Science.gov

Sample records for a-dependent redox biology

  1. Redox biology of the intestine

    PubMed Central

    Circu, Magdalena L.; Aw, Tak Yee

    2011-01-01

    The intestinal tract, known for its capability for self-renew, represents the first barrier of defense between the organism and its luminal environment. The thiol/disulfide redox systems comprising the glutathione/glutathione disulfide (GSH/GSSG), cysteine/cystine (Cys/CySS) and reduced and oxidized thioredoxin (Trx/TrxSS) redox couples play important roles in preserving tissue redox homeostasis, metabolic functions, and cellular integrity. Control of the thiol-disulfide status at the luminal surface is essential for maintaining mucus fluidity and absorption of nutrients, and protection against chemical-induced oxidant injury. Within intestinal cells, these redox couples preserve an environment that supports physiological processes and orchestrates networks of enzymatic reactions against oxidative stress. In this review, we focus on the intestinal redox and antioxidant systems, their subcellular compartmentation, redox signaling and epithelial turnover, and contribution of luminal microbiota, key aspects that are relevant to understanding redox-dependent processes in gut biology with implications for degenerative digestive disorders, such as inflammation and cancer. PMID:21831010

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

    PubMed

    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.

  3. Dissecting Redox Biology Using Fluorescent Protein Sensors.

    PubMed

    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.

  4. Redox biology of tuberculosis pathogenesis.

    PubMed

    Trivedi, Abhishek; Singh, Nisha; Bhat, Shabir Ahmed; Gupta, Pawan; Kumar, Ashwani

    2012-01-01

    Mycobacterium tuberculosis (Mtb) is one of the most successful human pathogens. Mtb is persistently exposed to numerous oxidoreductive stresses during its pathogenic cycle of infection and transmission. The distinctive ability of Mtb, not only to survive the redox stress manifested by the host but also to use it for synchronizing the metabolic pathways and expression of virulence factors, is central to its success as a pathogen. This review describes the paradigmatic redox and hypoxia sensors employed by Mtb to continuously monitor variations in the intracellular redox state and the surrounding microenvironment. Two component proteins, namely, DosS and DosT, are employed by Mtb to sense changes in oxygen, nitric oxide, and carbon monoxide levels, while WhiB3 and anti-sigma factor RsrA are used to monitor changes in intracellular redox state. Using these and other unidentified redox sensors, Mtb orchestrates its metabolic pathways to survive in nutrient-deficient, acidic, oxidative, nitrosative, and hypoxic environments inside granulomas or infectious lesions. A number of these metabolic pathways are unique to mycobacteria and thus represent potential drug targets. In addition, Mtb employs versatile machinery of the mycothiol and thioredoxin systems to ensure a reductive intracellular environment for optimal functioning of its proteins even upon exposure to oxidative stress. Mtb also utilizes a battery of protective enzymes, such as superoxide dismutase (SOD), catalase (KatG), alkyl hydroperoxidase (AhpC), and peroxiredoxins, to neutralize the redox stress generated by the host immune system. This chapter reviews the current understanding of mechanisms employed by Mtb to sense and neutralize redox stress and their importance in TB pathogenesis and drug development. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

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

    PubMed

    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.

  7. Connecting Biology to Electronics: Molecular Communication via Redox Modality.

    PubMed

    Liu, Yi; Li, Jinyang; Tschirhart, Tanya; Terrell, Jessica L; Kim, Eunkyoung; Tsao, Chen-Yu; Kelly, Deanna L; Bentley, William E; Payne, Gregory F

    2017-12-01

    Biology and electronics are both expert at for accessing, analyzing, and responding to information. Biology uses ions, small molecules, and macromolecules to receive, analyze, store, and transmit information, whereas electronic devices receive input in the form of electromagnetic radiation, process the information using electrons, and then transmit output as electromagnetic waves. Generating the capabilities to connect biology-electronic modalities offers exciting opportunities to shape the future of biosensors, point-of-care medicine, and wearable/implantable devices. Redox reactions offer unique opportunities for bio-device communication that spans the molecular modalities of biology and electrical modality of devices. Here, an approach to search for redox information through an interactive electrochemical probing that is analogous to sonar is adopted. The capabilities of this approach to access global chemical information as well as information of specific redox-active chemical entities are illustrated using recent examples. An example of the use of synthetic biology to recognize external molecular information, process this information through intracellular signal transduction pathways, and generate output responses that can be detected by electrical modalities is also provided. Finally, exciting results in the use of redox reactions to actuate biology are provided to illustrate that synthetic biology offers the potential to guide biological response through electrical cues. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Linking mitochondrial bioenergetics to insulin resistance via redox biology

    PubMed Central

    Fisher-Wellman, Kelsey H.; Neufer, P. Darrell

    2012-01-01

    Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H2O2) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal to ultimately decrease insulin sensitivity. H2O2 is a major input to cellular redox circuits that link to cysteine residues throughout the entire proteome to regulate cell function. Here we review the principles of mitochondrial bioenergetics and redox systems biology and offer new insight as to how H2O2 emission may be linked via redox biology to the etiology of insulin resistance. PMID:22305519

  9. Chemistry and Redox Biology of Mycothiol.

    PubMed

    Reyes, Aníbal M; Pedre, Brandán; De Armas, María Inés; Tossounian, Maria-Armineh; Radi, Rafael; Messens, Joris; Trujillo, Madia

    2018-02-20

    Mycothiol (MSH, AcCys-GlcN-Ins) is the main low-molecular weight (LMW) thiol of most Actinomycetes, including the human pathogen Mycobacterium tuberculosis that affects millions of people worldwide. Strains with decreased MSH content show increased susceptibilities to hydroperoxides and electrophilic compounds. In M. tuberculosis, MSH modulates the response to several antituberculosis drugs. Enzymatic routes involving MSH could provide clues for specific drug design. Recent Advances: Physicochemical data argue against a rapid, nonenzymatic reaction of MSH with oxidants, disulfides, or electrophiles. Moreover, exposure of the bacteria to high concentrations of two-electron oxidants resulted in protein mycothiolation. The recently described glutaredoxin-like protein mycoredoxin-1 (Mrx-1) provides a route for catalytic reduction of mycothiolated proteins, protecting critical cysteines from irreversible oxidation. The description of MSH/Mrx-1-dependent activities of peroxidases helped to explain the higher susceptibility to oxidants observed in Actinomycetes lacking MSH. Moreover, the first mycothiol-S-transferase, member of the DinB superfamily of proteins, was described. In Corynebacterium, both the MSH/Mrx-1 and the thioredoxin pathways reduce methionine sulfoxide reductase A. A novel tool for in vivo imaging of the MSH/mycothiol disulfide (MSSM) status allows following changes in the mycothiol redox state during macrophage infection and its relationship with antibiotic sensitivity. Redundancy of MSH with other LMW thiols is starting to be unraveled and could help to rationalize the differences in the reported importance of MSH synthesis observed in vitro versus in animal infection models. Future work should be directed to establish the structural bases of the specificity of MSH-dependent enzymes, thus facilitating drug developments. Antioxid. Redox Signal. 28, 487-504.

  10. Subcellular Redox Targeting: Bridging in Vitro and in Vivo Chemical Biology.

    PubMed

    Long, Marcus J C; Poganik, Jesse R; Ghosh, Souradyuti; Aye, Yimon

    2017-03-17

    Networks of redox sensor proteins within discrete microdomains regulate the flow of redox signaling. Yet, the inherent reactivity of redox signals complicates the study of specific redox events and pathways by traditional methods. Herein, we review designer chemistries capable of measuring flux and/or mimicking subcellular redox signaling at the cellular and organismal level. Such efforts have begun to decipher the logic underlying organelle-, site-, and target-specific redox signaling in vitro and in vivo. These data highlight chemical biology as a perfect gateway to interrogate how nature choreographs subcellular redox chemistry to drive precision redox biology.

  11. Redox Biology Course Evaluation Form | Center for Cancer Research

    Cancer.gov

    To improve the Redox Biology (RB) course in future years, we would appreciate your feedback by completing this course evaluation. Please score the course elements as poor, fair, average, good or excellent. Please type any comments that you have in response to the questions at the bottom of the form. Remember to include your name as you wish it to appear on the certificate.

  12. Redox Biology Final Examination 2016 | Center for Cancer Research

    Cancer.gov

    Numerous registrants have requested a certificate upon completion of the Redox Biology (RB) course. In order to obtain a certificate, you must answer 8 of the 12 questions below correctly. In the final examination, 1 question is derived from each of the 1-hour lectures. It is highly recommended that you have a copy of each PowerPoint presentation prior to taking the

  13. Circulating membrane-derived microvesicles in redox biology.

    PubMed

    Larson, Michael Craig; Hillery, Cheryl A; Hogg, Neil

    2014-08-01

    Microparticles or microvesicles (MVs) are subcellular membrane blebs shed from all cells in response to various stimuli. MVs carry a battery of signaling molecules, many of them related to redox-regulated processes. The role of MVs, either as a cause or as a result of cellular redox signaling, has been increasingly recognized over the past decade. This is in part due to advances in flow cytometry and its detection of MVs. Notably, recent studies have shown that circulating MVs from platelets and endothelial cells drive reactive species-dependent angiogenesis; circulating MVs in cancer alter the microenvironment and enhance invasion through horizontal transfer of mutated proteins and nucleic acids and harbor redox-regulated matrix metalloproteinases and procoagulative surface molecules; and circulating MVs from red blood cells and other cells modulate cell-cell interactions through scavenging or production of nitric oxide and other free radicals. Although our recognition of MVs in redox-related processes is growing, especially in the vascular biology field, much remains unknown regarding the various biologic and pathologic functions of MVs. Like reactive oxygen and nitrogen species, MVs were originally believed to have a solely pathological role in biology. And like our understanding of reactive species, it is now clear that MVs also play an important role in normal growth, development, and homeostasis. We are just beginning to understand how MVs are involved in various biological processes-developmental, homeostatic, and pathological-and the role of MVs in redox signaling is a rich and exciting area of investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Circulating Membrane-Derived Microvesicles in Redox Biology

    PubMed Central

    Larson, Michael Craig; Hillery, Cheryl A.; Hogg, Neil

    2015-01-01

    Microparticles or microvesicles (MV) are sub-cellular membrane blebs shed from all cells in response to various stimuli. MVs carry a battery of signaling molecules, many of them related to redox-regulated processes. The role of MVs, either as a cause or result of cellular redox signaling has been increasingly recognized over the past decade. This is in part due to advances in flow cytometry and its detection of MVs. Notably, recent studies have shown circulating MVs from platelets and endothelial cells drive reactive species-dependent angiogenesis; circulating MVs in cancer alter the microenvironment and enhance invasion through horizontal transfer of mutated proteins and nucleic acids, and harbor redox-regulated matrix metalloproteinases and pro-coagulative surface molecules; and circulating MVs from RBCs and other cells modulate cell-cell interactions through scavenging or production of nitric oxide and other free radicals. While our recognition of MVs in redox-related processes is growing, especially in the vascular biology field, much remains unknown regarding the various biologic and pathologic functions of MVs. Like reactive oxygen and nitrogen species, MVs were originally believed to have a solely a pathological role in biology. And like our understanding of reactive species, it is now clear that MVs also play an important role in normal growth, development, and homeostasis. We are just beginning to understand how MVs are involved in various biological processes—developmental, homeostatic and pathological—and the role of MVs in redox signaling is an rich and exciting area of investigation. PMID:24751526

  15. Redox Biology Course Evaluation Form | Center for Cancer Research

    Cancer.gov

    To improve the Redox Biology (RB) course in future years, we would appreciate your feedback by completing this course evaluation. Please score the course elements as poor, fair, average, good or excellent. Please type any comments that you have in response to the questions at the bottom of the form. Remember to include your name as you wish it to appear on the certificate. Thank you for your feedback.

  16. Redox Biology Final Examination 2016 | Center for Cancer Research

    Cancer.gov

    Numerous registrants have requested a certificate upon completion of the Redox Biology (RB) course. In order to obtain a certificate, you must answer 8 of the 12 questions below correctly. In the final examination, 1 question is derived from each of the 1-hour lectures. It is highly recommended that you have a copy of each PowerPoint presentation prior to taking the examination.

  17. Redox Biology Course Registration Form | Center for Cancer Research

    Cancer.gov

    The Redox Biology class is open to all NIH/NCI fellows and staff and will be held Septhember 27 - November 8, 2016. The last day to register is: September 21, 2016. The first 100 registrants will be accepted for the class. Those who plan to participate by Video TeleConference should also register so that you can receive the speaker handouts in advance.

  18. Redox biology response in germinating Phaseolus vulgaris seeds exposed to copper: Evidence for differential redox buffering in seedlings and cotyledon.

    PubMed

    Karmous, Inès; Trevisan, Rafael; El Ferjani, Ezzeddine; Chaoui, Abdelilah; Sheehan, David

    2017-01-01

    In agriculture, heavy metal contamination of soil interferes with processes associated with plant growth, development and productivity. Here, we describe oxidative and redox changes, and deleterious injury within cotyledons and seedlings caused by exposure of germinating (Phaseolus vulgaris L. var. soisson nain hâtif) seeds to copper (Cu). Cu induced a marked delay in seedling growth, and was associated with biochemical disturbances in terms of intracellular oxidative status, redox regulation and energy metabolism. In response to these alterations, modulation of activities of antioxidant proteins (thioredoxin and glutathione reductase, peroxiredoxin) occurred, thus preventing oxidative damage. In addition, oxidative modification of proteins was detected in both cotyledons and seedlings by one- and two-dimensional electrophoresis. These modified proteins may play roles in redox buffering. The changes in activities of redox proteins underline their fundamental roles in controlling redox homeostasis. However, observed differential redox responses in cotyledon and seedling tissues showed a major capacity of the seedlings' redox systems to protect the reduced status of protein thiols, thus suggesting quantitatively greater antioxidant protection of proteins in seedlings compared to cotyledon. To our knowledge, this is the first comprehensive redox biology investigation of the effect of Cu on seed germination.

  19. The redox biology network in cancer pathophysiology and therapeutics.

    PubMed

    Manda, Gina; Isvoranu, Gheorghita; Comanescu, Maria Victoria; Manea, Adrian; Debelec Butuner, Bilge; Korkmaz, Kemal Sami

    2015-08-01

    The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1) and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic), greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular heterogeneity and the

  20. Redox behavior and biological properties of ferrocene bearing porphyrins.

    PubMed

    Lippert, Rainer; Shubina, Tatyana E; Vojnovic, Sandra; Pavic, Aleksandar; Veselinovic, Jovana; Nikodinovic-Runic, Jasmina; Stankovic, Nada; Ivanović-Burmazović, Ivana

    2017-06-01

    In order to improve antimicrobial effects of previously studied meso-tetrakis(4-ferrocenylphenyl)porphyrin 1, we have modified its structure by replacing two trans-positioned ferrocenylphenyl moieties with methoxy methylene substituted tert-butylphenyl moieties. Newly synthesized 5 4 ,15 4 -bis-(ferrocenyl)-10 4 ,20 4 -bis-(tert-butyl)-10 2 ,10 6 ,20 2 ,20 6 -tetrakis-(methoxy-methylene)-5,10,15,20-tetraphenylporphyrin 4 was chemically characterized in detail (by NMR, UV/Vis, IR, MALDI-TOF and ESI MS spectrometry, cyclic voltammetry, prediction of the relative lipophilicity as well as computational methods) and its biological effects were studied in terms of its antibacterial and antifungal activity (both with and without photoactivation), cytotoxicity, hemolysis and DNA cleavage. New ferrocene bearing porphyrin 4 has demonstrated a broader antimicrobial spectrum and modified effects on eukaryotic cells compared to 1. This was discussed in terms of its i) increased lipophilicity, while exhibiting lower toxicity, and ii) the redox potential of a two-electron process that is shifted to lower values, in comparison to ferrocene, thus, entering the physiologically available range and being activated towards redox interactions with biomolecules. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. ROSICS: CHEMISTRY AND PROTEOMICS OF CYSTEINE MODIFICATIONS IN REDOX BIOLOGY

    PubMed Central

    Kim, Hee-Jung; Ha, Sura; Lee, Hee Yoon; Lee, Kong-Joo

    2015-01-01

    Post-translational modifications (PTMs) occurring in proteins determine their functions and regulations. Proteomic tools are available to identify PTMs and have proved invaluable to expanding the inventory of these tools of nature that hold the keys to biological processes. Cysteine (Cys), the least abundant (1–2%) of amino acid residues, are unique in that they play key roles in maintaining stability of protein structure, participating in active sites of enzymes, regulating protein function and binding to metals, among others. Cys residues are major targets of reactive oxygen species (ROS), which are important mediators and modulators of various biological processes. It is therefore necessary to identify the Cys-containing ROS target proteins, as well as the sites and species of their PTMs. Cutting edge proteomic tools which have helped identify the PTMs at reactive Cys residues, have also revealed that Cys residues are modified in numerous ways. These modifications include formation of disulfide, thiosulfinate and thiosulfonate, oxidation to sulfenic, sulfinic, sulfonic acids and thiosulfonic acid, transformation to dehydroalanine (DHA) and serine, palmitoylation and farnesylation, formation of chemical adducts with glutathione, 4-hydroxynonenal and 15-deoxy PGJ2, and various other chemicals. We present here, a review of relevant ROS biology, possible chemical reactions of Cys residues and details of the proteomic strategies employed for rapid, efficient and sensitive identification of diverse and novel PTMs involving reactive Cys residues of redox-sensitive proteins. We propose a new name, “ROSics,” for the science which describes the principles of mode of action of ROS at molecular levels. © 2014 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc. Rapid Commun. Mass Spec Rev 34:184–208, 2015. PMID:24916017

  2. Probing biological redox chemistry with large amplitude Fourier transformed ac voltammetry

    PubMed Central

    Adamson, Hope

    2017-01-01

    Biological electron-exchange reactions are fundamental to life on earth. Redox reactions underpin respiration, photosynthesis, molecular biosynthesis, cell signalling and protein folding. Chemical, biomedical and future energy technology developments are also inspired by these natural electron transfer processes. Further developments in techniques and data analysis are required to gain a deeper understanding of the redox biochemistry processes that power Nature. This review outlines the new insights gained from developing Fourier transformed ac voltammetry as a tool for protein film electrochemistry. PMID:28804798

  3. Biological Hydropersulfides and Related Polysulfides: A New Concept and Perspective in Redox Biology.

    PubMed

    Fukuto, Jon M; Ignarro, Louis J; Nagy, Peter; Wink, David A; Kevil, Christopher G; Feelisch, Martin; Cortese-Krott, Miriam M; Bianco, Christopher L; Kumagai, Yoshito; Hobbs, Adrian J; Lin, Joseph; Ida, Tomoaki; Akaike, Takaaki

    2018-05-12

    The chemical biology of thiols (RSH, e.g., cysteine and cysteine containing proteins/peptides) has been a topic of extreme interest for many decades due to their reported roles in protein structure/folding, redox signaling, metal ligation, cellular protection and enzymology. While many of the studies on thiol/sulfur biochemistry have focused on thiols, relatively ignored have been hydropersulfides (RSSH) and higher order polysulfur species (RSS n H, RSS n R, n > 1). Recent and provocative work has alluded to the prevalence and likely physiological importance of RSSH and related RSS n H. RSSH of cysteine (Cys-SSH) has been found to be prevalent in mammalian systems along with Cys-SSH-containing proteins. The RSSH functionality has not been examined to the extent of other biologically relevant sulfur derivatives (e.g., sulfenic acids, disulfides, etc.), whose roles in cell signaling are strongly indicated. The recent finding of Cys-SSH biosynthesis and translational incorporation into proteins is an unequivocal indication of its fundamental importance and necessitates a more profound look into the physiology of RSSH. In this Review, we discuss the currently reported chemical biology of RSSH (and related species) as a prelude to discussing their possible physiological roles. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Analysis of Cysteine Redox Post-Translational Modifications in Cell Biology and Drug Pharmacology.

