2015-01-01

    Homeostasis is a core concept necessary for understanding the many regulatory mechanisms in physiology. Claude Bernard originally proposed the concept of the constancy of the "milieu interieur," but his discussion was rather abstract. Walter Cannon introduced the term "homeostasis" and expanded Bernard's notion of…

  12. Simultaneous anionic and cationic redox

    Science.gov (United States)

    Jung, Sung-Kyun; Kang, Kisuk

    2017-12-01

    It is challenging to unlock anionic redox activity, accompanied by full utilization of available cationic redox process, to boost capacity of battery cathodes. Now, material design by tuning the metal-oxygen interaction is shown to be a promising solution.

  13. Redox Regulation of Mitochondrial Function

    Science.gov (United States)

    Handy, Diane E.

    2012-01-01

    Abstract Redox-dependent processes influence most cellular functions, such as differentiation, proliferation, and apoptosis. Mitochondria are at the center of these processes, as mitochondria both generate reactive oxygen species (ROS) that drive redox-sensitive events and respond to ROS-mediated changes in the cellular redox state. In this review, we examine the regulation of cellular ROS, their modes of production and removal, and the redox-sensitive targets that are modified by their flux. In particular, we focus on the actions of redox-sensitive targets that alter mitochondrial function and the role of these redox modifications on metabolism, mitochondrial biogenesis, receptor-mediated signaling, and apoptotic pathways. We also consider the role of mitochondria in modulating these pathways, and discuss how redox-dependent events may contribute to pathobiology by altering mitochondrial function. Antioxid. Redox Signal. 16, 1323–1367. PMID:22146081

  14. Pyridine nucleotide cycling and control of intracellular redox state in relation to poly (ADP-ribose) polymerase activity and nuclear localization of glutathione during exponential growth of Arabidopsis cells in culture.

    Science.gov (United States)

    Pellny, Till K; Locato, Vittoria; Vivancos, Pedro Diaz; Markovic, Jelena; De Gara, Laura; Pallardó, Federico V; Foyer, Christine H

    2009-05-01

    Pyridine nucleotides, ascorbate and glutathione are major redox metabolites in plant cells, with specific roles in cellular redox homeostasis and the regulation of the cell cycle. However, the regulation of these metabolite pools during exponential growth and their precise functions in the cell cycle remain to be characterized. The present analysis of the abundance of ascorbate, glutathione, and pyridine nucleotides during exponential growth of Arabidopsis cells in culture provides evidence for the differential regulation of each of these redox pools. Ascorbate was most abundant early in the growth cycle, but glutathione was low at this point. The cellular ascorbate to dehydroascorbate and reduced glutathione (GSH) to glutathione disulphide ratios were high and constant but the pyridine nucleotide pools were largely oxidized over the period of exponential growth and only became more reduced once growth had ceased. The glutathione pool increased in parallel with poly (ADP-ribose) polymerase (PARP) activities and with increases in the abundance of PARP1 and PARP2 mRNAs at a time of high cell cycle activity as indicated by transcriptome information. Marked changes in the intracellular partitioning of GSH between the cytoplasm and nucleus were observed. Extension of the exponential growth phase by dilution or changing the media led to increases in the glutathione and nicotinamide adenine dinucleotide, oxidized form (NAD)-plus-nicotinamide adenine dinucleotide, reduced form (NADH) pools and to higher NAD/NADH ratios but the nicotinamide adenine dinucleotide phosphate, oxidized form (NADP)-plus-nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) pool sizes, and NAPD/NADPH ratios were much less affected. The ascorbate, glutathione, and pyridine nucleotide pools and PARP activity decreased before the exponential growth phase ended. We conclude that there are marked changes in intracellular redox state during the growth cycle but that redox homeostasis is

  15. Redox processes in radiation biology and cancer

    International Nuclear Information System (INIS)

    Greenstock, C.L.

    1981-01-01

    Free-radical intermediates, particularly the activated oxygen species OH, O - 2 , and 1 O 2 , are implicated in many types of radiation damage to biological systems. In addition, these same species may be formed, either directly or indirectly through biochemical redox reactions, in both essential and aberrant metabolic processes. Cell survival and adaptation to an environment containing ionizing radiation and other physical and chemical carcinogens ultimately depend upon the cell's ability to maintain optimal function in response to free-radical damage at the chemical level. Many of these feedback control mechanisms are redox controlled. Radiation chemical techniques using selective radical scavengers, such as product analysis and pulse radiolysis, enable us to generate, observe, and characterize individually the nature and reactivity of potentially damaging free radicals. From an analysis of the chemical kinetics of free-radical involvement in biological damage, redox mechanisms are proposed to describe the early processes of radiation damage, redox mechanisms are proposed to describe the early processes of radiation damage, its protection and sensitization, and the role of free radicals in radiation and chemical carcinogenesis

  16. Treg cell-IgA axis in maintenance of host immune homeostasis with microbiota

    OpenAIRE

    Feng, Ting; Elson, Charles O.; Cong, Yingzi

    2010-01-01

    The intestine is the home to a vast diversity of microbiota and a complex of mucosal immune system. Multiple regulatory mechanisms control host immune responses to microbiota and maintain intestinal immune homeostasis. This mini review will provide evidence indicating a Treg cell-IgA axis and such axis playing a major role in maintenance of intestinal homeostasis.

  17. Redox regulation in photosynthetic organisms: signaling, acclimation, and practical implications.

    Science.gov (United States)

    Foyer, Christine H; Noctor, Graham

    2009-04-01

    Reactive oxygen species (ROS) have multifaceted roles in the orchestration of plant gene expression and gene-product regulation. Cellular redox homeostasis is considered to be an "integrator" of information from metabolism and the environment controlling plant growth and acclimation responses, as well as cell suicide events. The different ROS forms influence gene expression in specific and sometimes antagonistic ways. Low molecular antioxidants (e.g., ascorbate, glutathione) serve not only to limit the lifetime of the ROS signals but also to participate in an extensive range of other redox signaling and regulatory functions. In contrast to the low molecular weight antioxidants, the "redox" states of components involved in photosynthesis such as plastoquinone show rapid and often transient shifts in response to changes in light and other environmental signals. Whereas both types of "redox regulation" are intimately linked through the thioredoxin, peroxiredoxin, and pyridine nucleotide pools, they also act independently of each other to achieve overall energy balance between energy-producing and energy-utilizing pathways. This review focuses on current knowledge of the pathways of redox regulation, with discussion of the somewhat juxtaposed hypotheses of "oxidative damage" versus "oxidative signaling," within the wider context of physiological function, from plant cell biology to potential applications.

  18. Iron homeostasis during pregnancy.

    Science.gov (United States)

    Fisher, Allison L; Nemeth, Elizabeta

    2017-12-01

    During pregnancy, iron needs to increase substantially to support fetoplacental development and maternal adaptation to pregnancy. To meet these iron requirements, both dietary iron absorption and the mobilization of iron from stores increase, a mechanism that is in large part dependent on the iron-regulatory hormone hepcidin. In healthy human pregnancies, maternal hepcidin concentrations are suppressed in the second and third trimesters, thereby facilitating an increased supply of iron into the circulation. The mechanism of maternal hepcidin suppression in pregnancy is unknown, but hepcidin regulation by the known stimuli (i.e., iron, erythropoietic activity, and inflammation) appears to be preserved during pregnancy. Inappropriately increased maternal hepcidin during pregnancy can compromise the iron availability for placental transfer and impair the efficacy of iron supplementation. The role of fetal hepcidin in the regulation of placental iron transfer still remains to be characterized. This review summarizes the current understanding and addresses the gaps in knowledge about gestational changes in hematologic and iron variables and regulatory aspects of maternal, fetal, and placental iron homeostasis. © 2017 American Society for Nutrition.

  19. INTRACELLULAR Ca2+ HOMEOSTASIS

    Directory of Open Access Journals (Sweden)

    Shahdevi Nandar Kurniawan

    2015-01-01

    Full Text Available Ca2+ signaling functions to regulate many cellular processes. Dynamics of Ca2+ signaling or homeostasis is regulated by the interaction between ON and OFF reactions that control Ca2+ flux in both the plasma membrane and internal organelles such as the endoplasmic reticulum (ER and mitochondria. External stimuli activate the ON reactions, which include Ca2+ into the cytoplasm either through channels in the plasma membrane or from internal storage like in ER. Most of the cells utilize both channels/sources, butthere area few cells using an external or internal source to control certain processes. Most of the Ca2+ entering the cytoplasm adsorbed to the buffer, while a smaller part activate effect or to stimulate cellular processes. Reaction OFF is pumping of cytoplasmic Ca2+ using a combination mechanism of mitochondrial and others. Changes in Ca2+ signal has been detected in various tissues isolated from animals induced into diabetes as well as patients with diabetes. Ca2+ signal interference is also found in sensory neurons of experimental animals with diabetes. Ca2+ signaling is one of the main signaling systems in the cell.

  20. Neuroscience of glucose homeostasis

    NARCIS (Netherlands)

    La Fleur, S E; Fliers, E; Kalsbeek, A

    2014-01-01

    Plasma glucose concentrations are homeostatically regulated and maintained within strict boundaries. Several mechanisms are in place to increase glucose output when glucose levels in the circulation drop as a result of glucose utilization, or to decrease glucose output and increase tissue glucose

  1. Redox Flow Batteries, a Review

    Energy Technology Data Exchange (ETDEWEB)

    Knoxville, U. Tennessee; U. Texas Austin; U, McGill; Weber, Adam Z.; Mench, Matthew M.; Meyers, Jeremy P.; Ross, Philip N.; Gostick, Jeffrey T.; Liu, Qinghua

    2011-07-15

    Redox flow batteries are enjoying a renaissance due to their ability to store large amounts of electrical energy relatively cheaply and efficiently. In this review, we examine the components of redox flow batteries with a focus on understanding the underlying physical processes. The various transport and kinetic phenomena are discussed along with the most common redox couples.

  2. Changes in Thiol-Disulfide Homeostasis of the Body to Surgical Trauma in Laparoscopic Cholecystectomy Patients.

    Science.gov (United States)

    Polat, Murat; Ozcan, Onder; Sahan, Leyla; Üstündag-Budak, Yasemin; Alisik, Murat; Yilmaz, Nigar; Erel, Özcan

    2016-12-01

    We aimed to investigate the short-term effect of laparoscopic surgery on serum thiol-disulfide homeostasis levels as a marker of oxidant stress of surgical trauma in elective laparoscopic cholecystectomy patients. Venous blood samples were collected, and levels of native thiols, total thiols, and disulfides were determined with a novel automated assay. Total antioxidant capacity (measured as the ferric-reducing ability of plasma) and serum ischemia modified albumin, expressed as absorbance units assayed by the albumin cobalt binding test, were determined. The major findings of the present study were that native thiol (283 ± 45 versus 241 ± 61 μmol/L), total thiol (313 ± 49 versus 263 ± 67 μmol/L), and disulfide (14.9 ± 4.6 versus 11.0 ± 6.1 μmol/L) levels were decreased significantly during operation and although they increased, they did not return to preoperation levels 24 hours after laparoscopic surgery compared to the levels at baseline. Disulfide/native thiol and disulfide/total thiol levels did not change during laparoscopic surgery. The decrease in plasma level of native and total thiol groups suggests impairment of the antioxidant capacity of plasma; however, the delicate balance between the different redox forms of thiols was maintained during surgery.

  3. Adaptive mechanisms of homeostasis disorders

    Directory of Open Access Journals (Sweden)

    Anna Maria Dobosiewicz

    2017-08-01

    Full Text Available The ability to preserve a permanent level of internal environment in a human organism, against internal and external factors, which could breach the consistency, can be define as homeostasis. Scientific proven influence on the homeostasis has the periodicity of biological processes, which is also called circadian rhythm. The effect of circadian rhythm is also to see in the functioning of autonomic nervous system and cardiovascular system. Sleep deprivation is an example of how the disorders in circadian rhythm could have the influence on the homeostasis.

  4. Redox environment in stem and differentiated cells: A quantitative approach

    Directory of Open Access Journals (Sweden)

    O.G. Lyublinskaya

    2017-08-01

    Full Text Available Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity. However, biochemical normalization of these parameters to cell volume/protein leads to matching of normalized values in stem and differentiated cells and shows that tested in the present study cells (human embryonic stem cells and their fibroblast-like progenies, adult mesenchymal stem cells, lymphocytes, HeLa maintain similar intracellular redox status. Based on these observations, we propose to use ROS concentration averaged over the cell volume instead of ROS level as a measure of intracellular redox balance. We show that attempts to use ROS level for comparative analysis of redox status of morphologically different cells could lead to false conclusions. Methods for the assessment of ROS concentration based on flow cytometry analysis with the use of H2DCFDA dye and HyPer, genetically encoded probe for hydrogen peroxide, are discussed. Keywords: Embryonic stem cells, Differentiated cells, ROS, Redox status, H2DCFDA, HyPer, Flow cytometry, Quantitative redox biology

  5. Mechanisms of Cell Polarity-Controlled Epithelial Homeostasis and Immunity in the Intestine

    NARCIS (Netherlands)

    Klunder, Leon J.; Faber, Klaas Nico; Dijkstra, Gerard; van IJzendoorn, Sven C. D.

    Intestinal epithelial cell polarity is instrumental to maintain epithelial homeostasis and balance communications between the gut lumen and bodily tissue, thereby controlling the defense against gastrointestinal pathogens and maintenance of immune tolerance to commensal bacteria. In this review, we

  6. Redox-capacitor to connect electrochemistry to redox-biology.

    Science.gov (United States)

    Kim, Eunkyoung; Leverage, W Taylor; Liu, Yi; White, Ian M; Bentley, William E; Payne, Gregory F

    2014-01-07

    It is well-established that redox-reactions are integral to biology for energy harvesting (oxidative phosphorylation), immune defense (oxidative burst) and drug metabolism (phase I reactions), yet there is emerging evidence that redox may play broader roles in biology (e.g., redox signaling). A critical challenge is the need for tools that can probe biologically-relevant redox interactions simply, rapidly and without the need for a comprehensive suite of analytical methods. We propose that electrochemistry may provide such a tool. In this tutorial review, we describe recent studies with a redox-capacitor film that can serve as a bio-electrode interface that can accept, store and donate electrons from mediators commonly used in electrochemistry and also in biology. Specifically, we (i) describe the fabrication of this redox-capacitor from catechols and the polysaccharide chitosan, (ii) discuss the mechanistic basis for electron exchange, (iii) illustrate the properties of this redox-capacitor and its capabilities for promoting redox-communication between biology and electrodes, and (iv) suggest the potential for enlisting signal processing strategies to "extract" redox information. We believe these initial studies indicate broad possibilities for enlisting electrochemistry and signal processing to acquire "systems level" redox information from biology.

  7. Molecular aspects of bacterial pH sensing and homeostasis

    Science.gov (United States)

    Krulwich, Terry A.; Sachs, George; Padan, Etana

    2011-01-01

    Diverse mechanisms for pH-sensing and cytoplasmic pH homeostasis enable most bacteria to tolerate or grow at external pH values that are outside the cytoplasmic pH range they must maintain for growth. The most extreme cases are exemplified by the extremophiles that inhabit environments whose pH is below 3 or above 11. Here we describe how recent insights into the structure and function of key molecules and their regulators reveal novel strategies of bacterial pH-homeostasis. These insights may help us better target certain pathogens and better harness the capacities of environmental bacteria. PMID:21464825

  8. Microfluidic redox battery.

    Science.gov (United States)

    Lee, Jin Wook; Goulet, Marc-Antoni; Kjeang, Erik

    2013-07-07

    A miniaturized microfluidic battery is proposed, which is the first membraneless redox battery demonstrated to date. This unique concept capitalizes on dual-pass flow-through porous electrodes combined with stratified, co-laminar flow to generate electrical power on-chip. The fluidic design is symmetric to allow for both charging and discharging operations in forward, reverse, and recirculation modes. The proof-of-concept device fabricated using low-cost materials integrated in a microfluidic chip is shown to produce competitive power levels when operated on a vanadium redox electrolyte. A complete charge/discharge cycle is performed to demonstrate its operation as a rechargeable battery, which is an important step towards providing sustainable power to lab-on-a-chip and microelectronic applications.

  9. Aqueous liquid redox desulfurisation

    Energy Technology Data Exchange (ETDEWEB)

    Reicher, M.; Niemiec, B.; Katona, T.

    1999-12-01

    The LO-CAT II process is an aqueous liquid redox process which uses ferric and ferrous iron catalysts to oxidise hydrogen sulfide (from sour gas) to elemental sulfur: the relevant chemical equations are given. Chelating agents keep the iron in solution. The system is described under the headings of (i) LO-CAT chemistry, (ii) design parameters, (iii) startup challenges, (iv) present situation and (v) anticipated future conditions. Further improvements to the system are anticipated.

  10. Ediacaran Redox Fluctuations

    Science.gov (United States)

    Sahoo, S. K.; Jiang, G.; Planavsky, N. J.; Kendall, B.; Owens, J. D.; Anbar, A. D.; Lyons, T. W.

    2013-12-01

    Evidence for pervasive oxic conditions, and likely even deep ocean oxygenation has been documented at three intervals in the lower (ca. 632 Ma), middle (ca. 580 Ma) and upper (ca. 551 Ma) Ediacaran. The Doushantuo Formation in South China hosts large enrichments of redox-sensitive trace element (e.g., molybdenum, vanadium and uranium) in anoxic shales, which are indicative of a globally oxic ocean-atmosphere system. However, ocean redox conditions between these periods continue to be a topic of debate and remain elusive. We have found evidence for widespread anoxic conditions through much of the Ediacaran in the deep-water Wuhe section in South China. During most of the Ediacaran-early Cambrian in basinal sections is characterized by Fe speciation data and pyrite morphologies that indicate deposition under euxinic conditions with near-crustal enrichments of redox-sensitive element and positive pyrite-sulfur isotope values, which suggest low levels of marine sulfate and widespread euxinia. Our work reinforces an emerging view that the early Earth, including the Ediacaran, underwent numerous rises and falls in surface oxidation state, rather than a unidirectional rise as originally imagined. The Ediacaran ocean thus experienced repetitive expansion and contraction of marine chalcophilic trace-metal levels that may have had fundamental impact on the slow evolution of early animals and ecosystems. Further, this framework forces us to re-examine the relationship between Neoproterozoic oxygenation and metazoan diversification. Varying redox conditions through the Cryogenian and Ediacaran may help explain molecular clock and biomarker evidence for an early appearance and initial diversification of metazoans but with a delay in the appearance of most major metazoan crown groups until close to Ediacaran-Cambrian boundary.

  11. Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine

    Directory of Open Access Journals (Sweden)

    Tiziana Parasassi

    2010-01-01

    Full Text Available The functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox switches play a fundamental role that is just beginning to be understood. The maintenance of the redox status is, indeed, crucial for cellular homeostasis and its dysregulation towards a more oxidized intracellular environment is associated with aberrant proliferation, ultimately related to diseases such as cancer, cardiovascular disease, and diabetes. Redox transitions occur in sensitive cysteine residues of regulatory proteins relevant to signaling, their evolution to metastable disulfides accounting for the functional redox switch. N-acetylcysteine (NAC is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling. We here review the redox chemistry of NAC, then screen possible mechanisms to explain the effects observed in NAC-treated normal and cancer cells; such effects involve a modification of global gene expression, thus of functions and morphology, with a leitmotif of a switch from proliferation to terminal differentiation. The regulation of thiol redox transitions in cell signaling is, therefore, proposed as a new tool, holding promise not only for a deeper explanation of mechanisms, but indeed for innovative pharmacological interventions.

  12. Age affects the contraction-induced mitochondrial redox response in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Dennis R Claflin

    2015-02-01

    Full Text Available Compromised mitochondrial respiratory function is associated with advancing age. Damage due to an increase in reactive oxygen species (ROS with age is thought to contribute to the mitochondrial deficits. The coenzyme nicotinamide adenine dinucleotide in its reduced (NADH and oxidized (NAD+ forms plays an essential role in the cyclic sequence of reactions that result in the regeneration of ATP by oxidative phosphorylation in mitochondria. Monitoring mitochondrial NADH/NAD+ redox status during recovery from an episode of high energy demand thus allows assessment of mitochondrial function. NADH fluoresces when excited with ultraviolet light in the UV-A band and NAD+ does not, allowing NADH/NAD+ to be monitored in real time using fluorescence microscopy. Our goal was to assess mitochondrial function by monitoring the NADH fluorescence response following a brief period of high energy demand in muscle from adult and old wild-type (WT mice. This was accomplished by isolating whole lumbrical muscles from the hind paws of 7- and 28-month-old WT mice and making simultaneous measurements of force and NADH fluorescence responses during and after a 5 s maximum isometric contraction. All muscles exhibited fluorescence oscillations that were qualitatively similar and consisted of a brief transient increase followed by a longer transient period of reduced fluorescence and, finally, an increase that included an overshoot before recovering to resting level. Compared with the adult WT mice, muscles from the 28 mo WT mice exhibited a delayed peak during the first fluorescence transient and an attenuated recovery following the second transient. These findings indicate an impaired mitochondrial capacity to maintain NADH/NAD+ redox homeostasis during contractile activity in skeletal muscles of old mice.

  13. Skin Redox Balance Maintenance: The Need for an Nrf2-Activator Delivery System

    Directory of Open Access Journals (Sweden)

    Maya Ben-Yehuda Greenwald

    2016-01-01

    Full Text Available The skin, being the largest organ of the body, functions as a barrier between our body and the environment. It is consistently exposed to various exogenous and endogenous stressors (e.g., air pollutants, ionizing and non-ionizing irradiation, toxins, mitochondrial metabolism, enzyme activity, inflammatory process, etc. producing reactive oxygen species (ROS and physical damage (e.g., wounds, sunburns also resulting in reactive oxygen species production. Although skin is equipped with an array of defense mechanisms to counteract reactive oxygen species, augmented exposure and continued reactive oxygen species might result in excessive oxidative stress leading to many skin disorders including inflammatory diseases, pigmenting disorders and some types of cutaneous malignancy. The nuclear factor erythroid 2-related factor 2 (Nrf2 is an emerging regulator of cellular resistance and of defensive enzymes such as the phase II enzymes. Induction of the Keap1–Nrf2 pathway may have a beneficial effect in the treatment of a large number of skin disorders by stimulating an endogenous defense mechanism. However, prolonged and enhanced activation of this pathway is detrimental and, thus, limits the therapeutic potential of Keap1–Nrf2 modulators. Here, we review the consequences of oxidative stress to the skin, and the defense mechanisms that skin is equipped with. We describe the challenges of maintaining skin redox balance and its impact on skin status and function. Finally, we suggest a novel strategy for maintenance of skin redox homeostasis by modulating the Keap1–Nrf2 pathway using nanotechnology-based delivery systems.

  14. MicroRNAs at the epicenter of intestinal homeostasis.

    Science.gov (United States)

    Belcheva, Antoaneta

    2017-03-01

    Maintaining intestinal homeostasis is a key prerequisite for a healthy gut. Recent evidence points out that microRNAs (miRNAs) act at the epicenter of the signaling networks regulating this process. The fine balance in the interaction between gut microbiota, intestinal epithelial cells, and the host immune system is achieved by constant transmission of signals and their precise regulation. Gut microbes extensively communicate with the host immune system and modulate host gene expression. On the other hand, sensing of gut microbiota by the immune cells provides appropriate tolerant responses that facilitate the symbiotic relationships. While the role of many regulatory proteins, receptors and their signaling pathways in the regulation of the intestinal homeostasis is well documented, the involvement of non-coding RNA molecules in this process has just emerged. This review discusses the most recent knowledge about the contribution of miRNAs in the regulation of the intestinal homeostasis. © 2017 WILEY Periodicals, Inc.

  15. Iron Homeostasis in Yellowstone National Park Hot Spring Microbial Communities

    Science.gov (United States)

    Brown, I.; Tringe, S. G.; Franklin, H.; Bryant, D. A.; Klatt, C. G.; Sarkisova, S. A.; Guevara, M.

    2010-01-01

    It has been postulated that life may have originated on Earth, and possibly on Mars, in association with hydrothermal activity and high concentrations of ferrous iron. However, it is not clear how an iron-rich thermal hydrosphere could be hospitable to microbes, since reduced iron appears to stimulate oxidative stress in all domains of life and particularly in oxygenic phototrophs. Therefore, the study of microbial diversity in iron-depositing hot springs (IDHS) and the mechanisms of iron homeostasis and suppression of oxidative stress may help elucidate how Precambrian organisms could withstand the extremely high concentrations of reactive oxygen species (ROS) produced by interaction between environmental Fe(2+) and O2. Proteins and clusters of orthologous groups (COGs) involved in the maintenance of Fe homeostasis found in cyanobacteria (CB) inhabiting environments with high and low [Fe] were main target of this analysis. Preliminary results of the analysis suggest that the Chocolate Pots (CP) microbial community is heavily dominated by phototrophs from the cyanobacteria (CB), Chloroflexi and Chlorobi phyla, while the Mushroom Spring (MS) effluent channel harbors a more diverse community in which Chloroflexi are the dominant phototrophs. It is speculated that CB inhabiting IDHS have an increased tolerance to both high concentrations of Fe(2+) and ROS produced in the Fenton reaction. This hypothesis was explored via a comparative analysis of the diversity of proteins and COGs involved in Fe and redox homeostasis in the CP and MS microbiomes.

  16. Oxygen in human health from life to death – An approach to teaching redox biology and signaling to graduate and medical students

    Directory of Open Access Journals (Sweden)

    Margaret M. Briehl

    2015-08-01

    Full Text Available In the absence of oxygen human life is measured in minutes. In the presence of oxygen, normal metabolism generates reactive species (ROS that have the potential to cause cell injury contributing to human aging and disease. Between these extremes, organisms have developed means for sensing oxygen and ROS and regulating their cellular processes in response. Redox signaling contributes to the control of cell proliferation and death. Aberrant redox signaling underlies many human diseases. The attributes acquired by altered redox homeostasis in cancer cells illustrate this particularly well. This teaching review and the accompanying illustrations provide an introduction to redox biology and signaling aimed at instructors of graduate and medical students.

  17. Redox electrode materials for supercapatteries

    OpenAIRE

    Yu, Linpo; Chen, George Z.

    2016-01-01

    Redox electrode materials, including transition metal oxides and electronically conducting polymers, are capable of faradaic charge transfer reactions, and play important roles in most electrochemical energy storage devices, such as supercapacitor, battery and supercapattery. Batteries are often based on redox materials with low power capability and safety concerns in some cases. Supercapacitors, particularly those based on redox inactive materials, e.g. activated carbon, can offer high power...

  18. TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State.

    Science.gov (United States)

    Cardaci, Simone; Ciriolo, Maria Rosa

    2012-01-01

    Inborn defects of the tricarboxylic acid (TCA) cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH), fumarate hydratase (FH), and isocitrate dehydrogenase (IDH), pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology.

  19. TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State

    Directory of Open Access Journals (Sweden)

    Simone Cardaci

    2012-01-01

    Full Text Available Inborn defects of the tricarboxylic acid (TCA cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH, fumarate hydratase (FH, and isocitrate dehydrogenase (IDH, pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology.

  20. S-Glutathionylation and Redox Protein Signaling in Drug Addiction.

    Science.gov (United States)

    Womersley, Jacqueline S; Uys, Joachim D

    2016-01-01

    Drug addiction is a chronic relapsing disorder that comes at a high cost to individuals and society. Therefore understanding the mechanisms by which drugs exert their effects is of prime importance. Drugs of abuse increase the production of reactive oxygen and nitrogen species resulting in oxidative stress. This change in redox homeostasis increases the conjugation of glutathione to protein cysteine residues; a process called S-glutathionylation. Although traditionally regarded as a protective mechanism against irreversible protein oxidation, accumulated evidence suggests a more nuanced role for S-glutathionylation, namely as a mediator in redox-sensitive protein signaling. The reversible modification of protein thiols leading to alteration in function under different physiologic/pathologic conditions provides a mechanism whereby change in redox status can be translated into a functional response. As such, S-glutathionylation represents an understudied means of post-translational protein modification that may be important in the mechanisms underlying drug addiction. This review will discuss the evidence for S-glutathionylation as a redox-sensing mechanism and how this may be involved in the response to drug-induced oxidative stress. The function of S-glutathionylated proteins involved in neurotransmission, dendritic spine structure, and drug-induced behavioral outputs will be reviewed with specific reference to alcohol, cocaine, and heroin. Copyright © 2016. Published by Elsevier Inc.

  1. Geochemistry of Natural Redox Fronts

    International Nuclear Information System (INIS)

    Hofmann, B.A.

    1999-05-01

    Redox fronts are important geochemical boundaries which need to be considered in safety assessment of deep repositories for radioactive waste. In most cases, selected host-rock formations will be reducing due to the presence of ferrous minerals, sulphides, etc. During construction and operation of the repository, air will be introduced into the formation. After repository closure, oxidising conditions may persist locally until all oxygen is consumed. In the case of high-level waste, radiolysis of water may provide an additional source of oxidants. Oxidising conditions within a repository are thus possible and potentially have a strong influence on the mobility of many elements. The rate of movement of redox fronts, the boundary between oxidising and reducing environments, and their influence on migrating radionuclides are thus important factors influencing repository performance. The present report is a review of elemental behaviour at natural redox fronts, based on published information and work of the author. Redox fronts are geochemically and geometrically variable manifestations of a global interface between generally oxidising geochemical milieux in contact with the atmosphere and generally reducing milieux in contact with rocks containing ferrous iron, sulphide and/or organic carbon. A classification of redox fronts based on a subdivision into continental near-surface, marine near-surface, and deep environments is proposed. The global redox interface is often located close to the surface of rocks and sediments and, sometimes, within bodies of water. Temperature conditions are close to ambient. A deeper penetration of the global redox front to depths of several kilometres is found in basins containing oxidised sediments (red beds) and in some hydrothermal circulation systems. Temperatures at such deep redox fronts may reach 200 o C. Both near-surface and deep redox fronts are sites of formation of economic deposits of redox-sensitive elements, particularly of

  2. Macrophages in intestinal homeostasis and inflammation

    Science.gov (United States)

    Bain, Calum C; Mowat, Allan McI

    2014-01-01

    The intestine contains the largest pool of macrophages in the body which are essential for maintaining mucosal homeostasis in the face of the microbiota and the constant need for epithelial renewal but are also important components of protective immunity and are involved in the pathology of inflammatory bowel disease (IBD). However, defining the biological roles of intestinal macrophages has been impeded by problems in defining the phenotype and origins of different populations of myeloid cells in the mucosa. Here, we discuss how multiple parameters can be used in combination to discriminate between functionally distinct myeloid cells and discuss the roles of macrophages during homeostasis and how these may change when inflammation ensues. We also discuss the evidence that intestinal macrophages do not fit the current paradigm that tissue-resident macrophages are derived from embryonic precursors that self-renew in situ, but require constant replenishment by blood monocytes. We describe our recent work demonstrating that classical monocytes constantly enter the intestinal mucosa and how the environment dictates their subsequent fate. We believe that understanding the factors that drive intestinal macrophage development in the steady state and how these may change in response to pathogens or inflammation could provide important insights into the treatment of IBD. PMID:24942685

  3. Innate immunity orchestrates adipose tissue homeostasis.

    Science.gov (United States)

    Lin, Yi-Wei; Wei, Li-Na

    2017-06-23

    Obesity is strongly associated with multiple diseases including insulin resistance, type 2 diabetes, cardiovascular diseases, fatty liver disease, neurodegenerative diseases and cancers, etc. Adipose tissue (AT), mainly brown AT (BAT) and white AT (WAT), is an important metabolic and endocrine organ that maintains whole-body homeostasis. BAT contributes to non-shivering thermogenesis in a cold environment; WAT stores energy and produces adipokines that fine-tune metabolic and inflammatory responses. Obesity is often characterized by over-expansion and inflammation of WAT where inflammatory cells/mediators are abundant, especially pro-inflammatory (M1) macrophages, resulting in chronic low-grade inflammation and leading to insulin resistance and metabolic complications. Macrophages constitute the major component of innate immunity and can be activated as a M1 or M2 (anti-inflammatory) phenotype in response to environmental stimuli. Polarized M1 macrophage causes AT inflammation, whereas polarized M2 macrophage promotes WAT remodeling into the BAT phenotype, also known as WAT browning/beiging, which enhances insulin sensitivity and metabolic health. This review will discuss the regulation of AT homeostasis in relation to innate immunity.

  4. Redox regulation of the MED28 and MED32 mediator subunits is important for development and senescence.

    Science.gov (United States)

    Shaikhali, Jehad; Davoine, Céline; Björklund, Stefan; Wingsle, Gunnar

    2016-05-01

    Mediator is a conserved multi-protein complex that acts as a bridge between promoter-bound transcriptional regulators and RNA polymerase II. While redox signaling is important in adjusting plant metabolism and development, the involvement of Mediator in redox homeostasis and regulation only recently started to emerge. Our previous results show that the MED10a, MED28, and MED32 Mediator subunits form various types of covalent oligomers linked by intermolecular disulfide bonds in vitro. To link that with biological significance we have characterized Arabidopsis med32 and med28 mutants and found that they are affected in root development and senescence, phenotypes possibly associated to redox changes.

  5. Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status.

    Science.gov (United States)

    Trivedi, Malav S; Holger, Dana; Bui, Anh Tuyet; Craddock, Travis J A; Tartar, Jaime L

    2017-01-01

    Sleep is critical for repair as well as the rejuvenation processes in the body and many of these functions are regulated via underlying cellular metabolic homeostasis. Changes in sleep pattern are reported to alter such metabolic function resulting in altered disease susceptibility or behavior. Here, we measured the extent to which overnight total sleep deprivation (SD) in young adult humans can influence systemic (plasma-derived) redox-metabolism including the major antioxidant, glutathione as well as DNA methylation levels. Nineteen participants (n = 19, μ age = 21, SD = 3.09) underwent morning testing before and after overnight total SD. Biochemical measures before and after SD revealed that glutathione, ATP, cysteine, and homocysteine levels were significantly reduced following one night of sleep deprivation (all p's sleep deprivation (maintaining wakefulness) uses up metabolic reserves, we observed that morning cortisol levels were blunted after sleep deprivation. There were no significant correlations between self-reported or actigraphy-measured sleep and the biochemical measurements, strongly indicating that prior sleep behavior did not have any direct influence on the biochemical measures taken at baseline or after sleep deprivation. Results from the current investigation supports the previous literature implicating the induction of oxidative stress and ATP depletion with sleep deprivation. Furthermore, such altered antioxidant status can also induce downstream epigenetic changes. Although we did not measure the specific genes that were altered under the influence of such sleep deprivation, such epigenetic changes could potentially contribute towards disease predisposition.

  6. Liver immunology and its role in inflammation and homeostasis.

    Science.gov (United States)

    Robinson, Mark W; Harmon, Cathal; O'Farrelly, Cliona

    2016-05-01

    The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the non-diseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear 'dangerous' stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.

  7. Nitric oxide and plant iron homeostasis.

    Science.gov (United States)

    Buet, Agustina; Simontacchi, Marcela

    2015-03-01

    Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes. © 2015 New York Academy of Sciences.