    PubMed

    Wani, Revati; Murray, Brion W

    2017-01-01

    Reversible cysteine oxidation is an emerging class of protein post-translational modification (PTM) that regulates catalytic activity, modulates conformation, impacts protein-protein interactions, and affects subcellular trafficking of numerous proteins. Redox PTMs encompass a broad array of cysteine oxidation reactions with different half-lives, topographies, and reactivities such as S-glutathionylation and sulfoxidation. Recent studies from our group underscore the lesser known effect of redox protein modifications on drug binding. To date, biological studies to understand mechanistic and functional aspects of redox regulation are technically challenging. A prominent issue is the lack of tools for labeling proteins oxidized to select chemotype/oxidant species in cells. Predictive computational tools and curated databases of oxidized proteins are facilitating structural and functional insights into regulation of the network of oxidized proteins or redox proteome. In this chapter, we discuss analytical platforms for studying protein oxidation, suggest computational tools currently available in the field to determine redox sensitive proteins, and begin to illuminate roles of cysteine redox PTMs in drug pharmacology.

  5. Biological Redox Cycling Of Iron In Nontronite And Its Potential Application In Nitrate Removal

    SciTech Connect

    Zhao, Linduo; Dong, Hailiang; Kukkadapu, Ravi K.

    2015-05-05

    Redox cycling of structural Fe in phyllosilicates provides a potential method to remediate nitrate contamination in natural environment. Past research has only studied chemical redox cycles or a single biologically mediated redox cycle of Fe in phyllosilicates. The objective of this research was to study three microbially driven redox cycles of Fe in one phyllosilicate, nontronite (NAu-2). During the reduction phase structural Fe(III) in NAu-2 served as electron acceptor, lactate as electron donor, AQDS as electron shuttle, and dissimilatory Fe(III)-reducing bacteria Shewanella putrefaciens CN32 as mediator in bicarbonate-buffered and PIPES-buffered media. During the oxidation phase, biogenic Fe(II) served an electronmore » donor, nitrate as electron acceptor, and nitrate-dependent Fe(II)-oxidizing bacteria Pseudogulbenkiania sp. strain 2002 as mediator in the same media. For all three cycles, structural Fe in NAu-2 was able to reversibly undergo 3 redox cycles without significant reductive or oxidative dissolution. X-ray diffraction and scanning and transmission electron microscopy revealed that NAu-2 was the dominant residual mineral throughout the 3 redox cycles with some dissolution textures but no significant secondary mineralization. Mössbauer spectroscopy revealed that Fe(II) in bio-reduced samples likely occurred in two distinct environments, at edges and the interior of the NAu-2 structure. Nitrate was completely reduced to nitrogen gas under both buffer conditions and this extent and rate did not change with Fe redox cycles. Mössbauer spectroscopy further revealed that nitrate reduction was coupled to predominant/preferred oxidation of edge Fe(II). These results suggest that structural Fe in phyllosilicates may represent a renewable source to continuously remove nitrate in natural environments.« less

  6. Reactions of copper macrocycles with antioxidants and HOCl: potential for biological redox sensing.

    PubMed

    Sowden, Rebecca J; Trotter, Katherine D; Dunbar, Lynsey; Craig, Gemma; Erdemli, Omer; Spickett, Corinne M; Reglinski, John

    2013-02-01

    A series of simple copper N(2)S(2) macrocycles were examined for their potential as biological redox sensors, following previous characterization of their redox potentials and crystal structures. The divalent species were reduced by glutathione or ascorbate at a biologically relevant pH in aqueous buffer. A less efficient reduction was also achieved by vitamin E in DMSO. Oxidation of the corresponding univalent copper species by sodium hypochlorite resulted in only partial (~65 %) recovery of the divalent form. This was concluded to be due to competition between metal oxidation and ligand oxidation, which is believed to contribute to macrocycle demetallation. Electrospray mass spectrometry confirmed that ligand oxidation had occurred. Moreover, the macrocyclic complexes could be demetallated by incubation with EDTA and bovine serum albumin, demonstrating that they would be inappropriate for use in biological systems. The susceptibility to oxidation and demetallation was hypothesized to be due to oxidation of the secondary amines. Consequently these were modified to incorporate additional oxygen donor atoms. This modification led to greater resistance to demetallation and ligand oxidation, providing a better platform for further development of copper macrocycles as redox sensors for use in biological systems.

  7. Challenges and Opportunities for Small-Molecule Fluorescent Probes in Redox Biology Applications.

    PubMed

    Jiang, Xiqian; Wang, Lingfei; Carroll, Shaina L; Chen, Jianwei; Wang, Meng C; Wang, Jin

    2018-02-16

    The concentrations of reactive oxygen/nitrogen species (ROS/RNS) are critical to various biochemical processes. Small-molecule fluorescent probes have been widely used to detect and/or quantify ROS/RNS in many redox biology studies and serve as an important complementary to protein-based sensors with unique applications. Recent Advances: New sensing reactions have emerged in probe development, allowing more selective and quantitative detection of ROS/RNS, especially in live cells. Improvements have been made in sensing reactions, fluorophores, and bioavailability of probe molecules. In this review, we will not only summarize redox-related small-molecule fluorescent probes but also lay out the challenges of designing probes to help redox biologists independently evaluate the quality of reported small-molecule fluorescent probes, especially in the chemistry literature. We specifically highlight the advantages of reversibility in sensing reactions and its applications in ratiometric probe design for quantitative measurements in living cells. In addition, we compare the advantages and disadvantages of small-molecule probes and protein-based probes. The low physiological relevant concentrations of most ROS/RNS call for new sensing reactions with better selectivity, kinetics, and reversibility; fluorophores with high quantum yield, wide wavelength coverage, and Stokes shifts; and structural design with good aqueous solubility, membrane permeability, low protein interference, and organelle specificity. Antioxid. Redox Signal. 00, 000-000.

  8. Competing for phosphors under changing redox conditions: biological versus geochemical sinks

    NASA Astrophysics Data System (ADS)

    Gross, A.; Pett-Ridge, J.; Silver, W. L.

    2016-12-01

    Competing for phosphorus under changing redox conditions: biological versus geochemical sinksAvner Gross1, Jennifer Pett-Ridge2 and Whendee L Silver1 University of California Berkeley, Department of Environmental Science, Policy, & Management, Berkeley, CA, USA. Lawrence Livermore National Laboratory, Physical and Life Science Directorate, Livermore, CA, USA. The cycling of phosphorous (P) in highly weathered, humid tropical forest soils is tightly regulated by P sorption dynamics to the surfaces of Fe(III) (hydr)oxides and root and microbial demands for P. Periods of anoxic soil conditions, which are common in humid environments, induce the reduction of Fe (III) to Fe (II) and may release sorbed P into the soil solution. The microbial demand for P is influenced by the C and nutrient composition of their available substrates. Therefore, we hypothesize that soil redox conditions and substrate quality and availability will control the partitioning of P between microbial biomass and the soil mineral phase. The aim of this study was to examine how fluctuations in soil redox conditions and changes in microbial P demand affect the fate of new P that enters the soil solution. To achieve this aim we conducted a series of soil incubation experiments using a wet tropical soil from Puerto Rico (where redox conditions and P availability naturally oscillate) with a single pulse of phosphate (PO4), altering both the microbial activity and redox conditions. To follow the fate the added P, the added phosphate was labeled with 18O. As the exchange of oxygen between phosphate and water only occurs during biological processes, P-18O labeling can be used as an indicator of microbial use. To quantify sizes of the microbial and mineral P pools we used traditional chemical extractions in the bulk scale. We used NanoSIMS isotopic imaging to map the distribution of P-16O and P-18O and co-localization with Fe minerals at the nano scale. Our results show that the amount of the added P fixed

  9. Electrochemical reverse engineering: A systems-level tool to probe the redox-based molecular communication of biology.

    PubMed

    Li, Jinyang; Liu, Yi; Kim, Eunkyoung; March, John C; Bentley, William E; Payne, Gregory F

    2017-04-01

    The intestine is the site of digestion and forms a critical interface between the host and the outside world. This interface is composed of host epithelium and a complex microbiota which is "connected" through an extensive web of chemical and biological interactions that determine the balance between health and disease for the host. This biology and the associated chemical dialogues occur within a context of a steep oxygen gradient that provides the driving force for a variety of reduction and oxidation (redox) reactions. While some redox couples (e.g., catecholics) can spontaneously exchange electrons, many others are kinetically "insulated" (e.g., biothiols) allowing the biology to set and control their redox states far from equilibrium. It is well known that within cells, such non-equilibrated redox couples are poised to transfer electrons to perform reactions essential to immune defense (e.g., transfer from NADH to O 2 for reactive oxygen species, ROS, generation) and protection from such oxidative stresses (e.g., glutathione-based reduction of ROS). More recently, it has been recognized that some of these redox-active species (e.g., H 2 O 2 ) cross membranes and diffuse into the extracellular environment including lumen to transmit redox information that is received by atomically-specific receptors (e.g., cysteine-based sulfur switches) that regulate biological functions. Thus, redox has emerged as an important modality in the chemical signaling that occurs in the intestine and there have been emerging efforts to develop the experimental tools needed to probe this modality. We suggest that electrochemistry provides a unique tool to experimentally probe redox interactions at a systems level. Importantly, electrochemistry offers the potential to enlist the extensive theories established in signal processing in an effort to "reverse engineer" the molecular communication occurring in this complex biological system. Here, we review our efforts to develop this

  10. The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine.

    PubMed

    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.

  11. The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine

    PubMed Central

    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.

    2017-01-01

    Abstract Significance: 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. Critical Issues: 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. Future Directions: 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

  12. Species-Specific Thiol-Disulfide Equilibrium Constant: A Tool To Characterize Redox Transitions of Biological Importance.

    PubMed

    Mirzahosseini, Arash; Somlyay, Máté; Noszál, Béla

    2015-08-13

    Microscopic redox equilibrium constants, a new species-specific type of physicochemical parameters, were introduced and determined to quantify thiol-disulfide equilibria of biological significance. The thiol-disulfide redox equilibria of glutathione with cysteamine, cysteine, and homocysteine were approached from both sides, and the equilibrium mixtures were analyzed by quantitative NMR methods to characterize the highly composite, co-dependent acid-base and redox equilibria. The directly obtained, pH-dependent, conditional constants were then decomposed by a new evaluation method, resulting in pH-independent, microscopic redox equilibrium constants for the first time. The 80 different, microscopic redox equilibrium constant values show close correlation with the respective thiolate basicities and provide sound means for the development of potent agents against oxidative stress.

  13. Investigation of some biologically relevant redox reactions using electrochemical mass spectrometry interfaced by desorption electrospray ionization.

    PubMed

    Lu, Mei; Wolff, Chloe; Cui, Weidong; Chen, Hao

    2012-04-01

    Recently we have shown that, as a versatile ionization technique, desorption electrospray ionization (DESI) can serve as a useful interface to combine electrochemistry (EC) with mass spectrometry (MS). In this study, the EC/DESI-MS method has been further applied to investigate some aqueous phase redox reactions of biological significance, including the reduction of peptide disulfide bonds and nitroaromatics as well as the oxidation of phenothiazines. It was found that knotted/enclosed disulfide bonds in the peptides apamin and endothelin could be electrochemically cleaved. Subsequent tandem MS analysis of the resulting reduced peptide ions using collision-induced dissociation (CID) and electron-capture dissociation (ECD) gave rise to extensive fragment ions, providing a fast protocol for sequencing peptides with complicated disulfide bond linkages. Flunitrazepam and clonazepam, a class of nitroaromatic drugs, are known to undergo reduction into amines which was proposed to involve nitroso and N-hydroxyl intermediates. Now in this study, these corresponding intermediate ions were successfully intercepted and their structures were confirmed by CID. This provides mass spectrometric evidence for the mechanism of the nitro to amine conversion process during nitroreduction, an important redox reaction involved in carcinogenesis. In addition, the well-known oxidation reaction of chlorpromazine was also examined. The putative transient one-electron transfer product, the chlorpromazine radical cation (m/z 318), was captured by MS, for the first time, and its structure was also verified by CID. In addition to these observations, some features of the DESI-interfaced electrochemical mass spectrometry were discussed, such as simple instrumentation and the lack of background signal. These results further demonstrate the feasibility of EC/DESI-MS for the study of the biology-relevant redox chemistry and would find applications in proteomics and drug development research.

  14. Applying the Nernst equation to simulate redox potential variations for biological nitrification and denitrification processes.

    PubMed

    Chang, Cheng-Nan; Cheng, Hong-Bang; Chao, Allen C

    2004-03-15

    In this paper, various forms of Nernst equations have been developed based on the real stoichiometric relationship of biological nitrification and denitrification reactions. Instead of using the Nernst equation based on a one-to-one stoichiometric relation for the oxidizing and the reducing species, the basic Nernst equation is modified into slightly different forms. Each is suitable for simulating the redox potential (ORP) variation of a specific biological nitrification or denitrification process. Using the data published in the literature, the validity of these developed Nernst equations has been verified by close fits of the measured ORP data with the calculated ORP curve. The simulation results also indicate that if the biological process is simulated using an incorrect form of Nernst equation, the calculated ORP curve will not fit the measured data. Using these Nernst equations, the ORP value that corresponds to a predetermined degree of completion for the biochemical reaction can be calculated. Thus, these Nernst equations will enable a more efficient on-line control of the biological process.

  15. Redox chemistry of molybdenum in natural waters and its involvement in biological evolution

    PubMed Central

    Wang, Deli

    2012-01-01

    The transition element molybdenum (Mo) possesses diverse valances (+II to +VI), and is involved in forming cofactors in more than 60 enzymes in biology. Redox switching of the element in these enzymes catalyzes a series of metabolic reactions in both prokaryotes and eukaryotes, and the element therefore plays a fundamental role in the global carbon, nitrogen, and sulfur cycling. In the present oxygenated waters, oxidized Mo(VI) predominates thermodynamically, whilst reduced Mo species are mainly confined within specific niches including cytoplasm. Only recently has the reduced Mo(V) been separated from Mo(VI) in sulfidic mats and even in some reducing waters. Given the presence of reduced Mo(V) in contemporary anaerobic habitats, it seems that reduced Mo species were present in the ancient reducing ocean (probably under both ferruginous and sulfidic conditions), prompting the involvement of Mo in enzymes including nitrogenase and nitrate reductase. During the global transition to oxic conditions, reduced Mo species were constrained to specific anaerobic habitats, and efficient uptake systems of oxidized Mo(VI) became a selective advantage for current prokaryotic and eukaryotic cells. Some prokaryotes are still able to directly utilize reduced Mo if any exists in ambient environments. In total, this mini-review describes the redox chemistry and biogeochemistry of Mo over the Earth’s history. PMID:23267355

  16. Electron Bifurcation: Thermodynamics and Kinetics of Two-Electron Brokering in Biological Redox Chemistry

    SciTech Connect

    Zhang, Peng; Yuly, Jonathon L.; Lubner, Carolyn E.

    How can proteins drive two electrons from a redox active donor onto two acceptors at very different potentials and distances? And how can this transaction be conducted without dissipating very much energy or violating the laws of thermodynamics? Nature appears to have addressed these challenges by coupling thermodynamically uphill and downhill electron transfer reactions, using two-electron donor cofactors that have very different potentials for the removal of the first and second electron. Although electron bifurcation is carried out with near perfection from the standpoint of energy conservation and electron delivery yields, it is a biological energy transduction paradigm that hasmore » only come into focus recently. This Account provides an exegesis of the biophysical principles that underpin electron bifurcation.« less

  17. Electron Bifurcation: Thermodynamics and Kinetics of Two-Electron Brokering in Biological Redox Chemistry.

    PubMed

    Zhang, Peng; Yuly, Jonathon L; Lubner, Carolyn E; Mulder, David W; King, Paul W; Peters, John W; Beratan, David N

    2017-09-19

    How can proteins drive two electrons from a redox active donor onto two acceptors at very different potentials and distances? And how can this transaction be conducted without dissipating very much energy or violating the laws of thermodynamics? Nature appears to have addressed these challenges by coupling thermodynamically uphill and downhill electron transfer reactions, using two-electron donor cofactors that have very different potentials for the removal of the first and second electron. Although electron bifurcation is carried out with near perfection from the standpoint of energy conservation and electron delivery yields, it is a biological energy transduction paradigm that has only come into focus recently. This Account provides an exegesis of the biophysical principles that underpin electron bifurcation. Remarkably, bifurcating electron transfer (ET) proteins typically send one electron uphill and one electron downhill by similar energies, such that the overall reaction is spontaneous, but not profligate. Electron bifurcation in the NADH-dependent reduced ferredoxin: NADP + oxidoreductase I (Nfn) is explored in detail here. Recent experimental progress in understanding the structure and function of Nfn allows us to dissect its workings in the framework of modern ET theory. The first electron that leaves the two-electron donor flavin (L-FAD) executes a positive free energy "uphill" reaction, and the departure of this electron switches on a second thermodynamically spontaneous ET reaction from the flavin along a second pathway that moves electrons in the opposite direction and at a very different potential. The singly reduced ET products formed from the bifurcating flavin are more than two nanometers distant from each other. In Nfn, the second electron to leave the flavin is much more reducing than the first: the potentials are said to be "crossed." The eventually reduced cofactors, NADH and ferredoxin in the case of Nfn, perform crucial downstream redox

  18. Gold core/ceria shell-based redox active nanozyme mimicking the biological multienzyme complex phenomenon

    SciTech Connect

    Bhagat, Stuti; Srikanth Vallabani, N. V.; Shutthanandan, Vaithiyalingam

    Catalytically active individual gold (Au) and cerium oxide (CeO2) nanoparticles are well known to exhibit specific enzyme-like activities, such as natural catalase, oxidase, superoxide dismutase, and peroxidase enzymes. These activities have been maneuvered to design several biological applications such as immunoassays, glucose detection, radiation and free radical protection and tissue engineering. A functional nanozyme depicting multienzyme like properties that functions as a synthetic super enzyme has eluded the researchers in the nanoscience community for past decade. In current report, we have designed a functional multienzyme in the form of Gold (core)-CeO2 (shell) nanoparticles (Au@CeO2 CSNPs) exhibiting excellent peroxidase, catalase andmore » superoxide dismutase enzyme-like activities that are controlled simply by tuning the pH. The reaction kinetic parameters reveal that the peroxidase-like activity of this core shell nanozyme is comparable to natural HRP enzyme. Unlike peroxidase-like activity exhibited by other nanomaterials, Au@CeO2 CSNPs showed decrease in hydroxyl radical formation, suggesting that the bio catalytic reactions are performed by efficient electron transfers. A significant enzyme-like activity of this core shell nanoparticle was conserved at extreme pH (2 – 11) and temperatures (up to 90 °C), clearly suggesting the superiority over natural enzymes. Further, the utility of peroxidase-like activity of this core shell nanoparticles was extended for the detection of glucose, which showed a linear range of detection between (100 µM – 1 mM). It is hypothesized that the proximity of the redox potentials of Au+/Au and Ce (III)/Ce (IV) may result in a redox couple promoting the multienzyme activity of core shell nanoparticles. Au@CeO2 CSNPs may open new directions for development of single platform sensors in multiple biosensing applications.« less

  19. Gold core/Ceria shell-based redox active nanozyme mimicking the biological multienzyme complex phenomenon

    DOE PAGES

    Bhagat, Stuti; Srikanth Vallabani, NV; Shutthanandan, Vaithiyalingam; ...