  8. Activator Protein-1: redox switch controlling structure and DNA-binding.

    Science.gov (United States)

    Yin, Zhou; Machius, Mischa; Nestler, Eric J; Rudenko, Gabby

    2017-11-02

    The transcription factor, activator protein-1 (AP-1), binds to cognate DNA under redox control; yet, the underlying mechanism has remained enigmatic. A series of crystal structures of the AP-1 FosB/JunD bZIP domains reveal ordered DNA-binding regions in both FosB and JunD even in absence DNA. However, while JunD is competent to bind DNA, the FosB bZIP domain must undergo a large conformational rearrangement that is controlled by a 'redox switch' centered on an inter-molecular disulfide bond. Solution studies confirm that FosB/JunD cannot undergo structural transition and bind DNA when the redox-switch is in the 'OFF' state, and show that the mid-point redox potential of the redox switch affords it sensitivity to cellular redox homeostasis. The molecular and structural studies presented here thus reveal the mechanism underlying redox-regulation of AP-1 Fos/Jun transcription factors and provide structural insight for therapeutic interventions targeting AP-1 proteins. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Activator Protein-1: redox switch controlling structure and DNA-binding

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Zhou; Machius, Mischa; Nestler, Eric J.; Rudenko, Gabby (Texas-MED); (Icahn)

    2017-09-07

    The transcription factor, activator protein-1 (AP-1), binds to cognate DNA under redox control; yet, the underlying mechanism has remained enigmatic. A series of crystal structures of the AP-1 FosB/JunD bZIP domains reveal ordered DNA-binding regions in both FosB and JunD even in absence DNA. However, while JunD is competent to bind DNA, the FosB bZIP domain must undergo a large conformational rearrangement that is controlled by a ‘redox switch’ centered on an inter-molecular disulfide bond. Solution studies confirm that FosB/JunD cannot undergo structural transition and bind DNA when the redox-switch is in the ‘OFF’ state, and show that the mid-point redox potential of the redox switch affords it sensitivity to cellular redox homeostasis. The molecular and structural studies presented here thus reveal the mechanism underlying redox-regulation of AP-1 Fos/Jun transcription factors and provide structural insight for therapeutic interventions targeting AP-1 proteins.

  10. A novel role for Twist-1 in pulp homeostasis.

    Science.gov (United States)

    Galler, K M; Yasue, A; Cavender, A C; Bialek, P; Karsenty, G; D'Souza, R N

    2007-10-01

    The molecular mechanisms that maintain the equilibrium of odontoblast progenitor cells in dental pulp are unknown. Here we tested whether homeostasis in dental pulp is modulated by Twist-1, a nuclear protein that partners with Runx2 during osteoblast differentiation. Our analysis of Twist-1(+/-) mice revealed phenotypic changes that involved an earlier onset of dentin matrix formation, increased alkaline phosphatase activity, and pulp stones within the pulp. RT-PCR analyses revealed Twist-1 expression in several adult organs, including pulp. Decreased levels of Twist-1 led to higher levels of type I collagen and Dspp gene expression in perivascular cells associated with the pulp stones. In mice heterozygous for both Twist-1 and Runx2 inactivation, the phenotype of pulp stones appeared completely rescued. These findings suggest that Twist-1 plays a key role in restraining odontoblast differentiation, thus maintaining homeostasis in dental pulp. Furthermore, Twist-1 functions in dental pulp are dependent on its interaction with Runx2.

  11. Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

    KAUST Repository

    Liu, Peng

    2015-02-27

    Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response.

  12. Redox Cycling Realized in Paper-Based Biochemical Sensor for Selective Detection of Reversible Redox Molecules Without Micro/Nano Fabrication Process.

    Science.gov (United States)

    Yamamoto, So; Uno, Shigeyasu

    2018-02-28

    This paper describes a paper-based biochemical sensor that realizes redox cycling with close interelectrode distance. Two electrodes, the generator and collector electrodes, can detect steady-state oxidation and reduction currents when suitable potential is held at each electrode. The sensor has two gold plates on both sides of a piece of chromatography paper and defines the interelectrode distance by the thickness of the paper (180 μm) without any micro-fabrication processes. Our proposed sensor geometry has successfully exhibited signatures of redox cycling. As a result, the concentration of ferrocyanide as reversible redox molecules was successfully quantified under the interference by ascorbic acid as a strong irreversible reducing agent. This was possible because the ascorbic acids are completely consumed by the irreversible reaction, while maintaining redox cycling of reversible ferrocyanide. This suggests that a sensor based on the redox cycling method will be suitable for detecting target molecules at low concentration.

  13. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

    OpenAIRE

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pha...

  14. Regulation of intestinal homeostasis by innate and adaptive immunity.

    Science.gov (United States)

    Kayama, Hisako; Takeda, Kiyoshi

    2012-11-01

    The intestine is a unique tissue where an elaborate balance is maintained between tolerance and immune responses against a variety of environmental factors such as food and the microflora. In a healthy individual, the microflora stimulates innate and adaptive immune systems to maintain gut homeostasis. However, the interaction of environmental factors with particular genetic backgrounds can lead to dramatic changes in the composition of the microflora (i.e. dysbiosis). Many of the specific commensal-bacterial products and the signaling pathways they trigger have been characterized. The role of T(h)1, T(h)2 and T(h)17 cells in inflammatory bowel disease has been widely investigated, as has the contribution of epithelial cells and subsets of dendritic cells and macrophages. To date, multiple regulatory cells in adaptive immunity, such as regulatory T cells and regulatory B cells, have been shown to maintain gut homeostasis by preventing inappropriate innate and adaptive immune responses to commensal bacteria. Additionally, regulatory myeloid cells have recently been identified that prevent intestinal inflammation by inhibiting T-cell proliferation. An increasing body of evidence has shown that multiple regulatory mechanisms contribute to the maintenance of gut homeostasis.

  15. Ergonomics Contribution in Maintainability

    Science.gov (United States)

    Teymourian, Kiumars; Seneviratne, Dammika; Galar, Diego

    2017-09-01

    The objective of this paper is to describe an ergonomics contribution in maintainability. The economical designs, inputs and training helps to increase the maintainability indicators for industrial devices. This analysis can be helpful, among other cases, to compare systems, to achieve a better design regarding maintainability requirements, to improve this maintainability under specific industrial environment and to foresee maintainability problems due to eventual changes in a device operation conditions. With this purpose, this work first introduces the notion of ergonomics and human factors, maintainability and the implementation of assessment of human postures, including some important postures to perform maintenance activities. A simulation approach is used to identify the critical posture of the maintenance personnel and implements the defined postures with minimal loads on the personnel who use the equipment in a practical scenario. The simulation inputs are given to the designers to improve the workplace/equipment in order to high level of maintainability. Finally, the work concludes summarizing the more significant aspects and suggesting future research.

  16. [Acid-base homeostasis: metabolic acidosis and metabolic alkalosis].

    Science.gov (United States)

    Dussol, Bertrand

    2014-07-01

    Acid-base homeostasis ensured by the kidneys, which maintain the equilibrium between proton generation by cellular metabolism and proton excretion in urine. This requirement is lifesaving because of the protons' ability to bind to anionic proteins in the extracellular space, modifying their structure and functions. The kidneys also regenerate bicarbonates. The kidney is not the sole organ in charge of maintaining blood pH in a very narrow range; lungs are also involved since they allow a large amount of volatile acid generated by cellular respiration to be eliminated. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  17. The membrane stress response buffers lethal effects of lipid disequilibrium by reprogramming the protein homeostasis network.

    Science.gov (United States)

    Thibault, Guillaume; Shui, Guanghou; Kim, Woong; McAlister, Graeme C; Ismail, Nurzian; Gygi, Steven P; Wenk, Markus R; Ng, Davis T W

    2012-10-12

    Lipid composition can differ widely among organelles and even between leaflets of a membrane. Lipid homeostasis is critical because disequilibrium can have disease outcomes. Despite their importance, mechanisms maintaining lipid homeostasis remain poorly understood. Here, we establish a model system to study the global effects of lipid imbalance. Quantitative lipid profiling was integral to monitor changes to lipid composition and for system validation. Applying global transcriptional and proteomic analyses, a dramatically altered biochemical landscape was revealed from adaptive cells. The resulting composite regulation we term the "membrane stress response" (MSR) confers compensation, not through restoration of lipid composition, but by remodeling the protein homeostasis network. To validate its physiological significance, we analyzed the unfolded protein response (UPR), one facet of the MSR and a key regulator of protein homeostasis. We demonstrate that the UPR maintains protein biogenesis, quality control, and membrane integrity-functions otherwise lethally compromised in lipid dysregulated cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Redox electrodes comprised of polymer-modified carbon nanomaterials

    Science.gov (United States)

    Roberts, Mark; Emmett, Robert; Karakaya, Mehmet; Podila, Ramakrishna; Rao, Apparao; Clemson Physics Team; Clemson Chemical Engineering Team

    2013-03-01

    A shift in how we generate and use electricity requires new energy storage materials and systems compatible with hybrid electric transportation and the integration of renewable energy sources. Supercapacitors provide a solution to these needs by combining the high power, rapid switching, and exceptional cycle life of a capacitor with the high energy density of a battery. Our research brings together nanotechnology and materials chemistry to address the limitations of electrode materials. Paper electrodes fabricated with various forms of carbon nanomaterials, such as nanotubes, are modified with redox-polymers to increase the electrode's energy density while maintaining rapid discharge rates. In these systems, the carbon nanomaterials provide the high surface area, electrical conductivity, nanoscale and porosity, while the redox polymers provide a mechanism for charge storage through Faradaic charge transfer. The design of redox polymers and their incorporation into nanomaterial electrodes will be discussed with a focus on enabling high power and high energy density electrodes.

  19. Sleep Homeostasis and Synaptic Plasticity

    Science.gov (United States)

    2017-06-01

    Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202...circuit (a homeostat) that operates in concert with the circadian circuitry or does sleep drive accumulate everywhere in the brain? To answer these...neurons is capable of generating sleep drive. RNAi-mediated knockdown of insomniac in R2 neurons abolished sleep homeostasis without affecting baseline

  20. Antioxidantes na manutenção do equilíbrio redox cutâneo: uso e avaliação de sua eficácia Antioxidants in the skin: applications and evaluation of their efficacy

    Directory of Open Access Journals (Sweden)

    Thais Guaratini

    2007-02-01

    Full Text Available The skin is a very complex organ, continuously exposed to physical, chemical and microbiological agents. Enzymes as well as low-molecular weight antioxidants are present in the cutaneous tissue to counterbalance the deleterious effect caused by an oxidative stress and thus maintain homeostasis. Antioxidants such as vitamins C and E, carotenoids, and extracts with these properties have been extensively used for treatment of pathologies and skin aging prevention. We review here different mechanisms that can interfere in the redox equilibrium of the skin, as well as the chemical reactions involved in these processes. Moreover, we discuss the importance of endogenous or exogenous antioxidants that can be acquired from the diet or from oral or topical administration, and methodologies that have been developed to evaluate their efficacy.

  1. Grasshoppers regulate N:p stoichiometric homeostasis by changing phosphorus contents in their frass.

    Science.gov (United States)

    Zhang, Zijia; Elser, James J; Cease, Arianne J; Zhang, Ximei; Yu, Qiang; Han, Xingguo; Zhang, Guangming

    2014-01-01

    Nitrogen (N) and phosphorus (P) are important limiting nutrients for plant production and consumer performance in a variety of ecosystems. As a result, the N:P stoichiometry of herbivores has received increased attention in ecology. However, the mechanisms by which herbivores maintain N:P stoichiometric homeostasis are poorly understood. Here, using a field manipulation experiment we show that the grasshopper Oedaleus asiaticus maintains strong N:P stoichiometric homeostasis regardless of whether grasshoppers were reared at low or high density. Grasshoppers maintained homeostasis by increasing P excretion when eating plants with higher P contents. However, while grasshoppers also maintained constant body N contents, we found no changes in N excretion in response to changing plant N content over the range measured. These results suggest that O. asiaticus maintains P homeostasis primarily by changing P absorption and excretion rates, but that other mechanisms may be more important for regulating N homeostasis. Our findings improve our understanding of consumer-driven P recycling and may help in understanding the factors affecting plant-herbivore interactions and ecosystem processes in grasslands.

  2. Mechanisms of Cell Polarity-Controlled Epithelial Homeostasis and Immunity in the Intestine.

    Science.gov (United States)

    Klunder, Leon J; Faber, Klaas Nico; Dijkstra, Gerard; van IJzendoorn, Sven C D

    2017-07-05

    Intestinal epithelial cell polarity is instrumental to maintain epithelial homeostasis and balance communications between the gut lumen and bodily tissue, thereby controlling the defense against gastrointestinal pathogens and maintenance of immune tolerance to commensal bacteria. In this review, we highlight recent advances with regard to the molecular mechanisms of cell polarity-controlled epithelial homeostasis and immunity in the human intestine. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  3. The Interplay between Feedback and Buffering in Cellular Homeostasis.

    Science.gov (United States)

    Hancock, Edward J; Ang, Jordan; Papachristodoulou, Antonis; Stan, Guy-Bart

    2017-11-22

    Buffering, the use of reservoirs of molecules to maintain concentrations of key molecular species, and negative feedback are the primary known mechanisms for robust homeostatic regulation. To our knowledge, however, the fundamental principles behind their combined effect have not been elucidated. Here, we study the interplay between buffering and negative feedback in the context of cellular homeostasis. We show that negative feedback counteracts slow-changing disturbances, whereas buffering counteracts fast-changing disturbances. Furthermore, feedback and buffering have limitations that create trade-offs for regulation: instability in the case of feedback and molecular noise in the case of buffering. However, because buffering stabilizes feedback and feedback attenuates noise from slower-acting buffering, their combined effect on homeostasis can be synergistic. These effects can be explained within a traditional control theory framework and are consistent with experimental observations of both ATP homeostasis and pH regulation in vivo. These principles are critical for studying robustness and homeostasis in biology and biotechnology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Lifespan extension by preserving proliferative homeostasis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Benoît Biteau

    2010-10-01

    Full Text Available Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan.

  5. Thioredoxins, Glutaredoxins, and Peroxiredoxins—Molecular Mechanisms and Health Significance: from Cofactors to Antioxidants to Redox Signaling

    Science.gov (United States)

    Hanschmann, Eva-Maria; Godoy, José Rodrigo; Berndt, Carsten; Hudemann, Christoph

    2013-01-01

    Abstract Thioredoxins (Trxs), glutaredoxins (Grxs), and peroxiredoxins (Prxs) have been characterized as electron donors, guards of the intracellular redox state, and “antioxidants”. Today, these redox catalysts are increasingly recognized for their specific role in redox signaling. The number of publications published on the functions of these proteins continues to increase exponentially. The field is experiencing an exciting transformation, from looking at a general redox homeostasis and the pathological oxidative stress model to realizing redox changes as a part of localized, rapid, specific, and reversible redox-regulated signaling events. This review summarizes the almost 50 years of research on these proteins, focusing primarily on data from vertebrates and mammals. The role of Trx fold proteins in redox signaling is discussed by looking at reaction mechanisms, reversible oxidative post-translational modifications of proteins, and characterized interaction partners. On the basis of this analysis, the specific regulatory functions are exemplified for the cellular processes of apoptosis, proliferation, and iron metabolism. The importance of Trxs, Grxs, and Prxs for human health is addressed in the second part of this review, that is, their potential impact and functions in different cell types, tissues, and various pathological conditions. Antioxid. Redox Signal. 19, 1539–1605. PMID:23397885

  6. Feasibility of assessing health state by detecting redox state of human body based on Chinese medicine constitution.

    Science.gov (United States)

    Li, Ling-Ru; Wang, Qi; Wang, Ji; Wang, Qian-Fei; Yang, Ling-Ling; Zheng, Lu-Yu; Zhang, Yan

    2016-08-01

    This article discussed the feasibility of assessing health state by detecting redox state of human body. Firstly, the balance of redox state is the basis of homeostasis, and the balance ability of redox can reflflect health state of human body. Secondly, the redox state of human body is a sensitive index of multiple risk factors of health such as age, external environment and psychological factors. It participates in the occurrence and development of multiple diseases involving metabolic diseases and nervous system diseases, and can serve as a cut-in point for treatment of these diseases. Detecting the redox state of high risk people is signifificantly important for early detection and treatment of disease. The blood plasma and urine could be selected to detect, which is convenient. It is pointed that the indexes not only involve oxidation product and antioxidant enzyme but also redox couple. Chinese medicine constitution reflflects the state of body itself and the ability of adapting to external environment, which is consistent with the connotation of health. It is found that there are nine basic types of constitution in Chinese population, which provides a theoretical basis of health preservation, preventive treatment of disease and personalized treatment. With the combination of redox state detection and the Chinese medicine constitution theory, the heath state can be systemically assessed by conducting large-scale epidemiological survey with classifified detection on redox state of human body.

  7. Bifunctional redox flow battery

    International Nuclear Information System (INIS)

    Wen, Y.H.; Cheng, J.; Xun, Y.; Ma, P.H.; Yang, Y.S.

    2008-01-01

    A new bifunctional redox flow battery (BRFB) system, V(III)/V(II)-L-cystine(O 2 ), was systematically investigated by using different separators. It is shown that during charge, water transfer is significantly restricted with increasing the concentration of HBr when the Nafion 115 cation exchange membrane is employed. The same result can be obtained when the gas diffusion layer (GDL) hot-pressed separator is used. The organic electro-synthesis is directly correlated with the crossover of vanadium. When employing the anion exchange membrane, the electro-synthesis efficiency is over 96% due to a minimal crossover of vanadium. When the GDL hot-pressed separator is applied, the crossover of vanadium and water transfer are noticeably prevented and the electro-synthesis efficiency of over 99% is obtained. Those impurities such as vanadium ions and bromine can be eliminated through the purification of organic electro-synthesized products. The purified product is identified to be L-cysteic acid by IR spectrum. The BRFB shows a favorable discharge performance at a current density of 20 mA cm -2 . Best discharge performance is achieved by using the GDL hot-pressed separator. The coulombic efficiency of 87% and energy efficiency of about 58% can be obtained. The cause of major energy losses is mainly associated with the cross-contamination of anodic and cathodic active electrolytes

  8. Homeostasis of metals in the progression of Alzheimer's disease.

    Science.gov (United States)

    González-Domínguez, Raúl; García-Barrera, Tamara; Gómez-Ariza, José Luis

    2014-06-01

    In order to study the involvement of metals in the progression of Alzheimer's disease, serum samples from patients with Alzheimer and mild cognitive impairment were investigated. For this purpose, metal content was analyzed after size-fractionation of species and then, inter-element and inter-fraction ratios were computed. In this way, the analysis allowed discovering changes that could be used as markers of disease, but also provided a new insight into the interactions in the homeostasis of elements in neurodegeneration and its progression. Aluminum and labile forms of iron and copper were increased in demented patients, while manganese, zinc and selenium were reduced. Interestingly, levels of different elements, principally iron, aluminum and manganese, were closely inter-related, which could evidence a complex interdependency between the homeostasis of the different metals in this disorder. On the other hand, imbalances in metabolism of copper, zinc and selenium could be associated to abnormal redox status. Therefore, this study may contribute to our understanding of the pathological mechanisms related to metals in Alzheimer's disease.

  9. Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

    Science.gov (United States)

    Chausse, Bruno; Vieira-Lara, Marcel A; Sanchez, Angélica B; Medeiros, Marisa H G; Kowaltowski, Alicia J

    2015-01-01

    Intermittent fasting (IF) is a dietary intervention often used as an alternative to caloric restriction (CR) and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.

  10. Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

    Directory of Open Access Journals (Sweden)

    Bruno Chausse

    Full Text Available Intermittent fasting (IF is a dietary intervention often used as an alternative to caloric restriction (CR and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.

  11. Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities

    Science.gov (United States)

    Jones, Dean P.; Brown, Lou Ann S.

    2012-01-01

    Abstract Asthma is a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness and airflow limitation in response to specific triggers. Whereas inflammation is important for tissue regeneration and wound healing, the profound and sustained inflammatory response associated with asthma may result in airway remodeling that involves smooth muscle hypertrophy, epithelial goblet-cell hyperplasia, and permanent deposition of airway extracellular matrix proteins. Although the specific mechanisms responsible for asthma are still being unraveled, free radicals such as reactive oxygen species and reactive nitrogen species are important mediators of airway tissue damage that are increased in subjects with asthma. There is also a growing body of literature implicating disturbances in oxidation/reduction (redox) reactions and impaired antioxidant defenses as a risk factor for asthma development and asthma severity. Ultimately, these redox-related perturbations result in a vicious cycle of airway inflammation and injury that is not always amenable to current asthma therapy, particularly in cases of severe asthma. This review will discuss disruptions of redox signaling and control in asthma with a focus on the thiol, glutathione, and reduced (thiol) form (GSH). First, GSH synthesis, GSH distribution, and GSH function and homeostasis are discussed. We then review the literature related to GSH redox balance in health and asthma, with an emphasis on human studies. Finally, therapeutic opportunities to restore the GSH redox balance in subjects with asthma are discussed. Antioxid. Redox Signal. 17, 375–408. PMID:22304503

  12. The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P.; Yi, Ling; Kaler, Stephen G.; Lutsenko, Svetlana; Ralle, Martina

    2016-05-16

    Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia).

  13. Redox environment in stem and differentiated cells: A quantitative approach.

    Science.gov (United States)

    Lyublinskaya, O G; Ivanova, Ju S; Pugovkina, N A; Kozhukharova, I V; Kovaleva, Z V; Shatrova, A N; Aksenov, N D; Zenin, V V; Kaulin, Yu A; Gamaley, I A; Nikolsky, N N

    2017-08-01

    Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity. However, biochemical normalization of these parameters to cell volume/protein leads to matching of normalized values in stem and differentiated cells and shows that tested in the present study cells (human embryonic stem cells and their fibroblast-like progenies, adult mesenchymal stem cells, lymphocytes, HeLa) maintain similar intracellular redox status. Based on these observations, we propose to use ROS concentration averaged over the cell volume instead of ROS level as a measure of intracellular redox balance. We show that attempts to use ROS level for comparative analysis of redox status of morphologically different cells could lead to false conclusions. Methods for the assessment of ROS concentration based on flow cytometry analysis with the use of H 2 DCFDA dye and HyPer, genetically encoded probe for hydrogen peroxide, are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Therapeutic Targeting of Redox Signaling in Myofibroblast Differentiation and Age-Related Fibrotic Disease

    Directory of Open Access Journals (Sweden)

    Natalie Sampson

    2012-01-01

    Full Text Available Myofibroblast activation plays a central role during normal wound healing. Whereas insufficient myofibroblast activation impairs wound healing, excessive myofibroblast activation promotes fibrosis in diverse tissues (including benign prostatic hyperplasia, BPH leading to organ dysfunction and also promotes a stromal response that supports tumor progression. The incidence of impaired wound healing, tissue fibrosis, BPH, and certain cancers strongly increases with age. This paper summarizes findings from in vitro fibroblast-to-myofibroblast differentiation systems that serve as cellular models to study fibrogenesis of diverse tissues. Supported by substantial in vivo data, a large body of evidence indicates that myofibroblast differentiation induced by the profibrotic cytokine transforming growth factor beta is driven by a prooxidant shift in redox homeostasis due to elevated production of NADPH oxidase 4 (NOX4-derived hydrogen peroxide and supported by concomitant decreases in nitric oxide/cGMP signaling and reactive oxygen species (ROS scavenging enzymes. Fibroblast-to-myofibroblast differentiation can be inhibited and reversed by restoring redox homeostasis using antioxidants or NOX4 inactivation as well as enhancing nitric oxide/cGMP signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases. Current evidence indicates the therapeutic potential of targeting the prooxidant shift in redox homeostasis for the treatment of age-related diseases associated with myofibroblast dysregulation.

  15. Kinetic and Thermodynamic Aspects of Cellular Thiol-Disulfide Redox Regulation

    DEFF Research Database (Denmark)

    Jensen, Kristine Steen; Hansen, Rosa Erritzøe; Winther, Jakob R

    2009-01-01

    . In the cytosol regulatory disulfide bonds are typically formed in spite of the prevailing reducing conditions and may thereby function as redox switches. Such disulfide bonds are protected from enzymatic reduction by kinetic barriers and are thus allowed to exist long enough to elicit the signal. Factors......Regulation of intracellular thiol-disulfide redox status is an essential part of cellular homeostasis. This involves the regulation of both oxidative and reductive pathways, production of oxidant scavengers and, importantly, the ability of cells to respond to changes in the redox environment...... that affect the rate of thiol-disulfide exchange and stability of disulfide bonds are discussed within the framework of the underlying chemical foundations. This includes the effect of thiol acidity (pKa), the local electrostatic environment, molecular strain and entropy. Even though a thiol-disulfide...

  16. Redox Regulation in Cancer: A Double-edged Sword with Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Asha Acharya

    2010-01-01

    Full Text Available Oxidative stress, implicated in the etiology of cancer, results from an imbalance in the production of reactive oxygen species (ROS and cell’s own antioxidant defenses. ROS deregulate the redox homeostasis and promote tumor formation by initiating an aberrant induction of signaling networks that cause tumorigenesis. Ultraviolet (UV exposures, γ-radiation and other environmental carcinogens generate ROS in the cells, which can exert apoptosis in the tumors, thereby killing the malignant cells or induce the progression of the cancer growth by blocking cellular defense system. Cancer stem cells take the advantage of the aberrant redox system and spontaneously proliferate. Oxidative stress and gene-environment interactions play a significant role in the development of breast, prostate, pancreatic and colon cancer. Prolonged lifetime exposure to estrogen is associated with several kinds of DNA damage. Oxidative stress and estrogen receptor-associated proliferative changes are suggested to play important roles in estrogen-induced breast carcinogenesis. BRCA1, a tumor suppressor against hormone responsive cancers such as breast and prostate cancer, plays a significant role in inhibiting ROS and estrogen mediated DNA damage; thereby regulate the redox homeostasis of the cells. Several transcription factors and tumor suppressors are involved during stress response such as Nrf2, NFκB and BRCA1. A promising strategy for targeting redox status of the cells is to use readily available natural substances from vegetables, fruits, herbs and spices. Many of the phytochemicals have already been identified to have chemopreventive potential, capable of intervening in carcinogenesis.

  17. Maintaining dignity in vulnerability

    DEFF Research Database (Denmark)

    Høy, Bente

    2016-01-01

    to understand the meaning of the narrated text. Results. The meaning of maintaining dignity was constituted in a sense of vulnerability to the self, and elucidated in three major interrelated themes: Being involved as a human being, being involved as the person one is and strives to become, and being involved...

  18. Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility

    OpenAIRE

    Kristina Wedege; Emil Dražević; Denes Konya; Anders Bentien

    2016-01-01

    Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined ...

  19. Oxidative stress homeostasis in grapevine (Vitis vinifera L.

    Directory of Open Access Journals (Sweden)

    Luisa C Carvalho

    2015-03-01

    Full Text Available Plants can maintain growth and reproductive success by sensing changes in the environment and reacting through mechanisms at molecular, cellular, physiological and developmental levels. Each stress condition prompts a unique response although some overlap between the reactions to abiotic stress (drought, heat, cold, salt or high light and to biotic stress (pathogens does occur. A common feature in the response to all stresses is the onset of oxidative stress, through the production of reactive oxygen species (ROS. As hydrogen peroxide and superoxide are involved in stress signaling, a tight control in ROS homeostasis requires a delicate balance of systems involved in their generation and degradation. If the plant lacks the capacity to generate scavenging potential, this can ultimately lead to death. In grapevine, antioxidant homeostasis can be considered at whole plant levels and during the development cycle. The most striking example lies in berries and their derivatives, such as wine, with nutraceutical properties associated with their antioxidant capacity. Antioxidant homeostasis is tightly regulated in leaves, assuring a positive balance between photosynthesis and respiration, explaining the tolerance of many grapevine varieties to extreme environments.In this review we will focus on antioxidant metabolites, antioxidant enzymes, transcriptional regulation and cross-talk with hormones prompted by abiotic stress conditions. We will also discuss three situations that require specific homeostasis balance: biotic stress, the oxidative burst in berries at veraison and in vitro systems. The genetic plasticity of the antioxidant homeostasis response put in evidence by the different levels of tolerance to stress presented by grapevine varieties will be addressed. The gathered information is relevant to foster varietal adaptation to impending climate changes, to assist breeders in choosing the more adapted varieties and to suitable viticulture

  20. The role of gut microbiota in immune homeostasis and autoimmunity.

    Science.gov (United States)

    Wu, Hsin-Jung; Wu, Eric

    2012-01-01

    Keeping a delicate balance in the immune system by eliminating invading pathogens, while still maintaining self-tolerance to avoid autoimmunity, is critical for the body's health. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis. Moreover, it has recently become obvious that alterations of these gut microbial communities can cause immune dysregulation, leading to autoimmune disorders. Here we review the advances in our understanding of how the gut microbiota regulates innate and adaptive immune homeostasis, which in turn can affect the development of not only intestinal but also systemic autoimmune diseases. Exploring the interaction of gut microbes and the host immune system will not only allow us to understand the pathogenesis of autoimmune diseases but will also provide us new foundations for the design of novel immuno- or microbe-based therapies.

  1. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

    Science.gov (United States)

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

  2. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.

    Science.gov (United States)

    Bevins, Charles L; Salzman, Nita H

    2011-05-01

    Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.

  3. A Dual-Sensing Receptor Confers Robust Cellular Homeostasis

    Directory of Open Access Journals (Sweden)

    Hannah Schramke

    2016-06-01

    Full Text Available Cells have evolved diverse mechanisms that maintain intracellular homeostasis in fluctuating environments. In bacteria, control is often exerted by bifunctional receptors acting as both kinase and phosphatase to regulate gene expression, a design known to provide robustness against noise. Yet how such antagonistic enzymatic activities are balanced as a function of environmental change remains poorly understood. We find that the bifunctional receptor that regulates K+ uptake in Escherichia coli is a dual sensor, which modulates its autokinase and phosphatase activities in response to both extracellular and intracellular K+ concentration. Using mathematical modeling, we show that dual sensing is a superior strategy for ensuring homeostasis when both the supply of and demand for a limiting resource fluctuate. By engineering standards, this molecular control system displays a strikingly high degree of functional integration, providing a reference for the vast numbers of receptors for which the sensing strategy remains elusive.

  4. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

    Science.gov (United States)

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

  5. Integrating physiological regulation with stem cell and tissue homeostasis

    Science.gov (United States)

    Nakada, Daisuke; Levi, Boaz P.; Morrison, Sean J.

    2015-01-01

    Summary Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation. Emerging evidence suggests that other aspects of cellular physiology, including mitosis, signal transduction, and metabolic regulation also differ between stem cells and their progeny. These differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms, changes in metabolism, diet, exercise, mating, aging, infection, and disease. This allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change. Stem cells are therefore not only regulated by short-range signals that maintain homeostasis within their tissue of origin, but also by long-range signals that integrate stem cell function with systemic physiology. PMID:21609826

  6. The Greater Phenotypic Homeostasis of the Allopolyploid Coffea arabica Improved the Transcriptional Homeostasis Over that of Both Diploid Parents.

    Science.gov (United States)

    Bertrand, Benoît; Bardil, Amélie; Baraille, Hélène; Dussert, Stéphane; Doulbeau, Sylvie; Dubois, Emeric; Severac, Dany; Dereeper, Alexis; Etienne, Hervé

    2015-10-01

    Polyploidy impacts the diversity of plant species, giving rise to novel phenotypes and leading to ecological diversification. In order to observe adaptive and evolutionary capacities of polyploids, we compared the growth, primary metabolism and transcriptomic expression level in the leaves of the newly formed allotetraploid Coffea arabica species compared with its two diploid parental species (Coffea eugenioides and Coffea canephora), exposed to four thermal regimes (TRs; 18-14, 23-19, 28-24 and 33-29°C). The growth rate of the allopolyploid C. arabica was similar to that of C. canephora under the hottest TR and that of C. eugenioides under the coldest TR. For metabolite contents measured at the hottest TR, the allopolyploid showed similar behavior to C. canephora, the parent which tolerates higher growth temperatures in the natural environment. However, at the coldest TR, the allopolyploid displayed higher sucrose, raffinose and ABA contents than those of its two parents and similar linolenic acid leaf composition and Chl content to those of C. eugenioides. At the gene expression level, few differences between the allopolyploid and its parents were observed for studied genes linked to photosynthesis, respiration and the circadian clock, whereas genes linked to redox activity showed a greater capacity of the allopolyploid for homeostasis. Finally, we found that the overall transcriptional response to TRs of the allopolyploid was more homeostatic compared with its parents. This better transcriptional homeostasis of the allopolyploid C. arabica afforded a greater phenotypic homeostasis when faced with environments that are unsuited to the diploid parental species. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Homeostasis, inflammation, and disease susceptibility.

    Science.gov (United States)

    Kotas, Maya E; Medzhitov, Ruslan

    2015-02-26

    While modernization has dramatically increased lifespan, it has also witnessed the increasing prevalence of diseases such as obesity, hypertension, and type 2 diabetes. Such chronic, acquired diseases result when normal physiologic control goes awry and may thus be viewed as failures of homeostasis. However, while nearly every process in human physiology relies on homeostatic mechanisms for stability, only some have demonstrated vulnerability to dysregulation. Additionally, chronic inflammation is a common accomplice of the diseases of homeostasis, yet the basis for this connection is not fully understood. Here we review the design of homeostatic systems and discuss universal features of control circuits that operate at the cellular, tissue, and organismal levels. We suggest a framework for classification of homeostatic signals that is based on different classes of homeostatic variables they report on. Finally, we discuss how adaptability of homeostatic systems with adjustable set points creates vulnerability to dysregulation and disease. This framework highlights the fundamental parallels between homeostatic and inflammatory control mechanisms and provides a new perspective on the physiological origin of inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Oxidative Stress, Redox Signaling, and Autophagy: Cell Death Versus Survival

    Science.gov (United States)

    Navarro-Yepes, Juliana; Burns, Michaela; Anandhan, Annadurai; Khalimonchuk, Oleh; del Razo, Luz Maria; Quintanilla-Vega, Betzabet; Pappa, Aglaia; Panayiotidis, Mihalis I.

    2014-01-01

    Abstract Significance: The molecular machinery regulating autophagy has started becoming elucidated, and a number of studies have undertaken the task to determine the role of autophagy in cell fate determination within the context of human disease progression. Oxidative stress and redox signaling are also largely involved in the etiology of human diseases, where both survival and cell death signaling cascades have been reported to be modulated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recent Advances: To date, there is a good understanding of the signaling events regulating autophagy, as well as the signaling processes by which alterations in redox homeostasis are transduced to the activation/regulation of signaling cascades. However, very little is known about the molecular events linking them to the regulation of autophagy. This lack of information has hampered the understanding of the role of oxidative stress and autophagy in human disease progression. Critical Issues: In this review, we will focus on (i) the molecular mechanism by which ROS/RNS generation, redox signaling, and/or oxidative stress/damage alter autophagic flux rates; (ii) the role of autophagy as a cell death process or survival mechanism in response to oxidative stress; and (iii) alternative mechanisms by which autophagy-related signaling regulate mitochondrial function and antioxidant response. Future Directions: Our research efforts should now focus on understanding the molecular basis of events by which autophagy is fine tuned by oxidation/reduction events. This knowledge will enable us to understand the mechanisms by which oxidative stress and autophagy regulate human diseases such as cancer and neurodegenerative disorders. Antioxid. Redox Signal. 21, 66–85. PMID:24483238

  9. Redox regulation of plant development.

    Science.gov (United States)

    Considine, Michael J; Foyer, Christine H

    2014-09-20

    We provide a conceptual framework for the interactions between the cellular redox signaling hub and the phytohormone signaling network that controls plant growth and development to maximize plant productivity under stress-free situations, while limiting growth and altering development on exposure to stress. Enhanced cellular oxidation plays a key role in the regulation of plant growth and stress responses. Oxidative signals or cycles of oxidation and reduction are crucial for the alleviation of dormancy and quiescence, activating the cell cycle and triggering genetic and epigenetic control that underpin growth and differentiation responses to changing environmental conditions. The redox signaling hub interfaces directly with the phytohormone network in the synergistic control of growth and its modulation in response to environmental stress, but a few components have been identified. Accumulating evidence points to a complex interplay of phytohormone and redox controls that operate at multiple levels. For simplicity, we focus here on redox-dependent processes that control root growth and development and bud burst. The multiple roles of reactive oxygen species in the control of plant growth and development have been identified, but increasing emphasis should now be placed on the functions of redox-regulated proteins, along with the central roles of reductants such as NAD(P)H, thioredoxins, glutathione, glutaredoxins, peroxiredoxins, ascorbate, and reduced ferredoxin in the regulation of the genetic and epigenetic factors that modulate the growth and vigor of crop plants, particularly within an agricultural context.

  10. Constructability and maintainability

    International Nuclear Information System (INIS)

    Hart, R.S.