    2017-12-02

    Catalytically active individual gold (Au) and cerium oxide (CeO 2) nanoparticles (NPs) are well known to exhibit specific enzyme-like activities, such as natural catalase, oxidase, superoxide dismutase, and peroxidase enzymes. Our activities have been maneuvered to design several biological applications such as immunoassays, glucose detection, radiation and free radical protection and tissue engineering. In biological systems, multienzyme complexes are involved in catalyzing important reactions of essential metabolic processes such as respiration, biomolecule synthesis, and photosynthesis. It is well known that metabolic processes linked with multienzyme complexes offer several advantages over reactions catalyzed by individual enzymes. A functional nanozyme depicting multienzymemore » like properties has eluded the researchers in the nanoscience community for the past few decades. Here, we have designed a functional multienzyme in the form of Gold (core)-CeO 2 (shell) nanoparticles (Au/CeO 2 CSNPs) exhibiting excellent peroxidase, catalase, and superoxide dismutase enzyme-like activities that are controlled simply by tuning the pH. The reaction kinetic parameters reveal that the peroxidase-like activity of this core-shell nanozyme is comparable to natural horseradish peroxidase (HRP) enzyme. Unlike peroxidase-like activity exhibited by other nanomaterials, Au/CeO 2 CSNPs showed a decrease in hydroxyl radical formation, suggesting that the biocatalytic reactions are performed by efficient electron transfers. A significant enzyme-like activity of this core-shell nanoparticle was conserved at extreme pH (2 – 11) and temperatures (up to 90 °C), clearly suggesting the superiority over natural enzymes. Further, the utility of peroxidase-like activity of this core-shell nanoparticles was extended for the detection of glucose, which showed a linear range of detection between (100 µM – 1 mM). It is hypothesized that the proximity of the redox potentials of Au

  20. Gold core/Ceria shell-based redox active nanozyme mimicking the biological multienzyme complex phenomenon

    SciTech Connect

    Bhagat, Stuti; Srikanth Vallabani, NV; Shutthanandan, Vaithiyalingam

    Catalytically active individual gold (Au) and cerium oxide (CeO 2) nanoparticles (NPs) are well known to exhibit specific enzyme-like activities, such as natural catalase, oxidase, superoxide dismutase, and peroxidase enzymes. Our activities have been maneuvered to design several biological applications such as immunoassays, glucose detection, radiation and free radical protection and tissue engineering. In biological systems, multienzyme complexes are involved in catalyzing important reactions of essential metabolic processes such as respiration, biomolecule synthesis, and photosynthesis. It is well known that metabolic processes linked with multienzyme complexes offer several advantages over reactions catalyzed by individual enzymes. A functional nanozyme depicting multienzymemore » like properties has eluded the researchers in the nanoscience community for the past few decades. Here, we have designed a functional multienzyme in the form of Gold (core)-CeO 2 (shell) nanoparticles (Au/CeO 2 CSNPs) exhibiting excellent peroxidase, catalase, and superoxide dismutase enzyme-like activities that are controlled simply by tuning the pH. The reaction kinetic parameters reveal that the peroxidase-like activity of this core-shell nanozyme is comparable to natural horseradish peroxidase (HRP) enzyme. Unlike peroxidase-like activity exhibited by other nanomaterials, Au/CeO 2 CSNPs showed a decrease in hydroxyl radical formation, suggesting that the biocatalytic reactions are performed by efficient electron transfers. A significant enzyme-like activity of this core-shell nanoparticle was conserved at extreme pH (2 – 11) and temperatures (up to 90 °C), clearly suggesting the superiority over natural enzymes. Further, the utility of peroxidase-like activity of this core-shell nanoparticles was extended for the detection of glucose, which showed a linear range of detection between (100 µM – 1 mM). It is hypothesized that the proximity of the redox potentials of Au

  1. Using a Redox Modality to Connect Synthetic Biology to Electronics: Hydrogel-Based Chemo-Electro Signal Transduction for Molecular Communication.

    PubMed

    Liu, Yi; Tsao, Chen-Yu; Kim, Eunkyoung; Tschirhart, Tanya; Terrell, Jessica L; Bentley, William E; Payne, Gregory F

    2017-01-01

    A hydrogel-based dual film coating is electrofabricated for transducing bio-relevant chemical information into electronical output. The outer film has a synthetic biology construct that recognizes an external molecular signal and transduces this input into the expression of an enzyme that converts redox-inactive substrate into a redox-active intermediate, which is detected through an amplification mechanism of the inner redox-capacitor film. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

    PubMed Central

    Kaur, Sukhbir

    2017-01-01

    Abstract Significance: In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H2S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H2S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Critical Issues: Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Future Directions: Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874–911. PMID:28712304

  3. Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer.

    PubMed

    Roberts, David D; Kaur, Sukhbir; Isenberg, Jeffrey S

    2017-10-20

    In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H 2 S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H 2 S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874-911.

  4. Elucidation of the Biological Redox Chemistry of Purines Using Electrochemical Techniques.

    ERIC Educational Resources Information Center

    Dryhurst, Glenn; And Others

    1983-01-01

    Electrochemical studies can give insights into the chemical aspects of enzymatic and in vivo redox reactions of naturally occurring organic compounds. This is illustrated by studies of the electrochemical oxidation of the purinem uric acid. The discussion is limited to information at pH 7 or greater. (JN)

  5. Hemoglobin and Myoglobin as Reducing Agents in Biological Systems. Redox Reactions of Globins with Copper and Iron Salts and Complexes.

    PubMed

    Postnikova, G B; Shekhovtsova, E A

    2016-12-01

    In addition to reversible O2 binding, respiratory proteins of the globin family, hemoglobin (Hb) and myoglobin (Mb), participate in redox reactions with various metal complexes, including biologically significant ones, such as those of copper and iron. HbO 2 and MbO 2 are present in cells in large amounts and, as redox agents, can contribute to maintaining cell redox state and resisting oxidative stress. Divalent copper complexes with high redox potentials (E 0 , 200-600 mV) and high stability constants, such as [Cu(phen) 2 ] 2+ , [Cu(dmphen) 2 ] 2+ , and CuDTA oxidize ferrous heme proteins by the simple outer-sphere electron transfer mechanism through overlapping π-orbitals of the heme and the copper complex. Weaker oxidants, such as Cu2+, CuEDTA, CuNTA, CuCit, CuATP, and CuHis (E 0 ≤ 100-150 mV) react with HbO 2 and MbO 2 through preliminary binding to the protein with substitution of the metal ligands with protein groups and subsequent intramolecular electron transfer in the complex (the site-specific outer-sphere electron transfer mechanism). Oxidation of HbO 2 and MbO 2 by potassium ferricyanide and Fe(3) complexes with NTA, EDTA, CDTA, ATP, 2,3-DPG, citrate, and pyrophosphate PP i proceeds mainly through the simple outer-sphere electron transfer mechanism via the exposed heme edge. According to Marcus theory, the rate of this reaction correlates with the difference in redox potentials of the reagents and their self-exchange rates. For charged reagents, the reaction may be preceded by their nonspecific binding to the protein due to electrostatic interactions. The reactions of LbO 2 with carboxylate Fe complexes, unlike its reactions with ferricyanide, occur via the site-specific outer-sphere electron transfer mechanism, even though the same reagents oxidize structurally similar MbO 2 and cytochrome b 5 via the simple outer-sphere electron transfer mechanism. Of particular biological interest is HbO 2 and MbO 2 transformation into met-forms in the presence

  6. The Redox Code

    PubMed Central

    Jones, Dean P.

    2015-01-01

    Abstract Significance: 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. Recent Advances: 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. Critical Issues: Complexity of redox networks and redox regulation is being revealed step by step, yet much still needs to be learned. Future Directions: 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. Antioxid. Redox Signal. 23, 734–746. PMID:25891126

  7. Redox biology and the interface between bioenergetics, autophagy and circadian control of metabolism.

    PubMed

    Wende, Adam R; Young, Martin E; Chatham, John; Zhang, Jianhua; Rajasekaran, Namakkal S; Darley-Usmar, Victor M

    2016-11-01

    Understanding molecular mechanisms that underlie the recent emergence of metabolic diseases such as diabetes and heart failure has revealed the need for a multi-disciplinary research integrating the key metabolic pathways which change the susceptibility to environmental or pathologic stress. At the physiological level these include the circadian control of metabolism which aligns metabolism with temporal demand. The mitochondria play an important role in integrating the redox signals and metabolic flux in response to the changing activities associated with chronobiology, exercise and diet. At the molecular level this involves dynamic post-translational modifications regulating transcription, metabolism and autophagy. In this review we will discuss different examples of mechanisms which link these processes together. An important pathway capable of linking signaling to metabolism is the post-translational modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc). This is a nutrient regulated protein modification that plays an important role in impaired cellular stress responses. Circadian clocks have also emerged as critical regulators of numerous cardiometabolic processes, including glucose/lipid homeostasis, hormone secretion, redox status and cardiovascular function. Central to these pathways are the response of autophagy, bioenergetics to oxidative stress, regulated by Keap1/Nrf2 and mechanisms of metabolic control. The extension of these ideas to the emerging concept of bioenergetic health will be discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Ebselen, a useful tool for understanding cellular redox biology and a promising drug candidate for use in human diseases.

    PubMed

    Noguchi, Noriko

    2016-04-01

    Ebselen is an organoselenium compound with glutathione peroxidase (GPx)-like hydroperoxide reducing activity. Moreover, ebselen has its own unique reactivity, with functions that GPx does not have, since it reacts with many kinds of thiols other than glutathione. Ebselen may affect the thioredoxin systems, through which it may contribute to regulation of cell function. With high reactivity toward thiols, hydroperoxides, and peroxynitrite, ebselen has been used as a useful tool in research on cellular redox mechanisms. Unlike α-tocopherol, ebselen does not scavenge lipid peroxyl radicals, which is another advantage of ebselen for use as a research tool in comparison with radical scavenging antioxidants. Selenium is not released from the ebselen molecule, which explains the low toxicity of ebselen. To further understand the mechanism of cellular redox biology, it should be interesting to compare the effects of ebselen with that of selenoprotein P, which supplies selenium to GPx. New medical applications of ebselen as a drug candidate for human diseases such as cancer and diabetes mellitus as well as brain stroke and ischemia will be expected. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The basics of thiols and cysteines in redox biology and chemistry.

    PubMed

    Poole, Leslie B

    2015-03-01

    Cysteine is one of the least abundant amino acids, yet it is frequently found as a highly conserved residue within functional (regulatory, catalytic, or binding) sites in proteins. It is the unique chemistry of the thiol or thiolate group of cysteine that imparts to functional sites their specialized properties (e.g., nucleophilicity, high-affinity metal binding, and/or ability to form disulfide bonds). Highlighted in this review are some of the basic biophysical and biochemical properties of cysteine groups and the equations that apply to them, particularly with respect to pKa and redox potential. Also summarized are the types of low-molecular-weight thiols present in high concentrations in most cells, as well as the ways in which modifications of cysteinyl residues can impart or regulate molecular functions important to cellular processes, including signal transduction. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. The Redox Code.

    PubMed

    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.

  11. The Redox Proteome*

    PubMed Central

    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. Cerium oxide nanozyme modulate the ‘exercise’ redox biology of skeletal muscle

    NASA Astrophysics Data System (ADS)

    Arya, Aditya; Sethy, Niroj Kumar; Gangwar, Anamika; Bhargava, Neelima; Dubey, Amarish; Roy, Manas; Srivastava, Gaurav; Singh, Sushil Kumar; Das, Mainak; Bhargava, Kalpana

    2017-05-01

    ‘Exercise’ is a double-edged sword for the skeletal muscle. Small amount of ROS generated during mild exercise, is essential for normal force generation; whereas large quantity of ROS generated during intense exercise, may cause contractile dysfunction, resulting in muscle weakness and fatigue. One of the key question in skeletal muscle physiology is ‘could antioxidant therapy improve the skeletal muscle endurance? A question, which has resulted in contradictory experimental findings till this date. This work has addressed this ‘very question’ using a synthetic, inorganic, antioxidant nano-material viz., ‘cerium oxide nanozyme’ (CON). It has been introduced in the rat by intramuscular injection, and the skeletal muscle endurance has been evaluated. Intramuscular injections of CON, concurrent with exercise, enhanced muscle mass, glycogen and ATP content, type I fiber ratio, thus resulting in significantly higher muscle endurance. Electron microscope studies confirmed the presence of CON in the vicinity of muscle mitochondria. There was an increase in the number and size of the muscle mitochondria in the CON treated muscle, following exercise, as compared to the untreated group with only exercised muscle. Quantitative proteomics data and subsequent biological network analysis studies, identified higher levels of oxidative phosphorylation, TCA cycle output and glycolysis in CON supplemented exercised muscle over only exercised muscle. This was further associated with significant increase in the mitochondrial respiratory capacity and muscle contraction, primarily due to higher levels of electron transport chain proteins like NDUFA9, SDHA, ATP5B and ATP5D, which were validated by real-time PCR and western blotting. Along with this, persistence of CON in muscle was evaluated with ICP-MS analysis, which revealed clearance of the particles after 90 d, without exhibiting any inflammation or adverse affects on the health of the experimental animals. Thus a

  13. Redox-signals and macrophage biology (for the upcoming issue of molecular aspects of medicine on signaling by reactive oxygen species).

    PubMed

    Weigert, Andreas; von Knethen, Andreas; Fuhrmann, Dominik; Dehne, Nathalie; Brüne, Bernhard

    2018-01-11

    Macrophages are known for their versatile role in biology. They sense and clear structures that contain exogenous or endogenous pathogen-associated molecular patterns. This process is tightly linked to the production of a mixture of potentially harmful oxidants and cytokines. Their inherent destructive behavior is directed against foreign material or structures of 'altered self', which explains the role of macrophages during innate immune reactions and inflammation. However, there is also another side of macrophages when they turn into a tissue regenerative, pro-resolving, and healing phenotype. Phenotype changes of macrophages are termed macrophage polarization, representing a continuum between classical and alternative activation. Macrophages as the dominating producers of superoxide/hydrogen peroxide and nitric oxide are not only prone to oxidative modifications but also to more subtle signaling properties of redox-active molecules conveying redox regulation. We review basic concepts of the enzymatic nitric oxide and superoxide production within macrophages, refer to their unique chemical reactions and outline biological consequences not only for macrophage biology but also for their communication with cells in the microenvironment. These considerations link hypoxia to the NO system, addressing feedforward as well as feedback circuits. Moreover, we summarize the role of redox-signaling affecting epigenetics and reflect the central role of mitochondrial-derived oxygen species in inflammation. To better understand the diverse functions of macrophages during initiation as well as resolution of inflammation and to decode their versatile roles during innate and adaptive immunity with the entire spectrum of cell protective towards cell destructive activities we need to appreciate the signaling properties of redox-active species. Herein we discuss macrophage responses in terms of nitric oxide and superoxide formation with the modulating impact of hypoxia. Copyright

  14. Enzymes as modular catalysts for redox half-reactions in H2-powered chemical synthesis: from biology to technology.

    PubMed

    Reeve, Holly A; Ash, Philip A; Park, HyunSeo; Huang, Ailun; Posidias, Michalis; Tomlinson, Chloe; Lenz, Oliver; Vincent, Kylie A

    2017-01-15

    The present study considers the ways in which redox enzyme modules are coupled in living cells for linking reductive and oxidative half-reactions, and then reviews examples in which this concept can be exploited technologically in applications of coupled enzyme pairs. We discuss many examples in which enzymes are interfaced with electronically conductive particles to build up heterogeneous catalytic systems in an approach which could be termed synthetic biochemistry We focus on reactions involving the H + /H 2 redox couple catalysed by NiFe hydrogenase moieties in conjunction with other biocatalysed reactions to assemble systems directed towards synthesis of specialised chemicals, chemical building blocks or bio-derived fuel molecules. We review our work in which this approach is applied in designing enzyme-modified particles for H 2 -driven recycling of the nicotinamide cofactor NADH to provide a clean cofactor source for applications of NADH-dependent enzymes in chemical synthesis, presenting a combination of published and new work on these systems. We also consider related photobiocatalytic approaches for light-driven production of chemicals or H 2 as a fuel. We emphasise the techniques available for understanding detailed catalytic properties of the enzymes responsible for individual redox half-reactions, and the importance of a fundamental understanding of the enzyme characteristics in enabling effective applications of redox biocatalysis. © 2017 The Author(s).

  15. Novel Perspectives in Redox Biology and Pathophysiology of Failing Myocytes: Modulation of the Intramyocardial Redox Milieu for Therapeutic Interventions—A Review Article from the Working Group of Cardiac Cell Biology, Italian Society of Cardiology

    PubMed Central

    Arcaro, Alessia; Pirozzi, Flora; Angelini, Annalisa; Chimenti, Cristina; Crotti, Lia; Giordano, Carla; Mancardi, Daniele; Torella, Daniele; Tocchetti, Carlo G.

    2016-01-01

    The prevalence of heart failure (HF) is still increasing worldwide, with enormous human, social, and economic costs, in spite of huge efforts in understanding pathogenetic mechanisms and in developing effective therapies that have transformed this syndrome into a chronic disease. Myocardial redox imbalance is a hallmark of this syndrome, since excessive reactive oxygen and nitrogen species can behave as signaling molecules in the pathogenesis of hypertrophy and heart failure, leading to dysregulation of cellular calcium handling, of the contractile machinery, of myocardial energetics and metabolism, and of extracellular matrix deposition. Recently, following new interesting advances in understanding myocardial ROS and RNS signaling pathways, new promising therapeutical approaches with antioxidant properties are being developed, keeping in mind that scavenging ROS and RNS tout court is detrimental as well, since these molecules also play a role in physiological myocardial homeostasis. PMID:26881035

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

    PubMed

    Kim, Hong Seok; Asmis, Reto

    2017-08-01

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

  17. Biological and chemical redox transformations of mercury in fresh and salt waters of the high arctic during spring and summer.

    PubMed

    Poulain, Alexandre J; Garcia, Edenise; Amyot, Marc; Campbell, Peter G C; Raofie, Farhad; Ariya, Parisa A

    2007-03-15

    It is well-established that atmospheric deposition transports Hg to Arctic regions, but the postdepositional dynamics of Hg that can alter its impact on Arctic food chains are less understood. Through a series of in situ experiments, we investigated the redox transformations of Hg in coastal and inland aquatic systems. During spring and summer, Hg reduction in streams and pond waters decreased across a 4-fold increase in salinity. This alteration of Hg reduction due to chloride was counterbalanced by the presence of particles, which favored the conversion of oxidized Hg to its elemental form. In saline waters, biogenic organic materials, produced by algae, were able to promote oxidation of Hg(O) even under dark conditions. Overall these results point to the vulnerability of marine/ coastal Arctic systems to Hg, compared to inland systems, with oxidation processes enhancing Hg residence times and thus increasing its potential to enter the food chain.

  18. Maleimide-activated aryl diazonium salts for electrode surface functionalization with biological and redox-active molecules.

    PubMed

    Harper, Jason C; Polsky, Ronen; Wheeler, David R; Brozik, Susan M

    2008-03-04

    A versatile and simple method is introduced for formation of maleimide-functionalized surfaces using maleimide-activated aryl diazonium salts. We show for the first time electrodeposition of N-(4-diazophenyl)maleimide tetrafluoroborate on gold and carbon electrodes which was characterized via voltammetry, grazing angle FTIR, and ellipsometry. Electrodeposition conditions were used to control film thickness and yielded submonolayer-to-multilayer grafting. The resulting phenylmaleimide surfaces served as effective coupling agents for electrode functionalization with ferrocene and the redox-active protein cytochrome c. The utility of phenylmaleimide diazonium toward formation of a diazonium-activated conjugate, followed by direct electrodeposition of the diazonium-modified DNA onto the electrode surface, was also demonstrated. Effective electron transfer was obtained between immobilized molecules and the electrodes. This novel application of N-phenylmaleimide diazonium may facilitate the development of bioelectronic devices including biofuel cells, biosensors, and DNA and protein microarrays.

  19. Biological definition of multiple chemical sensitivity from redox state and cytokine profiling and not from polymorphisms of xenobiotic-metabolizing enzymes

    SciTech Connect

    De Luca, Chiara; Scordo, Maria G.; Cesareo, Eleonora

    Background: Multiple chemical sensitivity (MCS) is a poorly clinically and biologically defined environment-associated syndrome. Although dysfunctions of phase I/phase II metabolizing enzymes and redox imbalance have been hypothesized, corresponding genetic and metabolic parameters in MCS have not been systematically examined. Objectives: We sought for genetic, immunological, and metabolic markers in MCS. Methods: We genotyped patients with diagnosis of MCS, suspected MCS and Italian healthy controls for allelic variants of cytochrome P450 isoforms (CYP2C9, CYP2C19, CYP2D6, and CYP3A5), UDP-glucuronosyl transferase (UGT1A1), and glutathione S-transferases (GSTP1, GSTM1, and GSTT1). Erythrocyte membrane fatty acids, antioxidant (catalase, superoxide dismutase (SOD)) and glutathione metabolizing (GST,more » glutathione peroxidase (Gpx)) enzymes, whole blood chemiluminescence, total antioxidant capacity, levels of nitrites/nitrates, glutathione, HNE-protein adducts, and a wide spectrum of cytokines in the plasma were determined. Results: Allele and genotype frequencies of CYPs, UGT, GSTM, GSTT, and GSTP were similar in the Italian MCS patients and in the control populations. The activities of erythrocyte catalase and GST were lower, whereas Gpx was higher than normal. Both reduced and oxidised glutathione were decreased, whereas nitrites/nitrates were increased in the MCS groups. The MCS fatty acid profile was shifted to saturated compartment and IFNgamma, IL-8, IL-10, MCP-1, PDGFbb, and VEGF were increased. Conclusions: Altered redox and cytokine patterns suggest inhibition of expression/activity of metabolizing and antioxidant enzymes in MCS. Metabolic parameters indicating accelerated lipid oxidation, increased nitric oxide production and glutathione depletion in combination with increased plasma inflammatory cytokines should be considered in biological definition and diagnosis of MCS.« less

  20. Subcellular Redox Signaling.

    PubMed

    Zhu, Liping; Lu, Yankai; Zhang, Jiwei; Hu, Qinghua

    2017-01-01

    Oxidative and antioxidative system of cells and tissues maintains a balanced state under physiological conditions. A disruption in this balance of redox status has been associated with numerous pathological processes. Reactive oxygen species (ROS) as a major redox signaling generates in a spatiotemporally dependent manner. Subcellular organelles such as mitochondria, endoplasmic reticulum, plasma membrane and nuclei contribute to the production of ROS. In addition to downstream effects of ROS signaling regulated by average ROS changes in cytoplasm, whether subcelluar ROS mediate biological effect(s) has drawn greater attentions. With the advance in redox-sensitive probes targeted to different subcellular compartments, the investigation of subcellular ROS signaling and its associated cellular function has become feasible. In this review, we discuss the subcellular ROS signaling, with particular focus on mechanisms of subcellular ROS production and its downstream effects.