    1985-01-01

    A set of principles for minimizing the construction schedule was established at the outset of the CANDU 300 programme. Consideration of these principles and other factors led to the development of the unique CANDU 300 station layout. The paper discusses the CANDU 300 station layout and construction methods. In summary, the station layout provides 360 deg. construction access to all buildings, separation of nuclear and non-nuclear systems, precise and minimal physical interfaces between buildings, accommodation of many contractors and construction activities without interference, and maximum flexibility in terms of constructional, financial and supply arrangements. The CANDU 300 further employs modularization, shop fabrication and advanced instrumentation (multiplexers, remote processors, data highways) to minimize construction time. Many of the CANDU 300 features that enhance constructability also contribute to maintainability. These include the 360 deg. access to all principal buildings, the uncluttered and spacious building layouts, the simplification of systems and the high level of modularization. The CANDU 300 has also been designed to facilitate the replacement of all key components, thereby offering an essentially unlimited station life. A prime example is a reduction in the fuel channel inlet end-fitting diameter such that the fuel channels can be shop assembled and easily replaced after the initial 40 years of operation, without an extended unit outage. Maintainability within the reactor building has been given particular attention in the CANDU 300 design; key features of other CANDU reactors (the ability to replace a heat transport system pump motor at power, for example) have been incorporated, while accessibility and maintainability of all systems and components have been enhanced. These and other aspects of maintainability are discussed. (author)

  11. Reliability and maintainability

    International Nuclear Information System (INIS)

    1994-01-01

    Several communications in this conference are concerned with nuclear plant reliability and maintainability; their titles are: maintenance optimization of stand-by Diesels of 900 MW nuclear power plants; CLAIRE: an event-based simulation tool for software testing; reliability as one important issue within the periodic safety review of nuclear power plants; design of nuclear building ventilation by the means of functional analysis; operation characteristic analysis for a power industry plant park, as a function of influence parameters

  12. Gravity and positional homeostasis of the cell

    Science.gov (United States)

    Nace, G. W.

    1983-01-01

    The effect of gravity upon cytoplasmic aggregates of the size present in eggs and upon cells is investigated. An expression is developed to describe the tendency of torque to rotate the egg and reorganize its constituents. This expression provides the net torque resulting from buoyancy and gravity acting upon a dumbbell-shaped cell, with heavy and light masses at either end and floating in a medium. Torques of approximately 2.5 x 10 to the -13th to 0.85 dyne-cm are found to act upon cells ranging from 6.4 microns to 31 mm (chicken egg). It is noted that cells must expend energy to maintain positional homeostasis against gravity, as demonstrated by results from Skylab 3, where tissue cultures used 58 percent more glucose on earth than in space. The implications for developmental biology, physiology, genetics, and evolution are discussed. It is argued that at the cellular and tissue levels the concept of gravity receptors may be unnecessary.

  13. [Contribution of the kidney to glucose homeostasis].

    Science.gov (United States)

    Segura, Julián; Ruilope, Luis Miguel

    2013-09-01

    The kidney is involved in glucose homeostasis through three major mechanisms: renal gluconeogenesis, renal glucose consumption, and glucose reabsorption in the proximal tubule. Glucose reabsorption is one of the most important physiological functions of the kidney, allowing full recovery of filtered glucose, elimination of glucose from the urine, and prevention of calorie loss. Approximately 90% of the glucose is reabsorbed in the S1 segment of the proximal tubule, where glucose transporter-2 (GLUT2) and sodium-glucose transporter-2 (SGLT2) are located, while the remaining 10% is reabsorbed in the S3 segment by SGLT1 and GLUT1 transporters. In patients with hyperglycemia, the kidney continues to reabsorb glucose, thus maintaining hyperglycemia. Most of the renal glucose reabsorption is mediated by SGLT2. Several experimental and clinical studies suggest that pharmacological blockade of this transporter might be beneficial in the management of hyperglycemia in patients with type 2 diabetes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  14. CHF: circulatory homeostasis gone awry.

    Science.gov (United States)

    Weber, Karl T; Burlew, Brad S; Davis, Richard C; Newman, Kevin P; D'Cruz, Ivan A; Hawkins, Ralph G; Wall, Barry M; Parker, Robert B

    2002-01-01

    The role of the renin-angiotensin-aldosterone system (RAAS) is integral to salt and water retention, particularly by the kidneys. Over time, positive sodium balance leads first to intra- and then to extravascular volume expansion, with subsequent symptomatic heart failure. This report examines the role of the RAAS in regulating a less well recognized component essential to circulatory homeostasis--central blood volume. The regulation of central blood volume draws on integrative cardiorenal physiology and a key role played by the RAAS in its regulation. In presenting insights into the role of the RAAS in regulating central blood volume, this review also addresses other sodium-retaining states with a predisposition to edema formation, such as cirrhosis and nephrosis. (c)2002 CHF, Inc

  15. Redox Couples with Unequal Diffusion Coefficients: Effect on Redox Cycling

    NARCIS (Netherlands)

    Mampallil Augustine, Dileep; Mathwig, Klaus; Kang, Shuo; Lemay, Serge Joseph Guy

    2013-01-01

    Redox cycling between two electrodes separated by a narrow gap allows dramatic amplification of the faradaic current. Unlike conventional electrochemistry at a single electrode, however, the mass-transport-limited current is controlled by the diffusion coefficient of both the reduced and oxidized

  16. Seamless service: maintaining momentum.

    Science.gov (United States)

    Grinstead, N; Timoney, R

    1994-01-01

    Describes the process used by the Mater Infirmorum Hospital in Belfast in 1992-1994 to achieve high quality care (Seamless Service), motivate staff to deliver and measure performance. Aims of the project include focusing the organization on the customer, improving teamwork and motivation at all levels. After comprehensive data collection from GPs, patients and staff management forums developed a full TQM strategy to gain support and maintain momentum including innovative staff events (every staff member was given the opportunity to attend) where multilevel, multidisciplinary workshops enabled staff to design customer care standards, develop teams and lead customer-driven change.

  17. Gestures maintain spatial imagery.

    Science.gov (United States)

    Wesp, R; Hesse, J; Keutmann, D; Wheaton, K

    2001-01-01

    Recent theories suggest alternatives to the commonly held belief that the sole role of gestures is to communicate meaning directly to listeners. Evidence suggests that gestures may serve a cognitive function for speakers, possibly acting as lexical primes. We observed that participants gestured more often when describing a picture from memory than when the picture was present and that gestures were not influenced by manipulating eye contact of a listener. We argue that spatial imagery serves a short-term memory function during lexical search and that gestures may help maintain spatial images. When spatial imagery is not necessary, as in conditions of direct visual stimulation, reliance on gestures is reduced or eliminated.

  18. Maintainability design guide

    International Nuclear Information System (INIS)

    Pack, R.W.

    1985-01-01

    The Human Factors Design Guide for Maintainability provides guidance for systematically incorporating good human factors techniques into the design of power plants. The guide describes a means of developing a comprehensive program plan to ensure compliance with the human factors approaches specified by the utility. The guide also provides specific recommendations for design practices, with examples, bases, and references. The recommendations are formatted for easy use by nuclear power plant design teams and by utility personnel involved in specification and design review. The guide was developed under EPRI research project RP2166-4 and is currently being published

  19. Osmotic homeostasis and NKLy lymphoma cells radiosensitivity

    International Nuclear Information System (INIS)

    Tishchenko, V.V.; Magda, I.N.

    1992-01-01

    In experiments with cells of ascites NKLy lymphoma differing in ploidy and position in the cell cycle, a study was made of the radiosensitivity, osmotic homeostasis peculiarities and thermoradiation changes in potassium content. It was shown that the resistance of osmotic homeostasis of NKLy cells to thermoradiation correlated with their radioresistance

  20. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Giovanni Dalmasso

    Full Text Available Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis and the removal of damaged mitochondria by selective autophagy (mitophagy. While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1 mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2 restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3 maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4 our model suggests sources of, and stress conditions

  1. Facing the challenges of Cu, Fe and Zn homeostasis in plants.

    Science.gov (United States)

    Palmer, Christine M; Guerinot, Mary Lou

    2009-05-01

    Plants have recently moved into the spotlight owing to the growing realization that the world needs solutions to energy and food production that are sustainable and environmentally sound. Iron, copper and zinc are essential for plant growth and development, yet the same properties that make these transition metals indispensable can also make them deadly in excess. Iron and copper are most often used for their redox properties, whereas zinc is primarily used for its ability to act as a Lewis acid. Here we review recent advances in the field of metal homeostasis and integrate the findings on uptake and transport of these three metals.

  2. Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status.

    Directory of Open Access Journals (Sweden)

    Malav S Trivedi

    Full Text Available Sleep is critical for repair as well as the rejuvenation processes in the body and many of these functions are regulated via underlying cellular metabolic homeostasis. Changes in sleep pattern are reported to alter such metabolic function resulting in altered disease susceptibility or behavior. Here, we measured the extent to which overnight total sleep deprivation (SD in young adult humans can influence systemic (plasma-derived redox-metabolism including the major antioxidant, glutathione as well as DNA methylation levels. Nineteen participants (n = 19, μ age = 21, SD = 3.09 underwent morning testing before and after overnight total SD. Biochemical measures before and after SD revealed that glutathione, ATP, cysteine, and homocysteine levels were significantly reduced following one night of sleep deprivation (all p's < 0.01. Parallel to the well-recognized fact that sleep deprivation (maintaining wakefulness uses up metabolic reserves, we observed that morning cortisol levels were blunted after sleep deprivation. There were no significant correlations between self-reported or actigraphy-measured sleep and the biochemical measurements, strongly indicating that prior sleep behavior did not have any direct influence on the biochemical measures taken at baseline or after sleep deprivation. Results from the current investigation supports the previous literature implicating the induction of oxidative stress and ATP depletion with sleep deprivation. Furthermore, such altered antioxidant status can also induce downstream epigenetic changes. Although we did not measure the specific genes that were altered under the influence of such sleep deprivation, such epigenetic changes could potentially contribute towards disease predisposition.

  3. Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota.

    Science.gov (United States)

    Peterson, C T; Sharma, V; Elmén, L; Peterson, S N

    2015-03-01

    The distal gut harbours ∼10(13) bacteria, representing the most densely populated ecosystem known. The functional diversity expressed by these communities is enormous and relatively unexplored. The past decade of research has unveiled the profound influence that the resident microbial populations bestow to host immunity and metabolism. The evolution of these communities from birth generates a highly adapted and highly personalized microbiota that is stable in healthy individuals. Immune homeostasis is achieved and maintained due in part to the extensive interplay between the gut microbiota and host mucosal immune system. Imbalances of gut microbiota may lead to a number of pathologies such as obesity, type I and type II diabetes, inflammatory bowel disease (IBD), colorectal cancer (CRC) and inflammaging/immunosenscence in the elderly. In-depth understanding of the underlying mechanisms that control homeostasis and dysbiosis of the gut microbiota represents an important step in our ability to reliably modulate the gut microbiota with positive clinical outcomes. The potential of microbiome-based therapeutics to treat epidemic human disease is of great interest. New therapeutic paradigms, including second-generation personalized probiotics, prebiotics, narrow spectrum antibiotic treatment and faecal microbiome transplantation, may provide safer and natural alternatives to traditional clinical interventions for chronic diseases. This review discusses host-microbiota homeostasis, consequences of its perturbation and the associated challenges in therapeutic developments that lie ahead. © 2014 British Society for Immunology.

  4. Taste bud homeostasis in health, disease, and aging.

    Science.gov (United States)

    Feng, Pu; Huang, Liquan; Wang, Hong

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging.

  5. Taste Bud Homeostasis in Health, Disease, and Aging

    Science.gov (United States)

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50–100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8–12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging. PMID:24287552

  6. The redox-Mannich reaction.

    Science.gov (United States)

    Chen, Weijie; Seidel, Daniel

    2014-06-06

    A complement to the classic three-component Mannich reaction, the redox-Mannich reaction, utilizes the same starting materials but incorporates an isomerization step that enables the facile preparation of ring-substituted β-amino ketones. Reactions occur under relatively mild conditions and are facilitated by benzoic acid.

  7. Control of Immune Cell Homeostasis and Function by lncRNAs.

    Science.gov (United States)

    Mowel, Walter K; Kotzin, Jonathan J; McCright, Sam J; Neal, Vanessa D; Henao-Mejia, Jorge

    2018-01-01

    The immune system is composed of diverse cell types that coordinate responses to infection and maintain tissue homeostasis. In each of these cells, extracellular cues determine highly specific epigenetic landscapes and transcriptional profiles to promote immunity while maintaining homeostasis. New evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in epigenetic and transcriptional regulation in mammals. Thus, lncRNAs have emerged as key regulatory molecules of immune cell gene expression programs in response to microbial and tissue-derived cues. We review here how lncRNAs control the function and homeostasis of cell populations during immune responses, emphasizing the diverse molecular mechanisms by which lncRNAs tune highly contextualized transcriptional programs. In addition, we discuss the new challenges faced in interrogating lncRNA mechanisms and function in the immune system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Exercise intensity, redox homeostasis and inflammation in type 2 diabetes mellitus.

    Science.gov (United States)

    Mallard, Alistair R; Hollekim-Strand, Siri Marte; Coombes, Jeff S; Ingul, Charlotte B

    2017-10-01

    To compare 12 weeks of exercise training at two intensities on oxidative stress, antioxidants and inflammatory biomarkers in patients with type 2 diabetes (T2D). Randomized trial. Thirty-six participants with T2D were randomized to complete either 12 weeks of treadmill based high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT), followed by 40 weeks of home-based training at the same intensities. Plasma inflammation, oxidative stress and antioxidant biomarkers (total F2-isoprostanes, protein carbonyls, total antioxidant capacity, glutathione peroxidase activity, interleukin-10, interleukin-6, interleukin-8 and TNF-α) were measured at baseline, 12-weeks and 1-year. There were no significant changes (p>0.05) in oxidative stress and inflammation biomarkers from baseline to 12-weeks in either intervention. A decrease in total antioxidant capacity in the MICT group from baseline to 1-year by 0.05mmol/L (p=0.05) was observed. There was a significant difference (p<0.05) when groups were separated by sex with females in the MICT group having a 22.1% (p<0.05) decrease in protein carbonyls from baseline to 1-year. HIIT and MICT had no acute effect on oxidative stress and inflammatory biomarkers in patients with T2D. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  9. Yulangsan polysaccharide improves redox homeostasis and immune impairment in D-galactose-induced mimetic aging.

    Science.gov (United States)

    Doan, Van Minh; Chen, Chunxia; Lin, Xing; Nguyen, Van Phuc; Nong, Zhihuan; Li, Weisi; Chen, Qingquan; Ming, Jianjun; Xie, Qiuqiao; Huang, Renbin

    2015-05-01

    Yulangsan polysaccharide (YLSP) is a traditional Chinese medicine used in long-term treatment as a modulator of brain dysfunction and immunity. In this study, we evaluated the protective effect of YLSP against D-galactose-induced impairment of oxidative stress and the immune system and evaluated its possible mechanism of action. D-galactose was subcutaneously injected into the dorsal neck of mice daily for 8 weeks to establish the aging model. YLSP was simultaneously administered once daily. The results indicate that YLSP significantly improves the general appearance of the aging mice. YLSP significantly increased the levels of antioxidant enzymes, such as super oxide dismutase, glutathione peroxidase, catalase and total anti-oxidation capability, while decreasing the content of malondialdehyde in different tissues, including the liver, brain, and serum. YLSP also increased the interleukin-2 level while decreasing the interleukin-6 level. Moreover, YLSP significantly inhibited advanced glycation end product formation. Furthermore, YLSP decreased p21 and p53 gene expressions in the liver and brain of D-galactose-treated mice. These results suggest that YLSP may have a protective effect suppressing the aging process by enhancing antioxidant activity and immunity, as well as modulating aging-related gene expression.

  10. Cellular redox homeostasis in endothelial cells treated with nonmodified and Fenton-modified nanodiamond powders.

    Science.gov (United States)

    Solarska-Ściuk, K; Gajewska, A; Skolimowski, J; Gajek, A; Bartosz, G

    2014-01-01

    Diamond nanoparticles find numerous applications in pharmacy, medicine, cosmetics, and biotechnology. However, possible adverse cellular effects of diamond nanoparticle cells have been reported, which may limit their use. The aim of this study was to compare the effect of nonmodified diamond nanoparticles (D) and diamond nanoparticles modified by the Fenton reaction (D+OH) on human umbilical cord endothelial cells (HUVEC-ST). We found that both D and D+OH show time- and concentration-dependent cytotoxicity, inducing apoptosis and necrosis of HUVEC-ST. Interaction with D and D+OH also induced changes in the production of reactive oxygen and nitrogen species and changes in the level of glutathione and activities of antioxidant enzymes in the cells. These data demonstrate that diamond nanoparticles may induce oxidative stress in human endothelial cells, which contributes to their cytotoxic effects seen at higher concentrations of D and D+OH. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  11. Influence of Quercetin in the Temporal Regulation of Redox Homeostasis in Drosophila melanogaster.

    Science.gov (United States)

    Subramanian, Perumal; Kaliyamoorthy, Kanimozhi; Jayapalan, Jaime Jacqueline; Abdul-Rahman, Puteri Shafinaz; Haji Hashim, Onn

    2017-01-01

    Numerous biological processes are governed by the biological clock. Studies using Drosophila melanogaster (L.) are valuable that could be of importance for their effective applications on rodent studies. In this study, the beneficial role of quercetin (a flavonoid) on H2O2 induced stress in D. melanogaster was investigated. D. melanogaster flies were divided into four groups (group I - control, group II - H2O2 (acute exposure), group III - quercetin, and group IV - quercetin + H2O2 treated). Negative geotaxis assay, oxidative stress indicators (protein carbonyls, thiobarbituric reactive substances [TBARS]), and antioxidants (superoxide dismutase [SOD], catalase [CAT], glutathione-S-transferase [GST], glutathione peroxidase, and reduced glutathione [GSH]) were measured at 4 h intervals over 24 h and temporal expression of heat shock protein-70 (Hsp70), Upd1 (homolog of IL-6 in Drosophila), and nitric oxide synthase (Nos) was analyzed by Western blotting. Groups II and IV showed altered biochemical rhythms (compared with controls). Decreased mesor values of negative geotaxis, SOD, CAT, GST, and GSH were noticed in H2O2, increased mesor of oxidative stress indicators (TBARS and protein carbonyl content) and a reversibility of the rhythmic characteristics were conspicuous after quercetin treatment. The expression levels of Hsp70, Upd1, and Nos were noticeably maximum at 04:00. Significant elevation of expression by H2O2 was nearly normalized by quercetin treatment. The possible mechanism by which quercetin modulates oxidant-antioxidant imbalance under oxidative stress could be ascribed to the modulation of the rhythmic properties. Our results will be helpful to understand the molecular interlink between circadian rhythm and oxidative stress mechanism. © The Author 2017. Published by Oxford University Press on behalf of the Entomological Society of America.

  12. Maintaining Relationship Based Procurement

    Directory of Open Access Journals (Sweden)

    Peter Davis

    2012-11-01

    Full Text Available Alliance and relationship projects are increasingin number and represent a large pool of work. Tobe successful relationship style contracts dependon soft-dollar factors, particularly the participants'ability to work together within an agreedframework, generally they are not based on lowbid tendering. Participants should be prepared todo business in an open environment based ontrust and mutually agreed governance. Theresearch evaluates relationship maintenance inthe implementation phase of constructionalliances - a particular derivative of relationshipstyle contracts. To determine the factors thatcontribute to relationship maintenance forty-nineexperienced Australian alliance projectmanagers were interviewed. The main findingswere; the development of relationships early inthe project form building blocks of success fromwhich relationships are maintained and projectvalue added; quality facilitation plays animportant part in relationship maintenance and ahybrid organisation created as a result of alliancedevelopment overcomes destructiveorganisational boundaries. Relationshipmaintenance is integral to alliance project controland failure to formalise it and pay attention toprocess and past outcomes will undermine analliance project's potential for success.

  13. Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis.

    Science.gov (United States)

    Ananieva, Elitsa A; Van Horn, Cynthia G; Jones, Meghan R; Hutson, Susan M

    2017-02-01

    Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass first-pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart and kidney were impacted. Expression of the hepatic BCATm transgene lowered the concentrations of hepatic BCAAs while enhancing the concentrations of some nonessential amino acids. Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely unaffected, and no growth rate or body composition differences were observed in the transgenic animals as compared to wild-type mice. Feeding the transgenic animals a high-fat diet did not reverse the effect of the BCATm transgene on the hepatic BCAA catabolism, nor did the high-fat diet cause elevation in plasma BCAAs. However, the high-fat-diet-fed BCATm transgenic animals experienced attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and had impaired blood glucose tolerance. These results suggest that complete liver BCAA metabolism influences the regulation of glucose utilization during diet-induced obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Wilson Disease Protein ATP7B Utilizes Lysosomal Exocytosis to Maintain Copper Homeostasis

    NARCIS (Netherlands)

    Polishchuk, Elena V.; Concilli, Mafalda; Iacobacci, Simona; Chesi, Giancarlo; Pastore, Nunzia; Piccolo, Pasquale; Paladino, Simona; Baldantoni, Daniela; van IJzendoorn, Sven C. D.; Chan, Jefferson; Chang, Christopher J.; Amoresano, Angela; Pane, Francesca; Pucci, Piero; Tarallo, Antonietta; Parenti, Giancarlo; Brunetti-Pierri, Nicola; Settembre, Carmine; Ballabio, Andrea; Polishchuk, Roman S.

    2014-01-01

    Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we

  15. The ubiquitin editing enzyme A20 maintains immune homeostasis and prevents autoimmunity

    OpenAIRE

    Tavares, Rita M.

    2010-01-01

    Dissertation presented to obtain the Doctorate degree (Ph.D.) in Biology at Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa The immune system is vital to ensure the surveillance of organisms against pathogens or malignant cells. However, the negative regulation of the immune system is equally essential, and defects in the termination of immune signals can result in autoimmunity and other pathologies. The functioning of the immune system results from the integrati...

  16. Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis

    NARCIS (Netherlands)

    Mayerl, Steffen; Müller, Julia; Bauer, Reinhard; Richert, Sarah; Kassmann, Celia M.; Darras, Veerle M.; Buder, Katrin; Boelen, Anita; Visser, Theo J.; Heuer, Heike

    2014-01-01

    Allan-Herndon-Dudley syndrome (AHDS), a severe form of psychomotor retardation with abnormal thyroid hormone (TH) parameters, is linked to mutations in the TH-specific monocarboxylate transporter MCT8. In mice, deletion of Mct8 (Mct8 KO) faithfully replicates AHDS-associated endocrine abnormalities;

  17. Human Epidermal Langerhans Cells Maintain Immune Homeostasis in Skin by Activating Skin Resident Regulatory T Cells

    Science.gov (United States)

    Seneschal, Julien; Clark, Rachael A.; Gehad, Ahmed; Baecher-Allan, Clare M.; Kupper, Thomas S.

    2013-01-01

    Recent discoveries indicate that the skin of a normal individual contains 10-20 billion resident memory T cells ( which include various T helper, T cytotoxic, and T regulatory subsets, that are poised to respond to environmental antigens. Using only autologous human tissues, we report that both in vitro and in vivo, resting epidermal Langerhan cells (LC) selectively and specifically induced the activation and proliferation of skin resident regulatory T cells (Treg), a minor subset of skin resident memory T cells. In the presence of foreign pathogen, however, the same LC activated and induced proliferation of effector memory T (Tem) cells and limited Treg cells activation. These underappreciated properties of LC: namely maintenance of tolerance in normal skin, and activation of protective skin resident memory T cells upon infectious challenge, help clarify the role of LC in skin. PMID:22560445

  18. ROLE OF THE MICROFLORA IN DISTAL INTESTINAL TRACT BY MAINTAINING OXALATE HOMEOSTASIS

    Directory of Open Access Journals (Sweden)

    Osolodchenko T.P.

    2015-05-01

    Full Text Available Human intestinal microflora is part of the human body and performs numerous function. Considerable research interest is in the field of probiotics for the prevention of kidney stones, which is one of the most common urological diseases.Urolithiasis is one of the most common urological diseases. This is polyetiological disease congenital and acquired character with complex physical and chemical processes that occur not only in the urinary system, but also the whole body. None of the treatments does not guarantee full recovery of the patient and often leads to relapse. The open methods of removal stones yield news minimally invasive the technologys. Development of stone formation depends on the presence of many factors, metabolic disorders, chronic urinary tract infections, genetic disorders and more. Most have the following metabolic disorders as hypercalciuria, hiperurikuria, hipotsytraturia , hyperoxaluria and hipomahniuria. Among all types of urolithiasis kaltsiyoksalatnyy ranked first in the prevalence rate - about 75.0 - 85.0 % of cases. Dietary restriction by oxalates іs the unreliable method of preventing disease. Although there is evidence for the growth inhibition normobiocenosis representatives, which in turn enhances the absorption of salts of oxalic acid oxalate in the application of sodium , magnesium and cobalt in their intragastric administration. Recently published many papers on the impact on the level of oxalate intestinal microflora. The first publications appeared on the influence of gram-negative obligate anaerobes O. formigenes the concentration of oxalate in the urine. This anaerobic bacteria living in the colon, its prevalence - 46.0 % - 77.0 % of the adult population. O. formigenes reveals the symbiotic interaction with the human body by reducing absorption of oxalate in the intestinal cavity with subsequent decrease in their concentration in plasma and urine. O. formigenes has two key enzymes - oksalyl - koadecarboxylase and formyl - koatransferase performing metabolic conversion of oxalate in the cavity of the colon.The polymerase chain reaction has advantages over previously adopted methods - culture and photometric in the diagnosis of the presence of O. formigenes. The taking of antibiotics reduces of O. formigenes in the colon. The microorganism is resistant to amoxicillin, ceftriaxone, vancomycin and is sensitive to ciprofloxacin, clarithromycin, azitromitsyn, clindamycin, doxycycline, gentamicin levofloxacin, tetracycline and metranidazol. In the metabolism of oxalate involved and other microorganisms. There are studies that prove the value of other taxonomic groups oxalate degradation: E. coli, Lactobacillus spp. There is the concept that the use of probiotics is capable of degradation of oxalate in the gut and reducing their absorption in the gastrointestinal tract. There is investigated microbiological method for the treatment of urolithiasis and hyperoxaluria through the use of probiotic O. formigenes (at the stage of clinical trials. This method is not traumatic, it can be efficient, cost-effective and environmentally safe. Implicitly that Lactobacillus spp. and E. coli, along with O. formigenes, are promising targets for further research and their application in the field of biotechnological production. To improve the efficiency and expanding the range of their application further work in search and development of new probiotics , given the requirements for food and pharmaceuticals that will effectively dostato prevent or reduce the number of recurrent stone formation.

  19. CYTOKININ OXIDASE/DEHYDROGENASE3 Maintains Cytokinin Homeostasis during Root and Nodule Development in Lotus japonicus

    Czech Academy of Sciences Publication Activity Database

    Reid, D.E.; Heckmann, A.B.; Novák, Ondřej; Kelly, S.; Stougaard, J.

    2016-01-01

    Roč. 170, č. 2 (2016), s. 1060-1074 ISSN 0032-0889 R&D Projects: GA MŠk LK21306 Institutional support: RVO:61389030 Keywords : DEPENDENT PROTEIN-KINASE * NODULATION SIGNALING PATHWAY * SYMBIOTIC ORGAN DEVELOPMENT Subject RIV: EF - Botanics Impact factor: 6.456, year: 2016

  20. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis : LAMP-2 deficient mice develop pancreatitis

    NARCIS (Netherlands)

    Mareninova, Olga A; Sendler, Matthias; Malla, Sudarshan Ravi; Yakubov, Iskandar; French, Samuel W; Tokhtaeva, Elmira; Vagin, Olga; Oorschot, Viola; Lüllmann-Rauch, Renate; Blanz, Judith; Dawson, David; Klumperman, Judith; Lerch, Markus M; Mayerle, Julia; Gukovsky, Ilya; Gukovskaya, Anna S

    2015-01-01

    BACKGROUND & AIMS: The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated

  1. Checks and balances in membrane phospholipid class and acyl chain homeostasis, the yeast perspective

    NARCIS (Netherlands)

    de Kroon, A.I.P.M.|info:eu-repo/dai/nl/084765283; Rijken, P.J.|info:eu-repo/dai/nl/32716297X; De Smet, C.H.|info:eu-repo/dai/nl/304824224

    2013-01-01

    Glycerophospholipids are the most abundant membrane lipid constituents in most eukaryotic cells. As a consequence, phospholipid class and acyl chain homeostasis are crucial for maintaining optimal physical properties of membranes that in turn are crucial for membrane function. The topic of this

  2. Oxygen Generating Biomaterials Preserve Skeletal Muscle Homeostasis under Hypoxic and Ischemic Conditions

    Science.gov (United States)

    2013-08-26

    injection” protocol for myogenic cell transplantation throughout large volumes of muscles in a Duchenne muscular dystrophy patient: eighteen months follow-up...Oxygen Generating Biomaterials Preserve Skeletal Muscle Homeostasis under Hypoxic and Ischemic Conditions Catherine L. Ward, Benjamin T. Corona...investigation was to determine if sodium percarbonate (SPO), an oxygen generating biomaterial, is capable of maintaining resting skeletal muscle

  3. Is It Hot in Here? Thermoregulation and Homeostasis through an Exercise Activity

    Science.gov (United States)

    Dean, Lewis G.; Breslin, Angela; Ross, Emma Z.

    2014-01-01

    Homeostasis, the control of an internal environment to maintain stable, relatively constant conditions, is a key concept in physiology. In endothermic species, including humans ("Homo sapiens"), the control of body temperature is fundamental to the control of a suitable internal environment. To help regulate core body temperature, the…

  4. Protein synthesis controls phosphate homeostasis.

    Science.gov (United States)

    Pontes, Mauricio H; Groisman, Eduardo A

    2018-01-01

    Phosphorus is an essential element assimilated largely as orthophosphate (Pi). Cells respond to Pi starvation by importing Pi from their surroundings. We now report that impaired protein synthesis alone triggers a Pi starvation response even when Pi is plentiful in the extracellular milieu. In the bacterium Salmonella enterica serovar Typhimurium , this response entails phosphorylation of the regulatory protein PhoB and transcription of PhoB-dependent Pi transporter genes and is eliminated upon stimulation of adenosine triphosphate (ATP) hydrolysis. When protein synthesis is impaired due to low cytoplasmic magnesium (Mg 2+ ), Salmonella triggers the Pi starvation response because ribosomes are destabilized, which reduces ATP consumption and thus free cytoplasmic Pi. This response is transient because low cytoplasmic Mg 2+ promotes an uptake in Mg 2+ and a decrease in ATP levels, which stabilizes ribosomes, resulting in ATP consumption and Pi increase, thus ending the response. Notably, pharmacological inhibition of protein synthesis also elicited a Pi starvation response in the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae Our findings identify a regulatory connection between protein synthesis and Pi homeostasis that is widespread in nature. © 2018 Pontes and Groisman; Published by Cold Spring Harbor Laboratory Press.

  5. DR2539 is a novel DtxR-like regulator of Mn/Fe ion homeostasis and antioxidant enzyme in Deinococcus radiodurans

    International Nuclear Information System (INIS)

    Chen, Huan; Wu, Rongrong; Xu, Guangzhi; Fang, Xu; Qiu, Xiaoli; Guo, Hongyin; Tian, Bing; Hua, Yuejin

    2010-01-01

    Transcriptional regulators of the diphtheria toxin repressor (DtxR) family control the expression of genes involved in the uptake of iron and manganese, which is not only necessitous nutrients but also was suggested to be essential for intracellular redox cycling of microorganisms. We identified a unique DtxR homologue (DR2539) with special characteristics from Deinococcus radiodurans, which is known for its extreme resistance to radiation and oxidants. The dr2539 mutant showed higher resistance to hydrogen peroxide than the wild-type strain R1. Intracellular catalase activity assay and semiquantitative PCR analysis demonstrated that this DtxR is a negative regulator of catalase (katE). Furthermore, quantitative real-time PCR, global transcription profile and inductively coupled plasma-mass spectrometry analysis showed that the DtxR is involved in the regulation of antioxidant system by maintaining the intracellular Mn/Fe ion homeostasis of D. radiodurans. However, unlike the other DtxR homologues, the DtxR of D. radiodurans acts as a negative regulator of a Mn transporter gene (dr2283) and as a positive regulator of Fe-dependent transporter genes (dr1219, drb0125) in D. radiodurans.

  6. DR2539 is a novel DtxR-like regulator of Mn/Fe ion homeostasis and antioxidant enzyme in Deinococcus radiodurans

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Huan [Key Laboratory for Nuclear-Agricultural Sciences of Chinese Ministry of Agriculture and Zhejiang Province, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China); Zhejiang Institute of Microbiology, Zhejiang Province, Hangzhou 310012 (China); Wu, Rongrong [Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009 (China); Xu, Guangzhi [Key Laboratory for Nuclear-Agricultural Sciences of Chinese Ministry of Agriculture and Zhejiang Province, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China); Fang, Xu; Qiu, Xiaoli; Guo, Hongyin [Zhejiang Institute of Microbiology, Zhejiang Province, Hangzhou 310012 (China); Tian, Bing, E-mail: tianbing@zju.edu.cn [Key Laboratory for Nuclear-Agricultural Sciences of Chinese Ministry of Agriculture and Zhejiang Province, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China); Hua, Yuejin, E-mail: yjhua@zju.edu.cn [Key Laboratory for Nuclear-Agricultural Sciences of Chinese Ministry of Agriculture and Zhejiang Province, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310029 (China)

    2010-05-28

    Transcriptional regulators of the diphtheria toxin repressor (DtxR) family control the expression of genes involved in the uptake of iron and manganese, which is not only necessitous nutrients but also was suggested to be essential for intracellular redox cycling of microorganisms. We identified a unique DtxR homologue (DR2539) with special characteristics from Deinococcus radiodurans, which is known for its extreme resistance to radiation and oxidants. The dr2539 mutant showed higher resistance to hydrogen peroxide than the wild-type strain R1. Intracellular catalase activity assay and semiquantitative PCR analysis demonstrated that this DtxR is a negative regulator of catalase (katE). Furthermore, quantitative real-time PCR, global transcription profile and inductively coupled plasma-mass spectrometry analysis showed that the DtxR is involved in the regulation of antioxidant system by maintaining the intracellular Mn/Fe ion homeostasis of D. radiodurans. However, unlike the other DtxR homologues, the DtxR of D. radiodurans acts as a negative regulator of a Mn transporter gene (dr2283) and as a positive regulator of Fe-dependent transporter genes (dr1219, drb0125) in D. radiodurans.

  7. The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

    OpenAIRE

    Horner, Michael A.; Pardee, Keith; Liu, Suya; King-Jones, Kirst; Lajoie, Gilles; Edwards, Aled; Krause, Henry M.; Thummel, Carl S.

    2009-01-01

    Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-choleste...

  8. Mechanical homeostasis regulating adipose tissue volume

    Directory of Open Access Journals (Sweden)

    Svedman Paul

    2007-09-01

    Full Text Available Abstract Background The total body adipose tissue volume is regulated by hormonal, nutritional, paracrine, neuronal and genetic control signals, as well as components of cell-cell or cell-matrix interactions. There are no known locally acting homeostatic mechanisms by which growing adipose tissue might adapt its volume. Presentation of the hypothesis Mechanosensitivity has been demonstrated by mesenchymal cells in tissue culture. Adipocyte differentiation has been shown to be inhibited by stretching in vitro, and a pathway for the response has been elucidated. In humans, intermittent stretching of skin for reconstructional purposes leads to thinning of adipose tissue and thickening of epidermis – findings matching those observed in vitro in response to mechanical stimuli. Furthermore, protracted suspension of one leg increases the intermuscular adipose tissue volume of the limb. These findings may indicate a local homeostatic adipose tissue volume-regulating mechanism based on movement-induced reduction of adipocyte differentiation. This function might, during evolution, have been of importance in confined spaces, where overgrowth of adipose tissue could lead to functional disturbance, as for instance in the turtle. In humans, adipose tissue near muscle might in particular be affected, for instance intermuscularly, extraperitoneally and epicardially. Mechanical homeostasis might also contribute to protracted maintainment of soft tissue shape in the face and neck region. Testing of the hypothesis Assessment of messenger RNA-expression of human adipocytes following activity in adjacent muscle is planned, and study of biochemical and volumetric adipose tissue changes in man are proposed. Implications of the hypothesis The interpretation of metabolic disturbances by means of adipose tissue might be influenced. Possible applications in the head and neck were discussed.

  9. Lung Homeostasis: Influence of Age, Microbes, and the Immune System.

    Science.gov (United States)

    Lloyd, Clare M; Marsland, Benjamin J

    2017-04-18

    Pulmonary immune homeostasis is maintained by a network of tissue-resident cells that continually monitor the external environment, and in health, instruct tolerance to innocuous inhaled particles while ensuring that efficient and rapid immune responses can be mounted against invading pathogens. Here we review the multiple pathways that underlie effective lung immunity in health, and discuss how these may be affected by external environmental factors and contribute to chronic inflammation during disease. In this context, we examine the current understanding of the impact of the microbiota in immune development and function and in the setting of the threshold for immune responses that maintains the balance between tolerance and chronic inflammation in the lung. We propose that host interactions with microbes are critical for establishing the immune landscape of the lungs. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Analysis of vegetative homeostasis state of elite handball players

    Directory of Open Access Journals (Sweden)

    Y.N. Prystupa

    2015-12-01

    Full Text Available Purpose: to study characteristics and dynamic of elite handball players’ physiological indicators. Material: In experiment elite handball players (n=112, age 18-35 years participated. For determination of vegetative homeostasis state we analyzed variability of heart rhythm. The researches were conducted in laboratory conditions in rest state, in lying position during 5 minutes. Results: it was found that organism’s adaptation reactions to training loads go with different tension of regulation systems. At the end of competition period there appears hyper-kinetic syndrome. It witnessed insufficiency of means, which permit to maintain optimal regulation of cardio-vascular system and increase its functional potentials. Conclusions: indicators of cardio-vascular system and their dynamic w3itnessed maintaining of high level of handball players’ organism hemodynamic provisioning. High level of vegetative homeostasis pointed at certain degree of sportsmen’s fitness. Such state is sufficient for preservation of high potential of sympathetic -adrenaline system and overcoming of fatigue processes.

  11. Maintaining Web Cache Coherency

    Directory of Open Access Journals (Sweden)

    2000-01-01

    Full Text Available Document coherency is a challenging problem for Web caching. Once the documents are cached throughout the Internet, it is often difficult to keep them coherent with the origin document without generating a new traffic that could increase the traffic on the international backbone and overload the popular servers. Several solutions have been proposed to solve this problem, among them two categories have been widely discussed: the strong document coherency and the weak document coherency. The cost and the efficiency of the two categories are still a controversial issue, while in some studies the strong coherency is far too expensive to be used in the Web context, in other studies it could be maintained at a low cost. The accuracy of these analysis is depending very much on how the document updating process is approximated. In this study, we compare some of the coherence methods proposed for Web caching. Among other points, we study the side effects of these methods on the Internet traffic. The ultimate goal is to study the cache behavior under several conditions, which will cover some of the factors that play an important role in the Web cache performance evaluation and quantify their impact on the simulation accuracy. The results presented in this study show indeed some differences in the outcome of the simulation of a Web cache depending on the workload being used, and the probability distribution used to approximate updates on the cached documents. Each experiment shows two case studies that outline the impact of the considered parameter on the performance of the cache.

  12. ADAS Update and Maintainability

    Science.gov (United States)

    Watson, Leela R.

    2010-01-01

    Since 2000, both the National Weather Service Melbourne (NWS MLB) and the Spaceflight Meteorology Group (SMG) have used a local data integration system (LOIS) as part of their forecast and warning operations. The original LOIS was developed by the Applied Meteorology Unit (AMU) in 1998 (Manobianco and Case 1998) and has undergone subsequent improvements. Each has benefited from three-dimensional (3-D) analyses that are delivered to forecasters every 15 minutes across the peninsula of Florida. The intent is to generate products that enhance short-range weather forecasts issued in support of NWS MLB and SMG operational requirements within East Central Florida. The current LDIS uses the Advanced Regional Prediction System (ARPS) Data Analysis System (AD AS) package as its core, which integrates a wide variety of national, regional, and local observational data sets. It assimilates all available real-time data within its domain and is run at a finer spatial and temporal resolution than current national or regional-scale analysis packages. As such, it provides local forecasters with a more comprehensive understanding of evolving fine-scale weather features. Over the years, the LDIS has become problematic to maintain since it depends on AMU-developed shell scripts that were written for an earlier version of the ADAS software. The goals of this task were to update the NWS MLB/SMG LDIS with the latest version of ADAS, incorporate new sources of observational data, and upgrade and modify the AMU-developed shell scripts written to govern the system. In addition, the previously developed ADAS graphical user interface (GUI) was updated. Operationally, these upgrades will result in more accurate depictions of the current local environment to help with short-range weather forecasting applications, while also offering an improved initialization for local versions of the Weather Research and Forecasting (WRF) model used by both groups.

  13. Cascade redox flow battery systems

    Science.gov (United States)

    Horne, Craig R.; Kinoshita, Kim; Hickey, Darren B.; Sha, Jay E.; Bose, Deepak

    2014-07-22

    A reduction/oxidation ("redox") flow battery system includes a series of electrochemical cells arranged in a cascade, whereby liquid electrolyte reacts in a first electrochemical cell (or group of cells) before being directed into a second cell (or group of cells) where it reacts before being directed to subsequent cells. The cascade includes 2 to n stages, each stage having one or more electrochemical cells. During a charge reaction, electrolyte entering a first stage will have a lower state-of-charge than electrolyte entering the nth stage. In some embodiments, cell components and/or characteristics may be configured based on a state-of-charge of electrolytes expected at each cascade stage. Such engineered cascades provide redox flow battery systems with higher energy efficiency over a broader range of current density than prior art arrangements.

  14. Redox signaling in acute pancreatitis

    Science.gov (United States)

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-01-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551

  15. Redox signaling in acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Salvador Pérez

    2015-08-01

    Full Text Available Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  16. Air pollution particles and iron homeostasis

    Science.gov (United States)

    Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, fun...

  17. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

    Science.gov (United States)

    Zhu, Xiao-Hong; Lu, Ming; Lee, Byeong-Yeul; Ugurbil, Kamil; Chen, Wei

    2015-01-01

    NAD is an essential metabolite that exists in NAD+ or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD+/NADH redox state and modulating cellular signaling processes through the activity of the NAD+-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD+ and NADH contents and the NAD+/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD+, total NAD contents, and NAD+/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ. PMID:25730862

  18. Mapping the diatom redox-sensitive proteome provides insight into response to nitrogen stress in the marine environment.

    Science.gov (United States)

    Rosenwasser, Shilo; Graff van Creveld, Shiri; Schatz, Daniella; Malitsky, Sergey; Tzfadia, Oren; Aharoni, Asaph; Levin, Yishai; Gabashvili, Alexandra; Feldmesser, Ester; Vardi, Assaf

    2014-02-18

    Diatoms are ubiquitous marine photosynthetic eukaryotes responsible for approximately 20% of global photosynthesis. Little is known about the redox-based mechanisms that mediate diatom sensing and acclimation to environmental stress. Here we used a quantitative mass spectrometry-based approach to elucidate the redox-sensitive signaling network (redoxome) mediating the response of diatoms to oxidative stress. We quantified the degree of oxidation of 3,845 cysteines in the Phaeodactylum tricornutum proteome and identified approximately 300 redox-sensitive proteins. Intriguingly, we found redox-sensitive thiols in numerous enzymes composing the nitrogen assimilation pathway and the recently discovered diatom urea cycle. In agreement with this finding, the flux from nitrate into glutamine and glutamate, measured by the incorporation of (15)N, was strongly inhibited under oxidative stress conditions. Furthermore, by targeting the redox-sensitive GFP sensor to various subcellular localizations, we mapped organelle-specific oxidation patterns in response to variations in nitrogen quota and quality. We propose that redox regulation of nitrogen metabolism allows rapid metabolic plasticity to ensure cellular homeostasis, and thus is essential for the ecological success of diatoms in the marine ecosystem.

  19. Redox reaction studies by nanosecond pulse radiolysis

    International Nuclear Information System (INIS)

    Moorthy, P.N.

    1979-01-01

    Free radicals are formed as intermediates in many chemical and biochemical reactions. An important type of reaction which they can undergo is a one electron or redox process. The direction and rate of such electron transfer reactions is governed by the relative redox potentials of the participating species. Because of the generally short lived nature of free radicals, evaluation of their redox potentials poses a number of problems. Two techniques are described for the experimental determination of the redox potentials of short lived species generated by either a nanosecond electron pulse or laser flash. In the first method, redox titration of the short lived species with stable molecules of known redox potential is carried out, employing the technique of fast kinetic spectrophotometry. Conversely, by the same method it is also possible to evaluate the one electron redox potentials of stable molecules by redox titration with free radicals of known redox potential produced as above. In the second method, electrochemical reduction or oxidation of the short lived species at an appropriate electrode (generally a mercury drop) is carried out at different fixed potentials, and the redox potential evaluated from the current-potential curves (polarograms). Full description of the experimental set up and theoretical considerations for interpretation of the raw data are given. The relative merits of the two methods and their practical applicability are discussed. (auth.)

  20. Dissecting Redox Biology Using Fluorescent Protein Sensors.

    Science.gov (United States)

    Schwarzländer, Markus; Dick, Tobias P; Meyer, Andreas J; Morgan, Bruce

    2016-05-01

    Fluorescent protein sensors have revitalized the field of redox biology by revolutionizing the study of redox processes in living cells and organisms. Within one decade, a set of fundamental new insights has been gained, driven by the rapid technical development of in vivo redox sensing. Redox-sensitive yellow and green fluorescent protein variants (rxYFP and roGFPs) have been the central players. Although widely used as an established standard tool, important questions remain surrounding their meaningful use in vivo. We review the growing range of thiol redox sensor variants and their application in different cells, tissues, and organisms. We highlight five key findings where in vivo sensing has been instrumental in changing our understanding of redox biology, critically assess the interpretation of in vivo redox data, and discuss technical and biological limitations of current redox sensors and sensing approaches. We explore how novel sensor variants may further add to the current momentum toward a novel mechanistic and integrated understanding of redox biology in vivo. Antioxid. Redox Signal. 24, 680-712.

  1. Neuroimmune regulation during intestinal development and homeostasis.

    Science.gov (United States)

    Veiga-Fernandes, Henrique; Pachnis, Vassilis

    2017-02-01

    Interactions between the nervous system and immune system are required for organ function and homeostasis. Evidence suggests that enteric neurons and intestinal immune cells share common regulatory mechanisms and can coordinate their responses to developmental challenges and environmental aggressions. These discoveries shed light on the physiology of system interactions and open novel perspectives for therapy designs that target underappreciated neurological-immunological commonalities. Here we highlight findings that address the importance of neuroimmune cell units (NICUs) in intestinal development, homeostasis and disease.

  2. Amplified and in situ detection of redox-active metabolite using a biobased redox capacitor.

    Science.gov (United States)

    Kim, Eunkyoung; Gordonov, Tanya; Bentley, William E; Payne, Gregory F

    2013-02-19

    Redox cycling provides a mechanism to amplify electrochemical signals for analyte detection. Previous studies have shown that diverse mediators/shuttles can engage in redox-cycling reactions with a biobased redox capacitor that is fabricated by grafting redox-active catechols onto a chitosan film. Here, we report that redox cycling with this catechol-chitosan redox capacitor can amplify electrochemical signals for detecting a redox-active bacterial metabolite. Specifically, we studied the redox-active bacterial metabolite pyocyanin that is reported to be a virulence factor and signaling molecule for the opportunistic pathogen P. aeruginosa. We demonstrate that redox cycling can amplify outputs from various electrochemical methods (cyclic voltammetry, chronocoulometry, and differential pulse voltammetry) and can lower the detection limit of pyocyanin to 50 nM. Further, the compatibility of this biobased redox capacitor allows the in situ monitoring of the production of redox-active metabolites (e.g., pyocyanin) during the course of P. aeruginosa cultivation. We anticipate that the amplified output of redox-active virulence factors should permit an earlier detection of life-threatening infections by the opportunistic pathogen P. aeruginosa while the "bio-compatibility" of this measurement approach should facilitate in situ study of the spatiotemporal dynamics of bacterial redox signaling.

  3. Redox buffered hydrofluoric acid etchant for the reduction of galvanic attack during release etching of MEMS devices having noble material films

    Science.gov (United States)

    Hankins, Matthew G [Albuquerque, NM

    2009-10-06

    Etchant solutions comprising a redox buffer can be used during the release etch step to reduce damage to the structural layers of a MEMS device that has noble material films. A preferred redox buffer comprises a soluble thiophosphoric acid, ester, or salt that maintains the electrochemical potential of the etchant solution at a level that prevents oxidation of the structural material. Therefore, the redox buffer preferentially oxidizes in place of the structural material. The sacrificial redox buffer thereby protects the exposed structural layers while permitting the dissolution of sacrificial oxide layers during the release etch.

  4. Radii of Redox Components from Absolute Redox Potentials Compared with Covalent and Aqueous Ionic Radii

    Czech Academy of Sciences Publication Activity Database

    Heyrovská, Raji

    2010-01-01

    Roč. 22, č. 9 (2010), s. 903-907 ISSN 1040-0397 Institutional support: RVO:68081707 Keywords : Electrochemistry * Absolute redox potentials * Radii of redox components Subject RIV: BO - Biophysics Impact factor: 2.721, year: 2010

  5. Redox Pioneer: Professor Vadim N. Gladyshev.

    Science.gov (United States)

    Hatfield, Dolph L

    2016-07-01

    Professor Vadim N. Gladyshev is recognized here as a Redox Pioneer, because he has published an article on antioxidant/redox biology that has been cited more than 1000 times and 29 articles that have been cited more than 100 times. Gladyshev is world renowned for his characterization of the human selenoproteome encoded by 25 genes, identification of the majority of known selenoprotein genes in the three domains of life, and discoveries related to thiol oxidoreductases and mechanisms of redox control. Gladyshev's first faculty position was in the Department of Biochemistry, the University of Nebraska. There, he was a Charles Bessey Professor and Director of the Redox Biology Center. He then moved to the Department of Medicine at Brigham and Women's Hospital, Harvard Medical School, where he is Professor of Medicine and Director of the Center for Redox Medicine. His discoveries in redox biology relate to selenoenzymes, such as methionine sulfoxide reductases and thioredoxin reductases, and various thiol oxidoreductases. He is responsible for the genome-wide identification of catalytic redox-active cysteines and for advancing our understanding of the general use of cysteines by proteins. In addition, Gladyshev has characterized hydrogen peroxide metabolism and signaling and regulation of protein function by methionine-R-sulfoxidation. He has also made important contributions in the areas of aging and lifespan control and pioneered applications of comparative genomics in redox biology, selenium biology, and aging. Gladyshev's discoveries have had a profound impact on redox biology and the role of redox control in health and disease. He is a true Redox Pioneer. Antioxid. Redox Signal. 25, 1-9.

  6. Characterization of redox proteins using electrochemical methods

    OpenAIRE

    Verhagen, M.

    1995-01-01

    The use of electrochemical techniques in combination with proteins started approximately a decade ago and has since then developed into a powerfull technique for the study of small redox proteins. In addition to the determination of redox potentials, electrochemistry can be used to obtain information about the kinetics of electron transfer between proteins and about the dynamic behaviour of redox cofactors in proteins. This thesis describes the results of a study, initiated to get a ...

  7. Redox flow batteries having multiple electroactive elements

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei; Li, Liyu; Yang, Zhenguo; Nie, Zimin

    2018-05-01

    Introducing multiple redox reactions with a suitable voltage range can improve the energy density of redox flow battery (RFB) systems. One example includes RFB systems utilizing multiple redox pairs in the positive half cell, the negative half cell, or in both. Such RFB systems can have a negative electrolyte, a positive electrolyte, and a membrane between the negative electrolyte and the positive electrolyte, in which at least two electrochemically active elements exist in the negative electrolyte, the positive electrolyte, or both.

  8. Membranes for Redox Flow Battery Applications

    OpenAIRE

    Prifti, Helen; Parasuraman, Aishwarya; Winardi, Suminto; Lim, Tuti Mariana; Skyllas-Kazacos, Maria

    2012-01-01

    The need for large scale energy storage has become a priority to integrate renewable energy sources into the electricity grid. Redox flow batteries are considered the best option to store electricity from medium to large scale applications. However, the current high cost of redox flow batteries impedes the wide spread adoption of this technology. The membrane is a critical component of redox flow batteries as it determines the performance as well as the economic viability of the batteries. Th...

  9. Lipid peroxidation regulates podocyte migration and cytoskeletal structure through redox sensitive RhoA signaling

    Directory of Open Access Journals (Sweden)

    Claudia Kruger

    2018-06-01

    Full Text Available Early podocyte loss is characteristic of chronic kidney diseases (CKD in obesity and diabetes. Since treatments for hyperglycemia and hypertension do not prevent podocyte loss, there must be additional factors causing podocyte depletion. The role of oxidative stress has been implicated in CKD but it is not known how exactly free radicals affect podocyte physiology. To assess this relationship, we investigated the effects of lipid radicals on podocytes, as lipid peroxidation is a major form of oxidative stress in diabetes. We found that lipid radicals govern changes in podocyte homeostasis through redox sensitive RhoA signaling: lipid radicals inhibit migration and cause loss of F-actin fibers. These effects were prevented by mutating the redox sensitive cysteines of RhoA. We therefore suggest that in diseases associated with increased lipid peroxidation, lipid radicals can determine podocyte function with potentially pathogenic consequences for kidney physiology. Keywords: Lipid peroxidation, Reactive lipids, Podocyte, RhoA, Cysteine, Chronic kidney disease

  10. Regulatory redox state in tree seeds

    Directory of Open Access Journals (Sweden)

    Ewelina Ratajczak

    2017-12-01

    Full Text Available Peroxiredoxins (Prx are important regulators of the redox status of tree seeds during maturation and long-term storage. Thioredoxins (Trx are redox transmitters and thereby regulate Prx activity. Current research is focused on the association of Trx with Prx in tree seeds differing in the tolerance to desiccation. The results will allow for better understanding the regulation of the redox status in orthodox, recalcitrant, and intermediate seeds. The findings will also elucidate the role of the redox status during the loss of viability of sensitive seeds during drying and long-term storage.

  11. Atypical antipsychotics and glucose homeostasis.

    Science.gov (United States)

    Bergman, Richard N; Ader, Marilyn

    2005-04-01

    Persistent reports have linked atypical antipsychotics with diabetes, yet causative mechanisms responsible for this linkage are unclear. Goals of this review are to outline the pathogenesis of nonimmune diabetes and to survey the available literature related to why antipsychotics may lead to this disease. We accessed the literature regarding atypical antipsychotics and glucose homeostasis using PubMed. The search included English-language publications from 1990 through October 2004. Keywords used included atypical antipsychotics plus one of the following: glucose, insulin, glucose tolerance, obesity, or diabetes. In addition, we culled information from published abstracts from several national and international scientific meetings for the years 2001 through 2004, including the American Diabetes Association, the International Congress on Schizophrenia Research, and the American College of Neuropsychopharmacology. The latter search was necessary because of the paucity of well-controlled prospective studies. We examined publications with significant new data or publications that contributed to the overall comprehension of the impact of atypical antipsychotics on glucose metabolism. We favored original peer-reviewed articles and were less likely to cite single case studies and/or anecdotal information. Approximately 75% of the fewer than 150 identified articles were examined and included in this review. Validity of data was evaluated using the existence of peer-review status as well as our own experience with methodology described in the specific articles. The metabolic profile caused by atypical antipsychotic treatment resembles type 2 diabetes. These agents cause weight gain in treated subjects and may induce obesity in both visceral and subcutaneous depots, as occurs in diabetes. Insulin resistance, usually associated with obesity, occurs to varying degrees with different antipsychotics, although more comparative studies with direct assessment of resistance are

  12. Systems and methods for rebalancing redox flow battery electrolytes

    Science.gov (United States)

    Pham, Ai Quoc; Chang, On Kok

    2015-03-17

    Various methods of rebalancing electrolytes in a redox flow battery system include various systems using a catalyzed hydrogen rebalance cell configured to minimize the risk of dissolved catalyst negatively affecting flow battery performance. Some systems described herein reduce the chance of catalyst contamination of RFB electrolytes by employing a mediator solution to eliminate direct contact between the catalyzed membrane and the RFB electrolyte. Other methods use a rebalance cell chemistry that maintains the catalyzed electrode at a potential low enough to prevent the catalyst from dissolving.

  13. Redox reactions in food fermentations

    DEFF Research Database (Denmark)

    Hansen, Egon Bech

    2018-01-01

    involves oxidative steps in the early part of the pathways whereas a multitude of different reactions are used as compensating reductions. Much of the diversity seen between food fermentations arise from the different routes and the different electron acceptors used by microorganisms to counterbalance...... and this contributes to the diversity in flavor, color, texture, and shelf life. The review concludes that these reactions are still only incompletely understood and that they represent an interesting area for fundamental research and also represent a fertile field for product development through a more conscious use...... of the redox properties of strains used to compose food cultures....

  14. Method for producing redox shuttles

    Science.gov (United States)

    Pupek, Krzysztof Z.; Dzwiniel, Trevor L.; Krumdick, Gregory K.

    2015-03-03

    A single step method for producing a redox shuttle having the formula 2,5-di-tert-butyl-1,4-phenylene tetraethyl bis(phosphate) is provided, the method comprising phosphorylating tert butyl hydroquinone with a phosphate-containing reagent. Also provided is method for producing 2,5-di-tert-butyl-1,4-phenylene tetraethyl bis(phosphate), the method comprising solubilizing tert-butyl hydroquinone and tetrabutylammonium bromide with methyltetrahydrofuran to create a mixture; heating the mixture while adding base to the mixture in an amount to turn the mixture orange; and adding diethyl chlorophosphate to the orange mixture in an amount to phosphorylate the hydroquinone.

  15. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    Science.gov (United States)

    Kosan, Christian; Godmann, Maren

    2016-01-01

    All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function. PMID:26798358

  16. Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes Intestinal Homeostasis

    Science.gov (United States)

    Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Spencer, Sean P.; Belkaid, Yasmine; Merad, Miriam

    2014-01-01

    The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (Treg) numbers and impaired oral tolerance. We observed that RORγt+ innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1β. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine. PMID:24625929

  17. Highly controlled nest homeostasis of honey bees helps deactivate phenolics in nectar

    Science.gov (United States)

    Liu, Fanglin; He, Jianzhong; Fu, Wenjun

    2005-06-01

    Honey bees have a highly developed nest homeostasis, for example, maintaining low CO2 levels and stable nest temperatures at 35°C.We investigate the role of nest homeostasis in deactivating phenolic compounds present in the nectar of Aloe littoralis. We show that the phenolic content in nectar was reduced (from 0.65% to 0.49%) after nectar was incubated in a nest of Apis cerana, and that it was reduced still more (from 0.65% to 0.37%) if nectar was mixed with hypopharyngeal gland proteins (HGP) of worker bees before being placed inside a nest. HGP had little effect on samples outside a nest, indicating that nest conditions are necessary for HGP to deactivate phenolics in nectar. Consequently, the highly controlled nest homeostasis of honey bees facilitates direct deactivation of phenolics in nectar, and plays a role in the action of HGP as well.

  18. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis.

    Science.gov (United States)

    Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Spencer, Sean P; Belkaid, Yasmine; Merad, Miriam

    2014-03-28

    The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (T(reg)) numbers and impaired oral tolerance. We observed that RORγt(+) innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1β. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine.

  19. Atmospheric Convective Organization: Self-Organized Criticality or Homeostasis?

    Science.gov (United States)

    Yano, Jun-Ichi

    2015-04-01

    Atmospheric convection has a tendency organized on a hierarchy of scales ranging from the mesoscale to the planetary scales, with the latter especially manifested by the Madden-Julian oscillation. The present talk examines two major possible mechanisms of self-organization identified in wider literature from a phenomenological thermodynamic point of view by analysing a planetary-scale cloud-resolving model simulation. The first mechanism is self-organized criticality. A saturation tendency of precipitation rate with the increasing column-integrated water, reminiscence of critical phenomena, indicates self-organized criticality. The second is a self-regulation mechanism that is known as homeostasis in biology. A thermodynamic argument suggests that such self-regulation maintains the column-integrated water below a threshold by increasing the precipitation rate. Previous analyses of both observational data as well as cloud-resolving model (CRM) experiments give mixed results. A satellite data analysis suggests self-organized criticality. Some observational data as well as CRM experiments support homeostasis. Other analyses point to a combination of these two interpretations. In this study, a CRM experiment over a planetary-scale domain with a constant sea-surface temperature is analyzed. This analysis shows that the relation between the column-integrated total water and precipitation suggests self-organized criticality, whereas the one between the column-integrated water vapor and precipitation suggests homeostasis. The concurrent presence of these two mechanisms are further elaborated by detailed statistical and budget analyses. These statistics are scale invariant, reflecting a spatial scaling of precipitation processes. These self-organization mechanisms are most likely be best theoretically understood by the energy cycle of the convective systems consisting of the kinetic energy and the cloud-work function. The author has already investigated the behavior of this

  20. Information processing through a bio-based redox capacitor: signatures for redox-cycling.

    Science.gov (United States)

    Liu, Yi; Kim, Eunkyoung; White, Ian M; Bentley, William E; Payne, Gregory F

    2014-08-01

    Redox-cycling compounds can significantly impact biological systems and can be responsible for activities that range from pathogen virulence and contaminant toxicities, to therapeutic drug mechanisms. Current methods to identify redox-cycling activities rely on the generation of reactive oxygen species (ROS), and employ enzymatic or chemical methods to detect ROS. Here, we couple the speed and sensitivity of electrochemistry with the molecular-electronic properties of a bio-based redox-capacitor to generate signatures of redox-cycling. The redox capacitor film is electrochemically-fabricated at the electrode surface and is composed of a polysaccharide hydrogel with grafted catechol moieties. This capacitor film is redox-active but non-conducting and can engage diffusible compounds in either oxidative or reductive redox-cycling. Using standard electrochemical mediators ferrocene dimethanol (Fc) and Ru(NH3)6Cl3 (Ru(3+)) as model redox-cyclers, we observed signal amplifications and rectifications that serve as signatures of redox-cycling. Three bio-relevant compounds were then probed for these signatures: (i) ascorbate, a redox-active compound that does not redox-cycle; (ii) pyocyanin, a virulence factor well-known for its reductive redox-cycling; and (iii) acetaminophen, an analgesic that oxidatively redox-cycles but also undergoes conjugation reactions. These studies demonstrate that the redox-capacitor can enlist the capabilities of electrochemistry to generate rapid and sensitive signatures of biologically-relevant chemical activities (i.e., redox-cycling). Published by Elsevier B.V.

  1. Potential redox behaviour on industrial wastes treatment; Evolucion del potencial redox en tratamiento y depuracion industrial de aguas

    Energy Technology Data Exchange (ETDEWEB)

    Marin Galvin, R.; rodriguez Mellado, J. M.; Ruiz Montoya, M.; Jimenez Gamero, C. [Departamento Quimica Fisica y Termodinamica aplicada, Facultad de ciencias, Universidad de Cordoba (Spain)

    1995-12-31

    A study over the behaviour of redox potential in waters and wastewaters under industrial treatment processes has been carried out. In both cases, the potential-time curves obtained were in a logarithmical shape being more strongly distorted when the waters contained more dissolved and suspended compounds. Oxygen fundamentally leads the redox state in wastewaters, although ozone and chlorine almost oxygen lead the redox potential in raw waters intended to drinking water production. In this way, by increasing 210 m V the E{sub H} value of water or maintaining the rH>21.8 it can be industrially sterilized the drinking water. On the other hand, increases of 350 mV in the EH values from wastewaters influent to plant to the treated waters, allowed discarding 450 mg/l of DQO and 9 mg/l of NH{sub 3} from the former. Finally, the exploitation of the Wastewaters Treatment Plant by regulation of the E{sub H} values can suppose a good practice. (Author) 14 refs.

  2. Regulatory T Cells in Post-stroke Immune Homeostasis.

    Science.gov (United States)

    Liesz, Arthur; Kleinschnitz, Christoph

    2016-08-01

    The secondary neuroinflammatory response has come into focus of experimental stroke research. Immunological mechanisms after acute stroke are being investigated in the hope to identify novel and druggable pathways that contribute to secondary infarct growth after stroke. Among a variety of neuroimmunological events after acute brain ischemia, including microglial activation, brain leukocyte invasion, and secretion of pro-inflammatory factors, lymphocytes have been identified as the key leukocyte subpopulation driving the neuroinflammatory response and contributing to stroke outcome. Several studies have shown that pro-inflammatory lymphocyte subpopulations worsen stroke outcome and that inhibiting their invasion to the injured brain is neuroprotective. In contrast to the effector functions of pro-inflammatory lymphocytes, regulatory T cells (Treg) are critically involved in maintaining immune homeostasis and have been characterized as disease-limiting protective cells in several inflammatory conditions, particularly in primary inflammatory diseases of the central nervous system (CNS). However, due to the complex function of regulatory cells in immune homeostasis and disease, divergent findings have been described for the role of Treg in stroke models. Emerging evidence suggests that this discrepancy arises from potentially differing functions of Treg depending on the predominant site of action within the neurovascular unit and the surrounding inflammatory milieu. This article will provide a comprehensive review of current findings on Treg in brain ischemia models and discuss potential reasons for the observed discrepancies.

  3. A role of the adaptive immune system in glucose homeostasis.

    Science.gov (United States)

    Bronsart, Laura L; Contag, Christopher H

    2016-01-01

    The immune system, including the adaptive immune response, has recently been recognized as having a significant role in diet-induced insulin resistance. In this study, we aimed to determine if the adaptive immune system also functions in maintaining physiological glucose homeostasis in the absence of diet-induced disease. SCID mice and immunocompetent control animals were phenotypically assessed for variations in metabolic parameters and cytokine profiles. Additionally, the glucose tolerance of SCID and immunocompetent control animals was assessed following introduction of a high-fat diet. SCID mice on a normal chow diet were significantly insulin resistant relative to control animals despite having less fat mass. This was associated with a significant increase in the innate immunity-stimulating cytokines granulocyte colony-stimulating factor, monocyte chemoattractant protein 1 (MCP1), and MCP3. Additionally, the SCID mouse phenotype was exacerbated in response to a high-fat diet as evidenced by the further significant progression of glucose intolerance. These results support the notion that the adaptive immune system plays a fundamental biological role in glucose homeostasis, and that the absence of functional B and T cells results in disruption in the concentrations of various cytokines associated with macrophage proliferation and recruitment. Additionally, the absence of functional B and T cells is not protective against diet-induced pathology.

  4. Innate lymphoid cells in tissue homeostasis and diseases.

    Science.gov (United States)

    Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

    2017-08-18

    Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

  5. The nucleolus—guardian of cellular homeostasis and genome integrity.

    Science.gov (United States)

    Grummt, Ingrid

    2013-12-01

    All organisms sense and respond to conditions that stress their homeostasis by downregulating the synthesis of rRNA and ribosome biogenesis, thus designating the nucleolus as the central hub in coordinating the cellular stress response. One of the most intriguing roles of the nucleolus, long regarded as a mere ribosome-producing factory, is its participation in monitoring cellular stress signals and transmitting them to the RNA polymerase I (Pol I) transcription machinery. As rRNA synthesis is a most energy-consuming process, switching off transcription of rRNA genes is an effective way of saving the energy required to maintain cellular homeostasis during acute stress. The Pol I transcription machinery is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production which, in turn, guides cell growth and proliferation. This review focuses on the mechanisms that link cell physiology to rDNA silencing, a prerequisite for nucleolar integrity and cell survival.

  6. Characterization of redox conditions in pollution plumes

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Bjerg, Poul Løgstrup; Banwart, Steven A.

    2000-01-01

    Evalution of redox conditions in groundwater pollution plumes is often a prerequisite for understanding the behviour of the pollutants in the plume and for selecting remediation approaches. Measuring of redox conditions in pollution plumes is, however, a fairly recent issue and yet relative few...

  7. Redox properties of small semiconductor particles

    International Nuclear Information System (INIS)

    Liver, N.; Nitzan, A.

    1992-01-01

    The size dependence of electrical and thermodynamic quantities of intermediate-sized semiconductor particles in an electrolyte solution with a given redox pair are studied. The equilibrium constant for this system is then derived based on the relationship of the electrolytic redox components to the size, charges, and concentration of the semiconductor particles. 25 refs., 9 figs., 1 tab

  8. Characterization of redox proteins using electrochemical methods

    NARCIS (Netherlands)

    Verhagen, M.

    1995-01-01

    The use of electrochemical techniques in combination with proteins started approximately a decade ago and has since then developed into a powerfull technique for the study of small redox proteins. In addition to the determination of redox potentials, electrochemistry can be used to obtain

  9. Neuronal and molecular mechanisms of sleep homeostasis.

    Science.gov (United States)

    Donlea, Jeffrey M

    2017-12-01

    Sleep is necessary for survival, and prolonged waking causes a homeostatic increase in the need for recovery sleep. Homeostasis is a core component of sleep regulation and has been tightly conserved across evolution from invertebrates to man. Homeostatic sleep regulation was first identified among insects in cockroaches several decades ago, but the characterization of sleep rebound in Drosophila melanogaster opened the use of insect model species to understand homeostatic functions and regulation of sleep. This review describes circuits in two neuropil structures, the central complex and mushroom bodies, that influence sleep homeostasis and neuromodulatory systems that influence the accrual of homeostatic sleep need. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Regulation of intestinal homeostasis by innate immune cells.

    Science.gov (United States)

    Kayama, Hisako; Nishimura, Junichi; Takeda, Kiyoshi

    2013-12-01

    The intestinal immune system has an ability to distinguish between the microbiota and pathogenic bacteria, and then activate pro-inflammatory pathways against pathogens for host defense while remaining unresponsive to the microbiota and dietary antigens. In the intestine, abnormal activation of innate immunity causes development of several inflammatory disorders such as inflammatory bowel diseases (IBD). Thus, activity of innate immunity is finely regulated in the intestine. To date, multiple innate immune cells have been shown to maintain gut homeostasis by preventing inadequate adaptive immune responses in the murine intestine. Additionally, several innate immune subsets, which promote Th1 and Th17 responses and are implicated in the pathogenesis of IBD, have recently been identified in the human intestinal mucosa. The demonstration of both murine and human intestinal innate immune subsets contributing to regulation of adaptive immunity emphasizes the conserved innate immune functions across species and might promote development of the intestinal innate immunity-based clinical therapy.

  11. Stem/progenitor cells in pituitary organ homeostasis and tumourigenesis

    Science.gov (United States)

    Manshaei, Saba

    2018-01-01

    Evidence for the presence of pituitary gland stem cells has been provided over the last decade using a combination of approaches including in vitro clonogenicity assays, flow cytometric side population analysis, immunohistochemical analysis and genetic approaches. These cells have been demonstrated to be able to self-renew and undergo multipotent differentiation to give rise to all hormonal lineages of the anterior pituitary. Furthermore, evidence exists for their contribution to regeneration of the organ and plastic responses to changing physiological demand. Recently, stem-like cells have been isolated from pituitary neoplasms raising the possibility that a cytological hierarchy exists, in keeping with the cancer stem cell paradigm. In this manuscript, we review the evidence for the existence of pituitary stem cells, their role in maintaining organ homeostasis and the regulation of their differentiation. Furthermore, we explore the emerging concept of stem cells in pituitary tumours and their potential roles in these diseases. PMID:28855316

  12. Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.

    Science.gov (United States)

    Olson, D K; Fröhlich, F; Farese, R V; Walther, T C

    2016-08-01

    Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. Copyright © 2015. Published by Elsevier B.V.