  1. Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

    PubMed Central

    2015-01-01

    Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. Antioxid. Redox Signal. 23, 899–942. PMID:26261901

  2. [Radiation therapy and redox imaging].

    PubMed

    Matsumoto, Ken-ichiro

    2015-01-01

    Radiation therapy kills cancer cells in part by flood of free radicals. Radiation ionizes and/or excites water molecules to create highly reactive species, i.e. free radicals and/or reactive oxygen species. Free radical chain reactions oxidize biologically important molecules and thereby disrupt their function. Tissue oxygen and/or redox status, which can influence the course of the free radical chain reaction, can affect the efficacy of radiation therapy. Prior observation of tissue oxygen and/or redox status is helpful for planning a safe and efficient course of radiation therapy. Magnetic resonance-based redox imaging techniques, which can estimate tissue redox status non-invasively, have been developed not only for diagnostic information but also for estimating the efficacy of treatment. Redox imaging is now spotlighted to achieve radiation theranostics.

  3. The Redox Chemistry and Chemical Biology of H2S, Hydropersulfides and Derived Species: Implications to Their Possible Biological Activity and Utility

    PubMed Central

    Ono, Katsuhiko; Akaike, Takaake; Sawa, Tomohiro; Kumagai, Yoshito; Wink, David A.; Tantillo, Dean J.; Hobbs, Adrian J.; Nagy, Peter; Xian, Ming; Lin, Joseph; Fukuto, Jon M.

    2014-01-01

    Hydrogen sulfide (H2S) is an endogenously generated and putative signaling/effector molecule. In spite of its numerous reported functions, the chemistry by which it elicits its functions is not understood. Moreover, recent studies allude to the existence of other sulfur species besides H2S that may play critical physiological roles. Herein, the basic chemical biology of H2S as well as other related or derived species is discussed and reviewed. A particular focus of this review are the per- and poly-sulfides which are likely in equilibrium with free H2S and which may be important biological effectors themselves. PMID:25229186

  4. Redox Pioneer: Professor Vadim N. Gladyshev

    PubMed Central

    2016-01-01

    Abstract 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. PMID:26984707

  5. Redox Pioneer: Professor Vadim N. Gladyshev.

    PubMed

    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. Redox Redone.

    ERIC Educational Resources Information Center

    Petty, John T.

    1996-01-01

    Presents an extension of the change in oxidation number method that is used for balancing skeletal redox reactions in aqueous solutions. Retains most of the simplicity of the change in oxidation number method but provides the additional step-by-step process necessary for the beginner to balance an equation. (JRH)

  7. Environmental Redox Potential and Redox Capacity Concepts Using a Simple Polarographic Experiment

    NASA Astrophysics Data System (ADS)

    Pidello, Alejandro

    2003-01-01

    The redox status of a system may be analyzed in terms of the redox potential (redox intensity component) and the size of the pool of electrons able to be transferred (redox capacity component). In single chemical systems, both terms are thermodynamically related by means of the Nernst equation, the classical redox equilibrium equation. Consequently, either the redox potential measurement or the redox capacity may be used without distinction to define the redox characteristics of these systems. However, in natural environments, which are a complex mixture of compounds undergoing redox reactions in several stages of nonequilibrium, it is difficult to establish the relationships linking redox potential and redox capacity. In this situation, as suggested by various authors, the complementary use of intensity and capacity measurements improves the characterization of the redox status of these systems. The aim of this laboratory experiment is to enable undergraduate students of applied biology (agronomy, veterinary or environmental sciences) to distinguish clearly between redox potential and redox capacity concepts through concrete results obtained in complex natural system such as soil, and to discuss the ecological significance of both concepts.

  8. A Systems Biology Approach to Reveal Putative Host-Derived Biomarkers of Periodontitis by Network Topology Characterization of MMP-REDOX/NO and Apoptosis Integrated Pathways.

    PubMed

    Zeidán-Chuliá, Fares; Gürsoy, Mervi; Neves de Oliveira, Ben-Hur; Özdemir, Vural; Könönen, Eija; Gürsoy, Ulvi K

    2015-01-01

    Periodontitis, a formidable global health burden, is a common chronic disease that destroys tooth-supporting tissues. Biomarkers of the early phase of this progressive disease are of utmost importance for global health. In this context, saliva represents a non-invasive biosample. By using systems biology tools, we aimed to (1) identify an integrated interactome between matrix metalloproteinase (MMP)-REDOX/nitric oxide (NO) and apoptosis upstream pathways of periodontal inflammation, and (2) characterize the attendant topological network properties to uncover putative biomarkers to be tested in saliva from patients with periodontitis. Hence, we first generated a protein-protein network model of interactions ("BIOMARK" interactome) by using the STRING 10 database, a search tool for the retrieval of interacting genes/proteins, with "Experiments" and "Databases" as input options and a confidence score of 0.400. Second, we determined the centrality values (closeness, stress, degree or connectivity, and betweenness) for the "BIOMARK" members by using the Cytoscape software. We found Ubiquitin C (UBC), Jun proto-oncogene (JUN), and matrix metalloproteinase-14 (MMP14) as the most central hub- and non-hub-bottlenecks among the 211 genes/proteins of the whole interactome. We conclude that UBC, JUN, and MMP14 are likely an optimal candidate group of host-derived biomarkers, in combination with oral pathogenic bacteria-derived proteins, for detecting periodontitis at its early phase by using salivary samples from patients. These findings therefore have broader relevance for systems medicine in global health as well.

  9. Understanding the Adsorption Interface of Polyelectrolyte Coating on Redox Active Nanoparticles Using Soft Particle Electrokinetics and Its Biological Activity

    PubMed Central

    2015-01-01

    The application of cerium oxide nanoparticles (CNPs) for therapeutic purposes requires a stable dispersion of nanoparticles in a biological environment. The objective of this study is to tailor the properties of polyelectrolyte coated CNPs as a function of molecular weight to achieve a stable and catalytic active dispersion. The coating of CNPs with polyacrylic acid (PAA) has increased the dispersion stability of CNPs and enhanced the catalytic ability. The stability of PAA coating was analyzed using the change in the Gibbs free energy computed by the Langmuir adsorption model. The adsorption isotherms were determined using soft particle electrokinetics which overcomes the challenges presented by other techniques. The change in Gibbs free energy was highest for CNPs coated with PAA of 250 kg/mol indicating the most stable coating. The change in free energy for PAA of 100 kg/mol coated CNPs was 85% lower than the PAA of 250 kg/mol coated CNPs. This significant difference is caused by the strong adsorption of PAA of 100 kg/mol on CNPs. Catalytic activity of PAA-CNPs is assessed by the catalase enzymatic mimetic activity of nanoparticles. The catalase activity was higher for PAA coated CNPs as compared to bare CNPs which indicated preferential adsorption of hydrogen peroxide induced by coating. This indicates that the catalase activity is also affected by the structure of the coating layer. PMID:24673655

  10. The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology

    NASA Astrophysics Data System (ADS)

    Graves, David B.

    2012-07-01

    Reactive oxygen species (ROS) and the closely related reactive nitrogen species (RNS) are often generated in applications of atmospheric pressure plasmas intended for biomedical purposes. These species are also central players in what is sometimes referred to as ‘redox’ or oxidation-reduction biology. Oxidation-reduction biochemistry is fundamental to all of aerobic biology. ROS and RNS are perhaps best known as disease-associated agents, implicated in diabetes, cancer, heart and lung disease, autoimmune disease and a host of other maladies including ageing and various infectious diseases. These species are also known to play active roles in the immune systems of both animals and plants and are key signalling molecules, among many other important roles. Indeed, the latest research has shown that ROS/RNS play a much more complex and nuanced role in health and ageing than previously thought. Some of the most potentially profound therapeutic roles played by ROS and RNS in various medical interventions have emerged only in the last several years. Recent research suggests that ROS/RNS are significant and perhaps even central actors in the actions of antimicrobial and anti-parasite drugs, cancer therapies, wound healing therapies and therapies involving the cardiovascular system. Understanding the ways ROS/RNS act in established therapies may help guide future efforts in exploiting novel plasma medical therapies. The importance of ROS and RNS to plant biology has been relatively little appreciated in the plasma biomedicine community, but these species are just as important in plants. It appears that there are opportunities for useful applications of plasmas in this area as well.

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

    PubMed

    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.

  12. Differential coordination demands in Fe vs Mn water-soluble cationic metalloporphyrins translates into remarkably different aqueous redox chemistry and biology

    PubMed Central

    Tovmasyan, Artak; Weitner, Tin; Sheng, Huaxin; Lu, MiaoMiao; Rajic, Zrinka; Warner, David S.; Spasojevic, Ivan; Reboucas, Julio S.; Benov, Ludmil; Batinic-Haberle, Ines

    2013-01-01

    The different biological behavior of cationic Fe and Mn pyridylporphyrins in Escherichia coli and mouse studies prompted us to revisit and compare their chemistry. For that purpose the series of ortho and meta isomers of Fe(III) meso-tetrakis-N-alkylpyridylporphyrins, alkyl being methyl to n-octyl, were synthesized and characterized by elemental analysis, UV/vis spectroscopy, mass spectrometry, lipophilicity, protonation equilibria of axial waters, metal-centered reduction potential, E1/2 for MIIIP/MIIP redox couple (M = Fe, Mn, P=porphyrin), kcat for the catalysis of O2•− dismutation, stability towards peroxide-driven porphyrin oxidative degradation (produced in the catalysis of ascorbate oxidation by MP), ability to affect growth of SOD-deficient E. coli and toxicity to mice. Electron-deficiency of the metal site is modulated by the porphyrin ligand, which renders Fe(III) porphyrins ≥ 5 orders of magnitude more acidic than the analogous Mn(III) porphyrins, as revealed by the pKa1 of axially coordinated waters. The 5 log units difference in the acidity between the Mn and Fe sites in porphyrin translates into the predominance of tetracationic (OH)(H2O)FeP complexes relative to pentacationic (H2O)2MnP species at pH ~7.8. This is evidenced in large differences in the thermodynamic parameters - pKa of axial waters and E1/2 of MIII/MII redox couple. The presence of hydroxo ligand labilizes trans-axial water which results in higher reactivity of Fe- relative to Mn center. The differences in the catalysis of O2•− dismutation (log kcat) between Fe and Mn porphyrins is modest, 2.5-5-fold, due to predominantly outer-sphere, with partial inner-sphere character of two reaction steps. However, the rate constant for the inner-sphere H2O2-based porphyrin oxidative degradation is 18-fold larger for (OH)(H2O)FeP than for (H2O)2MnP. The in vivo consequences of the differences between the Fe- and Mn porphyrins were best demonstrated in SOD-deficient E. coli growth. Based

  13. Redox Pioneer: Professor Helmut Sies

    PubMed Central

    Radi, Rafael

    2014-01-01

    Abstract Professor Helmut Sies Dr. Helmut Sies (MD, 1967) is recognized as a Redox Pioneer, because he authored five articles on oxidative stress, lycopene, and glutathione, each of which has been cited more than 1000 times, and coauthored an article on hydroperoxide metabolism in mammalian systems cited more than 5000 times (Google Scholar). He obtained preclinical education at the University of Tübingen and the University of Munich, clinical training at Munich (MD, 1967) and Paris, and completed Habilitation at Munich (Physiological Chemistry and Physical Biochemistry, 1972). In early research, he first identified hydrogen peroxide (H2O2) as a normal aerobic metabolite and devised a method to quantify H2O2 concentration and turnover in cells. He quantified central redox systems for energy metabolism (NAD, NADP systems) and antioxidant GSH in subcellular compartments. He first described ebselen, a selenoorganic compound, as a glutathione peroxidase mimic. He contributed a fundamental discovery to the physiology of GSH, selenium nutrition, singlet oxygen biochemistry, and health benefits of dietary lycopene and cocoa flavonoids. He has published more than 600 articles, 134 of which are cited at least 100 times, and edited 28 books. His h-index is 115. During the last quarter of the 20th century and well into the 21st, he has served as a scout, trailblazer, and pioneer in redox biology. His formulation of the concept of oxidative stress stimulated and guided research in oxidants and antioxidants; his pioneering research on carotenoids and flavonoids informed nutritional strategies against cancer, cardiovascular disease, and aging; and his quantitative approach to redox biochemistry provides a foundation for modern redox systems biology. Helmut Sies is a true Redox Pioneer. Antioxid. Redox Signal. 21, 2459–2468. The joy of exploring the unknown and finding something novel and noteworthy: what a privilege! —Prof. Helmut Sies PMID:25178739

  14. Redox proteomics and drug development.

    PubMed

    D'Alessandro, Angelo; Rinalducci, Sara; Zolla, Lello

    2011-11-18

    As alterations of the redox homeostasis lie at the root of many pathophysiological processes in human health, redox proteomics holds the promise to shed further light on fundamental biological processes. In this review, the mechanisms of reactive oxygen species (ROS) and reactive nitrogen species (RNS) production are reviewed, mainly addressing those chemical phenomena which have already been associated with pathological conditions (of the central nervous system, cardiovascular system, or simply related to aging and altered-cell cycle regulation). From Alzheimer's to Parkinson's and Hungtinton's disease, from ageing to cancer, oxidative stress (OS) appears to represent a common trait in so many relevant biological aspects of human health, that further investments in the field of redox proteomics ought to be mandatory. For the foreseeable future, redox proteomics will likely play a pivotal role in the quest for new therapeutical targets and their validation, in the process of determining OS-triggered cellular alteration upon drug treatments and thus in the very heart of the design and testing of new drugs and their metabolites against those pathologies relying on altered redox homeostasis. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Thiol/disulfide redox states in signaling and sensing

    PubMed Central

    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

  16. Redox Strategies for Crop Improvement.

    PubMed

    Kerchev, Pavel; De Smet, Barbara; Waszczak, Cezary; Messens, Joris; Van Breusegem, Frank

    2015-11-10

    Recently, the agro-biotech industry has been driven by overcoming the limitations imposed by fluctuating environmental stress conditions on crop productivity. A common theme among (a)biotic stresses is the perturbation of the redox homeostasis. As a strategy to engineer stress-tolerant crops, many approaches have been centered on restricting the negative impact of reactive oxygen species (ROS) accumulation. In this study, we discuss the scientific background of the existing redox-based strategies to improve crop performance and quality. In this respect, a special focus goes to summarizing the current patent landscape because this aspect is very often ignored, despite constituting the forefront of applied research. The current increased understanding of ROS acting as signaling molecules has opened new avenues to exploit redox biology for crop improvement required for sustainable food security.

  17. Engineered Proteins: Redox Properties and Their Applications

    PubMed Central

    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

  18. Redox signaling in cardiovascular health and disease

    PubMed Central

    Madamanchi, Nageswara R.; Runge, Marschall S.

    2013-01-01

    Spatiotemporal regulation of the activity of a vast array of intracellular proteins and signaling pathways by reactive oxygen species (ROS) governs normal cardiovascular function. However, data from experimental and animal studies strongly support that dysregulated redox signaling, resulting from hyper-activation of various cellular oxidases or mitochondrial dysfunction, is integral to the pathogenesis and progression of cardiovascular disease (CVD). In this review, we address how redox signaling modulates the protein function, the various sources of increased oxidative stress in CVD, and the labyrinth of redox-sensitive molecular mechanisms involved in the development of atherosclerosis, hypertension, cardiac hypertrophy and heart failure, and ischemia–reperfusion injury. Advances in redox biology and pharmacology for inhibiting ROS production in specific cell types and subcellular organelles combined with the development of nanotechnology-based new in vivo imaging systems and targeted drug delivery mechanisms may enable fine-tuning of redox signaling for the treatment and prevention of CVD. PMID:23583330

  19. Teaching the basics of reactive oxygen species and their relevance to cancer biology: Mitochondrial reactive oxygen species detection, redox signaling, and targeted therapies.

    PubMed

    Kalyanaraman, Balaraman; Cheng, Gang; Hardy, Micael; Ouari, Olivier; Bennett, Brian; Zielonka, Jacek

    2018-05-01

    Reactive oxygen species (ROS) have been implicated in tumorigenesis (tumor initiation, tumor progression, and metastasis). Of the many cellular sources of ROS generation, the mitochondria and the NADPH oxidase family of enzymes are possibly the most prevalent intracellular sources. In this article, we discuss the methodologies to detect mitochondria-derived superoxide and hydrogen peroxide using conventional probes as well as newly developed assays and probes, and the necessity of characterizing the diagnostic marker products with HPLC and LC-MS in order to rigorously identify the oxidizing species. The redox signaling roles of mitochondrial ROS, mitochondrial thiol peroxidases, and transcription factors in response to mitochondria-targeted drugs are highlighted. ROS generation and ROS detoxification in drug-resistant cancer cells and the relationship to metabolic reprogramming are discussed. Understanding the subtle role of ROS in redox signaling and in tumor proliferation, progression, and metastasis as well as the molecular and cellular mechanisms (e.g., autophagy) could help in the development of combination therapies. The paradoxical aspects of antioxidants in cancer treatment are highlighted in relation to the ROS mechanisms in normal and cancer cells. Finally, the potential uses of newly synthesized exomarker probes for in vivo superoxide and hydrogen peroxide detection and the low-temperature electron paramagnetic resonance technique for monitoring oxidant production in tumor tissues are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Back-reactions, short-circuits, leaks and other energy wasteful reactions in biological electron transfer: redox tuning to survive life in O(2).

    PubMed

    Rutherford, A William; Osyczka, Artur; Rappaport, Fabrice

    2012-03-09

    The energy-converting redox enzymes perform productive reactions efficiently despite the involvement of high energy intermediates in their catalytic cycles. This is achieved by kinetic control: with forward reactions being faster than competing, energy-wasteful reactions. This requires appropriate cofactor spacing, driving forces and reorganizational energies. These features evolved in ancestral enzymes in a low O(2) environment. When O(2) appeared, energy-converting enzymes had to deal with its troublesome chemistry. Various protective mechanisms duly evolved that are not directly related to the enzymes' principal redox roles. These protective mechanisms involve fine-tuning of reduction potentials, switching of pathways and the use of short circuits, back-reactions and side-paths, all of which compromise efficiency. This energetic loss is worth it since it minimises damage from reactive derivatives of O(2) and thus gives the organism a better chance of survival. We examine photosynthetic reaction centres, bc(1) and b(6)f complexes from this view point. In particular, the evolution of the heterodimeric PSI from its homodimeric ancestors is explained as providing a protective back-reaction pathway. This "sacrifice-of-efficiency-for-protection" concept should be generally applicable to bioenergetic enzymes in aerobic environments. Copyright © 2012 Federation of European Biochemical Societies. All rights reserved.