  13. Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

    Science.gov (United States)

    Chonchol, Michel; Levi, Moshe

    2015-01-01

    Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. PMID:25287933

  14. Stress responses during ageing: molecular pathways regulating protein homeostasis.

    Science.gov (United States)

    Kyriakakis, Emmanouil; Princz, Andrea; Tavernarakis, Nektarios

    2015-01-01

    The ageing process is characterized by deterioration of physiological function accompanied by frailty and ageing-associated diseases. The most broadly and well-studied pathways influencing ageing are the insulin/insulin-like growth factor 1 signaling pathway and the dietary restriction pathway. Recent studies in diverse organisms have also delineated emerging pathways, which collectively or independently contribute to ageing. Among them the proteostatic-stress-response networks, inextricably affect normal ageing by maintaining or restoring protein homeostasis to preserve proper cellular and organismal function. In this chapter, we survey the involvement of heat stress and endoplasmic reticulum stress responses in the regulation of longevity, placing emphasis on the cross talk between different response mechanisms and their systemic effects. We further discuss novel insights relevant to the molecular pathways mediating these stress responses that may facilitate the development of innovative interventions targeting age-related pathologies such as diabetes, cancer, cardiovascular and neurodegenerative diseases.

  15. Engineered Proteins: Redox Properties and Their Applications

    Science.gov (United States)

    Prabhulkar, Shradha; Tian, Hui; Wang, Xiaotang; Zhu, Jun-Jie

    2012-01-01

    Abstract Oxidoreductases and metalloproteins, representing more than one third of all known proteins, serve as significant catalysts for numerous biological processes that involve electron transfers such as photosynthesis, respiration, metabolism, and molecular signaling. The functional properties of the oxidoreductases/metalloproteins are determined by the nature of their redox centers. Protein engineering is a powerful approach that is used to incorporate biological and abiological redox cofactors as well as novel enzymes and redox proteins with predictable structures and desirable functions for important biological and chemical applications. The methods of protein engineering, mainly rational design, directed evolution, protein surface modifications, and domain shuffling, have allowed the creation and study of a number of redox proteins. This review presents a selection of engineered redox proteins achieved through these methods, resulting in a manipulation in redox potentials, an increase in electron-transfer efficiency, and an expansion of native proteins by de novo design. Such engineered/modified redox proteins with desired properties have led to a broad spectrum of practical applications, ranging from biosensors, biofuel cells, to pharmaceuticals and hybrid catalysis. Glucose biosensors are one of the most successful products in enzyme electrochemistry, with reconstituted glucose oxidase achieving effective electrical communication with the sensor electrode; direct electron-transfer-type biofuel cells are developed to avoid thermodynamic loss and mediator leakage; and fusion proteins of P450s and redox partners make the biocatalytic generation of drug metabolites possible. In summary, this review includes the properties and applications of the engineered redox proteins as well as their significance and great potential in the exploration of bioelectrochemical sensing devices. Antioxid. Redox Signal. 17, 1796–1822. PMID:22435347

  16. Low glutathione regulates gene expression and the redox potentials of the nucleus and cytosol in Arabidopsis thaliana.

    Science.gov (United States)

    Schnaubelt, Daniel; Queval, Guillaume; Dong, Yingping; Diaz-Vivancos, Pedro; Makgopa, Matome Eugene; Howell, Gareth; De Simone, Ambra; Bai, Juan; Hannah, Matthew A; Foyer, Christine H

    2015-02-01

    Reduced glutathione (GSH) is considered to exert a strong influence on cellular redox homeostasis and to regulate gene expression, but these processes remain poorly characterized. Severe GSH depletion specifically inhibited root meristem development, while low root GSH levels decreased lateral root densities. The redox potential of the nucleus and cytosol of Arabidopsis thaliana roots determined using roGFP probes was between -300 and -320 mV. Growth in the presence of the GSH-synthesis inhibitor buthionine sulfoximine (BSO) increased the nuclear and cytosolic redox potentials to approximately -260 mV. GSH-responsive genes including transcription factors (SPATULA, MYB15, MYB75), proteins involved in cell division, redox regulation (glutaredoxinS17, thioredoxins, ACHT5 and TH8) and auxin signalling (HECATE), were identified in the GSH-deficient root meristemless 1-1 (rml1-1) mutant, and in other GSH-synthesis mutants (rax1-1, cad2-1, pad2-1) as well as in the wild type following the addition of BSO. Inhibition of auxin transport had no effect on organ GSH levels, but exogenous auxin decreased the root GSH pool. We conclude that GSH depletion significantly increases the redox potentials of the nucleus and cytosol, and causes arrest of the cell cycle in roots but not shoots, with accompanying transcript changes linked to altered hormone responses, but not oxidative stress. © 2013 John Wiley & Sons Ltd.

  17. Maintaining Healthy Skin -- Part 2

    Science.gov (United States)

    ... and SCI • Depression and SCI • Taking Care of Pressure Sores • Maintaining Healthy Skin (Part I) • Maintaining Healthy Skin ( ... For information on establishing skin tolerance, see our “Pressure Sores” pamphlet.) Pressure releases in a wheelchair can be ...

  18. AECL's reliability and maintainability program

    International Nuclear Information System (INIS)

    Wolfe, W.A.; Nieuwhof, G.W.E.

    1976-05-01

    AECL's reliability and maintainability program for nuclear generating stations is described. How the various resources of the company are organized to design and construct stations that operate reliably and safely is shown. Reliability and maintainability includes not only special mathematically oriented techniques, but also the technical skills and organizational abilities of the company. (author)

  19. Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

    Science.gov (United States)

    Haldar, Swati; Tripathi, Ajai K.; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K.; Singh, Ajay

    2014-01-01

    Abstract Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324–1363. PMID:23815406

  20. Calcium homeostasis in fly photoreceptor cells

    NARCIS (Netherlands)

    Oberwinkler, J

    2002-01-01

    In fly photoreceptor cells, two processes dominate the Ca2+ homeostasis: light-induced Ca2+ influx through members of the TRP family of ion channels, and Ca2+ extrusion by Na+/Ca2+ exchange.Ca2+ release from intracellular stores is quantitatively insignificant. Both, the light-activated channels and

  1. Effectiveness of carnosine on disturbed electrolytes homeostasis ...

    African Journals Online (AJOL)

    Jane

    2011-07-20

    Jul 20, 2011 ... of the cells to cisplatin may result from the interaction of specific proteins with ..... respiration, which is similar to uncoupling of oxidative phosphorylation (Binet ... cellular ion homeostasis with decreased cellular K+ content, increased ... of sodium and hydrogen ions will take place passively. Also, magnesium ...

  2. Pharmacological modulation of mitochondrial calcium homeostasis.

    Science.gov (United States)

    Arduino, Daniela M; Perocchi, Fabiana

    2018-01-10

    Mitochondria are pivotal organelles in calcium (Ca 2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca 2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca 2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca 2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca 2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca 2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca 2+ homeostasis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

  3. Molecular monitoring of equine joint homeostasis

    NARCIS (Netherlands)

    de Grauw, J.C.

    2010-01-01

    Chronic joint disorders are a major cause of impaired mobility and loss of quality of life in both humans and horses. Regardless of the primary insult, any joint disorder is characterized by an upset in normal joint homeostasis, the balance between tissue anabolism and catabolism that is normally

  4. Brain glucose sensing, counterregulation, and energy homeostasis.

    Science.gov (United States)

    Marty, Nell; Dallaporta, Michel; Thorens, Bernard

    2007-08-01

    Neuronal circuits in the central nervous system play a critical role in orchestrating the control of glucose and energy homeostasis. Glucose, beside being a nutrient, is also a signal detected by several glucose-sensing units that are located at different anatomical sites and converge to the hypothalamus to cooperate with leptin and insulin in controlling the melanocortin pathway.

  5. Ruthenium nanocatalysis on redox reactions.

    Science.gov (United States)

    Veerakumar, Pitchaimani; Ramdass, Arumugam; Rajagopal, Seenivasan

    2013-07-01

    Nanoparticles have generated intense interest over the past 20 years due to their high potential applications in different areas such as catalysis, sensors, nanoscale electronics, fuel and solar cells and optoelectronics. As the large fractions of metal atoms are exposed to the surface, the use of metal nanoparticles as nanocatalysts allows mild reaction conditions and high catalytic efficiency in a large number of chemical transformations. They have emerged as sustainable heterogeneous catalysts and catalyst supports alternative to conventional materials. This review focuses on the synthesis, characterization and catalytic role of ruthenium nanoparticles (RuNPs) on the redox reactions of heteroatom containing organic compounds with the green reagent H2O2, a field that has attracted immense interest among the chemical, materials and industrial communities. We intend to present a broad overview of Ru nanocatalysts for redox reactions with an emphasis on their performance, stability and reusability. The growth in the chemistry of organic sulfoxides and N-oxides during last decade was due to their importance as synthetic intermediates for the production of a wide range of chemically and biologically active molecules. Thus design of efficient methods for the synthesis of sulfoxides and N-oxides becomes important. This review concentrates on the catalysis of RuNPs on the H2O2 oxidation of organic sulfides to sulfoxides and amines to N-oxides. The deoxygenation reactions of sulfoxides to sulfides and reduction of nitro compounds to amines are fundamental reactions in both chemistry and biology. Here, we also highlight the catalysis of metal nanoparticles on the deoxygenation of sulfoxides and sulfones and reduction of nitro compounds with particular emphasis on the mechanistic aspects.

  6. Alterations in vitamin A/retinoic acid homeostasis in diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Mody, Nimesh

    2017-11-01

    Vitamin A is an essential micronutrient for life and the phytochemical β-carotene, also known as pro-vitamin A, is an important dietary source of this vitamin. Vitamin A (retinol) is the parent compound of all bioactive retinoids but it is retinoic acid (RA) that is the active metabolite of vitamin A. The plasma concentration of retinol is maintained in a narrow range and its normal biological activities strictly regulated since excessive intake can lead to toxicity and thus also be detrimental to life. The present review will give an overview of how vitamin A homeostasis is maintained and move on to focus on the link between circulating vitamin A and metabolic disease states. Finally, we will examine how pharmacological or genetic alterations in vitamin A homeostasis and RA-signalling can influence body fat and blood glucose levels including a novel link to the liver secreted hormone fibroblast growth factor 21, an important metabolic regulator.

  7. Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

    Science.gov (United States)

    Chen, Qian; Xiao, De-Sheng

    2014-01-30

    Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility

    Science.gov (United States)

    Wedege, Kristina; Dražević, Emil; Konya, Denes; Bentien, Anders

    2016-01-01

    Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined with single cell battery RFB tests on selected redox pairs. Data shows that both the solubility and redox potential are determined by the position of the side groups and only to a small extent by the number of side groups. Additionally, the chemical stability and possible degradation mechanisms leading to capacity loss over time are discussed. The main challenge for the development of all-organic RFBs is to identify a redox pair for the positive side with sufficiently high stability and redox potential that enables battery cell potentials above 1 V. PMID:27966605

  9. Redox behaviors of iron by absorption spectroscopy and redox potential measurement

    International Nuclear Information System (INIS)

    Oh, Jae Yong

    2010-02-01

    This work is performed to study the redox (reduction/oxidation) behaviors of iron in aqueous system by a combination of absorption spectroscopy and redox potential measurements. There are many doubts on redox potential measurements generally showing low accuracies and high uncertainties. In the present study, redox potentials are measured by utilizing various redox electrodes such as Pt, Au, Ag, and glassy carbon (GC) electrodes. Measured redox potentials are compared with calculated redox potentials based on the chemical oxidation speciation of iron and thermodynamic data by absorption spectroscopy, which provides one of the sensitive and selective spectroscopic methods for the chemical speciation of Fe(II/III). From the comparison analyses, redox potential values measured by the Ag redox electrode are fairly consistent with those calculated by the chemical aqueous speciation of iron in the whole system. In summary, the uncertainties of measured redox potentials are closely related with the total Fe concentration and affected by the formation of mixed potentials due to Fe(III) precipitates in the pH range of 6 ∼ 9 beyond the solubility of Fe(III), whilst being independent of the initially prepared concentration ratios between Fe(II) and Fe(III)

  10. Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility

    Science.gov (United States)

    Wedege, Kristina; Dražević, Emil; Konya, Denes; Bentien, Anders

    2016-12-01

    Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined with single cell battery RFB tests on selected redox pairs. Data shows that both the solubility and redox potential are determined by the position of the side groups and only to a small extent by the number of side groups. Additionally, the chemical stability and possible degradation mechanisms leading to capacity loss over time are discussed. The main challenge for the development of all-organic RFBs is to identify a redox pair for the positive side with sufficiently high stability and redox potential that enables battery cell potentials above 1 V.

  11. Redox kinetics and mechanism in silicate melts

    International Nuclear Information System (INIS)

    Cochain, B.

    2009-12-01

    This work contributes to better understand iron redox reactions and mechanisms in silicate melts. It was conducted on compositions in both Na 2 O-B 2 O 3 -SiO 2 -FeO and Na 2 O-Al 2 O 3 -SiO 2 -FeO systems. The influence of boron-sodium and aluminum-sodium substitutions and iron content on properties and structure of glasses and on the iron redox kinetics has been studied by Raman, Moessbauer and XANES spectroscopies at the B and Fe K-edges. In borosilicate glasses, an increase in iron content or in the Fe 3+ /ΣFe redox state implies a structural rearrangement of the BO 4 species in the glass network whereas the BO 3 and BO 4 relative proportions remain nearly constant. In all studied glasses and melts, Fe 3+ is a network former in tetrahedral coordination, unless for aluminosilicates of ratio Al/Na≥1 where Fe 3+ is a network modifier in five-fold coordination. Near Tg, diffusion of network modifying cations controls the iron redox kinetics along with a flux of electron holes. At liquidus temperatures, oxygen diffusion is considered to be the mechanism that governs redox reactions. This study shows the role played by the silicate network polymerization on the redox kinetics. In borosilicate melts, iron redox kinetics depends on the boron speciation between BO 3 and BO 4 that depends itself on the sodium content. Furthermore, an increase in the network-former/network-modifier ratio implies a decrease in oxygen diffusion that results in a slowing down of the redox kinetics. The obtained results allow a description of the iron redox kinetics for more complex compositions as natural lavas or nuclear waste model glasses. (author)

  12. Redox regulation in metabolic programming and inflammation.

    Science.gov (United States)

    Griffiths, Helen R; Gao, Dan; Pararasa, Chathyan

    2017-08-01

    Energy metabolism and redox state are intrinsically linked. In order to mount an adequate immune response, cells must have an adequate and rapidly available energy resource to migrate to the inflammatory site, to generate reactive oxygen species using NADPH as a cofactor and to engulf bacteria or damaged tissue. The first responder cells of the innate immune response, neutrophils, are largely dependent on glycolysis. Neutrophils are relatively short-lived, dying via apoptosis in the process of bacterial killing through production of hypochlorous acid and release of extracellular NETs. Later on, the most prevalent recruited innate immune cells are monocytes. Their role is to complete a damage limitation exercise initiated by neutrophils and then, as re-programmed M2 macrophages, to resolve the inflammatory event. Almost twenty five years ago, it was noted that macrophages lose their glycolytic capacity and become anti-inflammatory after treatment with corticosteroids. In support of this we now understand that, in contrast to early responders, M2 macrophages are predominantly dependent on oxidative phosphorylation for energy. During early inflammation, polarisation towards M1 macrophages is dependent on NOX2 activation which, via protein tyrosine phosphatase oxidation and AKT activation, increases trafficking of glucose transporters to the membrane and consequently increases glucose uptake for glycolysis. In parallel, mitochondrial efficiency is likely to be compromised via nitrosylation of the electron transport chain. Resolution of inflammation is triggered by encounter with apoptotic membranes exposing oxidised phosphatidylserine that interact with the scavenger receptor, CD36. Downstream of CD36, activation of AMPK and PPARγ elicits mitochondrial biogenesis, arginase expression and a switch towards oxidative phosphorylation in the M2 macrophage. Proinflammatory cytokine production by M2 cells decreases, but anti-inflammatory and wound healing growth factor

  13. Redox sensor proteins for highly sensitive direct imaging of intracellular redox state.

    Science.gov (United States)

    Sugiura, Kazunori; Nagai, Takeharu; Nakano, Masahiro; Ichinose, Hiroshi; Nakabayashi, Takakazu; Ohta, Nobuhiro; Hisabori, Toru

    2015-02-13

    Intracellular redox state is a critical factor for fundamental cellular functions, including regulation of the activities of various metabolic enzymes as well as ROS production and elimination. Genetically-encoded fluorescent redox sensors, such as roGFP (Hanson, G. T., et al. (2004)) and Redoxfluor (Yano, T., et al. (2010)), have been developed to investigate the redox state of living cells. However, these sensors are not useful in cells that contain, for example, other colored pigments. We therefore intended to obtain simpler redox sensor proteins, and have developed oxidation-sensitive fluorescent proteins called Oba-Q (oxidation balance sensed quenching) proteins. Our sensor proteins derived from CFP and Sirius can be used to monitor the intracellular redox state as their fluorescence is drastically quenched upon oxidation. These blue-shifted spectra of the Oba-Q proteins enable us to monitor various redox states in conjunction with other sensor proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Novel insights in the molecular pathogenesis of human copper homeostasis disorders through studies of protein-protein interactions

    NARCIS (Netherlands)

    Bie, P. de

    2007-01-01

    Copper is an essential element for living organisms, yet it is very toxic when present in amounts exceeding cellular needs. Delicate mechanisms have evolved to ensure proper copper homeostasis is maintained for the organism, as well as at a cellular level, and perturbations in these mechanisms give

  15. Redox regulation of cell proliferation: Bioinformatics and redox proteomics approaches to identify redox-sensitive cell cycle regulators.

    Science.gov (United States)

    Foyer, Christine H; Wilson, Michael H; Wright, Megan H

    2018-03-29

    Plant stem cells are the foundation of plant growth and development. The balance of quiescence and division is highly regulated, while ensuring that proliferating cells are protected from the adverse effects of environment fluctuations that may damage the genome. Redox regulation is important in both the activation of proliferation and arrest of the cell cycle upon perception of environmental stress. Within this context, reactive oxygen species serve as 'pro-life' signals with positive roles in the regulation of the cell cycle and survival. However, very little is known about the metabolic mechanisms and redox-sensitive proteins that influence cell cycle progression. We have identified cysteine residues on known cell cycle regulators in Arabidopsis that are potentially accessible, and could play a role in redox regulation, based on secondary structure and solvent accessibility likelihoods for each protein. We propose that redox regulation may function alongside other known posttranslational modifications to control the functions of core cell cycle regulators such as the retinoblastoma protein. Since our current understanding of how redox regulation is involved in cell cycle control is hindered by a lack of knowledge regarding both which residues are important and how modification of those residues alters protein function, we discuss how critical redox modifications can be mapped at the molecular level. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  16. Metabolic Control of Redox and Redox Control of Metabolism in Plants

    Science.gov (United States)

    Fernie, Alisdair R.

    2014-01-01

    Abstract Significance: Reduction-oxidation (Redox) status operates as a major integrator of subcellular and extracellular metabolism and is simultaneously itself regulated by metabolic processes. Redox status not only dominates cellular metabolism due to the prominence of NAD(H) and NADP(H) couples in myriad metabolic reactions but also acts as an effective signal that informs the cell of the prevailing environmental conditions. After relay of this information, the cell is able to appropriately respond via a range of mechanisms, including directly affecting cellular functioning and reprogramming nuclear gene expression. Recent Advances: The facile accession of Arabidopsis knockout mutants alongside the adoption of broad-scale post-genomic approaches, which are able to provide transcriptomic-, proteomic-, and metabolomic-level information alongside traditional biochemical and emerging cell biological techniques, has dramatically advanced our understanding of redox status control. This review summarizes redox status control of metabolism and the metabolic control of redox status at both cellular and subcellular levels. Critical Issues: It is becoming apparent that plastid, mitochondria, and peroxisome functions influence a wide range of processes outside of the organelles themselves. While knowledge of the network of metabolic pathways and their intraorganellar redox status regulation has increased in the last years, little is known about the interorganellar redox signals coordinating these networks. A current challenge is, therefore, synthesizing our knowledge and planning experiments that tackle redox status regulation at both inter- and intracellular levels. Future Directions: Emerging tools are enabling ever-increasing spatiotemporal resolution of metabolism and imaging of redox status components. Broader application of these tools will likely greatly enhance our understanding of the interplay of redox status and metabolism as well as elucidating and

  17. Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions.

    Science.gov (United States)

    Mailloux, Ryan J; Jin, Xiaolei; Willmore, William G

    2014-01-01

    Mitochondria have a myriad of essential functions including metabolism and apoptosis. These chief functions are reliant on electron transfer reactions and the production of ATP and reactive oxygen species (ROS). The production of ATP and ROS are intimately linked to the electron transport chain (ETC). Electrons from nutrients are passed through the ETC via a series of acceptor and donor molecules to the terminal electron acceptor molecular oxygen (O2) which ultimately drives the synthesis of ATP. Electron transfer through the respiratory chain and nutrient oxidation also produces ROS. At high enough concentrations ROS can activate mitochondrial apoptotic machinery which ultimately leads to cell death. However, if maintained at low enough concentrations ROS can serve as important signaling molecules. Various regulatory mechanisms converge upon mitochondria to modulate ATP synthesis and ROS production. Given that mitochondrial function depends on redox reactions, it is important to consider how redox signals modulate mitochondrial processes. Here, we provide the first comprehensive review on how redox signals mediated through cysteine oxidation, namely S-oxidation (sulfenylation, sulfinylation), S-glutathionylation, and S-nitrosylation, regulate key mitochondrial functions including nutrient oxidation, oxidative phosphorylation, ROS production, mitochondrial permeability transition (MPT), apoptosis, and mitochondrial fission and fusion. We also consider the chemistry behind these reactions and how they are modulated in mitochondria. In addition, we also discuss emerging knowledge on disorders and disease states that are associated with deregulated redox signaling in mitochondria and how mitochondria-targeted medicines can be utilized to restore mitochondrial redox signaling.

  18. Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions☆

    Science.gov (United States)

    Mailloux, Ryan J.; Jin, Xiaolei; Willmore, William G.

    2013-01-01

    Mitochondria have a myriad of essential functions including metabolism and apoptosis. These chief functions are reliant on electron transfer reactions and the production of ATP and reactive oxygen species (ROS). The production of ATP and ROS are intimately linked to the electron transport chain (ETC). Electrons from nutrients are passed through the ETC via a series of acceptor and donor molecules to the terminal electron acceptor molecular oxygen (O2) which ultimately drives the synthesis of ATP. Electron transfer through the respiratory chain and nutrient oxidation also produces ROS. At high enough concentrations ROS can activate mitochondrial apoptotic machinery which ultimately leads to cell death. However, if maintained at low enough concentrations ROS can serve as important signaling molecules. Various regulatory mechanisms converge upon mitochondria to modulate ATP synthesis and ROS production. Given that mitochondrial function depends on redox reactions, it is important to consider how redox signals modulate mitochondrial processes. Here, we provide the first comprehensive review on how redox signals mediated through cysteine oxidation, namely S-oxidation (sulfenylation, sulfinylation), S-glutathionylation, and S-nitrosylation, regulate key mitochondrial functions including nutrient oxidation, oxidative phosphorylation, ROS production, mitochondrial permeability transition (MPT), apoptosis, and mitochondrial fission and fusion. We also consider the chemistry behind these reactions and how they are modulated in mitochondria. In addition, we also discuss emerging knowledge on disorders and disease states that are associated with deregulated redox signaling in mitochondria and how mitochondria-targeted medicines can be utilized to restore mitochondrial redox signaling. PMID:24455476

  19. Redox Behavior of Fe2+/Fe3+ Redox Couple by Absorption Spectroscopy and Measurement

    International Nuclear Information System (INIS)

    Oh, J. Y.; Park, S.; Yun, J. I.

    2010-01-01

    Redox behavior has influences on speciation and other geochemical reactions of radionuclides such as sorption, solubility, and colloid formation, etc. It is one of the factors for evaluation of long-term safety assessment under high-level radioactive waste (HLW) disposal conditions. Accordingly, redox potential (Eh) measurement in aquatic system is important to investigate the redox conditions. Eh is usually measured with redox active electrodes (Pt, Au, glassy carbon, etc.). Nevertheless, Eh measurements by general methods using electrodes provide low accuracy and high uncertainty problem. Therefore, Eh calculated from the concentration of redox active elements with a proper complexing reagent by using UV-Vis absorption spectroscopy is progressed. Iron exists mostly as spent nuclear waste container material and in hydro-geologic minerals. In this system, iron controls the redox condition in near-field area and influences chemical behavior and speciation of radionuclides including redox sensitive actinides such as U, Np, and Pu. In the present work, we present the investigation on redox phenomena of iron in aquatic system by a combination of absorption spectroscopy and redox potential measurements

  20. Symproportionation versus Disproportionation in Bromine Redox Systems

    International Nuclear Information System (INIS)

    Toporek, Marcin; Michałowska-Kaczmarczyk, Anna M.; Michałowski, Tadeusz

    2015-01-01

    Graphical abstract: Display Omitted -- Highlights: • The disproportionation and symproportionation of bromine in different media is presented. • All the redox systems are elaborated according to the principles of the generalized approach to electrolytic redox systems (GATES/GEB). • All physicochemical knowledge is involved in the algorithm applied for this purpose. • The graphical representation of the systems is the basis of gaining the detailed physicochemical knowledge on the systems in question. -- Abstract: The paper refers to dynamic (titration) redox systems where symproportionation or disproportionation of bromine species occur. The related systems are modeled according to principles assumed in the Generalized Approach to Electrolytic Redox Systems (GATES), with Generalized Electron Balance (GEB) concept involved in the GATES/GEB software. The results obtained from calculations made with use of iterative computer programs prepared according to MATLAB computational software, are presented graphically, as 2D and 3D graphs

  1. Polyarene mediators for mediated redox flow battery

    Science.gov (United States)

    Delnick, Frank M.; Ingersoll, David; Liang, Chengdu

    2018-01-02

    The fundamental charge storage mechanisms in a number of currently studied high energy redox couples are based on intercalation, conversion, or displacement reactions. With exception to certain metal-air chemistries, most often the active redox materials are stored physically in the electrochemical cell stack thereby lowering the practical gravimetric and volumetric energy density as a tradeoff to achieve reasonable power density. In a general embodiment, a mediated redox flow battery includes a series of secondary organic molecules that form highly reduced anionic radicals as reaction mediator pairs for the reduction and oxidation of primary high capacity redox species ex situ from the electrochemical cell stack. Arenes are reduced to stable anionic radicals that in turn reduce a primary anode to the charged state. The primary anode is then discharged using a second lower potential (more positive) arene. Compatible separators and solvents are also disclosed herein.

  2. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy; Pillai, Ayyappan Harikrishna; Harikumar, Sankaran Kutty; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  3. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  4. Neutrophils in Homeostasis, Immunity, and Cancer.

    Science.gov (United States)

    Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

    2017-01-17

    Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Transcranial electrical stimulation accelerates human sleep homeostasis.

    Directory of Open Access Journals (Sweden)

    Davide Reato

    Full Text Available The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO in the human electro-encephalogram (EEG. A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

  7. The liver in regulation of iron homeostasis.

    Science.gov (United States)

    Rishi, Gautam; Subramaniam, V Nathan

    2017-09-01

    The liver is one of the largest and most functionally diverse organs in the human body. In addition to roles in detoxification of xenobiotics, digestion, synthesis of important plasma proteins, gluconeogenesis, lipid metabolism, and storage, the liver also plays a significant role in iron homeostasis. Apart from being the storage site for excess body iron, it also plays a vital role in regulating the amount of iron released into the blood by enterocytes and macrophages. Since iron is essential for many important physiological and molecular processes, it increases the importance of liver in the proper functioning of the body's metabolism. This hepatic iron-regulatory function can be attributed to the expression of many liver-specific or liver-enriched proteins, all of which play an important role in the regulation of iron homeostasis. This review focuses on these proteins and their known roles in the regulation of body iron metabolism. Copyright © 2017 the American Physiological Society.

  8. Mitochondrial Iron Transport and Homeostasis in Plants

    Directory of Open Access Journals (Sweden)

    Anshika eJain

    2013-09-01

    Full Text Available Iron (Fe is an essential nutrient for plants and although the mechanisms controlling iron uptake from the soil are relatively well understood, comparatively little is known about subcellular trafficking of iron in plant cells. Mitochondria represent a significant iron sink within cells, as iron is required for the proper functioning of respiratory chain protein complexes. Mitochondria are a site of Fe-S cluster synthesis, and possibly heme synthesis as well. Here we review recent insights into the molecular mechanisms controlling mitochondrial iron transport and homeostasis. We focus on the recent identification of a mitochondrial iron uptake transporter in rice and a possible role for metalloreductases in iron uptake by mitochondria. In addition, we highlight recent advances in mitochondrial iron homeostasis with an emphasis on the roles of frataxin and ferritin in iron trafficking and storage within mitochondria.

  9. MicroRNAs and Periodontal Homeostasis.

    Science.gov (United States)

    Luan, X; Zhou, X; Trombetta-eSilva, J; Francis, M; Gaharwar, A K; Atsawasuwan, P; Diekwisch, T G H

    2017-05-01

    MicroRNAs (miRNAs) are a group of small RNAs that control gene expression in all aspects of eukaryotic life, primarily through RNA silencing mechanisms. The purpose of the present review is to introduce key miRNAs involved in periodontal homeostasis, summarize the mechanisms by which they affect downstream genes and tissues, and provide an introduction into the therapeutic potential of periodontal miRNAs. In general, miRNAs function synergistically to fine-tune the regulation of biological processes and to remove expression noise rather than by causing drastic changes in expression levels. In the periodontium, miRNAs play key roles in development and periodontal homeostasis and during the loss of periodontal tissue integrity as a result of periodontal disease. As part of the anabolic phase of periodontal homeostasis and periodontal development, miRNAs direct periodontal fibroblasts toward alveolar bone lineage differentiation and new bone formation through WNT, bone morphogenetic protein, and Notch signaling pathways. miRNAs contribute equally to the catabolic aspect of periodontal homeostasis as they affect osteoclastogenesis and osteoclast function, either by directly promoting osteoclast activity or by inhibiting osteoclast signaling intermediaries or through negative feedback loops. Their small size and ability to target multiple regulatory networks of related sets of genes have predisposed miRNAs to become ideal candidates for drug delivery and tissue regeneration. To address the immense therapeutic potential of miRNAs and their antagomirs, an ever growing number of delivery approaches toward clinical applications have been developed, including nanoparticle carriers and secondary structure interference inhibitor systems. However, only a fraction of the miRNAs involved in periodontal health and disease are known today. It is anticipated that continued research will lead to a more comprehensive understanding of the periodontal miRNA world, and a systematic

  10. The Commensal Microbiota Drives Immune Homeostasis

    OpenAIRE

    Arrieta, Marie-Claire; Finlay, Barton Brett

    2012-01-01

    For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use t...

  11. A mathematical model of brain glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Kimura Hidenori

    2009-11-01

    Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

  12. THE WORLD VIEW, IDENTITY AND SOCIOCULTUR HOMEOSTASIS

    Directory of Open Access Journals (Sweden)

    Marina Yur’evna Neronova

    2016-02-01

    Full Text Available The paper presents the relationship between the phenomenon of world view and sociocultural identity both individuals and the community as a whole. The research is being carried out in the context of current crisis of world view accepted in so-called art Nouveau era. This paper also presents the identity crisis typical for modern civilized societies. A new notion of sociocultural homeostasis is introduced in connection with analyzable phenomena and their mutual relations.Purpose. Study of the relationship between the phenomenon of the world view and sociocultural identity as a structural and functional mechanism.Methodology. Phenomenological and systematic methods with the elements of historical method were employed. Cultural analysis is based on using both axiological and phenomenological approach, and also the elements of semiotic approach.Results. The dependence of identity on the world view is revealed (or is being revealed?, the phenomenon of sociocultural homeostasis is singled out (or is being singled out in the capacity of the mechanism setting up the correspondence in the contradictory unity between the world view as a subjective image and concrete reality as an objective part of this contradictory. The analysis of sociocultural homeostasis is carried out (or is being carried out and the conclusion is being drown that instability of the latter leads to serious problems in the identification of both individuals and communities as a whole. Besides, (moreover the relationship between the legitimacy level of the world view and stability of sociocultural homeostasis is established. (is being established.Practical implications: the system of education.

  13. Guest editor's introduction: Energy homeostasis in context.

    Science.gov (United States)

    Schneider, Jill E

    2014-06-01

    This article is part of a Special Issue "Energy Balance". Energy homeostasis is achieved through neuroendocrine and metabolic control of energy intake, storage, and expenditure. Traditionally, these controls have been studied in an unrealistic and narrow context. The appetite for food, for example, is most often assumed to be independent of other motivations, such as sexual desire, fearfulness, and competition. Furthermore, our understanding of all aspects of energy homeostasis is based on studying males of only a few species. The baseline control subjects are most often housed in enclosed spaces, with continuous, unlimited access to food. In the last century, this approach has generated useful information, but all the while, the global prevalence of obesity has increased and remains at unprecedented levels (Ogden et al., 2013, 2014). It is likely, however, that the mechanisms that control ingestive behavior were molded by evolutionary forces, and that few, if any vertebrate species evolved in the presence of a limitless food supply, in an enclosed 0.5 × 1 ft space, and exposed to a constant ambient temperature of 22+2 °C. This special issue of Hormones and Behavior therefore contains 9 review articles and 7 data articles that consider energy homeostasis within the context of other motivations and physiological processes, such as early development, sexual differentiation, sexual motivation, reproduction, seasonality, hibernation, and migration. Each article is focused on a different species or on a set of species, and most vertebrate classes are represented. Energy homeostasis is viewed in the context of the selection pressures that simultaneously molded multiple aspects of energy intake, storage, and expenditure. This approach yields surprising conclusions regarding the function of those traits and their underlying neuroendocrine mechanisms. Copyright © 2014. Published by Elsevier Inc.

  14. Orm family proteins mediate sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Breslow, David K; Collins, Sean R; Bodenmiller, Bernd

    2010-01-01

    a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression...... or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma....

  15. Endoplasmic reticulum-dependent redox reactions control endoplasmic reticulum-associated degradation and pathogen entry.

    Science.gov (United States)

    Walczak, Christopher P; Bernardi, Kaleena M; Tsai, Billy

    2012-04-15

    Protein misfolding within the endoplasmic reticulum (ER) is managed by an ER quality control system that retro-translocates aberrant proteins into the cytosol for proteasomal destruction. This process, known as ER-associated degradation, utilizes the action of ER redox enzymes to accommodate the disulfide-bonded nature of misfolded proteins. Strikingly, various pathogenic viruses and toxins co-opt these redox components to reach the cytosol during entry. These redox factors thus regulate critical cellular homeostasis and host-pathogen interactions. Recent studies identify specific members of the protein disulfide isomerase (PDI) family, which use their chaperone and catalytic activities, in engaging both misfolded ER proteins and pathogens. The precise molecular mechanism by which a dedicated PDI family member disrupts the disulfide bonds in the misfolded ER proteins and pathogens, as well as how they act to unfold these substrates to promote their ER-to-cytosol membrane transport, remain poorly characterized. How PDI family members distinguish folded versus misfolded ER substrates remains enigmatic. What physical characteristics surrounding a substrate's disulfide bond instruct PDI that it is mispaired or native? For the pathogens, as their disulfide bonds normally serve a critical role in providing physical support, what conformational changes experienced in the host enable their disulfide bonds to be disrupted? A combination of more rigorous biochemical and high-resolution structural studies should begin to address these questions.

  16. The role of thyroid hormone calorigenesis in the redox regulation of gene expression

    Directory of Open Access Journals (Sweden)

    PATRICIA VARELA

    2006-01-01

    Full Text Available Thyroid hormone (TH; 3,3',5-triiodothyronine, T3 is required for the normal function of most tissues, with major effects on 0(2 consumption and metabolic rate. These are due to transcriptional activation of respiratory genes through the interaction of T3-liganded TH receptors with TH response elements or the activation of intermediate factors, with the consequent higher production of reactive 0(2 species (ROS and antioxidant depletion. T3-induced oxidative stress in the liver triggers the redox upregulation of the expression of cytokines (tumor necrosis factor-á [TNF-á], interleukin-10, enzymes (inducible nitric oxide synthase, manganese superoxide dismutase, and anti-apoptotic proteins (Bcl-2, via a cascade initiated by TNF-á produced by Kupffer cells, involving inhibitor of κB phosphorylation and nuclear factor-κB activation. Thus, TH calorigenesis triggers an expression pattern that may represent an adaptive mechanism to re-establish redox homeostasis and promote cell survival under conditions of ROS toxicity secondary to TH-induced oxidative stress. Mechanisms of expression of respiratory and redox-sensitive genes may be functionally integrated, which could be of importance to understand the complexities of TH action and the outcome of thyroid gland dysfunction

  17. Photorespiratory metabolism: genes, mutants, energetics, and redox signaling.

    Science.gov (United States)

    Foyer, Christine H; Bloom, Arnold J; Queval, Guillaume; Noctor, Graham

    2009-01-01

    Photorespiration is a high-flux pathway that operates alongside carbon assimilation in C(3) plants. Because most higher plant species photosynthesize using only the C(3) pathway, photorespiration has a major impact on cellular metabolism, particularly under high light, high temperatures, and CO(2) or water deficits. Although the functions of photorespiration remain controversial, it is widely accepted that this pathway influences a wide range of processes from bioenergetics, photosystem II function, and carbon metabolism to nitrogen assimilation and respiration. Crucially, the photorespiratory pathway is a major source of H(2)O(2) in photosynthetic cells. Through H(2)O(2) production and pyridine nucleotide interactions, photorespiration makes a key contribution to cellular redox homeostasis. In so doing, it influences multiple signaling pathways, particularly those that govern plant hormonal responses controlling growth, environmental and defense responses, and programmed cell death. The potential influence of photorespiration on cell physiology and fate is thus complex and wide ranging. The genes, pathways, and signaling functions of photorespiration are considered here in the context of whole plant biology, with reference to future challenges and human interventions to diminish photorespiratory flux.

  18. Membranes for Redox Flow Battery Applications

    Science.gov (United States)

    Prifti, Helen; Parasuraman, Aishwarya; Winardi, Suminto; Lim, Tuti Mariana; Skyllas-Kazacos, Maria

    2012-01-01

    The need for large scale energy storage has become a priority to integrate renewable energy sources into the electricity grid. Redox flow batteries are considered the best option to store electricity from medium to large scale applications. However, the current high cost of redox flow batteries impedes the wide spread adoption of this technology. The membrane is a critical component of redox flow batteries as it determines the performance as well as the economic viability of the batteries. The membrane acts as a separator to prevent cross-mixing of the positive and negative electrolytes, while still allowing the transport of ions to complete the circuit during the passage of current. An ideal membrane should have high ionic conductivity, low water intake and excellent chemical and thermal stability as well as good ionic exchange capacity. Developing a low cost, chemically stable membrane for redox flow cell batteries has been a major focus for many groups around the world in recent years. This paper reviews the research work on membranes for redox flow batteries, in particular for the all-vanadium redox flow battery which has received the most attention. PMID:24958177

  19. Redox Regulation of Endothelial Cell Fate

    Science.gov (United States)

    Song, Ping; Zou, Ming-Hui

    2014-01-01

    Endothelial cells (ECs) are present throughout blood vessels and have variable roles in both physiological and pathological settings. EC fate is altered and regulated by several key factors in physiological or pathological conditions. Reactive nitrogen species and reactive oxygen species derived from NAD(P)H oxidases, mitochondria, or nitric oxide-producing enzymes are not only cytotoxic but also compose a signaling network in the redox system. The formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. We review the identities, sources, and biological actions of oxidants and reductants produced during EC function or dysfunction. Further, we discuss how ECs shape key redox sensors and examine the biological functions, transcriptional responses, and post-translational modifications evoked by the redox system in ECs. We summarize recent findings regarding the mechanisms by which redox signals regulate the fate of ECs and address the outcome of altered EC fate in health and disease. Future studies will examine if the redox biology of ECs can be targeted in pathophysiological conditions. PMID:24633153

  20. Membranes for redox flow battery applications.

    Science.gov (United States)

    Prifti, Helen; Parasuraman, Aishwarya; Winardi, Suminto; Lim, Tuti Mariana; Skyllas-Kazacos, Maria

    2012-06-19

    The need for large scale energy storage has become a priority to integrate renewable energy sources into the electricity grid. Redox flow batteries are considered the best option to store electricity from medium to large scale applications. However, the current high cost of redox flow batteries impedes the wide spread adoption of this technology. The membrane is a critical component of redox flow batteries as it determines the performance as well as the economic viability of the batteries. The membrane acts as a separator to prevent cross-mixing of the positive and negative electrolytes, while still allowing the transport of ions to complete the circuit during the passage of current. An ideal membrane should have high ionic conductivity, low water intake and excellent chemical and thermal stability as well as good ionic exchange capacity. Developing a low cost, chemically stable membrane for redox flow cell batteries has been a major focus for many groups around the world in recent years. This paper reviews the research work on membranes for redox flow batteries, in particular for the all-vanadium redox flow battery which has received the most attention.

  1. Membranes for Redox Flow Battery Applications

    Directory of Open Access Journals (Sweden)

    Maria Skyllas-Kazacos

    2012-06-01

    Full Text Available The need for large scale energy storage has become a priority to integrate renewable energy sources into the electricity grid. Redox flow batteries are considered the best option to store electricity from medium to large scale applications. However, the current high cost of redox flow batteries impedes the wide spread adoption of this technology. The membrane is a critical component of redox flow batteries as it determines the performance as well as the economic viability of the batteries. The membrane acts as a separator to prevent cross-mixing of the positive and negative electrolytes, while still allowing the transport of ions to complete the circuit during the passage of current. An ideal membrane should have high ionic conductivity, low water intake and excellent chemical and thermal stability as well as good ionic exchange capacity. Developing a low cost, chemically stable membrane for redox flow cell batteries has been a major focus for many groups around the world in recent years. This paper reviews the research work on membranes for redox flow batteries, in particular for the all-vanadium redox flow battery which has received the most attention.

  2. Impact of intermittent fasting on glucose homeostasis.

    Science.gov (United States)

    Varady, Krista A

    2016-07-01

    This article provides an overview of the most recent human trials that have examined the impact of intermittent fasting on glucose homeostasis. Our literature search retrieved one human trial of alternate day fasting, and three trials of Ramadan fasting published in the past 12 months. Current evidence suggests that 8 weeks of alternate day fasting that produces mild weight loss (4% from baseline) has no effect on glucose homeostasis. As for Ramadan fasting, decreases in fasting glucose, insulin, and insulin resistance have been noted after 4 weeks in healthy normal weight individuals with mild weight loss (1-2% from baseline). However, Ramadan fasting may have little impact on glucoregulatory parameters in women with polycystic ovarian syndrome who failed to observe weight loss. Whether intermittent fasting is an effective means of regulating glucose homeostasis remains unclear because of the scarcity of studies in this area. Large-scale, longer-term randomized controlled trials will be required before the use of fasting can be recommended for the prevention and treatment of metabolic diseases.

  3. Regulation of energy homeostasis via GPR120

    Directory of Open Access Journals (Sweden)

    Atsuhiko eIchimura

    2014-07-01

    Full Text Available Free fatty acids (FFAs are fundamental units of key nutrients. FFAs exert various biological functions, depending on the chain length and degree of desaturation. Recent studies have shown that several FFAs act as ligands of G-protein-coupled receptors (GPCRs, activate intracellular signaling and exert physiological functions via these GPCRs. GPR120 (also known as free fatty acid receptor 4, FFAR4 is activated by unsaturated medium- to long-chain FFAs and has a critical role in various physiological homeostasis mechanisms such as incretin hormone secretion, food preference, anti-inflammation and adipogenesis. Recent studies showed that a lipid sensor GPR120 has a key role in sensing dietary fat in white adipose tissue and regulates the whole body energy homeostasis in both humans and rodents. Genetic study in human identified the loss-of-functional mutation of GPR120 associated with obesity and insulin resistance. In addition, dysfunction of GPR120 has been linked as a novel risk factor for diet-induced obesity. This review aims to provide evidence from the recent development in physiological function of GPR120 and discusses its functional roles in regulation of energy homeostasis and its potential as drug targets.

  4. Pseudomonas aeruginosa Trent and zinc homeostasis.

    Science.gov (United States)

    Davies, Corey B; Harrison, Mark D; Huygens, Flavia

    2017-09-01

    Pseudomonas aeruginosa is a Gram-negative pathogen and the major cause of mortality in patients with cystic fibrosis. The mechanisms that P. aeruginosa strains use to regulate intracellular zinc have an effect on infection, antibiotic resistance and the propensity to form biofilms. However, zinc homeostasis in P. aeruginosa strains of variable infectivity has not been compared. In this study, zinc homeostasis in P. aeruginosa Trent, a highly infectious clinical strain, was compared to that of a laboratory P. aeruginosa strain, ATCC27853. Trent was able to tolerate higher concentrations of additional zinc in rich media than ATCC27853. Further, pre-adaptation to additional zinc enhanced the growth of Trent at non-inhibitory concentrations but the impact of pre-adaption on the growth of ATCC27853 under the same conditions was minimal. The results establish clear differences in zinc-induced responses in Trent and ATCC27853, and how zinc homeostasis can be a promising target for the development of novel antimicrobial strategies for P. aeruginosa infection in cystic fibrosis patients. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Auditable safety analysis for the surveillance and maintenance of the REDOX complex

    International Nuclear Information System (INIS)

    Cuneo, V.J.

    1997-02-01

    The Reduction-Oxidation (REDOX) Complex is an inactive surplus facility that contains two former fuel processing facilities (the 202-S Canyon Building and the 233-S Plutonium Concentration Facility) and a number of ancillary support structures. Deactivation started in 1967 and was completed in 1969 when the plant was transferred to surveillance and maintenance (S ampersand M). This document provides the auditable safety analysis (ASA) for the post-deactivation, long-term S ampersand M phase of the above grade structures of the REDOX Complex. The S ampersand M phase is conducted for the following reasons: (1) Maintain confinement of residual inventories of radioactive materials and other contaminants until the facility is ultimately dispositioned, (2) Prevent deterioration of confinement structures, (3) Respond to potential accident conditions requiring response and mitigation, (4) Provide for the safety of workers involved in the S ampersand M phase, and (5) Provide the basis for evaluation and selection of ultimate disposal alternatives. The ability of the existing facilities to withstand the effects of natural phenomena hazard events is evaluated and the active support systems used to maintain ventilation and/or prevent the spread of contamination are described. This auditable safety analysis document evaluates the routinely required S ampersand M activities (i.e., the S ampersand M of facility barriers, equipment, structures, and postings [including repair and upgrade]; measures to identify, remove, or repair damaged asbestos; measures to identify, remove, or appropriately manage existing containers of hazardous substances; and the performance of spill response measures as needed). For the REDOX Complex, the movement of cell cover blocks is also evaluated, as D-cell cover block was removed a number of years ago and should be replaced. The type and nature of the hazards presented by the REDOX Complex and the REDOX-specific controls required to maintain these

  6. Redox-based epigenetic status in drug addiction: a potential contributor to gene priming and a mechanistic rationale for metabolic intervention.

    Science.gov (United States)

    Trivedi, Malav S; Deth, Richard

    2014-01-01

    Alcohol and other drugs of abuse, including psychostimulants and opioids, can induce epigenetic changes: a contributing factor for drug addiction, tolerance, and associated withdrawal symptoms. DNA methylation is a major epigenetic mechanism and it is one of more than 200 methylation reactions supported by methyl donor S-adenosylmethionine (SAM). Levels of SAM are controlled by cellular redox status via the folate and vitamin B12-dependent enzyme methionine synthase (MS). For example, under oxidative conditions MS is inhibited, diverting its substrate homocysteine (HCY) to the trans sulfuration pathway. Alcohol, dopamine, and morphine, can alter intracellular levels of glutathione (GSH)-based cellular redox status, subsequently affecting SAM levels and DNA methylation status. Here, existing evidence is presented in a coherent manner to propose a novel hypothesis implicating the involvement of redox-based epigenetic changes in drug addiction. Further, we discuss how a "gene priming" phenomenon can contribute to the maintenance of redox and methylation status homeostasis under various stimuli including drugs of abuse. Additionally, a new mechanistic rationale for the use of metabolic interventions/redox-replenishers as symptomatic treatment of alcohol and other drug addiction and associated withdrawal symptoms is also provided. Hence, the current review article strengthens the hypothesis that neuronal metabolism has a critical bidirectional coupling with epigenetic changes in drug addiction exemplified by the link between redox-based metabolic changes and resultant epigenetic consequences under the effect of drugs of abuse.

  7. New Approach in Translational Medicine: Effects of Electrolyzed Reduced Water (ERW on NF-κB/iNOS Pathway in U937 Cell Line under Altered Redox State

    Directory of Open Access Journals (Sweden)

    Sara Franceschelli

    2016-09-01

    Full Text Available It is known that increased levels of reactive oxygen species (ROS and reactive nitrogen species (RNS can exert harmful effects, altering the cellular redox state. Electrolyzed Reduced Water (ERW produced near the cathode during water electrolysis exhibits high pH, high concentration of dissolved hydrogen and an extremely negative redox potential. Several findings indicate that ERW had the ability of a scavenger free radical, which results from hydrogen molecules with a high reducing ability and may participate in the redox regulation of cellular function. We investigated the effect of ERW on H2O2-induced U937 damage by evaluating the modulation of redox cellular state. Western blotting and spectrophotometrical analysis showed that ERW inhibited oxidative stress by restoring the antioxidant capacity of superoxide dismutase, catalase and glutathione peroxidase. Consequently, ERW restores the ability of the glutathione reductase to supply the cell of an important endogenous antioxidant, such as GSH, reversing the inhibitory effect of H2O2 on redox balance of U937 cells. Therefore, this means a reduction of cytotoxicity induced by peroxynitrite via a downregulation of the NF-κB/iNOS pathway and could be used as an antioxidant for preventive and therapeutic application. In conclusion, ERW can protect the cellular redox balance, reducing the risk of several diseases with altered cellular homeostasis such as inflammation.

  8. Reaction-based small-molecule fluorescent probes for dynamic detection of ROS and transient redox changes in living cells and small animals.

    Science.gov (United States)

    Lü, Rui

    2017-09-01

    Dynamic detection of transient redox changes in living cells and animals has broad implications for human health and disease diagnosis, because intracellular redox homeostasis regulated by reactive oxygen species (ROS) plays important role in cell functions, normal physiological functions and some serious human diseases (e.g., cancer, Alzheimer's disease, diabetes, etc.) usually have close relationship with the intracellular redox status. Small-molecule ROS-responsive fluorescent probes can act as powerful tools for dynamic detection of ROS and redox changes in living cells and animals through fluorescence imaging techniques; and great advances have been achieved recently in the design and synthesis of small-molecule ROS-responsive fluorescent probes. This article highlights up-to-date achievements in designing and using the reaction-based small-molecule fluorescent probes (with high sensitivity and selectivity to ROS and redox cycles) in the dynamic detection of ROS and transient redox changes in living cells and animals through fluorescence imaging. Copyright © 2017. Published by Elsevier Ltd.

  9. Redox-based Epigenetic status in Drug Addiction: Potential mediator of drug-induced gene priming phenomenon and use of metabolic intervention for symptomatic treatment in drug addiction.

    Directory of Open Access Journals (Sweden)

    Malav Suchin Trivedi

    2015-01-01

    Full Text Available Alcohol and other drugs of abuse, including psychostimulants and opioids, can induce epigenetic changes: a contributing factor for drug addiction, tolerance and associated withdrawal symptoms. DNA methylation is the major epigenetic mechanism and it is one of more than 200 methylation reactions supported by methyl donor S-adenosylmethionine (SAM. The levels of SAM are controlled by cellular redox status via the folate and vitamin B12-dependent enzyme methionine synthase (MS, for example; under oxidative conditions MS is inhibited, diverting its substrate homocysteine (HCY to the transsulfuration pathway. Alcohol, dopamine and morphine, can alter intracellular levels of glutathione (GSH-based cellular redox status, subsequently affecting S-adenosylmethionine (SAM levels and DNA methylation status. In this discussion, we compile this and other existing evidence in a coherent manner to present a novel hypothesis implicating the involvement of redox-based epigenetic changes in drug addiction. Next, we also discuss how gene priming phenomenon can contribute to maintenance of redox and methylation status homeostasis under various stimuli including drugs of abuse. Lastly, based on our hypothesis and some preliminary evidence, we discuss a mechanistic explanation for use of metabolic interventions / redox-replenishers as symptomatic treatment of alcohol addiction and associated withdrawal symptoms. Hence, the current review article strengthens the hypothesis that neuronal metabolism has a critical bidirectional coupling with epigenetic changes in drug addiction and we support this claim via exemplifying the link between redox-based metabolic changes and resultant epigenetic consequences under the effect of drugs of abuse.

  10. Maintainability effectiveness evaluations and enhancement

    International Nuclear Information System (INIS)

    Seminara, J.L.

    1985-01-01

    In the mid-seventies EPRI initiated a research project to review the human factors aspects of nuclear power plant control rooms. In the course of investigating operator-control room interfaces in five operational control rooms, it became evident that many plant outages had either been caused or prolonged by human factors problems associated with maintenance activities. Consequently, as one of several follow-on projects, EPRI sponsored a review of nine power plants (five nuclear and four fossil) to examine the human factors aspects of plant maintainability. This survey revealed a wide variety of generic human factors problems that could negatively impact the effectiveness of plant maintenance personnel. It was clear that plant maintainability features deserved no less attention to human factors concerns than the operational features of the control room. This paper describes subsequent EPRI-initiated efforts to assist the utilities in conducting self-reviews of maintainability effectiveness and effect needed enhancements

  11. FIG4 regulates lysosome membrane homeostasis independent of phosphatase function.

    Science.gov (United States)

    Bharadwaj, Rajnish; Cunningham, Kathleen M; Zhang, Ke; Lloyd, Thomas E

    2016-02-15

    FIG4 is a phosphoinositide phosphatase that is mutated in several diseases including Charcot-Marie-Tooth Disease 4J (CMT4J) and Yunis-Varon syndrome (YVS). To investigate the mechanism of disease pathogenesis, we generated Drosophila models of FIG4-related diseases. Fig4 null mutant animals are viable but exhibit marked enlargement of the lysosomal compartment in muscle cells and neurons, accompanied by an age-related decline in flight ability. Transgenic animals expressing Drosophila Fig4 missense mutations corresponding to human pathogenic mutations can partially rescue lysosomal expansion phenotypes, consistent with these mutations causing decreased FIG4 function. Interestingly, Fig4 mutations predicted to inactivate FIG4 phosphatase activity rescue lysosome expansion phenotypes, and mutations in the phosphoinositide (3) phosphate kinase Fab1 that performs the reverse enzymatic reaction also causes a lysosome expansion phenotype. Since FIG4 and FAB1 are present together in the same biochemical complex, these data are consistent with a model in which FIG4 serves a phosphatase-independent biosynthetic function that is essential for lysosomal membrane homeostasis. Lysosomal phenotypes are suppressed by genetic inhibition of Rab7 or the HOPS complex, demonstrating that FIG4 functions after endosome-to-lysosome fusion. Furthermore, disruption of the retromer complex, implicated in recycling from the lysosome to Golgi, does not lead to similar phenotypes as Fig4, suggesting that the lysosomal defects are not due to compromised retromer-mediated recycling of endolysosomal membranes. These data show that FIG4 plays a critical noncatalytic function in maintaining lysosomal membrane homeostasis, and that this function is disrupted by mutations that cause CMT4J and YVS. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. The Xenobiotic Transporter Mdr1 Enforces T Cell Homeostasis in the Presence of Intestinal Bile Acids.

    Science.gov (United States)

    Cao, Wei; Kayama, Hisako; Chen, Mei Lan; Delmas, Amber; Sun, Amy; Kim, Sang Yong; Rangarajan, Erumbi S; McKevitt, Kelly; Beck, Amanda P; Jackson, Cody B; Crynen, Gogce; Oikonomopoulos, Angelos; Lacey, Precious N; Martinez, Gustavo J; Izard, Tina; Lorenz, Robin G; Rodriguez-Palacios, Alex; Cominelli, Fabio; Abreu, Maria T; Hommes, Daniel W; Koralov, Sergei B; Takeda, Kiyoshi; Sundrud, Mark S

    2017-12-19

    CD4 + T cells are tightly regulated by microbiota in the intestine, but whether intestinal T cells interface with host-derived metabolites is less clear. Here, we show that CD4 + T effector (Teff) cells upregulated the xenobiotic transporter, Mdr1, in the ileum to maintain homeostasis in the presence of bile acids. Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn's disease-like ileitis following transfer into Rag1 -/- hosts. Mdr1 mitigated oxidative stress and enforced homeostasis in Teff cells exposed to conjugated bile acids (CBAs), a class of liver-derived emulsifying agents that actively circulate through the ileal mucosa. Blocking ileal CBA reabsorption in transferred Rag1 -/- mice restored Mdr1-deficient Teff cell homeostasis and attenuated ileitis. Further, a subset of ileal Crohn's disease patients displayed MDR1 loss of function. Together, these results suggest that coordinated interaction between mucosal Teff cells and CBAs in the ileum regulate intestinal immune homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Enteric Virome Sensing-Its Role in Intestinal Homeostasis and Immunity.

    Science.gov (United States)

    Metzger, Rebecca N; Krug, Anne B; Eisenächer, Katharina

    2018-03-23

    Pattern recognition receptors (PRRs) sensing commensal microorganisms in the intestine induce tightly controlled tonic signaling in the intestinal mucosa, which is required to maintain intestinal barrier integrity and immune homeostasis. At the same time, PRR signaling pathways rapidly trigger the innate immune defense against invasive pathogens in the intestine. Intestinal epithelial cells and mononuclear phagocytes in the intestine and the gut-associated lymphoid tissues are critically involved in sensing components of the microbiome and regulating immune responses in the intestine to sustain immune tolerance against harmless antigens and to prevent inflammation. These processes have been mostly investigated in the context of the bacterial components of the microbiome so far. The impact of viruses residing in the intestine and the virus sensors, which are activated by these enteric viruses, on intestinal homeostasis and inflammation is just beginning to be unraveled. In this review, we will summarize recent findings indicating an important role of the enteric virome for intestinal homeostasis as well as pathology when the immune system fails to control the enteric virome. We will provide an overview of the virus sensors and signaling pathways, operative in the intestine and the mononuclear phagocyte subsets, which can sense viruses and shape the intestinal immune response. We will discuss how these might interact with resident enteric viruses directly or in context with the bacterial microbiome to affect intestinal homeostasis.

  14. A Quick-responsive DNA Nanotechnology Device for Bio-molecular Homeostasis Regulation.

    Science.gov (United States)

    Wu, Songlin; Wang, Pei; Xiao, Chen; Li, Zheng; Yang, Bing; Fu, Jieyang; Chen, Jing; Wan, Neng; Ma, Cong; Li, Maoteng; Yang, Xiangliang; Zhan, Yi

    2016-08-10

    Physiological processes such as metabolism, cell apoptosis and immune responses, must be strictly regulated to maintain their homeostasis and achieve their normal physiological functions. The speed with which bio-molecular homeostatic regulation occurs directly determines the ability of an organism to adapt to conditional changes. To produce a quick-responsive regulatory system that can be easily utilized for various types of homeostasis, a device called nano-fingers that facilitates the regulation of physiological processes was constructed using DNA origami nanotechnology. This nano-fingers device functioned in linked open and closed phases using two types of DNA tweezers, which were covalently coupled with aptamers that captured specific molecules when the tweezer arms were sufficiently close. Via this specific interaction mechanism, certain physiological processes could be simultaneously regulated from two directions by capturing one biofactor and releasing the other to enhance the regulatory capacity of the device. To validate the universal application of this device, regulation of the homeostasis of the blood coagulant thrombin was attempted using the nano-fingers device. It was successfully demonstrated that this nano-fingers device achieved coagulation buffering upon the input of fuel DNA. This nano-device could also be utilized to regulate the homeostasis of other types of bio-molecules.

  15. A new vesicle trafficking regulator CTL1 plays a crucial role in ion homeostasis.

    Science.gov (United States)

    Gao, Yi-Qun; Chen, Jiu-Geng; Chen, Zi-Ru; An, Dong; Lv, Qiao-Yan; Han, Mei-Ling; Wang, Ya-Ling; Salt, David E; Chao, Dai-Yin

    2017-12-01

    Ion homeostasis is essential for plant growth and environmental adaptation, and maintaining ion homeostasis requires the precise regulation of various ion transporters, as well as correct root patterning. However, the mechanisms underlying these processes remain largely elusive. Here, we reported that a choline transporter gene, CTL1, controls ionome homeostasis by regulating the secretory trafficking of proteins required for plasmodesmata (PD) development, as well as the transport of some ion transporters. Map-based cloning studies revealed that CTL1 mutations alter the ion profile of Arabidopsis thaliana. We found that the phenotypes associated with these mutations are caused by a combination of PD defects and ion transporter misregulation. We also established that CTL1 is involved in regulating vesicle trafficking and is thus required for the trafficking of proteins essential for ion transport and PD development. Characterizing choline transporter-like 1 (CTL1) as a new regulator of protein sorting may enable researchers to understand not only ion homeostasis in plants but also vesicle trafficking in general.

  16. Enteric Virome Sensing—Its Role in Intestinal Homeostasis and Immunity

    Directory of Open Access Journals (Sweden)

    Rebecca N. Metzger

    2018-03-01

    Full Text Available Pattern recognition receptors (PRRs sensing commensal microorganisms in the intestine induce tightly controlled tonic signaling in the intestinal mucosa, which is required to maintain intestinal barrier integrity and immune homeostasis. At the same time, PRR signaling pathways rapidly trigger the innate immune defense against invasive pathogens in the intestine. Intestinal epithelial cells and mononuclear phagocytes in the intestine and the gut-associated lymphoid tissues are critically involved in sensing components of the microbiome and regulating immune responses in the intestine to sustain immune tolerance against harmless antigens and to prevent inflammation. These processes have been mostly investigated in the context of the bacterial components of the microbiome so far. The impact of viruses residing in the intestine and the virus sensors, which are activated by these enteric viruses, on intestinal homeostasis and inflammation is just beginning to be unraveled. In this review, we will summarize recent findings indicating an important role of the enteric virome for intestinal homeostasis as well as pathology when the immune system fails to control the enteric virome. We will provide an overview of the virus sensors and signaling pathways, operative in the intestine and the mononuclear phagocyte subsets, which can sense viruses and shape the intestinal immune response. We will discuss how these might interact with resident enteric viruses directly or in context with the bacterial microbiome to affect intestinal homeostasis.

  17. Developing and maintaining nuclear competencies

    International Nuclear Information System (INIS)

    Gobert, C.

    2004-01-01

    The paper discusses the following aspects on the nuclear knowledge management: assimilation of knowledge management, recognition of the nuclear specificity, attracting young talents. Another feature which, possibly, differentiates nuclear from other high-tech industries is that time constraints in some nuclear development may very well exceed the duration of a generation of professionals. That means, not only maintaining scientific and technical knowledge, which, as a minimum, leads to maintain: a rigorous supervision of human resources in quality and quantity; anticipatory planning of human resources, with a special focus on succession planning concerning expertise positions; a steady and continuous effort in training and retraining programs. Maintaining the safety culture is also one of the major managerial duties. Taking full account of the nuclear specificity in knowledge maintenance and development in the AREVA group, requests a multifunctional approach, which combines efforts of Research and Innovation, and Human Resources departments, plus the group Nuclear inspectorate. It is acknowledged that the industry, basically, would readily rely on the capabilities of the academic world and research centers in ensuring that training and education in nuclear science and technologies are attuned to the evolving needs of the industry, in maintaining the proper educational programs and in fostering fruitful cooperations between them

  18. [Maintaining patients' autonomy at home].

    Science.gov (United States)

    Niang, Bénédicte; Coudre, Jean Pierre

    2015-01-01

    To maintain the flow of hospital discharges, the patient's return home with support from a home nursing service is important. If any difficulties are identified, there are various programmes or good practices which can be put into place. The future law on adapting society to ageing also comprises a scheme combining home assistance and nursing care.

  19. Redox interplay between mitochondria and peroxisomes

    Directory of Open Access Journals (Sweden)

    Celien eLismont

    2015-05-01

    Full Text Available Reduction-oxidation or ‘redox’ reactions are an integral part of a broad range of cellular processes such as gene expression, energy metabolism, protein import and folding, and autophagy. As many of these processes are intimately linked with cell fate decisions, transient or chronic changes in cellular redox equilibrium are likely to contribute to the initiation and progression of a plethora of human diseases. Since a long time, it is known that mitochondria are major players in redox regulation and signaling. More recently, it has become clear that also peroxisomes have the capacity to impact redox-linked physiological processes. To serve this function, peroxisomes cooperate with other organelles, including mitochondria. This review provides a comprehensive picture of what is currently known about the redox interplay between mitochondria and peroxisomes in mammals. We first outline the pro- and antioxidant systems of both organelles and how they may function as redox signaling nodes. Next, we critically review and discuss emerging evidence that peroxisomes and mitochondria share an intricate redox-sensitive relationship and cooperate in cell fate decisions. Key issues include possible physiological roles, messengers, and mechanisms. We also provide examples of how data mining of publicly-available datasets from ‘omics’ technologies can be a powerful means to gain additional insights into potential redox signaling pathways between peroxisomes and mitochondria. Finally, we highlight the need for more studies that seek to clarify the mechanisms of how mitochondria may act as dynamic receivers, integrators, and transmitters of peroxisome-derived mediators of oxidative stress. The outcome of such studies may open up exciting new avenues for the community of researchers working on cellular responses to organelle-derived oxidative stress, a research field in which the role of peroxisomes is currently highly underestimated and an issue of

  20. Type I interferon is critical for the homeostasis and functional maturation of type 3 γδ T cells

    DEFF Research Database (Denmark)

    Agerholm, Rasmus; Kadekar, Darshana Dattatraya; Rizk, John

    2017-01-01

    Type I IFN (IFN-I) is highly expressed during viral infection and many autoimmune pathologies such as SLE and psoriasis. In addition, IFN-I is important to maintain the homeostasis of a number of different immune populations. Our aim was to identify whether IFN-I regulates type 3 γδ T (γδT3) cells...... behavior. Such γδT3 anergy is characterized by failure to induce skin inflammation and unresponsiveness to cytokine stimuli. Moreover, IFNAR deficient mice display deregulated γδT3homeostasis due to a neonatal maturation defect. In conclusion, our data show that tonic type I IFN signaling during neonatal...

  1. A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology

    Directory of Open Access Journals (Sweden)

    Michelle T. Burstein

    2014-01-01

    Full Text Available A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.

  2. Endoplasmic reticulum redox state is not perturbed by pharmacological or pathological endoplasmic reticulum stress in live pancreatic β-cells.

    Directory of Open Access Journals (Sweden)

    Irmgard Schuiki

    Full Text Available Accumulation of unfolded, misfolded and aggregated proteins in the endoplasmic reticulum (ER causes ER stress. ER stress can result from physiological situations such as acute increases in secretory protein biosynthesis or pathological conditions that perturb ER homeostasis such as alterations in the ER redox state. Here we monitored ER redox together with transcriptional output of the Unfolded Protein Response (UPR in INS-1 insulinoma cells stably expressing eroGFP (ER-redox-sensor and mCherry protein driven by a GRP78 promoter (UPR-sensor. Live cell imaging, flow cytometry and biochemical characterization were used to examine these parameters in response to various conditions known to induce ER stress. As expected, treatment of the cells with the reducing agent dithiothreitol caused a decrease in the oxidation state of the ER accompanied by an increase in XBP-1 splicing. Unexpectedly however, other treatments including tunicamycin, thapsigargin, DL-homocysteine, elevated free fatty acids or high glucose had essentially no influence on the ER redox state, despite inducing ER stress. Comparable results were obtained with dispersed rat islet cells expressing eroGFP. Thus, unlike in yeast cells, ER stress in pancreatic β-cells is not associated with a more reducing ER environment.

  3. The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine.

    Science.gov (United States)

    Cortese-Krott, Miriam M; Koning, Anne; Kuhnle, Gunter G C; Nagy, Peter; Bianco, Christopher L; Pasch, Andreas; Wink, David A; Fukuto, Jon M; Jackson, Alan A; van Goor, Harry; Olson, Kenneth R; Feelisch, Martin

    2017-10-01

    Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level. To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses. Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 00, 000-000.

  4. Electron Pathways through Erythrocyte Plasma Membrane in Human Physiology and Pathology: Potential Redox Biomarker?

    OpenAIRE

    Matteucci, Elena; Giampietro, Ottavio

    2007-01-01

    Erythrocytes are involved in the transport of oxygen and carbon dioxide in the body. Since pH is the influential factor in the Bohr-Haldane effect, pHi is actively maintained via secondary active transports Na+/H+ exchange and HC3 -/Cl- anion exchanger. Because of the redox properties of the iron, hemoglobin generates reactive oxygen species and thus, the human erythrocyte is constantly exposed to oxidative damage. Although the adult erythrocyte lacks protein synthesis and cannot restore dama...

  5. Characterization of Redox properties of humic materials

    International Nuclear Information System (INIS)

    Choppin, G.R.

    1995-01-01

    An important aspect of humic materials is the presence of stable free radicals as shown by the width of 1 H-NMR lines of humic acid in solution as well as ESR spectra of solid samples. Presumably, these are due to quinohdrone functional groups in the humic structure. These free radicals are assumed to be a source of the redox effects of humics in metal cations. Phenolic groups have also been proposed as a source of reduction potential in these substances. The reduction potential of humic material is 0.5-0.7 V (vs. the normal hydrogen electrode). In addition to this inherent redox property, humics undergo photolysis by sunlight in surface waters which results in the production of hydrogen peroxide. The latter can also result in redox reactions with metal cations. Such direct and indirect redox capability can have significant effects on the migration of reducible cations. Studies of the reduction of hexavalent actinide cations by humic acid showed the reactions Np O 2 2+ -> Np O 2 + (E 1/2 0 = 1.47 V) and Pu O 2 2+ -> Pu +4 (E 1/2 0 = 1.04 V) while U O 2 2+ was not reduced. The reduction of plutonium in sea water by humics is discussed. Evidence of the effects of redox by humic material on metal cations in natural waters and sediments are also reviewed. (authors). 16 refs., 2 figs., 1 tab

  6. De Novo Construction of Redox Active Proteins.

    Science.gov (United States)

    Moser, C C; Sheehan, M M; Ennist, N M; Kodali, G; Bialas, C; Englander, M T; Discher, B M; Dutton, P L

    2016-01-01

    Relatively simple principles can be used to plan and construct de novo proteins that bind redox cofactors and participate in a range of electron-transfer reactions analogous to those seen in natural oxidoreductase proteins. These designed redox proteins are called maquettes. Hydrophobic/hydrophilic binary patterning of heptad repeats of amino acids linked together in a single-chain self-assemble into 4-alpha-helix bundles. These bundles form a robust and adaptable frame for uncovering the default properties of protein embedded cofactors independent of the complexities introduced by generations of natural selection and allow us to better understand what factors can be exploited by man or nature to manipulate the physical chemical properties of these cofactors. Anchoring of redox cofactors such as hemes, light active tetrapyrroles, FeS clusters, and flavins by His and Cys residues allow cofactors to be placed at positions in which electron-tunneling rates between cofactors within or between proteins can be predicted in advance. The modularity of heptad repeat designs facilitates the construction of electron-transfer chains and novel combinations of redox cofactors and new redox cofactor assisted functions. Developing de novo designs that can support cofactor incorporation upon expression in a cell is needed to support a synthetic biology advance that integrates with natural bioenergetic pathways. © 2016 Elsevier Inc. All rights reserved.