  1. Redox Regulation of Endothelial Cell Fate

    PubMed Central

    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

  2. Redox potential tuning by redox-inactive cations in nature's water oxidizing catalyst and synthetic analogues.

    PubMed

    Krewald, Vera; Neese, Frank; Pantazis, Dimitrios A

    2016-04-28

    The redox potential of synthetic oligonuclear transition metal complexes has been shown to correlate with the Lewis acidity of a redox-inactive cation connected to the redox-active transition metals of the cluster via oxo or hydroxo bridges. Such heterometallic clusters are important cofactors in many metalloenzymes, where it is speculated that the redox-inactive constituent ion of the cluster serves to optimize its redox potential for electron transfer or catalysis. A principal example is the oxygen-evolving complex in photosystem II of natural photosynthesis, a Mn4CaO5 cofactor that oxidizes water into dioxygen, protons and electrons. Calcium is critical for catalytic function, but its precise role is not yet established. In analogy to synthetic complexes it has been suggested that Ca(2+) fine-tunes the redox potential of the manganese cluster. Here we evaluate this hypothesis by computing the relative redox potentials of substituted derivatives of the oxygen-evolving complex with the cations Sr(2+), Gd(3+), Cd(2+), Zn(2+), Mg(2+), Sc(3+), Na(+) and Y(3+) for two sequential transitions of its catalytic cycle. The theoretical approach is validated with a series of experimentally well-characterized Mn3AO4 cubane complexes that are structural mimics of the enzymatic cluster. Our results reproduce perfectly the experimentally observed correlation between the redox potential and the Lewis acidities of redox-inactive cations for the synthetic complexes. However, it is conclusively demonstrated that this correlation does not hold for the oxygen evolving complex. In the enzyme the redox potential of the cluster only responds to the charge of the redox-inactive cations and remains otherwise insensitive to their precise identity, precluding redox-tuning of the metal cluster as a primary role for Ca(2+) in biological water oxidation.

  3. Metabolic Control of Redox and Redox Control of Metabolism in Plants

    PubMed Central

    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

  4. Redox signaling: An evolution from free radicals to aging.

    PubMed

    Forman, Henry Jay

    2016-08-01

    Redox biology has evolved from studies of the pathology that involves oxidants to an understanding of how oxidants participate in normal as well as aberrant signal transduction. Although the concept that signal transduction involved changes in the redox state dates from the 1930s, the modern history of redox biology began with the discovery of superoxide dismutase by McCord and Fridovich. The initial focus was on free radicals and damage of macromolecules, which remains an important topic. But, over time it was realized that hydroperoxides, especially H2O2 produced by NADPH oxidases, and electrophiles derived from lipid peroxidation or metabolism, played essential roles in physiologically relevant signaling. The mechanisms through which H2O2 and other electrophiles signal became an important area of study that provided insight into how these reactive molecules were involved in major signaling pathways and regulation of transcription factors. Thus, the field of redox signaling that is the overlap of signal transduction with redox biology was established. Alterations in redox signaling are observed in aging, but we also now know that redox signaling is essential in physiological homeostasis and that sustained deviation from redox homeostasis results in disease. This is a review of the history of redox biology from a personal perspective of nearly fifty years working in this field that hopefully provides some insights for the reader. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Redox sensing: Orthogonal control in cell cycle and apoptosis signaling

    PubMed Central

    Jones, Dean P.

    2010-01-01

    Living systems have three major types of cell signaling systems that are dependent upon high-energy chemicals, redox environment and transmembranal ion gating mechanisms. Development of integrated systems biology descriptions of cell signaling require conceptual models incorporating all three. Recent advances in redox biology show that thiol/disulfide redox systems are regulated under dynamic, non-equilibrium conditions, progressively oxidized with the life cycle of cells and distinct in terms of redox potentials among subcellular compartments. The present article uses these observations as a basis to distinguish “redox-sensing” mechanisms, which are more global biologic redox control mechanisms, from “redox signaling”, which involves conveyance of discrete activating or inactivating signals. Both redox sensing and redox signaling use sulfur switches, especially cysteine (Cys) residues in proteins which are sensitive to reversible oxidation, nitrosylation, glutathionylation, acylation, sulfhydration or metal binding. Unlike specific signaling mechanisms, the redox-sensing mechanisms provide means to globally affect the rates and activities of the high-energy, ion gating and redox-signaling systems by controlling sensitivity, distribution, macromolecular interactions and mobility of signaling proteins. Effects mediated through Cys residues not directly involved in signaling means redox-sensing control can be orthogonal to the signaling mechanisms. This provides a capability to integrate signals according to cell cycle and physiologic state without fundamentally altering the signaling mechanisms. Recent findings that thiol/disulfide pools in humans are oxidized with age, environmental exposures and disease risk suggest that redox-sensing thiols could provide a central mechanistic link in disease development and progression. PMID:20964735

  6. Redox Modulations, Antioxidants, and Neuropsychiatric Disorders

    PubMed Central

    Fraunberger, Erik A.; Laliberté, Victoria L. M.; Duong, Angela; Andreazza, Ana C.

    2016-01-01

    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. PMID:26640614

  7. Metabolic control of redox and redox control of metabolism in plants.

    PubMed

    Geigenberger, Peter; Fernie, Alisdair R

    2014-09-20

    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. 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. 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. 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 characterizing signaling features thereof. We propose that such information will enable

  8. Redox biology of Mycobacterium tuberculosis H37Rv: protein-protein interaction between GlgB and WhiB1 involves exchange of thiol-disulfide

    PubMed Central

    Garg, Saurabh; Alam, Md Suhail; Bajpai, Richa; Kishan, KV Radha; Agrawal, Pushpa

    2009-01-01

    Background Mycobacterium tuberculosis, an intracellular pathogen encounters redox stress throughout its life inside the host. In order to protect itself from the redox onslaughts of host immune system, M. tuberculosis appears to have developed accessory thioredoxin-like proteins which are represented by ORFs encoding WhiB-like proteins. We have earlier reported that WhiB1/Rv3219 is a thioredoxin like protein of M. tuberculosis and functions as a protein disulfide reductase. Generally thioredoxins have many substrate proteins. The current study aims to identify the substrate protein(s) of M. tuberculosis WhiB1. Results Using yeast two-hybrid screen, we identified alpha (1,4)-glucan branching enzyme (GlgB) of M. tuberculosis as a interaction partner of WhiB1. In vitro GST pull down assay confirmed the direct physical interaction between GlgB and WhiB1. Both mass spectrometry data of tryptic digests and in vitro labeling of cysteine residues with 4-acetamido-4' maleimidyl-stilbene-2, 2'-disulfonic acid showed that in GlgB, C95 and C658 are free but C193 and C617 form an intra-molecular disulfide bond. WhiB1 has a C37XXC40 motif thus a C40S mutation renders C37 to exist as a free thiol to form a hetero-disulfide bond with the cysteine residue of substrate protein. A disulfide mediated binary complex formation between GlgB and WhiB1C40S was shown by both in-solution protein-protein interaction and thioredoxin affinity chromatography. Finally, transfer of reducing equivalent from WhiB1 to GlgB disulfide was confirmed by 4-acetamido-4' maleimidyl-stilbene-2, 2'-disulfonic acid trapping by the reduced disulfide of GlgB. Two different thioredoxins, TrxB/Rv1471 and TrxC/Rv3914 of M. tuberculosis could not perform this reaction suggesting that the reduction of GlgB by WhiB1 is specific. Conclusion We conclude that M. tuberculosis GlgB has one intra-molecular disulfide bond which is formed between C193 and C617. WhiB1, a thioredoxin like protein interacts with GlgB and

  9. Biological Evaluation and X-ray Co-crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase, an Enzyme from the Redox Metabolism of Trypanosoma.

    PubMed

    De Gasparo, Raoul; Brodbeck-Persch, Elke; Bryson, Steve; Hentzen, Nina B; Kaiser, Marcel; Pai, Emil F; Krauth-Siegel, R Luise; Diederich, François

    2018-05-08

    The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report the optimization of properties and potency of cyclohexylpyrrolidine inhibitors of TR by structure-based design. The best inhibitors were freely soluble and showed competitive inhibition constants (K i ) against Trypanosoma (T.) brucei TR and T. cruzi TR and in vitro activities (half-maximal inhibitory concentration, IC 50 ) against these parasites in the low micromolar range, with high selectivity against human glutathione reductase. X-ray co-crystal structures confirmed the binding of the ligands to the hydrophobic wall of the "mepacrine binding site" with the new, solubility-providing vectors oriented toward the surface of the large active site. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Synthesis, pH dependent photometric and electrochemical investigation, redox mechanism and biological applications of novel Schiff base and its metallic derivatives

    NASA Astrophysics Data System (ADS)

    Rauf, Abdur; Shah, Afzal; Khan, Abdul Aziz; Shah, Aamir Hassan; Abbasi, Rashda; Qureshi, Irfan Zia; Ali, Saqib

    2017-04-01

    A novel Schiff base, 1-((2, 4-dimethylphenylimino)methyl)naphthalen-2-ol abbreviated as (HL) and its four metallic complexes were synthesized and confirmed by 1H and 13C NMR, FTIR, TGA and UV-Visible spectroscopy. Schiff base was also characterized by X-ray analysis. The photometric and electrochemical responses of all the synthesized compounds were investigated in a wide pH range. Structures of the compounds were optimized computationally for the evaluation of different physico-chemical parameters. On the basis of electrochemical results the redox mechanistic pathways of the compounds were proposed. The cytotoxicity analysis on Hela cells revealed that HL and its complexes inhibit cell growth as revealed from their IC50 values (HL):106.7 μM, (L2VO): 40.66 μM, (L2Sn): 5.92 μM, (L2Zn): 42.82 and (L2Co): 107.68 μM. The compounds were tested for anti-diabetic, triglyceride, cholesterol, anti-microbial, anti-fungal and enzyme inhibition activities. The results revealed that HL and its complexes are promising new therapeutic options as these compounds exhibit strong activity against cancer cells, diabetics, fungal and microbial inhibition.

  11. Redox signaling in plants.

    PubMed

    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.

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

    PubMed Central

    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

  13. Methods for using redox liposome biosensors

    DOEpatents

    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.

  14. Reciprocal Control of the Circadian Clock and Cellular Redox State - a Critical Appraisal.

    PubMed

    Putker, Marrit; O'Neill, John Stuart

    2016-01-01

    Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation of redox-sensitive cysteines, many biological processes sense and respond to signals from the intracellular redox environment. Redox signals are therefore important regulators of cellular homeostasis. Recently, it has become apparent that the cellular redox state oscillates in vivo and in vitro, with a period of about one day (circadian). Circadian time-keeping allows cells and organisms to adapt their biology to resonate with the 24-hour cycle of day/night. The importance of this innate biological time-keeping is illustrated by the association of clock disruption with the early onset of several diseases (e.g. type II diabetes, stroke and several forms of cancer). Circadian regulation of cellular redox balance suggests potentially two distinct roles for redox signalling in relation to the cellular clock: one where it is regulated by the clock, and one where it regulates the clock. Here, we introduce the concepts of redox signalling and cellular timekeeping, and then critically appraise the evidence for the reciprocal regulation between cellular redox state and the circadian clock. We conclude there is a substantial body of evidence supporting circadian regulation of cellular redox state, but that it would be premature to conclude that the converse is also true. We therefore propose some approaches that might yield more insight into redox control of cellular timekeeping.

  15. Reciprocal Control of the Circadian Clock and Cellular Redox State - a Critical Appraisal

    PubMed Central

    Putker, Marrit; O’Neill, John Stuart

    2016-01-01

    Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation of redox-sensitive cysteines, many biological processes sense and respond to signals from the intracellular redox environment. Redox signals are therefore important regulators of cellular homeostasis. Recently, it has become apparent that the cellular redox state oscillates in vivo and in vitro, with a period of about one day (circadian). Circadian time-keeping allows cells and organisms to adapt their biology to resonate with the 24-hour cycle of day/night. The importance of this innate biological time-keeping is illustrated by the association of clock disruption with the early onset of several diseases (e.g. type II diabetes, stroke and several forms of cancer). Circadian regulation of cellular redox balance suggests potentially two distinct roles for redox signalling in relation to the cellular clock: one where it is regulated by the clock, and one where it regulates the clock. Here, we introduce the concepts of redox signalling and cellular timekeeping, and then critically appraise the evidence for the reciprocal regulation between cellular redox state and the circadian clock. We conclude there is a substantial body of evidence supporting circadian regulation of cellular redox state, but that it would be premature to conclude that the converse is also true. We therefore propose some approaches that might yield more insight into redox control of cellular timekeeping. PMID:26810072

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

    PubMed

    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.

  17. De Novo Construction of Redox Active Proteins.

    PubMed

    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.

  18. Redox Signaling in the Right Ventricle.

    PubMed

    Suzuki, Yuichiro J; Shults, Nataliia V

    2017-01-01

    Pulmonary hypertension is a devastating disease without cure. The major cause of death among patients with pulmonary hypertension is right heart failure; however, biology of the right heart is not well understood. This lack of knowledge interferes with developing effective therapeutic strategies to treat these patients. In this chapter, we summarize studies performed in our laboratory that investigated the role of redox signaling in the regulation of the right ventricle (RV), using rat models of experimental pulmonary hypertension and right heart failure. Specifically, this chapter covers the topics of (a) redox regulation of serotonin signaling in the RV, (b) the carbonylation-degradation pathway of signal transduction in RV hypertrophy and (c) oxidative modifications in the RV of the SU5416/ovalbumin model of pulmonary arterial hypertension. These studies revealed that redox regulation in the RV is complex and simply giving lots of antioxidants to patients will unlikely benefit them. Deeper understanding of specific and selective redox mechanisms should shed light on how we can develop therapeutic strategies by modulating redox reactions.

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

    PubMed

    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.

  20. Electronegativity and redox reactions.

    PubMed

    Miranda-Quintana, Ramón Alain; Martínez González, Marco; Ayers, Paul W

    2016-08-10

    Using the maximum hardness principle, we show that the oxidation potential of a molecule increases as its electronegativity increases and also increases as its electronegativity in its oxidized state increases. This insight can be used to construct a linear free energy relation for the oxidation potential, which we train on a set of 31 organic redox couples and test on a set of 10 different redox reactions. Better results are obtained when the electronegativity of the oxidized/reduced reagents are adjusted to account for the reagents' interaction with their chemical environment.

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

    PubMed

    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.

  2. Simultaneous anionic and cationic redox

    NASA Astrophysics Data System (ADS)

    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.

  3. Redox Regulation of Mitochondrial Function

    PubMed Central

    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

  4. Ruthenium nanocatalysis on redox reactions.

    PubMed

    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.

  5. Texaphyrins: Tumor Localizing Redox Active Expanded Porphyrins

    PubMed Central

    Arambula, Jonathan F.; Preihs, Christian; Borthwick, Derric; Magda, Darren; Sessler, Jonathan L.

    2011-01-01

    Texaphyrins, a class of tumor selective expanded porphyrins capable of coordinating large metals, have been found to act as redox mediators within biological systems. This review summarizes studies involving their experimentaluse in cancer chemotherapy. Mechanistic insights involving their presumed mode of action are also described, as well as certain structure activity relationships. Finally, newer texaphyrin-based applications associated with targeted drug delivery are presented. PMID:21355841

  6. Redox Control of Inflammation in Macrophages

    PubMed Central

    Dehne, Nathalie; Grossmann, Nina; Jung, Michaela; Namgaladze, Dmitry; Schmid, Tobias; von Knethen, Andreas; Weigert, Andreas

    2013-01-01

    Abstract Macrophages are present throughout the human body, constitute important immune effector cells, and have variable roles in a great number of pathological, but also physiological, settings. It is apparent that macrophages need to adjust their activation profile toward a steadily changing environment that requires altering their phenotype, a process known as macrophage polarization. Formation of reactive oxygen species (ROS), derived from NADPH-oxidases, mitochondria, or NO-producing enzymes, are not necessarily toxic, but rather compose a network signaling system, known as redox regulation. Formation of redox signals in classically versus alternatively activated macrophages, their action and interaction at the level of key targets, and the resulting physiology still are insufficiently understood. We review the identity, source, and biological activities of ROS produced during macrophage activation, and discuss how they shape the key transcriptional responses evoked by hypoxia-inducible transcription factors, nuclear-erythroid 2-p45-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor-γ. We summarize the mechanisms how redox signals add to the process of macrophage polarization and reprogramming, how this is controlled by the interaction of macrophages with their environment, and addresses the outcome of the polarization process in health and disease. Future studies need to tackle the option whether we can use the knowledge of redox biology in macrophages to shape their mediator profile in pathophysiology, to accelerate healing in injured tissue, to fight the invading pathogens, or to eliminate settings of altered self in tumors. Antioxid. Redox Signal. 19, 595–637. PMID:23311665

  7. Redox Flow Batteries, a Review

    SciTech Connect

    Knoxville, U. Tennessee; U. Texas Austin; U, McGill

    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.

  8. Redox-regulated chaperones.

    PubMed

    Kumsta, Caroline; Jakob, Ursula

    2009-06-09

    Redox regulation of stress proteins, such as molecular chaperones, guarantees an immediate response to oxidative stress conditions. This review focuses on the two major classes of redox-regulated chaperones, Hsp33 in bacteria and typical 2-Cys peroxiredoxins in eukaryotes. Both proteins employ redox-sensitive cysteines, whose oxidation status directly controls their affinity for unfolding proteins and therefore their chaperone function. We will first discuss Hsp33, whose oxidative stress-induced disulfide bond formation triggers the partial unfolding of the chaperone, which, in turn, leads to the exposure of a high-affinity binding site for unfolded proteins. This rapid mode of activation makes Hsp33 essential for protecting bacteria against severe oxidative stress conditions, such as hypochlorite (i.e., bleach) treatment, which leads to widespread protein unfolding and aggregation. We will compare Hsp33 to the highly abundant eukaryotic typical 2-Cys peroxiredoxin, whose oxidative stress-induced sulfinic acid formation turns the peroxidase into a molecular chaperone in vitro and presumably in vivo. These examples illustrate how proteins use reversible cysteine modifications to rapidly adjust to oxidative stress conditions and demonstrate that redox regulation plays a vital role in protecting organisms against reactive oxygen species-mediated cell death.

  9. Redox Control of Skeletal Muscle Regeneration.

    PubMed

    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.

  10. Redox Control of Skeletal Muscle Regeneration

    PubMed Central

    Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan; Groussard, Carole; Zouhal, Hassane

    2017-01-01

    Abstract 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. PMID:28027662

  11. Microfluidic redox battery.

    PubMed

    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.

  12. Managing the cellular redox hub in photosynthetic organisms.

    PubMed

    Foyer, Christine H; Noctor, Graham

    2012-02-01

    Light-driven redox chemistry is a powerful source of redox signals that has a decisive input into transcriptional control within the cell nucleus. Like photosynthetic electron transport pathways, the respiratory electron transport chain exerts a profound control over gene function, in order to balance energy (reductant and ATP) supply with demand, while preventing excessive over-reduction or over-oxidation that would be adversely affect metabolism. Photosynthetic and respiratory redox chemistries are not merely housekeeping processes but they exert a controlling influence over every aspect of plant biology, participating in the control of gene transcription and translation, post-translational modifications and the regulation of assimilatory reactions, assimilate partitioning and export. The number of processes influenced by redox controls and signals continues to increase as do the components that are recognized participants in the associated signalling pathways. A step change in our understanding of the overall importance of the cellular redox hub to plant cells has occurred in recent years as the complexity of the management of the cellular redox hub in relation to metabolic triggers and environmental cues has been elucidated. This special issue describes aspects of redox regulation and signalling at the cutting edge of current research in this dynamic and rapidly expanding field. © 2011 Blackwell Publishing Ltd.

  13. Bicarbonate Induced Redox Proteome Changes in Arabidopsis Suspension Cells.

    PubMed

    Yin, Zepeng; Balmant, Kelly; Geng, Sisi; Zhu, Ning; Zhang, Tong; Dufresne, Craig; Dai, Shaojun; Chen, Sixue

    2017-01-01

    Climate change as a result of increasing atmospheric CO 2 affects plant growth and productivity. CO 2 is not only a carbon donor for photosynthesis but also an environmental signal that can perturb cellular redox homeostasis and lead to modifications of redox-sensitive proteins. Although redox regulation of protein functions has emerged as an important mechanism in several biological processes, protein redox modifications and how they function in plant CO 2 response remain unclear. Here a new iodoTMTRAQ proteomics technology was employed to analyze changes in protein redox modifications in Arabidopsis thaliana suspension cells in response to bicarbonate (mimic of elevated CO 2 ) in a time-course study. A total of 47 potential redox-regulated proteins were identified with functions in carbohydrate and energy metabolism, transport, ROS scavenging, cell structure modulation and protein turnover. This inventory of previously unknown redox responsive proteins in Arabidopsis bicarbonate responses lays a foundation for future research toward understanding the molecular mechanisms underlying plant CO 2 responses.

  14. Bicarbonate Induced Redox Proteome Changes in Arabidopsis Suspension Cells

    PubMed Central

    Yin, Zepeng; Balmant, Kelly; Geng, Sisi; Zhu, Ning; Zhang, Tong; Dufresne, Craig; Dai, Shaojun; Chen, Sixue

    2017-01-01

    Climate change as a result of increasing atmospheric CO2 affects plant growth and productivity. CO2 is not only a carbon donor for photosynthesis but also an environmental signal that can perturb cellular redox homeostasis and lead to modifications of redox-sensitive proteins. Although redox regulation of protein functions has emerged as an important mechanism in several biological processes, protein redox modifications and how they function in plant CO2 response remain unclear. Here a new iodoTMTRAQ proteomics technology was employed to analyze changes in protein redox modifications in Arabidopsis thaliana suspension cells in response to bicarbonate (mimic of elevated CO2) in a time-course study. A total of 47 potential redox-regulated proteins were identified with functions in carbohydrate and energy metabolism, transport, ROS scavenging, cell structure modulation and protein turnover. This inventory of previously unknown redox responsive proteins in Arabidopsis bicarbonate responses lays a foundation for future research toward understanding the molecular mechanisms underlying plant CO2 responses. PMID:28184230

  15. General chemoselective and redox-responsive ligation and release strategy.

    PubMed

    Park, Sungjin; Westcott, Nathan P; Luo, Wei; Dutta, Debjit; Yousaf, Muhammad N

    2014-03-19

    We report a switchable redox click and cleave reaction strategy for conjugating and releasing a range of molecules on demand. This chemoselective redox-responsive ligation (CRRL) and release strategy is based on a redox switchable oxime linkage that is controlled by mild chemical or electrochemical redox signals and can be performed at physiological conditions without the use of a catalyst. Both conjugation and release reactions are kinetically well behaved and quantitative. The CRRL strategy is synthetically modular and easily monitored and characterized by routine analytical techniques. We demonstrate how the CRRL strategy can be used for the dynamic generation of cyclic peptides and the ligation of two different peptides that are stable but can be selectively cleaved upon changes in the redox environment. We also demonstrate a new redox based delivery of cargoes to live cells strategy via the CRRL methodology by synthesizing a FRET redox-responsive probe that is selectively activated within a cellular environment. We believe the ease of the CRRL strategy should find wide use in a range of applications in biology, tissue engineering, nanoscience, synthetic chemistry, and material science and will expand the suite of current conjugation and release strategies.

  16. The Expanding Landscape of the Thiol Redox Proteome*

    PubMed Central

    Yang, Jing; Carroll, Kate S.; Liebler, Daniel C.

    2016-01-01

    Cysteine occupies a unique place in protein chemistry. The nucleophilic thiol group allows cysteine to undergo a broad range of redox modifications beyond classical thiol-disulfide redox equilibria, including S-sulfenylation (-SOH), S-sulfinylation (-SO2H), S-sulfonylation (-SO3H), S-nitrosylation (-SNO), S-sulfhydration (-SSH), S-glutathionylation (-SSG), and others. Emerging evidence suggests that these post-translational modifications (PTM) are important in cellular redox regulation and protection against oxidative damage. Identification of protein targets of thiol redox modifications is crucial to understanding their roles in biology and disease. However, analysis of these highly labile and dynamic modifications poses challenges. Recent advances in the design of probes for thiol redox forms, together with innovative mass spectrometry based chemoproteomics methods make it possible to perform global, site-specific, and quantitative analyses of thiol redox modifications in complex proteomes. Here, we review chemical proteomic strategies used to expand the landscape of thiol redox modifications. PMID:26518762

  17. Ediacaran Redox Fluctuations

    NASA Astrophysics Data System (ADS)

    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.

  18. Oxidative stress, redox stress or redox success?

    PubMed

    Gutteridge, John M C; Halliwell, Barry

    2018-05-09

    The first life forms evolved in a highly reducing environment. This reduced state is still carried by cells today, which makes the concept of "reductive stress" somewhat redundant. When oxygen became abundant on the Earth, due to the evolution of photosynthesis, life forms had to adapt or become extinct. Living organisms did adapt, proliferated and an explosion of new life forms resulted, using reactive oxygen species (ROS) to drive their evolution. Adaptation to oxygen and its reduction intermediates necessitated the simultaneous evolution of select antioxidant defences, carefully regulated to allow ROS to perform their major roles. Clearly this "oxidative stress" did not cause a major problem to the evolution of complex life forms. Why not? Iron and oxygen share a close relationship in aerobic evolution. Iron is used in proteins to transport oxygen, promote electron transfers, and catalyse chemical reactions. In all of these functions, iron is carefully sequestered within proteins and restricted from reacting with ROS, this sequestration being one of our major antioxidant defences. Iron was abundant to life forms before the appearance of oxygen. However, oxygen caused its oxidative precipitation from solution and thereby decreased its bioavailability and thus the risk of iron-dependent oxidative damage. Micro-organisms had to adapt and develop strategies involving siderophores to acquire iron from the environment and eventually their host. This battle for iron between bacteria and animal hosts continues today, and is a much greater daily threat to our survival than "oxidative stress" and "redox stress". Copyright © 2018. Published by Elsevier Inc.

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

    SciTech Connect

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

    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,more » 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.« less

  20. Quantitative measures for redox signaling.

    PubMed

    Pillay, Ché S; Eagling, Beatrice D; Driscoll, Scott R E; Rohwer, Johann M

    2016-07-01

    Redox signaling is now recognized as an important regulatory mechanism for a number of cellular processes including the antioxidant response, phosphokinase signal transduction and redox metabolism. While there has been considerable progress in identifying the cellular machinery involved in redox signaling, quantitative measures of redox signals have been lacking, limiting efforts aimed at understanding and comparing redox signaling under normoxic and pathogenic conditions. Here we have outlined some of the accepted principles for redox signaling, including the description of hydrogen peroxide as a signaling molecule and the role of kinetics in conferring specificity to these signaling events. Based on these principles, we then develop a working definition for redox signaling and review a number of quantitative methods that have been employed to describe signaling in other systems. Using computational modeling and published data, we show how time- and concentration- dependent analyses, in particular, could be used to quantitatively describe redox signaling and therefore provide important insights into the functional organization of redox networks. Finally, we consider some of the key challenges with implementing these methods. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Suppression of single-wall carbon nanotube redox reaction by adsorbed proteins

    NASA Astrophysics Data System (ADS)

    Nakayama, Tomohito; Tanaka, Takeshi; Shiraki, Kentaro; Hase, Muneaki; Hirano, Atsushi

    2018-07-01

    Single-wall carbon nanotubes (SWCNTs) are widely used in biological applications. In biological systems, proteins readily adsorb to SWCNTs. However, little is known about the effects of proteins on the physicochemical properties of SWCNTs, such as their redox reaction. In this study, we measured the absorption and Raman spectra of SWCNTs dispersed in the presence of proteins such as bovine serum albumin to observe the redox reaction of the protein-adsorbed SWCNTs. The adsorbed proteins suppressed the redox reaction by forming thick and dense layers around the SWCNTs. Our findings are useful for understanding the behaviors of SWCNTs in biological systems.

  2. Breast cancer redox heterogeneity detectable with chemical exchange saturation transfer (CEST) MRI.

    PubMed

    Cai, Kejia; Xu, He N; Singh, Anup; Moon, Lily; Haris, Mohammad; Reddy, Ravinder; Li, Lin Z

    2014-10-01

    Tissue redox state is an important mediator of various biological processes in health and diseases such as cancer. Previously, we discovered that the mitochondrial redox state of ex vivo tissues detected by redox scanning (an optical imaging method) revealed interesting tumor redox state heterogeneity that could differentiate tumor aggressiveness. Because the noninvasive chemical exchange saturation transfer (CEST) MRI can probe the proton transfer and generate contrasts from endogenous metabolites, we aim to investigate if the in vivo CEST contrast is sensitive to proton transfer of the redox reactions so as to reveal the tissue redox states in breast cancer animal models. CEST MRI has been employed to characterize tumor metabolic heterogeneity and correlated with the redox states measured by the redox scanning in two human breast cancer mouse xenograft models, MDA-MB-231 and MCF-7. The possible biological mechanism on the correlation between the two imaging modalities was further investigated by phantom studies where the reductants and the oxidants of the representative redox reactions were measured. The CEST contrast is found linearly correlated with NADH concentration and the NADH redox ratio with high statistical significance, where NADH is the reduced form of nicotinamide adenine dinucleotide. The phantom studies showed that the reductants of the redox reactions have more CEST contrast than the corresponding oxidants, indicating that higher CEST effect corresponds to the more reduced redox state. This preliminary study suggests that CEST MRI, once calibrated, might provide a novel noninvasive imaging surrogate for the tissue redox state and a possible diagnostic biomarker for breast cancer in the clinic.

  3. Breast Cancer Redox Heterogeneity Detectable with Chemical Exchange Satruation Transfer (CEST) MRI

    PubMed Central

    Cai, Kejia; Xu, He N.; Singh, Anup; Moon, Lily; Haris, Mohammad; Reddy, Ravinder; Li, Lin

    2014-01-01

    Purpose Tissue redox state is an important mediator of various biological processes in health and diseases such as cancer. Previously, we discovered that the mitochondrial redox state of ex vivo tissues detected by redox scanning (an optical imaging method) revealed interesting tumor redox state heterogeneity that could differentiate tumor aggressiveness. Because the noninvasive chemical exchange saturation transfer (CEST) MRI can probe the proton transfer and generate contrasts from endogenous metabolites, we aim to investigate if the in vivo CEST contrast is sensitive to proton transfer of the redox reactions so as to reveal the tissue redox states in breast cancer animal models. Procedures CEST MRI has been employed to characterize tumor metabolic heterogeneity and correlated with the redox states measured by the redox scanning in two human breast cancer mouse xenograft models, MDA-MB-231 and MCF-7. The possible biological mechanism on the correlation between the two imaging modalities was further investigated by phantom studies where the reductants and the oxidants of the representative redox reactions were measured. Results The CEST contrast is found linearly correlated with NADH concentration and the NADH redox ratio with high statistical significance, where NADH is the reduced form of nicotinamide adenine dinucleotide. The phantom studies showed that the reductants of the redox reactions have more CEST contrast than the corresponding oxidants, indicating that higher CEST effect corresponds to the more reduced redox state. Conclusions This preliminary study suggests that CEST MRI, once calibrated, might provide a novel noninvasive imaging surrogate for the tissue redox state and a possible diagnostic biomarker for breast cancer in the clinic. PMID:24811957

  4. Spatial patterns in oxygen and redox sensitive biogeochemistry in tropical forest soils

    Treesearch

    Daniel Liptzin; Whendee L. Silver

    2015-01-01

    Humid tropical forest soils are characterized by warm temperatures, abundant rainfall, and high rates of biological activity that vary considerably in both space and time. These conditions, together with finely textured soils typical of humid tropical forests lead to periodic low redox conditions, even in well-drained upland environments. The relationship between redox...

  5. Redox control of plant growth and development.

    PubMed

    Kocsy, Gábor; Tari, Irma; Vanková, Radomíra; Zechmann, Bernd; Gulyás, Zsolt; Poór, Péter; Galiba, Gábor

    2013-10-01

    Redox changes determined by genetic and environmental factors display well-organized interactions in the control of plant growth and development. Diurnal and seasonal changes in the environmental conditions are important for the normal course of these physiological processes and, similarly to their mild irregular alterations, for stress adaptation. However, fast or large-scale environmental changes may lead to damage or death of sensitive plants. The spatial and temporal redox changes influence growth and development due to the reprogramming of metabolism. In this process reactive oxygen and nitrogen species and antioxidants are involved as components of signalling networks. The control of growth, development and flowering by reactive oxygen and nitrogen species and antioxidants in interaction with hormones at organ, tissue, cellular and subcellular level will be discussed in the present review. Unsolved problems of the field, among others the need for identification of new components and interactions in the redox regulatory network at various organization levels using systems biology approaches will be also indicated. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Redox artifacts in electrophysiological recordings

    PubMed Central

    Berman, Jonathan M.

    2013-01-01

    Electrophysiological techniques make use of Ag/AgCl electrodes that are in direct contact with cells or bath. In the bath, electrodes are exposed to numerous experimental conditions and chemical reagents that can modify electrode voltage. We examined voltage offsets created in Ag/AgCl electrodes by exposure to redox reagents used in electrophysiological studies. Voltage offsets were measured in reference to an electrode separated from the solution by an agar bridge. The reducing reagents Tris-2-carboxyethly-phosphine, dithiothreitol (DTT), and glutathione, as well as the oxidizing agent H2O2 used at experimentally relevant concentrations reacted with Ag in the electrodes to produce voltage offsets. Chloride ions and strong acids and bases produced offsets at millimolar concentrations. Electrolytic depletion of the AgCl layer, to replicate voltage clamp and sustained use, resulted in increased sensitivity to flow and DTT. Offsets were sensitive to electrode silver purity and to the amount and method of chloride deposition. For example, exposure to 10 μM DTT produced a voltage offset between 10 and 284 mV depending on the chloride deposition method. Currents generated by these offsets are significant and dependent on membrane conductance and by extension the expression of ion channels and may therefore appear to be biological in origin. These data demonstrate a new source of artifacts in electrophysiological recordings that can affect measurements obtained from a variety of experimental techniques from patch clamp to two-electrode voltage clamp. PMID:23344161

  7. Redox status in a model of cancer stem cells.

    PubMed

    Zaccarin, Mattia; Bosello-Travain, Valentina; Di Paolo, Maria Luisa; Falda, Marco; Maiorino, Matilde; Miotto, Giovanni; Piccolo, Stefano; Roveri, Antonella; Ursini, Fulvio; Venerando, Rina; Toppo, Stefano

    2017-03-01

    Reversible oxidation of Cys residues is a crucial element of redox homeostasis and signaling. According to a popular concept in oxidative stress signaling, the oxidation of targets of signals can only take place following an overwhelming of the cellular antioxidant capacity. This concept, however, ignores the activation of feedback mechanisms possibly leading to a paradoxical effect. In a model of cancer stem cells (CSC), stably overexpressing the TAZ oncogene, we observed that the increased formation of oxidants is associated with a globally more reduced state of proteins. Redox proteomics revealed that several proteins, capable of undergoing reversible redox transitions, are indeed more reduced while just few are more oxidized. Among the proteins more oxidized, G6PDH emerges as both more expressed and activated by oxidation. This accounts for the observed more reduced state of the NADPH/NADP + couple. The dynamic redox flux generating this apparently paradoxical effect is rationalized in a computational system biology model highlighting the crucial role of G6PDH activity on the rate of redox transitions eventually leading to the reduction of reversible redox switches. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Redox Disproportionation of Glucose as a Major Biosynthetic Energy Source

    NASA Technical Reports Server (NTRS)

    Weber, Arthur L.

    1996-01-01

    Previous studies have concluded that very little if any energy is required for the microbial biosynthesis of amino acids and lipids from glucose -- processes that yield almost as much ATP (adenosine triphosphate) as they consume. However, these studies did not establish the strength nor the nature of the energy source driving these biological transformations. To identify and estimate the strength of the energy source behind these processes, we calculated the free energy change due to the redox disproportionation of substrate carbon of (a) 26 redox-balanced fermentation reactions, and (b) the biosynthesis of amino acids, lipids, and nucleotides of E. coli from glucose. A plot of the negative free energy of these reactions per mmole of carbon as a function of the number of disproportionative electron transfers per mmol of carbon showed that the energy yields of these fermentations and biosyntheses were directly proportional to the degree of redox disproportionation of carbon. Since this linear relationship showed that redox disproportionation was the dominant energy source of these reactions, we were able to establish that amino acid and lipid biosynthesis obtained most of their energy from redox disproportionation (greater than 94%). In contrast nucleotide biosynthesis was not driven by redox disproportionation of carbon, and consequently depended completely on ATP for energy. This crucial and previously unrecognized role of sugars as an energy source of biosynthesis suggests that sugars were involved at the earliest stage in the origin of anabolic metabolism.

  9. Redox-activated MRI contrast agents based on lanthanide and transition metal ions.

    PubMed

    Tsitovich, Pavel B; Burns, Patrick J; McKay, Adam M; Morrow, Janet R

    2014-04-01

    The reduction/oxidation (redox) potential of tissue is tightly regulated in order to maintain normal physiological processes, but is disrupted in disease states. Thus, the development of new tools to map tissue redox potential may be clinically important for the diagnosis of diseases that lead to redox imbalances. One promising area of chemical research is the development of redox-activated probes for mapping tissue through magnetic resonance imaging (MRI). In this review, we summarize several strategies for the design of redox-responsive MRI contrast agents. Our emphasis is on both lanthanide(III) and transition metal(II/III) ion complexes that provide contrast either as T1 relaxivity MRI contrast agents or as paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents. These agents are redox-triggered by a variety of chemical reactions or switches including redox-activated thiol groups, and heterocyclic groups that interact with the metal ion or influence properties of other ancillary ligands. Metal ion centered redox is an approach which is ripe for development by coordination chemists. Redox-triggered metal ion approaches have great potential for creating large differences in magnetic properties that lead to changes in contrast. An attractive feature of these agents is the ease of fine-tuning the metal ion redox potential over a biologically relevant range. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Redox mediation and hydrogen-generation with bipyridinium reagents

    DOEpatents

    Wrighton, Mark S.; Bookbinder, Dana C.; Bruce, James A.; Dominey, Raymond N.; Lewis, Nathan S.

    1984-03-27

    A variety of redox mediating agents employing bipyridinium reagents and such reagents in conjunction with dispersed noble metals, such as platinium, are disclosed as coatings for substrates and electrodes. The agents may be charged by an applied voltage or by photoelectric effects or may be equilibrated with hydrogen. The agents are useful in reducing biological materials and electrolytic hydrogen production.