  7. Redox-flow battery of actinide complexes

    International Nuclear Information System (INIS)

    Yamamura, Tomoo; Shiokawa, Yoshinobu

    2006-01-01

    Np battery and U battery were developed. We suggested that Np redox-flow battery should be (-)|Np 3+ ,Np 4+ ||NpO 2 + ,NpO 2 2+ |(+), and U battery (-)|[U III T 2 ] - ,[U IV T 2 ] 0 ||[U V O 2 T] - ,[U VI O 2 T] 0 |(+). The electromotive force at 50 % charge of Np and U battery is 1.10 V and 1.04 V, respectively. The energy efficiency of 70 mA/cm 2 of Np and U battery shows 99 % and 98 %, respectively. V redox-flow battery, electrode reactions of An battery, Np battery, U battery and future of U battery are described. The concept of V redox-flow battery, comparison of energy efficiency of Np, U and V battery, oxidation state and ionic species of 3d transition metals and main An, Purbe diagram of Np and U aqueous solution, shift of redox potential of β-diketones by pKa, and specifications of three redox-flow batteries are reported. (S.Y.)

  8. Maintaining steam/condensate lines

    International Nuclear Information System (INIS)

    Russum, S.A.

    1992-01-01

    Steam and condensate systems must be maintained with the same diligence as the boiler itself. Unfortunately, they often are not. The water treatment program, critical to keeping the boiler at peak efficiency and optimizing operating life, should not stop with the boiler. The program must encompass the steam and condensate system as well. A properly maintained condensate system maximizes condensate recovery, which is a cost-free energy source. The fuel needed to turn the boiler feedwater into steam has already been provided. Returning the condensate allows a significant portion of that fuel cost to be recouped. Condensate has a high heat content. Condensate is a readily available, economical feedwater source. Properly treated, it is very pure. Condensate improves feedwater quality and reduces makeup water demand and pretreatment costs. Higher quality feedwater means more reliable boiler operation

  9. Disturbance maintains alternative biome states.

    Science.gov (United States)

    Dantas, Vinícius de L; Hirota, Marina; Oliveira, Rafael S; Pausas, Juli G

    2016-01-01

    Understanding the mechanisms controlling the distribution of biomes remains a challenge. Although tropical biome distribution has traditionally been explained by climate and soil, contrasting vegetation types often occur as mosaics with sharp boundaries under very similar environmental conditions. While evidence suggests that these biomes are alternative states, empirical broad-scale support to this hypothesis is still lacking. Using community-level field data and a novel resource-niche overlap approach, we show that, for a wide range of environmental conditions, fire feedbacks maintain savannas and forests as alternative biome states in both the Neotropics and the Afrotropics. In addition, wooded grasslands and savannas occurred as alternative grassy states in the Afrotropics, depending on the relative importance of fire and herbivory feedbacks. These results are consistent with landscape scale evidence and suggest that disturbance is a general factor driving and maintaining alternative biome states and vegetation mosaics in the tropics. © 2015 John Wiley & Sons Ltd/CNRS.

  10. Maintaining protein composition in cilia.

    Science.gov (United States)

    Stephen, Louise A; Elmaghloob, Yasmin; Ismail, Shehab

    2017-12-20

    The primary cilium is a sensory organelle that is vital in regulating several signalling pathways. Unlike most organelles cilia are open to the rest of the cell, not enclosed by membranes. The distinct protein composition is crucial to the function of cilia and many signalling proteins and receptors are specifically concentrated within distinct compartments. To maintain this composition, a mechanism is required to deliver proteins to the cilium whilst another must counter the entropic tendency of proteins to distribute throughout the cell. The combination of the two mechanisms should result in the concentration of ciliary proteins to the cilium. In this review we will look at different cellular mechanisms that play a role in maintaining the distinct composition of cilia, including regulation of ciliary access and trafficking of ciliary proteins to, from and within the cilium.

  11. Improving versus maintaining nuclear safety

    International Nuclear Information System (INIS)

    2002-01-01

    The concept of improving nuclear safety versus maintaining it has been discussed at a number of nuclear regulators meetings in recent years. National reports have indicated that there are philosophical differences between NEA member countries about whether their regulatory approaches require licensees to continuously improve nuclear safety or to continuously maintain it. It has been concluded that, while the actual level of safety achieved in all member countries is probably much the same, this is difficult to prove in a quantitative way. In practice, all regulatory approaches require improvements to be made to correct deficiencies and when otherwise warranted. Based on contributions from members of the NEA Committee on Nuclear Regulatory Activities (CNRA), this publication provides an overview of current nuclear regulatory philosophies and approaches, as well as insights into a selection of public perception issues. This publication's intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

  12. The commensal microbiota drives immune homeostasis

    Directory of Open Access Journals (Sweden)

    Marie-Claire eArrieta

    2012-03-01

    Full Text Available For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use to keep our immune system healthy, as opposed to trying to correct the immune imbalances caused by dysbiosis, may prove to be a more astute and efficient way of treating immune-mediated disease.

  13. Diuretics and disorders of calcium homeostasis.

    Science.gov (United States)

    Grieff, Marvin; Bushinsky, David A

    2011-11-01

    Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. BCAA Metabolism and NH3 Homeostasis.

    Science.gov (United States)

    Conway, M E; Hutson, S M

    2016-01-01

    The branched chain amino acids (BCAA) are essential amino acids required not only for growth and development, but also as nutrient signals and as nitrogen donors to neurotransmitter synthesis and glutamate/glutamine cycling. Transamination and oxidative decarboxylation of the BCAAs are catalysed by the branched-chain aminotransferase proteins (BCATm, mitochondrial and BCATc, cytosolic) and the branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC), respectively. These proteins show tissue, cell compartmentation, and protein-protein interactions, which call for substrate shuttling or channelling and nitrogen transfer for oxidation to occur. Efficient regulation of these pathways is mediated through the redox environment and phosphorylation in response to dietary and hormonal stimuli. The wide distribution of these proteins allows for effective BCAA utilisation. We discuss how BCAT, BCKDC, and glutamate dehydrogenase operate in supramolecular complexes, allowing for efficient channelling of substrates. The role of BCAAs in brain metabolism is highlighted in rodent and human brain, where differential expression of BCATm indicates differences in nitrogen metabolism between species. Finally, we introduce a new role for BCAT, where a change in function is triggered by oxidation of its redox-active switch. Our understanding of how BCAA metabolism and nitrogen transfer is regulated is important as many studies now point to BCAA metabolic dysregulation in metabolic and neurodegenerative conditions.

  15. REDOX IMAGING OF THE p53-DEPENDENT MITOCHONDRIAL REDOX STATE IN COLON CANCER EX VIVO

    Science.gov (United States)

    XU, HE N.; FENG, MIN; MOON, LILY; DOLLOFF, NATHAN; EL-DEIRY, WAFIK; LI, LIN Z.

    2015-01-01

    The mitochondrial redox state and its heterogeneity of colon cancer at tissue level have not been previously reported. Nor has how p53 regulates mitochondrial respiration been measured at (deep) tissue level, presumably due to the unavailability of the technology that has sufficient spatial resolution and tissue penetration depth. Our prior work demonstrated that the mitochondrial redox state and its intratumor heterogeneity is associated with cancer aggressiveness in human melanoma and breast cancer in mouse models, with the more metastatic tumors exhibiting localized regions of more oxidized redox state. Using the Chance redox scanner with an in-plane spatial resolution of 200 μm, we imaged the mitochondrial redox state of the wild-type p53 colon tumors (HCT116 p53 wt) and the p53-deleted colon tumors (HCT116 p53−/−) by collecting the fluorescence signals of nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins [Fp, including flavin adenine dinucleotide (FAD)] from the mouse xenografts snap-frozen at low temperature. Our results show that: (1) both tumor lines have significant degree of intratumor heterogeneity of the redox state, typically exhibiting a distinct bi-modal distribution that either correlates with the spatial core–rim pattern or the “hot/cold” oxidation-reduction patches; (2) the p53−/− group is significantly more heterogeneous in the mitochondrial redox state and has a more oxidized tumor core compared to the p53 wt group when the tumor sizes of the two groups are matched; (3) the tumor size dependence of the redox indices (such as Fp and Fp redox ratio) is significant in the p53−/− group with the larger ones being more oxidized and more heterogeneous in their redox state, particularly more oxidized in the tumor central regions; (4) the H&E staining images of tumor sections grossly correlate with the redox images. The present work is the first to reveal at the submillimeter scale the intratumor heterogeneity pattern

  16. Exercise improves mitochondrial and redox-regulated stress responses in the elderly: better late than never!

    Science.gov (United States)

    Cobley, James N; Moult, Peter R; Burniston, Jatin G; Morton, James P; Close, Graeme L

    2015-04-01

    Ageing is associated with several physiological declines to both the cardiovascular (e.g. reduced aerobic capacity) and musculoskeletal system (muscle function and mass). Ageing may also impair the adaptive response of skeletal muscle mitochondria and redox-regulated stress responses to an acute exercise bout, at least in mice and rodents. This is a functionally important phenomenon, since (1) aberrant mitochondrial and redox homeostasis are implicated in the pathophysiology of musculoskeletal ageing and (2) the response to repeated exercise bouts promotes exercise adaptations and some of these adaptations (e.g. improved aerobic capacity and exercise-induced mitochondrial remodelling) offset age-related physiological decline. Exercise-induced mitochondrial remodelling is mediated by upstream signalling events that converge on downstream transcriptional co-factors and factors that orchestrate a co-ordinated nuclear and mitochondrial transcriptional response associated with mitochondrial remodelling. Recent translational human investigations have demonstrated similar exercise-induced mitochondrial signalling responses in older compared with younger skeletal muscle, regardless of training status. This is consistent with data indicating normative mitochondrial remodelling responses to long-term exercise training in the elderly. Thus, human ageing is not accompanied by diminished mitochondrial plasticity to acute and chronic exercise stimuli, at least for the signalling pathways measured to date. Exercise-induced increases in reactive oxygen and nitrogen species promote an acute redox-regulated stress response that manifests as increased heat shock protein and antioxidant enzyme content. In accordance with previous reports in rodents and mice, it appears that sedentary ageing is associated with a severely attenuated exercise-induced redox stress response that might be related to an absent redox signal. In this regard, regular exercise training affords some protection

  17. Viral (hepatitis C virus, hepatitis B virus, HIV) persistence and immune homeostasis

    Science.gov (United States)

    Zhou, Yun; Zhang, Ying; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhan S

    2014-01-01

    Immune homeostasis is a host characteristic that maintains biological balance within a host. Humans have evolved many host defence mechanisms that ensure the survival of individuals upon encountering a pathogenic infection, with recovery or persistence from a viral infection being determined by both viral factors and host immunity. Chronic viral infections, such as hepatitis B virus, hepatitis C virus and HIV, often result in chronic fluctuating viraemia in the face of host cellular and humoral immune responses, which are dysregulated by multi-faceted mechanisms that are incompletely understood. This review attempts to illuminate the mechanisms involved in this process, focusing on immune homeostasis in the setting of persistent viral infection from the aspects of host defence mechanism, including interferon-stimulated genes, apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3), autophagy and interactions of various immune cells, cytokines and regulatory molecules. PMID:24965611

  18. MicroRNA-orchestrated pathophysiologic control in gut homeostasis and inflammation.

    Science.gov (United States)

    Lee, Juneyoung; Park, Eun Jeong; Kiyono, Hiroshi

    2016-05-01

    The intestine represents the largest and most elaborate immune system organ, in which dynamic and reciprocal interplay among numerous immune and epithelial cells, commensal microbiota, and external antigens contributes to establishing both homeostatic and pathologic conditions. The mechanisms that sustain gut homeostasis are pivotal in maintaining gut health in the harsh environment of the gut lumen. Intestinal epithelial cells are critical players in creating the mucosal platform for interplay between host immune cells and luminal stress inducers. Thus, knowledge of the epithelial interface between immune cells and the luminal environment is a prerequisite for a better understanding of gut homeostasis and pathophysiologies such as inflammation. In this review, we explore the importance of the epithelium in limiting or promoting gut inflammation (e.g., inflammatory bowel disease). We also introduce recent findings on how small RNAs such as microRNAs orchestrate pathophysiologic gene regulation. [BMB Reports 2016; 49(5): 263-269].

  19. Maintenance of the adult Drosophila intestine: all roads lead to homeostasis.

    Science.gov (United States)

    Guo, Zheng; Lucchetta, Elena; Rafel, Neus; Ohlstein, Benjamin

    2016-10-01

    Maintenance of tissue homeostasis is critical in tissues with high turnover such as the intestinal epithelium. The intestinal epithelium is under constant cellular assault due to its digestive functions and its function as a barrier to chemical and bacterial insults. The resulting high rate of cellular turnover necessitates highly controlled mechanisms of regeneration to maintain the integrity of the tissue over the lifetime of the organism. Transient increase in stem cell proliferation is a commonly used and elaborate mechanism to ensure fast and efficient repair of the gut. However, tissue repair is not limited to regulating ISC proliferation, as emerging evidence demonstrates that the Drosophila intestine uses multiple strategies to ensure proper tissue homeostasis that may also extend to other tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Atg9 antagonizes TOR signaling to regulate intestinal cell growth and epithelial homeostasis in Drosophila.

    Science.gov (United States)

    Wen, Jung-Kun; Wang, Yi-Ting; Chan, Chih-Chiang; Hsieh, Cheng-Wen; Liao, Hsiao-Man; Hung, Chin-Chun; Chen, Guang-Chao

    2017-11-16

    Autophagy is essential for maintaining cellular homeostasis and survival under various stress conditions. Autophagy-related gene 9 (Atg9) encodes a multipass transmembrane protein thought to act as a membrane carrier for forming autophagosomes. However, the molecular regulation and physiological importance of Atg9 in animal development remain largely unclear. Here, we generated Atg9 null mutant flies and found that loss of Atg9 led to shortened lifespan, locomotor defects, and increased susceptibility to stress. Atg9 loss also resulted in aberrant adult midgut morphology with dramatically enlarged enterocytes. Interestingly, inhibiting the TOR signaling pathway rescued the midgut defects of the Atg9 mutants. In addition, Atg9 interacted with PALS1-associated tight junction protein (Patj), which associates with TSC2 to regulate TOR activity. Depletion of Atg9 caused a marked decrease in TSC2 levels. Our findings revealed an antagonistic relationship between Atg9 and TOR signaling in the regulation of cell growth and tissue homeostasis.

  1. Essential Regulation of Lung Surfactant Homeostasis by the Orphan G Protein-Coupled Receptor GPR116

    Directory of Open Access Journals (Sweden)

    Mi Young Yang

    2013-05-01

    Full Text Available GPR116 is an orphan seven-pass transmembrane receptor whose function has been unclear. Global disruption of the Gpr116 gene in mice revealed an unexpected, critical role for this receptor in lung surfactant homeostasis, resulting in progressive accumulation of surfactant lipids and proteins in the alveolar space, labored breathing, and a reduced lifespan. GPR116 expression analysis, bone marrow transplantation studies, and characterization of conditional knockout mice revealed that GPR116 expression in ATII cells is required for maintaining normal surfactant levels. Aberrant packaging of surfactant proteins with lipids in the Gpr116 mutant mice resulted in compromised surfactant structure, function, uptake, and processing. Thus, GPR116 plays an indispensable role in lung surfactant homeostasis with important ramifications for the understanding and treatment of lung surfactant disorders.

  2. Central insulin and leptin-mediated autonomic control of glucose homeostasis.

    Science.gov (United States)

    Marino, Joseph S; Xu, Yong; Hill, Jennifer W

    2011-07-01

    Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Carbon Redox-Polymer-Gel Hybrid Supercapacitors

    Science.gov (United States)

    Vlad, A.; Singh, N.; Melinte, S.; Gohy, J.-F.; Ajayan, P.M.

    2016-01-01

    Energy storage devices that provide high specific power without compromising on specific energy are highly desirable for many electric-powered applications. Here, we demonstrate that polymer organic radical gel materials support fast bulk-redox charge storage, commensurate to surface double layer ion exchange at carbon electrodes. When integrated with a carbon-based electrical double layer capacitor, nearly ideal electrode properties such as high electrical and ionic conductivity, fast bulk redox and surface charge storage as well as excellent cycling stability are attained. Such hybrid carbon redox-polymer-gel electrodes support unprecedented discharge rate of 1,000C with 50% of the nominal capacity delivered in less than 2 seconds. Devices made with such electrodes hold the potential for battery-scale energy storage while attaining supercapacitor-like power performances. PMID:26917470

  4. Molecular aspects of glucose homeostasis in skeletal muscle--A focus on the molecular mechanisms of insulin resistance.

    Science.gov (United States)

    Carnagarin, Revathy; Dharmarajan, Arun M; Dass, Crispin R

    2015-12-05

    Among all the varied actions of insulin, regulation of glucose homeostasis is the most critical and intensively studied. With the availability of glucose from nutrient metabolism, insulin action in muscle results in increased glucose disposal via uptake from the circulation and storage of excess, thereby maintaining euglycemia. This major action of insulin is executed by redistribution of the glucose transporter protein, GLUT4 from intracellular storage sites to the plasma membrane and storage of glucose in the form of glycogen which also involves modulation of actin dynamics that govern trafficking of all the signal proteins of insulin signal transduction. The cellular mechanisms responsible for these trafficking events and the defects associated with insulin resistance are largely enigmatic, and this review provides a consolidated overview of the various molecular mechanisms involved in insulin-dependent glucose homeostasis in skeletal muscle, as insulin resistance at this major peripheral site impacts whole body glucose homeostasis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. [Glucose homeostasis and gut-brain connection].

    Science.gov (United States)

    De Vadder, Filipe; Mithieux, Gilles

    2015-02-01

    Since the XIX(th) century, the brain has been known for its role in regulating food intake (via the control of hunger sensation) and glucose homeostasis. Further interest has come from the discovery of gut hormones, which established a clear link between the gut and the brain in regulating glucose and energy homeostasis. The brain has two particular structures, the hypothalamus and the brainstem, which are sensitive to information coming either from peripheral organs or from the gut (via circulating hormones or nutrients) about the nutritional status of the organism. However, the efforts for a better understanding of these mechanisms have allowed to unveil a new gut-brain neural axis as a key regulator of the metabolic status of the organism. Certain nutrients control the hypothalamic homeostatic function via this axis. In this review, we describe how the gut is connected to the brain via different neural pathways, and how the interplay between these two organs drives the energy balance. © 2015 médecine/sciences – Inserm.

  6. Thiol/disulphide homeostasis in celiac disease

    Science.gov (United States)

    Kaplan, Mustafa; Ates, Ihsan; Yuksel, Mahmut; Ozderin Ozin, Yasemin; Alisik, Murat; Erel, Ozcan; Kayacetin, Ertugrul

    2017-01-01

    AIM To determine dynamic thiol/disulphide homeostasis in celiac disease and to examine the associate with celiac autoantibodies and gluten-free diet. METHODS Seventy three patients with celiac disease and 73 healthy volunteers were enrolled in the study. In both groups, thiol/disulphide homeostasis was examined with a new colorimetric method recently developed by Erel and Neselioglu. RESULTS In patients with celiac disease, native thiol (P = 0.027) and total thiol (P = 0.031) levels were lower, while disulphide (P < 0.001) level, disulphide/native thiol (P < 0.001) and disulphide/total thiol (P < 0.001) ratios were higher compared to the control group. In patients who do not comply with a gluten-free diet, disulphide/native thiol ratio was found higher compared to the patients who comply with the diet (P < 0.001). In patients with any autoantibody-positive, disulphide/native thiol ratio was observed higher compared to the patients with autoantibody-negative (P < 0.05). It is found that there is a negative correlation between celiac autoantibodies, and native thiol, total thiol levels and native thiol/total thiol ratio, while a positive correlation is observed between disulphide, disulphide/native thiol and disulphide/total thiol levels. CONCLUSION This study is first in the literature which found that the patients with celiac disease the dynamic thiol/disulphide balance shifts through disulphide form compared to the control group. PMID:28533921

  7. Air pollution particles and iron homeostasis | Science ...

    Science.gov (United States)

    Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, functional groups at the surface of retained particle complex iron available in the cell. In response to a reduction in concentrations of requisite iron, a functional deficiency can result intracellularly. Superoxide production by the cell exposed to a particle increases ferrireduction which facilitates import of iron with the objective being the reversal of the metal deficiency. Failure to resolve the functional iron deficiency following cell exposure to particles activates kinases and transcription factors resulting in a release of inflammatory mediators and inflammation. Tissue injury is the end product of this disruption in iron homeostasis initiated by the particle exposure. Elevation of available iron to the cell precludes deficiency of the metal and either diminishes or eliminates biological effects.General Significance: Recognition of the pathway for biological effects after particle exposure to involve a functional deficiency of iron suggests novel therapies such as metal supplementation (e.g. inhaled and oral). In addition, the demonstration of a shared mechanism of biological effects allows understanding the common clinical, physiological, and pathological presentation fol

  8. Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis

    Directory of Open Access Journals (Sweden)

    Arya Bagus Boedi Iswanto

    2017-04-01

    Full Text Available Abstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD, which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs is highly controlled by plasmodesmata callose (PDC, which is synthesized by callose synthases (CalS and degraded by β-1,3-glucanases (BGs. In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft–processed PDC.

  9. Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis.

    Science.gov (United States)

    Iswanto, Arya Bagus Boedi; Kim, Jae-Yean

    2017-04-03

    A bstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD), which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs) is highly controlled by plasmodesmata callose (PDC), which is synthesized by callose synthases (CalS) and degraded by β-1,3-glucanases (BGs). In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft-processed PDC.

  10. Developing and maintaining instructor capabilities

    International Nuclear Information System (INIS)

    Flynn, W.P.; Smith, G.

    1985-01-01

    The New York Power Authority, after surveying available courses, decided to develop an in-house instructor training program. Following the principles of the Systems Approach to Training the course embodied the results of a job analysis resulting in a program containing instruction in Educational Philosophy, the Systems Approach to Training, Methods and Media, and Testing. The course content is covered through classroom instruction, on-the-job training, instructor evaluations, and assignments. Instructors completing the program continue to maintain skills with inservice training

  11. Hindbrain ghrelin receptor signaling is sufficient to maintain fasting glucose.

    Directory of Open Access Journals (Sweden)

    Michael M Scott

    Full Text Available The neuronal coordination of metabolic homeostasis requires the integration of hormonal signals with multiple interrelated central neuronal circuits to produce appropriate levels of food intake, energy expenditure and fuel availability. Ghrelin, a peripherally produced peptide hormone, circulates at high concentrations during nutrient scarcity. Ghrelin promotes food intake, an action lost in ghrelin receptor null mice and also helps maintain fasting blood glucose levels, ensuring an adequate supply of nutrients to the central nervous system. To better understand mechanisms of ghrelin action, we have examined the roles of ghrelin receptor (GHSR expression in the mouse hindbrain. Notably, selective hindbrain ghrelin receptor expression was not sufficient to restore ghrelin-stimulated food intake. In contrast, the lowered fasting blood glucose levels observed in ghrelin receptor-deficient mice were returned to wild-type levels by selective re-expression of the ghrelin receptor in the hindbrain. Our results demonstrate the distributed nature of the neurons mediating ghrelin action.

  12. Electronically Induced Redox Barriers for Treatment of Groundwater

    National Research Council Canada - National Science Library

    Sale, Tom; Gilbert, David

    2006-01-01

    ...) and Colorado State University (CSU). The focus is an innovative electrolytic approach for managing redox-sensitive contaminants in groundwater, referred to as electrically induced redox barrier (e-barriers...

  13. Biogeochemical Barriers: Redox Behavior of Metals and Metalloids

    Science.gov (United States)

    Redox conditions and pH are arguably the most important geochemical parameters that control contaminant transport and fate in groundwater systems. Oxidation-reduction (redox) reactions mediate the chemical behavior of both inorganic and organic chemical constituents by affecting...

  14. [Acid-base homeostasis and the thyro-parathyroid glands].

    Science.gov (United States)

    Cuisinier-Gleizes, P; George, A; Thomasset, M; Mathieu, H

    1975-05-12

    Chronic metabolic acidosis entails hyperparathyroidism and osteopathy. In order to elucidate the role of the thyroparathyroids in this bone lesion production the effects of acidic diet for 7 weeks were studied in parathyroidectomized (PTX), thyroparathyroidectomized (TPTX) and shamoperated (Sh-O) growing rats. In all animals urinary excretion of calcium, phosphate, ammonium and titrable acidity was similarly increased. The rise in hydroxyproline excretion and urinary 85-sr (that was injected previous to acidic feeding) was more marked in PTX and TPTX rats. Moreover, in these animals the serum calcium level was increased, the blood pH was decreased. According to these data, an acidic diet intake that is not sufficient to elicit a fall in blood pH of normal young rats can induce severe acidosis in chronically parathyroidectomized or thyroparathyroidectomized animals; moreover the bone resorption appears more marked. It is concluded that parathyroids are involved in the extra-cellular fluid defense mechanism against acidosis by a no bone resorptive mechanism. We hypothesize that the parathyroids permit the necessary and adequate supply of bicarbonates by the bone to maintain blood pH homeostasis.

  15. The Food and Drug Addiction Epidemic: Targeting Dopamine Homeostasis.

    Science.gov (United States)

    Blum, Kenneth; Thanos, Panayotis K; Wang, Gene-Jack; Febo, Marcelo; Demetrovics, Zsolt; Modestino, Edward Justin; Braverman, Eric R; Baron, David; Badgaiyan, Rajendra D; Gold, Mark S

    2018-02-12

    Obesity is damaging the lives of more than 300 million people worldwide and maintaining a healthy weight using popular weight loss tactics remains a very difficult undertaking. Managing the obesity problem seems within reach, as better understanding develops, of the function of our genome in drug/nutrient responses. Strategies indicated by this understanding of nutriepigenomics and neurogenetics in the treatment and prevention of metabolic syndrome and obesity include moderation of mRNA expression by DNA methylation, and inhibition of histone deacetylation. Based on an individual's genetic makeup, deficient metabolic pathways can be targeted epigenetically by, for example, the provision of dietary supplementation that includes phytochemicals, vitamins, and importantly functional amino acids. Also, the chromatin structure of imprinted genes that control nutrients during fetal development can be modified. Pathways affecting dopamine signaling, molecular transport and nervous system development are implicated in these strategies. Obesity is a subtype of Reward Deficiency Syndrome (RDS) and these new strategies in the treatment and prevention of obesity target improved dopamine function. It is not merely a matter of gastrointestinal signaling linked to hypothalamic peptides, but alternatively, finding novel ways to improve ventral tegmental area (VTA) dopaminergic function and homeostasis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Insights into the Mechanisms Underlying Boron Homeostasis in Plants

    Directory of Open Access Journals (Sweden)

    Akira Yoshinari

    2017-11-01

    Full Text Available Boron is an essential element for plants but is toxic in excess. Therefore, plants must adapt to both limiting and excess boron conditions for normal growth. Boron transport in plants is primarily based on three transport mechanisms across the plasma membrane: passive diffusion of boric acid, facilitated diffusion of boric acid via channels, and export of borate anion via transporters. Under boron -limiting conditions, boric acid channels and borate exporters function in the uptake and translocation of boron to support growth of various plant species. In Arabidopsis thaliana, NIP5;1 and BOR1 are located in the plasma membrane and polarized toward soil and stele, respectively, in various root cells, for efficient transport of boron from the soil to the stele. Importantly, sufficient levels of boron induce downregulation of NIP5;1 and BOR1 through mRNA degradation and proteolysis through endocytosis, respectively. In addition, borate exporters, such as Arabidopsis BOR4 and barley Bot1, function in boron exclusion from tissues and cells under conditions of excess boron. Thus, plants actively regulate intracellular localization and abundance of transport proteins to maintain boron homeostasis. In this review, the physiological roles and regulatory mechanisms of intracellular localization and abundance of boron transport proteins are discussed.

  17. Role of carotenoid β-cryptoxanthin in bone homeostasis

    Directory of Open Access Journals (Sweden)

    Yamaguchi Masayoshi

    2012-04-01

    Full Text Available Abstract Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Aging induces bone loss due to decreased osteoblastic bone formation and increased osteoclastic bone resorption. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Nutritional factors may play a role in the prevention of bone loss with aging. Among various carotenoids (carotene and xanthophylls including beta (β-cryptoxanthin, lutein, lycopene, β-carotene, astaxanthin, and rutin, β-cryptoxanthin, which is abundant in Satsuma mandarin orange (Citrus unshiu MARC., has been found to have a stimulatory effect on bone calcification in vitro. β-cryptoxanthin has stimulatory effects on osteoblastic bone formation and inhibitory effects on osteoclastic bone resorption in vitro, thereby increasing bone mass. β-cryptoxanthin has an effect on the gene expression of various proteins that are related osteoblastic bone formation and osteoclastic bone resororption in vitro. The intake of β-cryptoxanthin may have a preventive effect on bone loss in animal models for osteoporosis and in healthy human or postmenopausal women. Epidemiological studies suggest a potential role of β-cryptoxanthin as a sustainable nutritional approach to improving bone health of human subjects. β-Cryptoxanthin may be an osteogenic factor in preventing osteoporosis in human subjects.

  18. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    Directory of Open Access Journals (Sweden)

    Christian Kosan

    2016-01-01

    Full Text Available All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function.

  19. The tumor necrosis factor-alpha-induced protein 8 family in immune homeostasis and inflammatory cancer diseases.

    Science.gov (United States)

    Luan, Y Y; Yao, Y M; Sheng, Z Y

    2013-01-01

    Within the immune system homeostasis is maintained by a myriad of mechanisms that include the regulation of immune cell activation and programmed cell death. The breakdown of immune homeostasis may lead to fatal inflammatory diseases. We set out to identify genes of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) family that has a functional role in the process of immune homeostasis. Tumor necrosis factor-alpha-induced protein 8 (TNFAIP8), which functions as an oncogenic molecule, is also associated with enhanced cell survival and inhibition of apoptosis. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) governs immune homeostasis in both the innate and adaptive immune system and prevents hyper-responsiveness by negatively regulating signaling via T cell receptors and Toll-like receptors (TLRs). There also exist two highly homologous but uncharacterized proteins, TIPE1 and TIPE3. This review is an attempt to provide a summary of TNFAIP8 family associated with immune homeostasis and inflammatory cancer diseases.

  20. Alleviating Redox Imbalance Enhances 7-Dehydrocholesterol Production in Engineered Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Wan Su

    Full Text Available Maintaining redox balance is critical for the production of heterologous secondary metabolites, whereas on various occasions the native cofactor balance does not match the needs in engineered microorganisms. In this study, 7-dehydrocholesterol (7-DHC, a crucial precursor of vitamin D3 biosynthesis pathway was constructed in Saccharomyces cerevisiae BY4742 with endogenous ergosterol synthesis pathway blocked by knocking out the erg5 gene (encoding C-22 desaturase. The deletion of erg5 led to redox imbalance with higher ratio of cytosolic free NADH/NAD+ and more glycerol and ethanol accumulation. To alleviate the redox imbalance, a water-forming NADH oxidase (NOX and an alternative oxidase (AOX1 were employed in our system based on cofactor regeneration strategy. Consequently, the production of 7-dehydrocholesterol was increased by 74.4% in shake flask culture. In the meanwhile, the ratio of free NADH/NAD+ and the concentration of glycerol and ethanol were reduced by 78.0%, 50.7% and 7.9% respectively. In a 5-L bioreactor, the optimal production of 7-DHC reached 44.49(±9.63 mg/L. This study provides a reference to increase the production of some desired compounds that are restricted by redox imbalance.

  1. Standardized extracts of Bacopa monniera protect against MPP+- and paraquat-induced toxicity by modulating mitochondrial activities, proteasomal functions, and redox pathways.

    Science.gov (United States)

    Singh, Manjeet; Murthy, Ven; Ramassamy, Charles

    2012-01-01

    Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases and affects millions of people worldwide. Strong evidence supports the role of free radicals, oxidative stress, mitochondrial, and proteasomal dysfunctions underlying neuronal death in PD. Environmental factors, especially pesticides, represent one of the primary classes of neurotoxic agents associated with PD, and several epidemiological studies have identified the exposure of the herbicide paraquat (PQ) as a potential risk factor for the onset of PD. The objective of our study was to investigate the neuroprotective effects of the standardized extracts of Bacopa monniera (BM) against PQ-induced and 1-methyl-4-phenyl-pyridinium iodide (MPP(+))-induced toxicities and to elucidate the mechanisms underlying this protection. Our results show that a pretreatment with the BM extract from 50 μg/ml protected the dopaminergic SK-N-SH cell line against MPP(+)- and PQ-induced toxicities in various cell survival assays. We demonstrate that BM pretreatment prevented the depletion of glutathione (GSH) besides preserving the mitochondrial membrane potential and maintaining the mitochondrial complex I activity. BM pretreatment from 10.0 μg/ml also prevented the generation of intracellular reactive oxygen species and decreased the mitochondrial superoxide level. BM treatment activated the nuclear factor erythroid 2-related factor 2 pathway by modulating the expression of Keap1, thereby upregulating the endogenous GSH synthesis. The effect of BM on the phosphorylation of Akt further strengthens its role in the promotion of cell survival. By preserving the cellular redox homeostasis and mitochondrial activities and by promoting cell survival pathways, BM extract may have therapeutic uses in various age-related neurodegenerative diseases such as PD.

  2. Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain

    Directory of Open Access Journals (Sweden)

    Katharine Askew

    2017-01-01

    Full Text Available Summary: Microglia play key roles in brain development, homeostasis, and function, and it is widely assumed that the adult population is long lived and maintained by self-renewal. However, the precise temporal and spatial dynamics of the microglial population are unknown. We show in mice and humans that the turnover of microglia is remarkably fast, allowing the whole population to be renewed several times during a lifetime. The number of microglial cells remains steady from late postnatal stages until aging and is maintained by the spatial and temporal coupling of proliferation and apoptosis, as shown by pulse-chase studies, chronic in vivo imaging of microglia, and the use of mouse models of dysregulated apoptosis. Our results reveal that the microglial population is constantly and rapidly remodeled, expanding our understanding of its role in the maintenance of brain homeostasis. : The mechanism or mechanisms underlying microglial homeostasis are unknown. Askew et al. show that microglia self-renewal is maintained by coupled proliferation and apoptosis, resulting in a stable microglia number over a mouse or human lifetime. Keywords: self-renewal, BrdU, CSF1R, CX3CR1, Macgreen, Vav-Bcl2, RNA-seq

  3. Cell Adhesion Molecule CD166/ALCAM Functions Within the Crypt to Orchestrate Murine Intestinal Stem Cell HomeostasisSummary

    Directory of Open Access Journals (Sweden)

    Nicholas R. Smith

    2017-05-01

    Full Text Available Background & Aims: Intestinal epithelial homeostasis is maintained by active-cycling and slow-cycling stem cells confined within an instructive crypt-based niche. Exquisite regulating of these stem cell populations along the proliferation-to-differentiation axis maintains a homeostatic balance to prevent hyperproliferation and cancer. Although recent studies focus on how secreted ligands from mesenchymal and epithelial populations regulate intestinal stem cells (ISCs, it remains unclear what role cell adhesion plays in shaping the regulatory niche. Previously we have shown that the cell adhesion molecule and cancer stem cell marker, CD166/ALCAM (activated leukocyte cell adhesion molecule, is highly expressed by both active-cycling Lgr5+ ISCs and adjacent Paneth cells within the crypt base, supporting the hypothesis that CD166 functions to mediate ISC maintenance and signal coordination. Methods: Here we tested this hypothesis by analyzing a CD166–/– mouse combined with immunohistochemical, flow cytometry, gene expression, and enteroid culture. Results: We found that animals lacking CD166 expression harbored fewer active-cycling Lgr5+ ISCs. Homeostasis was maintained by expansion of the transit-amplifying compartment and not by slow-cycling Bmi1+ ISC stimulation. Loss of active-cycling ISCs was coupled with deregulated Paneth cell homeostasis, manifested as increased numbers of immature Paneth progenitors due to decreased terminal differentiation, linked to defective Wnt signaling. CD166–/– Paneth cells expressed reduced Wnt3 ligand expression and depleted nuclear β-catenin. Conclusions: These data support a function for CD166 as an important cell adhesion molecule that shapes the signaling microenvironment by mediating ISC–niche cell interactions. Furthermore, loss of CD166 expression results in decreased ISC and Paneth cell homeostasis and an altered Wnt microenvironment. Keywords: Intestinal Stem Cell, Homeostasis

  4. Are bioassays useful tools to assess redox processes and biodegradation?

    DEFF Research Database (Denmark)

    Albrechtsen, Hans-Jørgen; Pedersen, Philip Grinder; Ludvigsen, L.