  11. Redox-Responsive Fluorescent Probes with Different Design Strategies.

    PubMed

    Lou, Zhangrong; Li, Peng; Han, Keli

    2015-05-19

    In an aerobic organism, reactive oxygen species (ROS) are an inevitable metabolic byproduct. Endogenously produced ROS have a significant role in physiological processes, but excess ROS can cause oxidative stress and can damage tissue. Cells possess elaborate mechanisms to regulate their internal redox status. The intracellular redox homeostasis plays an essential role in maintaining cellular function. However, moderate alterations in redox balance can accompany major transitions in a cell's life cycle. Because of the role of ROS in physiology and in pathology, researchers need new tools to study redox chemistry in biological systems.In recent years, researchers have made remarkable progress in developing new, highly sensitive and selective fluorescent probes that respond to redox changes, and in this Account we highlight related research, primarily from our own group. We present an overview of the design, photophysical properties, and fluorescence transduction mechanisms of reported molecules that probe redox changes. We have designed and synthesized a series of fluorescent probes for redox cycles in biological systems relying on the active center of glutathione peroxidase (GPx). We have also constructed probes based on the oxidation and reduction of hydroquinone and of 2,2,6,6-tetramethylpiperidinooxy (TEMPO). Most of these probes exhibit high sensitivity and good selectivity, absorb in the near-infrared, and respond rapidly. Such probes are useful for confocal fluorescence microscopy, a dynamic imaging technique that could allow researchers to observe biologically important ROS and antioxidants in real time. This technique and these probes provide potentially useful tools for exploring the generation, transport, physiological function, and pathogenic mechanisms of ROS and antioxidants.We also describe features that could improve the properties of redox-responsive fluorescent probes: greater photostability; rapid, dynamic, cyclic and ratiometric responses; and

  12. Redox potential: An indicator of site productivity in forest management

    NASA Astrophysics Data System (ADS)

    Sajedi, Toktam; Prescott, Cindy; Lavkulich, Les

    2010-05-01

    Redox potential (Eh) is an integrated soil measurement that reflects several environmental conditions in the soil associated with aeration, moisture and carbon (organic matter) dynamics. Its measurement can be related to water table fluctuations, precipitation and landscape gradients, organic matter decomposition rates, nutrient dynamics, biological diversity and plant species distribution. Redox is an excellent indicator of soil biological processes, as it is largely a reflection of microbial activities which to a large extent govern carbon dynamics and nutrient cycling. Redox thus serves as an ecological indicator of site productivity at the ecosystem scale and may be used for management purposes as its magnitude can be altered by activities such as harvesting and drainage. A threshold value of 300 mv has been documented as the critical value below which anaerobic conditions in the soil develop. However, redox measurements and its impacts on ecosystem processes such as nutrient cycling and productivity, especially in forest ecosystems, have not received the attention that this "master" variable deserves, On northern Vancouver Island, Canada, regenerating stands of western redcedar-western hemlock (CH) sites exhibit symptoms of nutrient deficiencies and slow growth, but this phenomenon does not occur on adjacent western hemlock- amabalis fir (HA) sites. We tested the hypothesis that differences in nutrient supply and distribution of plant species was caused by differences in moisture regime and redox potential. Redox potential, pH, soil aeration depth (steel rods), organic matter thickness, bulk density, soil carbon store, plant species distribution and richness were measured at five old-growth and five 10-year-old cutover blocks. Results of investigations confirmed that CH forests were wetter, had redox values lower than the critical 300mv and a shallower aerated zone, compared with adjacent regenerating HA sites. Fifty percent of the CH plots had redox values

  13. Redox Regulation of Cell Survival

    PubMed Central

    Trachootham, Dunyaporn; Lu, Weiqin; Ogasawara, Marcia A.; Valle, Nilsa Rivera-Del

    2008-01-01

    Abstract Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in regulation of cell survival. In general, moderate levels of ROS/RNS may function as signals to promote cell proliferation and survival, whereas severe increase of ROS/RNS can induce cell death. Under physiologic conditions, the balance between generation and elimination of ROS/RNS maintains the proper function of redox-sensitive signaling proteins. Normally, the redox homeostasis ensures that the cells respond properly to endogenous and exogenous stimuli. However, when the redox homeostasis is disturbed, oxidative stress may lead to aberrant cell death and contribute to disease development. This review focuses on the roles of key transcription factors, signal-transduction pathways, and cell-death regulators in affecting cell survival, and how the redox systems regulate the functions of these molecules. The current understanding of how disturbance in redox homeostasis may affect cell death and contribute to the development of diseases such as cancer and degenerative disorders is reviewed. We also discuss how the basic knowledge on redox regulation of cell survival can be used to develop strategies for the treatment or prevention of those diseases. Antioxid. Redox Signal. 10, 1343–1374. PMID:18522489

  14. The fairytale of the GSSG/GSH redox potential.

    PubMed

    Flohé, Leopold

    2013-05-01

    The term GSSG/GSH redox potential is frequently used to explain redox regulation and other biological processes. The relevance of the GSSG/GSH redox potential as driving force of biological processes is critically discussed. It is recalled that the concentration ratio of GSSG and GSH reflects little else than a steady state, which overwhelmingly results from fast enzymatic processes utilizing, degrading or regenerating GSH. A biological GSSG/GSH redox potential, as calculated by the Nernst equation, is a deduced electrochemical parameter based on direct measurements of GSH and GSSG that are often complicated by poorly substantiated assumptions. It is considered irrelevant to the steering of any biological process. GSH-utilizing enzymes depend on the concentration of GSH, not on [GSH](2), as is predicted by the Nernst equation, and are typically not affected by GSSG. Regulatory processes involving oxidants and GSH are considered to make use of mechanistic principles known for thiol peroxidases which catalyze the oxidation of hydroperoxides by GSH by means of an enzyme substitution mechanism involving only bimolecular reaction steps. The negligibly small rate constants of related spontaneous reactions as compared with enzyme-catalyzed ones underscore the superiority of kinetic parameters over electrochemical or thermodynamic ones for an in-depth understanding of GSH-dependent biological phenomena. At best, the GSSG/GSH potential might be useful as an analytical tool to disclose disturbances in redox metabolism. This article is part of a Special Issue entitled Cellular Functions of Glutathione. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Redox Properties of Free Radicals.

    ERIC Educational Resources Information Center

    Neta, P.

    1981-01-01

    Describes pulse radiolysis as a useful means in studing one-electron redox potentials. This method allows the production of radicals and the determination of their concentration and rates of reaction. (CS)

  16. A biomimetic redox flow battery based on flavin mononucleotide

    PubMed Central

    Orita, Akihiro; Verde, Michael G.; Sakai, Masanori; Meng, Ying Shirley

    2016-01-01

    The versatility in design of redox flow batteries makes them apt to efficiently store energy in large-scale applications at low cost. The discovery of inexpensive organic electroactive materials for use in aqueous flow battery electrolytes is highly attractive, but is thus far limited. Here we report on a flow battery using an aqueous electrolyte based on the sodium salt of flavin mononucleotide. Flavins are highly versatile electroactive molecules, which catalyse a multitude of redox reactions in biological systems. We use nicotinamide (vitamin B3) as a hydrotropic agent to enhance the water solubility of flavin mononucleotide. A redox flow battery using flavin mononucleotide negative and ferrocyanide positive electrolytes in strong base shows stable cycling performance, with over 99% capacity retention over the course of 100 cycles. We hypothesize that this is enabled due to the oxidized and reduced forms of FMN-Na being stabilized by resonance structures. PMID:27767026

  17. A biomimetic redox flow battery based on flavin mononucleotide

    NASA Astrophysics Data System (ADS)

    Orita, Akihiro; Verde, Michael G.; Sakai, Masanori; Meng, Ying Shirley

    2016-10-01

    The versatility in design of redox flow batteries makes them apt to efficiently store energy in large-scale applications at low cost. The discovery of inexpensive organic electroactive materials for use in aqueous flow battery electrolytes is highly attractive, but is thus far limited. Here we report on a flow battery using an aqueous electrolyte based on the sodium salt of flavin mononucleotide. Flavins are highly versatile electroactive molecules, which catalyse a multitude of redox reactions in biological systems. We use nicotinamide (vitamin B3) as a hydrotropic agent to enhance the water solubility of flavin mononucleotide. A redox flow battery using flavin mononucleotide negative and ferrocyanide positive electrolytes in strong base shows stable cycling performance, with over 99% capacity retention over the course of 100 cycles. We hypothesize that this is enabled due to the oxidized and reduced forms of FMN-Na being stabilized by resonance structures.

  18. A biomimetic redox flow battery based on flavin mononucleotide.

    PubMed

    Orita, Akihiro; Verde, Michael G; Sakai, Masanori; Meng, Ying Shirley

    2016-10-21

    The versatility in design of redox flow batteries makes them apt to efficiently store energy in large-scale applications at low cost. The discovery of inexpensive organic electroactive materials for use in aqueous flow battery electrolytes is highly attractive, but is thus far limited. Here we report on a flow battery using an aqueous electrolyte based on the sodium salt of flavin mononucleotide. Flavins are highly versatile electroactive molecules, which catalyse a multitude of redox reactions in biological systems. We use nicotinamide (vitamin B3) as a hydrotropic agent to enhance the water solubility of flavin mononucleotide. A redox flow battery using flavin mononucleotide negative and ferrocyanide positive electrolytes in strong base shows stable cycling performance, with over 99% capacity retention over the course of 100 cycles. We hypothesize that this is enabled due to the oxidized and reduced forms of FMN-Na being stabilized by resonance structures.

  19. Protein Thiol Redox Signaling in Monocytes and Macrophages.

    PubMed

    Short, John D; Downs, Kevin; Tavakoli, Sina; Asmis, Reto

    2016-11-20

    Monocyte and macrophage dysfunction plays a critical role in a wide range of inflammatory disease processes, including obesity, impaired wound healing diabetic complications, and atherosclerosis. Emerging evidence suggests that the earliest events in monocyte or macrophage dysregulation include elevated reactive oxygen species production, thiol modifications, and disruption of redox-sensitive signaling pathways. This review focuses on the current state of research in thiol redox signaling in monocytes and macrophages, including (i) the molecular mechanisms by which reversible protein-S-glutathionylation occurs, (ii) the identification of bona fide S-glutathionylated proteins that occur under physiological conditions, and (iii) how disruptions of thiol redox signaling affect monocyte and macrophage functions and contribute to atherosclerosis. Recent Advances: Recent advances in redox biochemistry and biology as well as redox proteomic techniques have led to the identification of many new thiol redox-regulated proteins and pathways. In addition, major advances have been made in expanding the list of S-glutathionylated proteins and assessing the role that protein-S-glutathionylation and S-glutathionylation-regulating enzymes play in monocyte and macrophage functions, including monocyte transmigration, macrophage polarization, foam cell formation, and macrophage cell death. Protein-S-glutathionylation/deglutathionylation in monocytes and macrophages has emerged as a new and important signaling paradigm, which provides a molecular basis for the well-established relationship between metabolic disorders, oxidative stress, and cardiovascular diseases. The identification of specific S-glutathionylated proteins as well as the mechanisms that control this post-translational protein modification in monocytes and macrophages will facilitate the development of new preventive and therapeutic strategies to combat atherosclerosis and other metabolic diseases. Antioxid. Redox Signal

  20. Redox theory of aging: implications for health and disease

    PubMed Central

    Go, Young-Mi; Jones, Dean P.

    2017-01-01

    Genetics ultimately defines an individual, yet the phenotype of an adult is extensively determined by the sequence of lifelong exposures, termed the exposome. The redox theory of aging recognizes that animals evolved within an oxygen-rich environment, which created a critical redox interface between an organism and its environment. Advances in redox biology show that redox elements are present throughout metabolic and structural systems and operate as functional networks to support the genome in adaptation to environmental resources and challenges during lifespan. These principles emphasize that physical and functional phenotypes of an adult are determined by gene–environment interactions from early life onward. The principles highlight the critical nature of cumulative exposure memories in defining changes in resilience progressively during life. Both plasma glutathione and cysteine systems become oxidized with aging, and the recent finding that cystine to glutathione ratio in human plasma predicts death in coronary artery disease (CAD) patients suggests this could provide a way to measure resilience of redox networks in aging and disease. The emerging concepts of cumulative gene–environment interactions warrant focused efforts to elucidate central mechanisms by which exposure memory governs health and etiology, onset and progression of disease. PMID:28667066

  1. Redox rhythm reinforces the circadian clock to gate immune response.

    PubMed

    Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E; Dong, Xinnian

    2015-07-23

    Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.

  2. Redox Heterogenity in MORB

    NASA Astrophysics Data System (ADS)

    Cottrell, E.; Kelley, K. A.

    2012-12-01

    Mantle oxygen fugacity (fO2) has a first-order effect on the petrogenesis of mantle-derived melts and the speciation of mantle fluids. Current debate centers on the spatial uniformity of upper mantle fO2 and its constancy through geologic time. We use iron K-edge X-ray absorption near-edge structure (μXANES) spectroscopy to provide Fe3+ /ΣFe ratios of submarine mantle-derived basalts from mid-ocean ridges (MORB) as a proxy for fO2. A global survey of primitive (>8.75 wt% MgO) MORB glasses at spreading centers, unaffected by plumes, reveals a decrease in Fe3+ /ΣFe ratio of 12% relative with indices of mantle enrichment such as 87/86Sr, 208/204Pb, Ba/La, and Rb/Sr ratios. The strong negative correlation between upper mantle fO2 and enrichment recorded by MORB glasses contrasts with the positive relationship hinted at by abyssal peridotite oxybarometry (e.g. Ballhaus, CMP, 1993) and the general prediction of a positive correlation born of the expectation that Fe3+ can be treated as more incompatible than Fe2+ during mantle melting. These data unequivocally link upper mantle oxidation state to mantle source enrichment. EMORB generation is commonly attributed to subduction-related processes. That EMORB is more reduced than NMORB implies that deeply subducted and recycled lithologies, such as anoxic sediment, may be more reduced than ambient mantle. Negative correlations between traditional tracers of recycled sediment (e.g. +Nb anomaly, high 87/86Sr, high LILE/LREE) and redox support this hypothesis. Preservation of redox signatures on plate-recycling timescales of hundreds of millions to billions of years would require the mantle to be very poorly buffered. Alternatively, MORB Fe3+ /ΣFe ratios may be generated in situ beneath ridges as a function of variable carbon content. The shallow MORB source is too oxidized to stabilize graphite (Cottrell and Kelley, EPSL, 2011) and carbon exists as oxides. Decreasing fO2 with increasing depth eventually stabilizes reduced

  3. Hydrogen peroxide and central redox theory for aerobic life: A tribute to Helmut Sies: Scout, trailblazer, and redox pioneer.

    PubMed

    Jones, Dean P

    2016-04-01

    When Rafael Radi and I wrote about Helmut Sies for the Redox Pioneer series, I was disappointed that the Editor restricted us to the use of "Pioneer" in the title. My view is that Helmut was always ahead of the pioneers: He was a scout discovering paths for exploration and a trailblazer developing strategies and methods for discovery. I have known him for nearly 40 years and greatly enjoyed his collegiality as well as brilliance in scientific scholarship. He made monumental contributions to 20th century physiological chemistry beginning with his first measurement of H2O2 in rat liver. While continuous H2O2 production is dogma today, the concept of H2O2 production in mammalian tissues was largely buried for half a century. He continued this leadership in research on oxidative stress, GSH, selenium, and singlet oxygen, during the timeframe when physiological chemistry and biochemistry transitioned to contemporary 21st century systems biology. His impact has been extensive in medical and health sciences, especially in nutrition, aging, toxicology and cancer. I briefly summarize my interactions with Helmut, stressing our work together on the redox code, a set of principles to link mitochondrial respiration, bioenergetics, H2O2 metabolism, redox signaling and redox proteomics into central redox theory. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  4. Novel insights into redox system and the mechanism of redox regulation.

    PubMed

    Wang, Xin; Hai, Chunxu

    2016-07-01

    In view of the critical role of redox system in numerous physiological and pathophysiological processes, it is important to clearly understand the family members and regulatory mechanism of redox system. In this work, we will systematically review the current data detailing the reactive oxygen species (ROS), enzymatic and non-enzymatic antioxidants and redox sensitive transcription factors and we give a brief description of redox-mediated epigenetic and post-translational regulation. We propose that the redox system functions as a "Redox Chain", consisting of "ROS-generating Enzyme Chain", "Combined Antioxidant Chain" and "Transcription Factor Chain". We suggest that an individualized assessment of the redox status in the body should be conducted for the redox intervention of a patient. The strategy of intervention is to maintain redox homeostasis via either facilitation of ROS signaling or enhancement of antioxidant defense. These findings provide valuable new insights into redox system and open up new paths for the control of redox-related disorders.

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

    PubMed

    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.

  6. NASA Redox Project status summary

    NASA Technical Reports Server (NTRS)

    Hagedorn, N. H.

    1983-01-01

    This report is a summary of the results of the Redox Project effort during Cy 1982. It was presented at the Fifth U.S. Department of Energy Battery and Electrochemical Contractors Conference, Arlington, Va., Dec. 7-9, 1982. The major development during 1982 was the shift from Redox system operation at 25 C with unmixed reactants to operation at 65 C with mixed reactants. This change has made possible a two- or three-fold increase in operating current density, to about 65 mA/sq cm, and an increase in reactant utilization from 40% to about 90%. Both of these improvements will lead to significant system cost reductions. Contract studies have indicated that Redox reactant costs also will be moderate. A new catalyst for the chromuim electrode offers all the advantages of the conventional gold-lead catalyst while being easier to apply and more forgiving in use.

  7. Redox Regulation of Plant Development

    PubMed Central

    Considine, Michael J.

    2014-01-01

    Abstract Significance: 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. Recent Advances: 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. Critical Issues: 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. Future Directions: 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. Antioxid. Redox Signal. 21, 1305–1326. PMID:24180689

  8. Two distinct redox cascades cooperatively regulate chloroplast functions and sustain plant viability.

    PubMed

    Yoshida, Keisuke; Hisabori, Toru

    2016-07-05

    The thiol-based redox regulation system is believed to adjust chloroplast functions in response to changes in light environments. A redox cascade via the ferredoxin-thioredoxin reductase (FTR)/thioredoxin (Trx) pathway has been traditionally considered to serve as a transmitter of light signals to target enzymes. However, emerging data indicate that chloroplasts have a complex redox network composed of diverse redox-mediator proteins and target enzymes. Despite extensive research addressing this system, two fundamental questions are still unresolved: How are redox pathways orchestrated within chloroplasts, and why are chloroplasts endowed with a complicated redox network? In this report, we show that NADPH-Trx reductase C (NTRC) is a key redox-mediator protein responsible for regulatory functions distinct from those of the classically known FTR/Trx system. Target screening and subsequent biochemical assays indicated that NTRC and the Trx family differentially recognize their target proteins. In addition, we found that NTRC is an electron donor to Trx-z, which is a key regulator of gene expression in chloroplasts. We further demonstrate that cooperative control of chloroplast functions via the FTR/Trx and NTRC pathways is essential for plant viability. Arabidopsis double mutants impaired in FTR and NTRC expression displayed lethal phenotypes under autotrophic growth conditions. This severe growth phenotype was related to a drastic loss of photosynthetic performance. These combined results provide an expanded map of the chloroplast redox network and its biological functions.

  9. Pyruvate dehydrogenase complex and nicotinamide nucleotide transhydrogenase constitute an energy-consuming redox circuit.

    PubMed

    Fisher-Wellman, Kelsey H; Lin, Chien-Te; Ryan, Terence E; Reese, Lauren R; Gilliam, Laura A A; Cathey, Brook L; Lark, Daniel S; Smith, Cody D; Muoio, Deborah M; Neufer, P Darrell

    2015-04-15

    Cellular proteins rely on reversible redox reactions to establish and maintain biological structure and function. How redox catabolic (NAD+/NADH) and anabolic (NADP+/NADPH) processes integrate during metabolism to maintain cellular redox homoeostasis, however, is unknown. The present work identifies a continuously cycling mitochondrial membrane potential (ΔΨm)-dependent redox circuit between the pyruvate dehydrogenase complex (PDHC) and nicotinamide nucleotide transhydrogenase (NNT). PDHC is shown to produce H2O2 in relation to reducing pressure within the complex. The H2O2 produced, however, is effectively masked by a continuously cycling redox circuit that links, via glutathione/thioredoxin, to NNT, which catalyses the regeneration of NADPH from NADH at the expense of ΔΨm. The net effect is an automatic fine-tuning of NNT-mediated energy expenditure to metabolic balance at the level of PDHC. In mitochondria, genetic or pharmacological disruptions in the PDHC-NNT redox circuit negate counterbalance changes in energy expenditure. At the whole animal level, mice lacking functional NNT (C57BL/6J) are characterized by lower energy-expenditure rates, consistent with their well-known susceptibility to diet-induced obesity. These findings suggest the integration of redox sensing of metabolic balance with compensatory changes in energy expenditure provides a potential mechanism by which cellular redox homoeostasis is maintained and body weight is defended during periods of positive and negative energy balance.