    2002-01-01

    sensitive hydrochemical or geochemical parameters, levels of hydrogen, and redox potential. However, all these approaches have to be evaluated against TEAP-bioassays as the most direct measure. We assessed successfully ongoing microbial-mediated redox processes by TEAP-bioassays in degradation studies...... of aromatic and chlorinated aliphatic compounds in landfill leachate plumes, and of pesticides in aquifers with various redox conditions....

  5. Le reazioni redox: un pasticcio concettuale?

    Directory of Open Access Journals (Sweden)

    Elena Ghibaudi

    2015-10-01

    Full Text Available Le reazioni di ossidoriduzione costituiscono un argomento centrale di qualsiasi corso di base di chimica, sia a livello scolastico che universitario. Il loro apprendimento comporta il superamento di svariati ostacoli concettuali, la cui difficoltà può risultare amplificata da prassi didattiche inadeguate. Gli errori più ricorrenti nel presentare l’argomento sono di due tipi: i fare implicitamente riferimento a modelli esplicativi distinti (es. il numero di ossidazione e il trasferimento elettronico, senza esplicitarli e senza evidenziarne la differente natura e il campo di validità; ii confondere il livello della spiegazione formale con quello della realtà fisica. I fenomeni redox sono normalmente interpretati sulla base di tre distinti modelli empirici, che fanno riferimento al trasferimento di atomi di ossigeno, di atomi di idrogeno, di elettroni; e di un quarto modello, formale, fondato sul cambiamento del numero di ossidazione. La confusione tra questi modelli può generare considerevoli problemi di apprendimento. Il presente lavoro riporta un’analisi critica delle implicazioni concettuali della didattica dei processi redox. L’analisi è articolata in tre sezioni: i disamina della evoluzione storica del concetto di ossidoriduzione; ii analisi dei modelli redox e del loro campo di validità; iii discussione di alcuni aspetti epistemologici inerenti i processi redox che sono rilevanti per la didattica della chimica.

  6. Methods for using redox liposome biosensors

    Science.gov (United States)

    Cheng, Quan; Stevens, Raymond C.

    2002-01-01

    The present invention provides methods and compositions for detecting the presence of biologically-important analytes by using redox liposome biosensors. In particular, the present invention provides liposome/sol-gel electrodes suitable for the detection of a wide variety of organic molecules, including but not limited to bacterial toxins.

  7. Redox regulation in cancer stem cells

    Science.gov (United States)

    Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processe...

  8. Redox fluctuations in the Early Ordovician oceans

    DEFF Research Database (Denmark)

    D'Arcy, Joan Mary; Gilleaudeau, Geoffrey Jon; Peralta, Silvio

    2017-01-01

    Chromium (Cr) stable isotopes are a useful tracer of changes in redox conditions because changes in its oxidation state are accompanied by an isotopic fractionation. Recent co-precipitation experiments have shown that Cr(VI) is incorporated into the calcite lattice, suggesting that carbonates......, accompanied by exceptionally low Cr concentrations (runoff or hydrothermal input into the global...

  9. Investigating improvements on redox flow batteries

    CSIR Research Space (South Africa)

    Swartbooi, AM

    2006-09-01

    Full Text Available storage devices coupled to most of their applications. Lead-acid batteries have long been used as the most economical option to store electricity in many small scale applications, but lately more interest have been shown in redox flow batteries. The low...

  10. Redox cycling of potential antitumor aziridinylquinones

    NARCIS (Netherlands)

    Lusthof, Klaas J.; de Mol, Nicolaas J.; Richter, Wilma; Janssen, Lambert H.M.; Butler, John; Hoey, Brigid M.; Verboom, Willem; Reinhoudt, David

    1992-01-01

    The formation of reactive oxygen intermediates (ROI) during redox cycling of newly synthetized potential antitumor 2,5-bis (1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied by assaying the production of ROI (superoxide, hydroxyl radical, and hydrogen peroxide) by xanthine oxidase

  11. Redox Control of Skeletal Muscle Regeneration.

    Science.gov (United States)

    Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan; Groussard, Carole; Zouhal, Hassane; Chazaud, Bénédicte; Mounier, Rémi

    2017-08-10

    Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276-310.

  12. Redox Modulations, Antioxidants, and Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Erik A. Fraunberger

    2016-01-01

    Full Text Available Although antioxidants, redox modulations, and neuropsychiatric disorders have been widely studied for many years, the field would benefit from an integrative and corroborative review. Our primary objective is to delineate the biological significance of compounds that modulate our redox status (i.e., reactive species and antioxidants as well as outline their current role in brain health and the impact of redox modulations on the severity of illnesses. Therefore, this review will not enter into the debate regarding the perceived medical legitimacy of antioxidants but rather seek to clarify their abilities and limitations. With this in mind, antioxidants may be interpreted as natural products with significant pharmacological actions in the body. A renewed understanding of these often overlooked compounds will allow us to critically appraise the current literature and provide an informed, novel perspective on an important healthcare issue. In this review, we will introduce the complex topics of redox modulations and their role in the development of select neuropsychiatric disorders.

  13. TAM Receptor Signaling in Immune Homeostasis

    Science.gov (United States)

    Rothlin, Carla V.; Carrera-Silva, Eugenio A.; Bosurgi, Lidia; Ghosh, Sourav

    2015-01-01

    The TAM receptor tyrosine kinases (RTKs)—TYRO3, AXL, and MERTK—together with their cognate agonists GAS6 and PROS1 play an essential role in the resolution of inflammation. Deficiencies in TAM signaling have been associated with chronic inflammatory and autoimmune diseases. Three processes regulated by TAM signaling may contribute, either independently or collectively, to immune homeostasis: the negative regulation of the innate immune response, the phagocytosis of apoptotic cells, and the restoration of vascular integrity. Recent studies have also revealed the function of TAMs in infectious diseases and cancer. Here, we review the important milestones in the discovery of these RTKs and their ligands and the studies that underscore the functional importance of this signaling pathway in physiological immune settings and disease. PMID:25594431

  14. Maintaining consistency in distributed systems

    Science.gov (United States)

    Birman, Kenneth P.

    1991-01-01

    In systems designed as assemblies of independently developed components, concurrent access to data or data structures normally arises within individual programs, and is controlled using mutual exclusion constructs, such as semaphores and monitors. Where data is persistent and/or sets of operation are related to one another, transactions or linearizability may be more appropriate. Systems that incorporate cooperative styles of distributed execution often replicate or distribute data within groups of components. In these cases, group oriented consistency properties must be maintained, and tools based on the virtual synchrony execution model greatly simplify the task confronting an application developer. All three styles of distributed computing are likely to be seen in future systems - often, within the same application. This leads us to propose an integrated approach that permits applications that use virtual synchrony with concurrent objects that respect a linearizability constraint, and vice versa. Transactional subsystems are treated as a special case of linearizability.

  15. Interference between nanoparticles and metal homeostasis

    International Nuclear Information System (INIS)

    Petit, A N; Catty, P; Charbonnier, P; Cuillel, M; Mintz, E; Moulis, J M; Niviere, V; Choudens, S Ollagnier de; Garcia, C Aude; Candeias, S; Chevallet, M; Collin-Faure, V; Lelong, C; Luche, S; Rabilloud, T; Casanova, A; Herlin-Boime, N; Douki, T; Ravanat, J L; Sauvaigo, S

    2011-01-01

    The TiO 2 nanoparticles (NPs) are now produced abundantly and widely used in a variety of consumer products. Due to the important increase in the production of TiO 2 -NPs, potential widespread exposure of humans and environment may occur during both the manufacturing process and final use. Therefore, the potential toxicity of TiO 2 -NPs on human health and environment has attracted particular attention. Unfortunately, the results of the large number of studies on the toxicity of TiO 2 -NPs differ significantly, mainly due to an incomplete characterization of the used nanomaterials in terms of size, shape and crystalline structure and to their unknown state of agglomeration/aggregation. The purpose of our project entitled NanoBioMet is to investigate if interferences between nanoparticles and metal homeostasis could be observed and to study the toxicity mechanisms of TiO 2 -NPs with well-characterized physicochemical parameters, using proteomic and molecular approaches. A perturbation of metal homeostasis will be evaluated upon TiO 2 -NPs exposure which could generate reactive oxygen species (ROS) production. Moreover, oxidative stress consequences such as DNA damage and lipid peroxidation will be studied. The toxicity of TiO 2 -NPs of different sizes and crystalline structures will be evaluated both in prokaryotic (E. coli) and eukaryotic cells (A549 human pneumocytes, macrophages, and hepatocytes). First results of the project will be presented concerning the dispersion of TiO 2 -NPs in bacterial medium, proteomic studies on total extracts of macrophages and genotoxicity on pneumocytes.

  16. A Membrane‐Free Redox Flow Battery with Two Immiscible Redox Electrolytes

    OpenAIRE

    Navalpotro, Paula; Palma, Jesus; Anderson, Marc; Marcilla, Rebeca

    2017-01-01

    Abstract Flexible and scalable energy storage solutions are necessary for mitigating fluctuations of renewable energy sources. The main advantage of redox flow batteries is their ability to decouple power and energy. However, they present some limitations including poor performance, short‐lifetimes, and expensive ion‐selective membranes as well as high price, toxicity, and scarcity of vanadium compounds. We report a membrane‐free battery that relies on the immiscibility of redox electrolytes ...

  17. Electrochemical redox processes involving soluble cerium species

    International Nuclear Information System (INIS)

    Arenas, L.F.; Ponce de León, C.; Walsh, F.C.

    2016-01-01

    Highlights: • The relevance of cerium in laboratory and industrial electrochemistry is considered. • The history of fundamental electrochemical studies and applications is considered. • The chemistry, redox thermodynamics and electrode kinetics of cerium are summarised. • The uses of cerium ions in synthesis, energy storage, analysis and environmental treatment are illustrated. • Research needs and development perspectives are discussed. - Abstract: Anodic oxidation of cerous ions and cathodic reduction of ceric ions, in aqueous acidic solutions, play an important role in electrochemical processes at laboratory and industrial scale. Ceric ions, which have been used for oxidation of organic wastes and off-gases in environmental treatment, are a well-established oxidant for indirect organic synthesis and specialised cleaning processes, including oxide film removal from tanks and process pipework in nuclear decontamination. They also provide a classical reagent for chemical analysis in the laboratory. The reversible oxidation of cerous ions is an important reaction in the positive compartment of various redox flow batteries during charge and discharge cycling. A knowledge of the thermodynamics and kinetics of the redox reaction is critical to an understanding of the role of cerium redox species in these applications. Suitable choices of electrode material (metal or ceramic; coated or uncoated), geometry/structure (2-or 3-dimensional) and electrolyte flow conditions (hence an acceptable mass transport rate) are critical to achieving effective electrocatalysis, a high performance and a long lifetime. This review considers the electrochemistry of soluble cerium species and their diverse uses in electrochemical technology, especially for redox flow batteries and mediated electrochemical oxidation.

  18. Extracellular Redox Regulation of Intracellular Reactive Oxygen Generation, Mitochondrial Function and Lipid Turnover in Cultured Human Adipocytes.

    Directory of Open Access Journals (Sweden)

    Albert R Jones

    Full Text Available Many tissues play an important role in metabolic homeostasis and the development of diabetes and obesity. We hypothesized that the circulating redox metabolome is a master metabolic regulatory system that impacts all organs and modulates reactive oxygen species (ROS production, lipid peroxidation, energy production and changes in lipid turnover in many cells including adipocytes.Differentiated human preadipocytes were exposed to the redox couples, lactate (L and pyruvate (P, β-hydroxybutyrate (βOHB and acetoacetate (Acoc, and the thiol-disulfides cysteine/ cystine (Cys/CySS and GSH/GSSG for 1.5-4 hours. ROS measurements were done with CM-H2DCFDA. Lipid peroxidation (LPO was assessed by a modification of the thiobarbituric acid method. Lipolysis was measured as glycerol release. Lipid synthesis was measured as 14C-glucose incorporated into lipid. Respiration was assessed using the SeaHorse XF24 analyzer and the proton leak was determined from the difference in respiration with oligomycin and antimycin A.Metabolites with increasing oxidation potentials (GSSG, CySS, Acoc increased adipocyte ROS. In contrast, P caused a decrease in ROS compared with L. Acoc also induced a significant increase in both LPO and lipid synthesis. L and Acoc increased lipolysis. βOHB increased respiration, mainly due to an increased proton leak. GSSG, when present throughout 14 days of differentiation significantly increased fat accumulation, but not when added later.We demonstrated that in human adipocytes changes in the external redox state impacted ROS production, LPO, energy efficiency, lipid handling, and differentiation. A more oxidized state generally led to increased ROS, LPO and lipid turnover and more reduction led to increased respiration and a proton leak. However, not all of the redox couples were the same suggesting compartmentalization. These data are consistent with the concept of the circulating redox metabolome as a master metabolic regulatory system.

  19. Dual redox catalysts for oxygen reduction and evolution reactions: towards a redox flow Li-O2 battery.

    Science.gov (United States)

    Zhu, Yun Guang; Jia, Chuankun; Yang, Jing; Pan, Feng; Huang, Qizhao; Wang, Qing

    2015-06-11

    A redox flow lithium-oxygen battery (RFLOB) by using soluble redox catalysts with good performance was demonstrated for large-scale energy storage. The new device enables the reversible formation and decomposition of Li2O2 via redox targeting reactions in a gas diffusion tank, spatially separated from the electrode, which obviates the passivation and pore clogging of the cathode.

  20. Disruption of redox homeostasis in liver function and activation of apoptosis on consumption of aspartame in folate deficient rat model

    Directory of Open Access Journals (Sweden)

    Ashok Iyaswamy

    2017-06-01

    Full Text Available This study assesses the effect of long-term intake of aspartame on liver function and apoptosis signaling pathway in the Wistar albino rats. Several reports have suggested that methanol is one of the major metabolites of Aspartame. Non-primate animals are usually resistant to methanol-induced metabolic acidosis due to high levels of hepatic folate content; hence a folate deficiency model was induced by treating animals with methotrexate (MTX prior to aspartame exposure. The aspartame treated MTX animals exhibited a marked significant increase in hepatic alanine transaminase (ALT, aspartate transaminase (AST, alkaline phosphatase (ALP and lactic acid dehydrogenase (LDH activity compared to controls. Aspartame treated MTX animals additionally exhibited down-regulation of genes namely B-cell lymphoma 2 (Bcl2 expression and up-regulation of Bcl-2-associated X protein (Bax, Fas-associated protein with death domain (FADD and Caspase 3, 9 genes and apoptotic protein expression, indicating the augmentation of hepatic apoptosis. Nuclear condensation, micro vacuole formation in the cytoplasm and necrosis were observed in the liver of the aspartame treated animals on histopathology evaluation. Additionally, Immunohistochemical analysis revealed a significant increase in positive cells expressing Fas, FADD, Bax and Caspase 9 protein, indicating an increase in apoptotic protein expression in the liver. Thus, Aspartame may act as a chemical stressor which alters the functional status of liver, leading to hepatotoxicity.

  1. Artesunate-induced testicular injury: Oil from selected spices blend modulates redox homeostasis and exacerbates steroidogenesis in rat models

    Directory of Open Access Journals (Sweden)

    John A. Ajiboye

    2016-12-01

    Full Text Available The therapeutic potential of oil from blends of selected culinary spices against artesunate-induced testicular injury in albino rats was investigated. Two groups of rats each were pretreated with the oil at 1.5 and 3.00 mL respectively for seven days and after which administered artesunate (100 mg/kg bw for seven days; two other groups were administered artesunate for seven days and after which post treated with the oil at both doses respectively for another seven days; another groups were co-administered artesunate and the oil for seven days. A group was administered artesunate only for seven days, while another was fed chows only. After sacrifice, the testicular homogenates of the rats were analysed for GSH, Superoxide Dismutase (SOD, Catalase (CAT, Lipid peroxidation (LPO, 3β-HSD and 17β-HSD activities. LPO and GSH levels, SOD and CAT activities were significantly (p < 0.05 higher in rats administered artesunate only, these were significantly lowered in all treatment groups. Administration of artesunate significantly suppressed steroidogenesis, this was attenuated in all treatment groups. The antioxidant, anti-lipid peroxidative and steriodogenetic effects of the oil indicate its protective potential against artesunate-induced oxidative testicular damage.

  2. Importance of glutamine metabolism in leukemia cells by energy production through TCA cycle and by redox homeostasis.

    Science.gov (United States)

    Goto, Mineaki; Miwa, Hiroshi; Shikami, Masato; Tsunekawa-Imai, Norikazu; Suganuma, Kazuto; Mizuno, Shohei; Takahashi, Miyuki; Mizutani, Motonori; Hanamura, Ichiro; Nitta, Masakazu

    2014-07-01

    Some cancer cells depend on glutamine despite of pronounced glycolysis. We examined the glutamine metabolism in leukemia cells, and found that HL-60 cells most depended on glutamine in the 4 acute myelogenous leukemia (AML) cell lines examined: growth of HL-60 cells was most suppressed by glutamine deprivation and by inhibition of glutaminolysis, which was rescued by tricarboxylic acid (TCA) cycle intermediate, oxaloacetic acid. Glutamine is also involved in antioxidant defense function by increasing glutathione. Glutamine deprivation suppressed the glutathione content and elevated reactive oxygen species most evidently in HL-60 cells. Glutamine metabolism might be a therapeutic target in some leukemia.

  3. Virgin coconut oil reverses hepatic steatosis by restoring redox homeostasis and lipid metabolism in male Wistar rats.

    Science.gov (United States)

    Narayanankutty, Arunaksharan; Palliyil, Devika Mukundan; Kuruvilla, Kezia; Raghavamenon, Achuthan C

    2018-03-01

    Hepatosteatosis, a form of nonalcoholic fatty liver disease (NAFLD), is being increasingly recognized as a major health burden worldwide. Insulin resistance, dyslipidemia and imbalances in adipokine/cytokine interplay are reported to be involved in the onset and progression of this disease. Use of dietary nutraceuticals in prevention and treatment of NAFLD is emerging. Virgin coconut oil (VCO), a fermented product of fresh coconut kernel, has been shown to impede the development of hepatosteatosis in rats. This study analyzes the potential of VCO to reverse the already developed hepatosteatosis condition. Hyperglycemia, reduced glucose tolerance, dyslipidemia, and hepatic macrovesicles in high-fructose-diet-fed rats (4 weeks) confirmed the development of hepatosteatosis. Natural reversion in these parameters was observed upon shifting to normal diet in untreated control animals. Administration of VCO, however, increased this natural reversion by improving high-density lipoprotein cholesterol level (53.5%) and reducing hepatic and serum triacylglycerols (78.0 and 51.7%). Increased hepatic glutathione level (P < 0.01), antioxidant enzyme activities (P < 0.05) and reduced lipid peroxidation were also noticed in these animals. These observations were in concordance with reduced liver enzyme activities (P < 0.01) and restoration of altered hepatic architecture. The study indicates that VCO can be used as a nutraceutical against hepatosteatosis. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  4. Redox homeostasis in stomach medium by foods: The Postprandial Oxidative Stress Index (POSI) for balancing nutrition and human health.

    Science.gov (United States)

    Kanner, Joseph; Selhub, Jacob; Shpaizer, Adi; Rabkin, Boris; Shacham, Inbal; Tirosh, Oren

    2017-08-01

    Red-meat lipid peroxidation in the stomach results in postprandial oxidative stress (POS) which is characterized by the generation of a variety of reactive cytotoxic aldehydes including malondialdehyde (MDA). MDA is absorbed in the blood system reacts with cell proteins to form adducts resulting in advanced lipid peroxidation end products (ALEs), producing dysfunctional proteins and cellular responses. The pathological consequences of ALEs tissue damage include inflammation and increased risk for many chronic diseases that are associated with a Western-type diet. In earlier studies we used the simulated gastric fluid (SGF) condition to show that the in vitro generation of MDA from red meat closely resembles that in human blood after consumption the same amount of meat. In vivo and in vitro MDA generations were similarly suppressed by polyphenol-rich beverages (red wine and coffee) consumed with the meal. The present study uses the in vitro SGF to assess the capacity of more than 50 foods of plant origin to suppress red meat peroxidation and formation of MDA. The results were calculated as reducing POS index (rPOSI) which represents the capacity in percent of 100g of the food used to inhibit lipid peroxidation of 200g red-meat a POSI enhancer (ePOSI). The index permitted to extrapolate the need of rPOSI from a food alone or in ensemble such Greek salad, to neutralize an ePOSI in stomach medium, (ePOS-rPOSI=0). The correlation between the rPOSI and polyphenols in the tested foods was R 2 =0.75. The Index was validated by comparison of the predicted rPOSI for a portion of Greek salad or red-wine to real inhibition of POS enhancers. The POS Index permit to better balancing nutrition for human health. Copyright © 2017. Published by Elsevier B.V.

  5. Redox homeostasis in stomach medium by foods: The Postprandial Oxidative Stress Index (POSI for balancing nutrition and human health

    Directory of Open Access Journals (Sweden)

    Joseph Kanner

    2017-08-01

    Full Text Available Red-meat lipid peroxidation in the stomach results in postprandial oxidative stress (POS which is characterized by the generation of a variety of reactive cytotoxic aldehydes including malondialdehyde (MDA. MDA is absorbed in the blood system reacts with cell proteins to form adducts resulting in advanced lipid peroxidation end products (ALEs, producing dysfunctional proteins and cellular responses. The pathological consequences of ALEs tissue damage include inflammation and increased risk for many chronic diseases that are associated with a Western-type diet. In earlier studies we used the simulated gastric fluid (SGF condition to show that the in vitro generation of MDA from red meat closely resembles that in human blood after consumption the same amount of meat. In vivo and in vitro MDA generations were similarly suppressed by polyphenol-rich beverages (red wine and coffee consumed with the meal. The present study uses the in vitro SGF to assess the capacity of more than 50 foods of plant origin to suppress red meat peroxidation and formation of MDA. The results were calculated as reducing POS index (rPOSI which represents the capacity in percent of 100 g of the food used to inhibit lipid peroxidation of 200 g red-meat a POSI enhancer (ePOSI. The index permitted to extrapolate the need of rPOSI from a food alone or in ensemble such Greek salad, to neutralize an ePOSI in stomach medium, (ePOS–rPOSI=0. The correlation between the rPOSI and polyphenols in the tested foods was R2=0.75. The Index was validated by comparison of the predicted rPOSI for a portion of Greek salad or red-wine to real inhibition of POS enhancers. The POS Index permit to better balancing nutrition for human health. Keywords: Stomach, Red-meat, Lipid-peroxidation, Malondialdehyde – MDA, Postprandial, Polyphenols

  6. Immune Homeostasis in Epithelial Cells: Evidence and Role of Inflammasome Signaling Reviewed.

    Science.gov (United States)

    Peeters, Paul M; Wouters, Emiel F; Reynaert, Niki L

    2015-01-01

    The epithelium regulates the interaction between the noxious xenogenous, as well as the microbial environment and the immune system, not only by providing a barrier but also by expressing a number of immunoregulatory membrane receptors, and intracellular danger sensors and their downstream effectors. Amongst these are a number of inflammasome sensor subtypes, which have been initially characterized in myeloid cells and described to be activated upon assembly into multiprotein complexes by microbial and environmental triggers. This review compiles a vast amount of literature that supports a pivotal role for inflammasomes in the various epithelial barriers of the human body as essential factors maintaining immune signaling and homeostasis.

  7. Epigenetic Control of Stem Cell Potential During Homeostasis, Aging, and Disease

    Science.gov (United States)

    Beerman, Isabel; Rossi, Derrick J.

    2015-01-01

    Stem cell decline is an important cellular driver of aging-associated pathophysiology in multiple tissues. Epigenetic regulation is central to establishing and maintaining stem cell function, and emerging evidence indicates that epigenetic dysregulation contributes to the altered potential of stem cells during aging. Unlike terminally differentiated cells, the impact of epigenetic dysregulation in stem cells is propagated beyond self; alterations can be heritably transmitted to differentiated progeny, in addition to being perpetuated and amplified within the stem cell pool through self-renewal divisions. This review focuses on recent studies examining epigenetic regulation of tissue-specific stem cells in homeostasis, aging, and aging-related disease. PMID:26046761

  8. Regulation of intestinal homeostasis and immunity with probiotic lactobacilli

    NARCIS (Netherlands)

    Baarlen, van P.; Wells, J.; Kleerebezem, M.

    2013-01-01

    The gut microbiota provide important stimuli to the human innate and adaptive immune system and co-mediate metabolic and immune homeostasis. Probiotic bacteria can be regarded as part of the natural human microbiota, and have been associated with improving homeostasis, albeit with different levels

  9. A Formal Explication of the Concept of Family Homeostasis.

    Science.gov (United States)

    Ariel, Shlomo; And Others

    1984-01-01

    Presents three articles discussing the concept of family homeostasis and the related concepts of family rules and family feedback. Includes a reply by Paul Dell citing the need for family therapy to go beyond homeostasis and further comments by Ariel, Carel, and Tyano. (JAC)

  10. Development and Validation of the Homeostasis Concept Inventory

    Science.gov (United States)

    McFarland, Jenny L.; Price, Rebecca M.; Wenderoth, Mary Pat; Martinková, Patrícia; Cliff, William; Michael, Joel; Modell, Harold; Wright, Ann

    2017-01-01

    We present the Homeostasis Concept Inventory (HCI), a 20-item multiple-choice instrument that assesses how well undergraduates understand this critical physiological concept. We used an iterative process to develop a set of questions based on elements in the Homeostasis Concept Framework. This process involved faculty experts and undergraduate…

  11. Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration.

    Science.gov (United States)

    Pisconti, Addolorata; Banks, Glen B; Babaeijandaghi, Farshad; Betta, Nicole Dalla; Rossi, Fabio M V; Chamberlain, Jeffrey S; Olwin, Bradley B

    2016-01-01

    The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in satellite cells, supports communication with the niche, providing cell interactions and signals to maintain quiescent satellite cells. Syndecan-3 ablation unexpectedly improves regeneration in repeatedly injured muscle and in dystrophic mice, accompanied by the persistence of sublaminar and interstitial, proliferating myoblasts. Additionally, muscle aging is improved in syndecan-3 null mice. Since syndecan-3 null myofiber-associated satellite cells downregulate Pax7 and migrate away from the niche more readily than wild type cells, syxndecan-3 appears to regulate satellite cell homeostasis and satellite cell homing to the niche. Manipulating syndecan-3 provides a promising target for development of therapies to enhance muscle regeneration in muscular dystrophies and in aged muscle.

  12. Anion exchanger 2 is critical for CD8(+) T cells to maintain pHi homeostasis and modulate immune responses

    NARCIS (Netherlands)

    Concepcion, Axel R.; Salas, January T.; Sarvide, Sarai; Sáez, Elena; Ferrer, Alex; López, María; Portu, Ainhoa; Banales, Jesús M.; Hervás-Stubbs, Sandra; Oude Elferink, Ronald P. J.; Prieto, Jesús; Medina, Juan F.

    2014-01-01

    Mitogenic stimulation of lymphocytes involves alkalinization of intracellular pH (pHi ). Subsequent pHi regulation may involve HCO3 (-) extrusion through Cl(-) /HCO3 (-) exchangers and/or Na(+) -HCO3 (-) co-transporters with acid-loading capability. Abnormalities in these mechanisms could result in

  13. SeP, ApoER2 and megalin as necessary factors to maintain Se homeostasis in mammals.

    Science.gov (United States)

    Krol, Magdalena Beata; Gromadzinska, Jolanta; Wasowicz, Wojciech

    2012-10-01

    Selenoprotein P (SeP) is an extracellular protein containing ten selenium atoms in the form of selenocysteine, secreted mainly from the liver. About 60% of the whole plasma selenium level is present in SeP, which makes it a useful biomarker of selenium nutritional status. The main functions of SeP are transport and storage of selenium in plasma. It is especially an important protein for the brain, testes and kidneys where the supplementation of the proper amount of Se ensures the synthesis of selenoenzymes with antioxidant properties.Recently, it has been found that SeP uptake in kidneys, testes and brain depends on the apolipoprotein receptor 2 (ApoER2) and lipoprotein megalin receptor (Lrp2). Megalin receptor represents a physiological SeP receptor in kidneys, mediating the re-uptake of secreted SeP from the primary urine. The absence of a functional megalin receptor causes a significant reduction of plasma selenium and the SeP levels as a result of Se excretion. ApoER2 is a SeP receptor in the brain and testes which uptakes Se from the extracellular fluid. Deletion of ApoER2 in mice leads to a lowered selenium level in the brain and testes, neurological dysfunction, production of abnormal spermatozoa, infertility and even death when the subjects are fed a low-selenium diet. Copyright © 2012 Elsevier GmbH. All rights reserved.

  14. Nrf1 CNC-bZIP protein promotes cell survival and nucleotide excision repair through maintaining glutathione homeostasis.

    Science.gov (United States)

    Han, Weinong; Ming, Mei; Zhao, Rui; Pi, Jingbo; Wu, Chunli; He, Yu-Ying

    2012-05-25

    Skin cancer is the most common cancer in the United States. Its major environmental risk factor is UVB radiation in sunlight. In response to UVB damage, epidermal keratinocytes activate a specific repair pathway, i.e. nucleotide excision repair, to remove UVB-induced DNA lesions. However, the regulation of UVB response is not fully understood. Here we show that the long isoform of the nuclear factor erythroid 2-related factor 1 (Nrf1, also called NFE2L1), a cytoprotective transcription factor critical for the expression of multiple antioxidant response element-dependent genes, plays an important role in the response of keratinocytes to UVB. Nrf1 loss sensitized keratinocytes to UVB-induced apoptosis by up-regulating the expression of the proapoptotic Bcl-2 family member Bik through reducing glutathione levels. Knocking down Bik reduced UVB-induced apoptosis in Nrf1-inhibited cells. In UVB-irradiated surviving cells, however, disruption of Nrf1 impaired nucleotide excision repair through suppressing the transcription of xeroderma pigmentosum C (XPC), a factor essential for initiating the global genome nucleotide excision repair by recognizing the DNA lesion and recruiting downstream factors. Nrf1 enhanced XPC expression by increasing glutathione availability but was independent of the transcription repressor of XPC. Adding XPC or glutathione restored the DNA repair capacity in Nrf1-inhibited cells. Finally, we demonstrate that Nrf1 levels are significantly reduced by UVB radiation in mouse skin and are lower in human skin tumors than in normal skin. These results indicate a novel role of Nrf1 in UVB-induced DNA damage repair and suggest Nrf1 as a tumor suppressor in the skin.

  15. The immune system, natural autoantibodies and general homeostasis in health and disease.

    Science.gov (United States)

    Poletaev, A; Boura, P

    2011-10-01

    It is generally accepted that the destination of the immune system is not only to discriminate between self and non-self but also to mount responses against non-self. During the last decades, it became evident that weak self-reactivity is a necessary condition for immune homeostasis. Natural self reactivity and the internal image created by autoantibodies, participate greatly to the maintenance of homeostasis. Under conditions of increased or altered antigenic pressure, the homeostatic status is disrupted and the organism becomes vulnerable to the emergence of diseases. "Immunculus" is the self-reactive and interconnected entity of the immune system, provided by a complicated network of natural autoantibobies of different specificity, as a mosaic picture. Quantitative changes in each part of the image are related to variations of expression of relative antigens. The immune system takes in account image information from the continuous screening of the antigenic status and compares between presented state and the desired (optimal) one. Substantial and prolonged deviations from the optimal state, triggers the induction of compensatory and reparative processes, aiming to restore molecular and functional homeostasis. So, natural autoimmunity through the ability of natural a-Abs to induce mechanisms of natural and acquired immunity, aims to prevent pathogenic processes and maintain or restore health status.

  16. Effect of intermittent cold exposure on brown fat activation, obesity, and energy homeostasis in mice.

    Directory of Open Access Journals (Sweden)

    Yann Ravussin

    Full Text Available Homeotherms have specific mechanisms to maintain a constant core body temperature despite changes in thermal environment, food supply, and metabolic demand. Brown adipose tissue, the principal thermogenic organ, quickly and efficiently increases heat production by dissipating the mitochondrial proton motive force. It has been suggested that activation of brown fat, via either environmental (i.e. cold exposure or pharmacologic means, could be used to increase metabolic rate and thus reduce body weight. Here we assess the effects of intermittent cold exposure (4°C for one to eight hours three times a week on C57BL/6J mice fed a high fat diet. Cold exposure increased metabolic rate approximately two-fold during the challenge and activated brown fat. In response, food intake increased to compensate fully for the increased energy expenditure; thus, the mice showed no reduction in body weight or adiposity. Despite the unchanged adiposity, the cold-treated mice showed transient improvements in glucose homeostasis. Administration of the cannabinoid receptor-1 inverse agonist AM251 caused weight loss and improvements in glucose homeostasis, but showed no further improvements when combined with cold exposure. These data suggest that intermittent cold exposure causes transient, meaningful improvements in glucose homeostasis, but without synergy when combined with AM251. Since energy expenditure is significantly increased during cold exposure, a drug that dissociates food intake from metabolic demand during cold exposure may achieve weight loss and further metabolic improvements.

  17. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    2008-09-01

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  18. A conceptual framework for homeostasis: development and validation

    Science.gov (United States)

    Wenderoth, Mary Pat; Michael, Joel; Cliff, William; Wright, Ann; Modell, Harold

    2016-01-01

    We have developed and validated a conceptual framework for understanding and teaching organismal homeostasis at the undergraduate level. The resulting homeostasis conceptual framework details critical components and constituent ideas underlying the concept of homeostasis. It has been validated by a broad range of physiology faculty members from community colleges, primarily undergraduate institutions, research universities, and medical schools. In online surveys, faculty members confirmed the relevance of each item in the framework for undergraduate physiology and rated the importance and difficulty of each. The homeostasis conceptual framework was constructed as a guide for teaching and learning of this critical core concept in physiology, and it also paves the way for the development of a concept inventory for homeostasis. PMID:27105740

  19. A conceptual framework for homeostasis: development and validation.

    Science.gov (United States)

    McFarland, Jenny; Wenderoth, Mary Pat; Michael, Joel; Cliff, William; Wright, Ann; Modell, Harold

    2016-06-01

    We have developed and validated a conceptual framework for understanding and teaching organismal homeostasis at the undergraduate level. The resulting homeostasis conceptual framework details critical components and constituent ideas underlying the concept of homeostasis. It has been validated by a broad range of physiology faculty members from community colleges, primarily undergraduate institutions, research universities, and medical schools. In online surveys, faculty members confirmed the relevance of each item in the framework for undergraduate physiology and rated the importance and difficulty of each. The homeostasis conceptual framework was constructed as a guide for teaching and learning of this critical core concept in physiology, and it also paves the way for the development of a concept inventory for homeostasis. Copyright © 2016 The American Physiological Society.

  20. Building and maintaining media contacts

    International Nuclear Information System (INIS)

    Fenton, Bob

    2000-01-01

    This presentation is answering the question: 'how does British Energy build and maintain its relationships with journalists in so many areas', not only the basic industrial correspondents that you would expect to have to deal with an industry British Energy, but those dealing with science and technology, the environment, personnel and training, city and financial, political, and on and on, and that is just the national press. Then add the local and regional media around power station sites - literally hundreds of contacts and you start to get an idea about the size of our media contact database. But it is managed it rather well. Every six months British Energy takes part in a survey run by one of the UK's leading market research companies who conducts a poll among journalists and then rate each company's performance. In the last three years British Energy has not been outside the top five in most categories, and in the top two in several. The answer is a lot of work over a long period of time. You cannot expect to build trusting relationships with a journalist overnight. At British Energy the key is being open and honest, and always available. Of course good media relations is not a one-way street, and there has to be some element of compromise if you are to achieve a relationship based on mutual trust