  10. Two distinct redox cascades cooperatively regulate chloroplast functions and sustain plant viability

    PubMed Central

    Yoshida, Keisuke; Hisabori, Toru

    2016-01-01

    The thiol-based redox regulation system is believed to adjust chloroplast functions in response to changes in light environments. A redox cascade via the ferredoxin-thioredoxin reductase (FTR)/thioredoxin (Trx) pathway has been traditionally considered to serve as a transmitter of light signals to target enzymes. However, emerging data indicate that chloroplasts have a complex redox network composed of diverse redox-mediator proteins and target enzymes. Despite extensive research addressing this system, two fundamental questions are still unresolved: How are redox pathways orchestrated within chloroplasts, and why are chloroplasts endowed with a complicated redox network? In this report, we show that NADPH-Trx reductase C (NTRC) is a key redox-mediator protein responsible for regulatory functions distinct from those of the classically known FTR/Trx system. Target screening and subsequent biochemical assays indicated that NTRC and the Trx family differentially recognize their target proteins. In addition, we found that NTRC is an electron donor to Trx-z, which is a key regulator of gene expression in chloroplasts. We further demonstrate that cooperative control of chloroplast functions via the FTR/Trx and NTRC pathways is essential for plant viability. Arabidopsis double mutants impaired in FTR and NTRC expression displayed lethal phenotypes under autotrophic growth conditions. This severe growth phenotype was related to a drastic loss of photosynthetic performance. These combined results provide an expanded map of the chloroplast redox network and its biological functions. PMID:27335455

  11. Pyruvate dehydrogenase complex and nicotinamide nucleotide transhydrogenase constitute an energy consuming redox circuit

    PubMed Central

    Fisher-Wellman, Kelsey H.; Lin, Chien-Te; Ryan, Terence E.; Reese, Lauren R.; Gilliam, Laura A. A.; Cathey, Brook L.; Lark, Daniel S.; Smith, Cody D.; Muoio, Deborah M.; Neufer, P. Darrell

    2015-01-01

    SUMMARY Cellular proteins rely on reversible redox reactions to establish and maintain biological structure and function. How redox catabolic (NAD+:NADH) and anabolic (NADP+:NADPH) processes integrate during metabolism to maintain cellular redox homeostasis however is unknown. The present work identifies a continuously cycling, mitochondrial membrane potential-dependent redox circuit between the pyruvate dehydrogenase complex (PDHC) and nicotinamide nucleotide transhydrogenase (NNT). PDHC is shown to produce H2O2 in relation to reducing pressure within the complex. The H2O2 produced however is effectively masked by a continuously cycling redox circuit that links, via glutathione/thioredoxin, to NNT, which catalyzes the regeneration of NADPH from NADH at the expense of the mitochondrial membrane potential. The net effect is an automatic fine tuning of NNT-mediated energy expenditure to metabolic balance at the level of PDHC. In mitochondria, genetic or pharmacological disruptions in the PDHC-NNT redox circuit negate counterbalance changes in energy expenditure. At the whole animal level, mice lacking functional NNT (C57BL/6J) are characterized by lower energy expenditure rates, consistent with their well known susceptibility to diet-induced obesity. These findings suggest the integration of redox sensing of metabolic balance with compensatory changes in energy expenditure provides a potential mechanism by which cellular redox homeostasis is maintained and body weight is defended during periods of positive and negative energy balance. PMID:25643703

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

    PubMed

    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.

  13. Real-time quantification of subcellular H2O2 and glutathione redox potential in living cardiovascular tissues.

    PubMed

    Panieri, Emiliano; Millia, Carlo; Santoro, Massimo M

    2017-08-01

    Detecting and measuring the dynamic redox events that occur in vivo is a prerequisite for understanding the impact of oxidants and redox events in normal and pathological conditions. These aspects are particularly relevant in cardiovascular tissues wherein alterations of the redox balance are associated with stroke, aging, and pharmacological intervention. An ambiguous aspect of redox biology is how redox events occur in subcellular organelles including mitochondria, and nuclei. Genetically-encoded Rogfp2 fluorescent probes have become powerful tools for real-time detection of redox events. These probes detect hydrogen peroxide (H 2 O 2 ) levels and glutathione redox potential (E GSH ), both with high spatiotemporal resolution. By generating novel transgenic (Tg) zebrafish lines that express compartment-specific Rogfp2-Orp1 and Grx1-Rogfp2 sensors we analyzed cytosolic, mitochondrial, and the nuclear redox state of endothelial cells and cardiomyocytes of living zebrafish embryos. We provide evidence for the usefulness of these Tg lines for pharmacological compounds screening by addressing the blocking of pentose phosphate pathways (PPP) and glutathione synthesis, thus altering subcellular redox state in vivo. Rogfp2-based transgenic zebrafish lines represent valuable tools to characterize the impact of redox changes in living tissues and offer new opportunities for studying metabolic driven antioxidant response in biomedical research. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Redox pathways of the mitochondrion.

    PubMed

    Koehler, Carla M; Beverly, Kristen N; Leverich, Edward P

    2006-01-01

    The mitochondrion houses a variety of redox pathways, utilized for protection from oxidative damage and assembly of the organelle. The glutathione/glutaredoxin and thioredoxin systems function in the mitochondrial matrix. The intermembrane space is protected from oxidative damage via superoxide dismutase and glutathione. Subunits in the cytochrome bc (1) complex utilize disulfide bonds for enzymatic activity, whereas cytochrome oxidase relies on disulfide linkages for copper acquisition. A redox pathway (Mia40p and Erv1p) mediates the import of intermembrane space proteins such as the small Tim proteins, Cox17p, and Cox19p, which have disulfide bonds. Many of the candidate proteins with disulfide bridges possess a twin CX3C motif or CX9C motif and utilize both metal binding and disulfide linkages for function. It may seem surprising that the intermembrane space has developed redox pathways, considering that the buffered environment should be reducing like the cytosol. However, the prokaryotic origin of the mitochondrion suggests that the intermembrane space may be akin to the oxidative environment of the bacterial periplasm. Although the players forming disulfide bonds are not conserved between mitochondria and prokaryotes, the mitochondrion may have maintained redox chemistry as an assembly mechanism in the intermembrane space for the import of proteins and metals and enzymatic activity.

  15. The redox-Mannich reaction.

    PubMed

    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.

  16. Arsenic behavior in river sediments under redox gradient: a review.

    PubMed

    Gorny, Josselin; Billon, Gabriel; Lesven, Ludovic; Dumoulin, David; Madé, Benoît; Noiriel, Catherine

    2015-02-01

    The fate of arsenic - a redox sensitive metalloid - in surface sediments is closely linked to early diagenetic processes. The review presents the main redox mechanisms and final products of As that have been evidenced over the last years. Oxidation of organic matter and concomitant reduction of oxidants by bacterial activity result in redox transformations of As species. The evolution of the sediment reactivity will also induce secondary abiotic reactions like complexation/de-complexation, sorption, precipitation/dissolution and biotic reactions that could, for instance, lead to the detoxification of some As species. Overall, abiotic redox reactions that govern the speciation of As mostly involve manganese (hydr)-oxides and reduced sulfur species produced by the sulfate-reducing bacteria. Bacterial activity is also responsible for the inter-conversion between As(V) and As(III), as well as for the production of methylated arsenic species. In surficial sediments, sorption processes also control the fate of inorganic As(V), through the formation of inner sphere complexes with iron (hydr)-oxides, that are biologically reduced in buried sediment. Arsenic species can also be bound to organic matter, either directly to functional groups or indirectly through metal complexes. Finally, even if the role of reduced sulfur species in the cycling of arsenic in sediments has been evidenced, some of the transformations remain hypothetical and deserve further investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23492768

  19. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease.

    PubMed

    Valko, Marian; Jomova, Klaudia; Rhodes, Christopher J; Kuča, Kamil; Musílek, Kamil

    2016-01-01

    Transition metal ions are key elements of various biological processes ranging from oxygen formation to hypoxia sensing, and therefore, their homeostasis is maintained within strict limits through tightly regulated mechanisms of uptake, storage and secretion. The breakdown of metal ion homeostasis can lead to an uncontrolled formation of reactive oxygen species, ROS (via the Fenton reaction, which produces hydroxyl radicals), and reactive nitrogen species, RNS, which may cause oxidative damage to biological macromolecules such as DNA, proteins and lipids. An imbalance between the formation of free radicals and their elimination by antioxidant defense systems is termed oxidative stress. Most vulnerable to free radical attack is the cell membrane which may undergo enhanced lipid peroxidation, finally producing mutagenic and carcinogenic malondialdehyde and 4-hydroxynonenal and other exocyclic DNA adducts. While redox-active iron (Fe) and copper (Cu) undergo redox-cycling reactions, for a second group of redox-inactive metals such as arsenic (As) and cadmium (Cd), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. While arsenic is known to bind directly to critical thiols, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. Redox-inert zinc (Zn) is the most abundant metal in the brain and an essential component of numerous proteins involved in biological defense mechanisms against oxidative stress. The depletion of zinc may enhance DNA damage by impairing DNA repair mechanisms. Intoxication of an organism by arsenic and cadmium may lead to metabolic disturbances of redox-active copper and iron, with the occurrence of oxidative stress induced by the enhanced formation of ROS/RNS. Oxidative stress occurs when excessive formation of ROS overwhelms the antioxidant defense system, as is maintained by antioxidants such as ascorbic acid, alpha

  20. Redox signaling in cardiac myocytes

    PubMed Central

    Santos, Celio X.C.; Anilkumar, Narayana; Zhang, Min; Brewer, Alison C.; Shah, Ajay M.

    2011-01-01

    The heart has complex mechanisms that facilitate the maintenance of an oxygen supply–demand balance necessary for its contractile function in response to physiological fluctuations in workload as well as in response to chronic stresses such as hypoxia, ischemia, and overload. Redox-sensitive signaling pathways are centrally involved in many of these homeostatic and stress-response mechanisms. Here, we review the main redox-regulated pathways that are involved in cardiac myocyte excitation–contraction coupling, differentiation, hypertrophy, and stress responses. We discuss specific sources of endogenously generated reactive oxygen species (e.g., mitochondria and NADPH oxidases of the Nox family), the particular pathways and processes that they affect, the role of modulators such as thioredoxin, and the specific molecular mechanisms that are involved—where this knowledge is available. A better understanding of this complex regulatory system may allow the development of more specific therapeutic strategies for heart diseases. PMID:21236334

  1. Cascade redox flow battery systems

    DOEpatents

    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.

  2. New insights into redox regulation of stem cell self-renewal and differentiation.

    PubMed

    Ren, Fenglian; Wang, Kui; Zhang, Tao; Jiang, Jingwen; Nice, Edouard Collins; Huang, Canhua

    2015-08-01

    Reactive oxygen species (ROS), the natural byproducts of aerobic metabolism, are precisely orchestrated to evoke diverse signaling pathways. To date, studies have focused mainly on the detrimental effects of ROS in stem cells. Recently, accumulating evidence has suggested that ROS also function as second messengers that modulate stem cell self-renewal and differentiation by regulating intricate signaling networks. Although many efforts have been made to clarify the general effects of ROS on signal transduction in stem cells, less is known about the initial and direct executors of ROS signaling, which are known as 'redox sensors'. Modifications of cysteine residues in redox sensors are of significant importance in the modulation of protein function in response to different redox conditions. Intriguingly, most key molecules in ROS signaling and cell cycle regulation (including transcriptional factors and kinases) that are crucial in the regulation of stem cell self-renewal and differentiation have the potential to be redox sensors. We highlight herein the importance of redox regulation of these key regulators in stem cell self-renewal and differentiation. Understanding the mechanisms of redox regulation in stem cell self-renewal and differentiation will open exciting new perspectives for stem cell biology. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  4. Redox zonation for different groundwater flow paths during bank filtration: a case study at Liao River, Shenyang, northeastern China

    NASA Astrophysics Data System (ADS)

    Su, Xiaosi; Lu, Shuai; Yuan, Wenzhen; Woo, Nam Chil; Dai, Zhenxue; Dong, Weihong; Du, Shanghai; Zhang, Xinyue

    2018-03-01

    The spatial and temporal distribution of redox zones in an aquifer is important when designing groundwater supply systems. Redox zonation can have direct or indirect control of the biological and chemical reactions and mobility of pollutants. In this study, redox conditions are characterized by interpreting the hydrogeological conditions and water chemistry in groundwater during bank infiltration at a site in Shenyang, northeast China. The relevant redox processes and zonal differences in a shallow flow path and deeper flow path at the field scale were revealed by monitoring the redox parameters and chemistry of groundwater near the Liao River. The results show obvious horizontal and vertical components of redox zones during bank filtration. Variations in the horizontal extent of the redox zone were controlled by the different permeabilities of the riverbed sediments and aquifer with depth. Horizontally, the redox zone was situated within 17 m of the riverbank for the shallow flow path and within 200 m for the deep flow path. The vertical extent of the redox zone was affected by precipitation and seasonal river floods and extended to 10 m below the surface. During bank filtration, iron and manganese oxides or hydroxides were reductively dissolved, and arsenic that was adsorbed onto the medium surface or coprecipitated is released into the groundwater. This leads to increased arsenic content in groundwater, which poses a serious threat to water supply security.

  5. Species-Specific Standard Redox Potential of Thiol-Disulfide Systems: A Key Parameter to Develop Agents against Oxidative Stress

    NASA Astrophysics Data System (ADS)

    Mirzahosseini, Arash; Noszál, Béla

    2016-11-01

    Microscopic standard redox potential, a new physico-chemical parameter was introduced and determined to quantify thiol-disulfide equilibria of biological significance. The highly composite, codependent acid-base and redox equilibria of thiols could so far be converted into pH-dependent, apparent redox potentials (E’°) only. Since the formation of stable metal-thiolate complexes precludes the direct thiol-disulfide redox potential measurements by usual electrochemical techniques, an indirect method had to be elaborated. In this work, the species-specific, pH-independent standard redox potentials of glutathione were determined primarily by comparing it to 1-methylnicotinamide, the simplest NAD+ analogue. Secondarily, the species-specific standard redox potentials of the two-electron redox transitions of cysteamine, cysteine, homocysteine, penicillamine, and ovothiol were determined using their microscopic redox equilibrium constants with glutathione. The 30 different, microscopic standard redox potential values show close correlation with the respective thiolate basicities and provide sound means for the development of potent agents against oxidative stress.

  6. Redox signaling in acute pancreatitis

    PubMed Central

    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

  7. Redox Regulation of Protein Kinases

    PubMed Central

    Truong, Thu H.; Carroll, Kate S.

    2015-01-01

    Protein kinases represent one of the largest families of genes found in eukaryotes. Kinases mediate distinct cellular processes ranging from proliferation, differentiation, survival, and apoptosis. Ligand-mediated activation of receptor kinases can lead to the production of endogenous H2O2 by membrane-bound NADPH oxidases. In turn, H2O2 can be utilized as a secondary messenger in signal transduction pathways. This review presents an overview of the molecular mechanisms involved in redox regulation of protein kinases and its effects on signaling cascades. In the first half, we will focus primarily on receptor tyrosine kinases (RTKs), whereas the latter will concentrate on downstream non-receptor kinases involved in relaying stimulant response. Select examples from the literature are used to highlight the functional role of H2O2 regarding kinase activity, as well as the components involved in H2O2 production and regulation during cellular signaling. In addition, studies demonstrating direct modulation of protein kinases by H2O2 through cysteine oxidation will be emphasized. Identification of these redox-sensitive residues may help uncover signaling mechanisms conserved within kinase subfamilies. In some cases, these residues can even be exploited as targets for the development of new therapeutics. Continued efforts in this field will further basic understanding of kinase redox regulation, and delineate the mechanisms involved in physiologic and pathological H2O2 responses. PMID:23639002

  8. Reactive Oxygen Species are Ubiquitous along Subsurface Redox Gradients

    NASA Astrophysics Data System (ADS)

    Nico, P. S.; Yuan, X.; Davis, J. A.; Dwivedi, D.; Williams, K. H.; Bhattacharyya, A.; Fox, P. M.

    2016-12-01

    Reactive oxygen species (hydroxyl radical, superoxide, hydrogen peroxide, etc.) are known to be important intermediates in many biological and earth system processes. They have been particularly well studied in the realms of atmospheric chemistry and aquatic photochemistry. However, recently there is increasing evidence that they are also present in impactful quantities in dark systems as a result of both biotic and abiotic reactions. Herein we will present a complementary suite of laboratory and field studies examining the presence and production of hydrogen peroxide under relevant subsurface conditions. The laboratory work examines the redox cycling between reduced organic matter, molecular oxygen, and Fe which results in not only the production of hydrogen peroxide and oxidation of organic functional groups but also the maintenance of steady-state concentration of Fe(II) under fully oxygenated aqueous conditions. The field studies involve three distinct locations, namely a shallow subsurface aquifer, a hyporheic zone redox gradient across a river meander, and a hillside shale seep. In all cases detectable quantities (tens of nanomolar) of hydrogen peroxide were measured. In general, concentrations peak under transitional redox conditions where there is the simultaneous presence of reduced Fe, organic matter, and at least trace dissolved oxygen. Many, but not all, of the observed dynamics in hydrogen peroxide production can be reproduced by a simple kinetic model representing the reactions between Fe, organic matter, and molecular oxygen, but many questions remain regarding the role of microorganisms and other redox active chemical species in determining the detected hydrogen peroxide concentrations. The consistent detection of hydrogen peroxide at these disparate locations supports the hypothesis that hydrogen peroxide, and by extension, the entire suite of reactive oxygen species are ubiquitous along subsurface redox gradients.

  9. Redox signaling in skeletal muscle: role of aging and exercise.

    PubMed

    Ji, Li Li

    2015-12-01

    Skeletal muscle contraction is associated with the production of ROS due to altered O2 distribution and flux in the cell. Despite a highly efficient antioxidant defense, a small surplus of ROS, such as hydrogen peroxide and nitric oxide, may serve as signaling molecules to stimulate cellular adaptation to reach new homeostasis largely due to the activation of redox-sensitive signaling pathways. Recent research has highlighted the important role of NF-κB, MAPK, and peroxisome proliferator-activated receptor-γ coactivator-1α, along with other newly discovered signaling pathways, in some of the most vital biological functions, such as mitochondrial biogenesis, antioxidant defense, inflammation, protein turnover, apoptosis, and autophagy. There is evidence that the inability of the cell to maintain proper redox signaling underlies some basic mechanisms of biological aging, during which inflammatory and catabolic pathways eventually predominate. Physical exercise has been shown to activate various redox signaling pathways that control the adaptation and remodeling process. Although this stimulatory effect of exercise declines with aging, it is not completed abolished. Thus, aged people can still benefit from regular physical activity in the appropriate forms and at proper intensity to preserve muscle function. Copyright © 2015 The American Physiological Society.

  10. The Importance of NADPH Oxidases and Redox Signaling in Angiogenesis

    PubMed Central

    Prieto-Bermejo, Rodrigo; Hernández-Hernández, Angel

    2017-01-01

    Eukaryotic cells have to cope with the constant generation of reactive oxygen species (ROS). Although the excessive production of ROS might be deleterious for cell biology, there is a plethora of evidence showing that moderate levels of ROS are important for the control of cell signaling and gene expression. The family of the nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases or Nox) has evolved to produce ROS in response to different signals; therefore, they fulfil a central role in the control of redox signaling. The role of NADPH oxidases in vascular physiology has been a field of intense study over the last two decades. In this review we will briefly analyze how ROS can regulate signaling and gene expression. We will address the implication of NADPH oxidases and redox signaling in angiogenesis, and finally, the therapeutic possibilities derived from this knowledge will be discussed. PMID:28505091

  11. Cellular Metabolic and Autophagic Pathways: Traffic Control by Redox Signaling

    PubMed Central

    Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua

    2013-01-01

    It has been established that the key metabolic pathways of glycolysis and oxidative phosphorylation are intimately related to redox biology through control of cell signaling. Under physiological conditions glucose metabolism is linked to control of the NADH/NAD redox couple, as well as providing the major reductant, NADPH, for thiol-dependent antioxidant defenses. Retrograde signaling from the mitochondrion to the nucleus or cytosol controls cell growth and differentiation. Under pathological conditions mitochondria are targets for reactive oxygen and nitrogen species and are critical in controlling apoptotic cell death. At the interface of these metabolic pathways, the autophagy-lysosomal pathway functions to maintain mitochondrial quality, and generally serves an important cytoprotective function. In this review we will discuss the autophagic response to reactive oxygen and nitrogen species that are generated from perturbations of cellular glucose metabolism and bioenergetic function. PMID:23702245

  12. Redox-dependent regulation of epidermal growth factor receptor signaling.

    PubMed

    Heppner, David E; van der Vliet, Albert

    2016-08-01

    Tyrosine phosphorylation-dependent cell signaling represents a unique feature of multicellular organisms, and is important in regulation of cell differentiation and specialized cell functions. Multicellular organisms also contain a diverse family of NADPH oxidases (NOXs) that have been closely linked with tyrosine kinase-based cell signaling and regulate tyrosine phosphorylation via reversible oxidation of cysteine residues that are highly conserved within many proteins involved in this signaling pathway. An example of redox-regulated tyrosine kinase signaling involves the epidermal growth factor receptor (EGFR), a widely studied receptor system with diverse functions in normal cell biology as well as pathologies associated with oxidative stress such as cancer. The purpose of this Graphical Redox Review is to highlight recently emerged concepts with respect to NOX-dependent regulation of this important signaling pathway. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  14. Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei.

    PubMed

    Zimmermann, Stefanie; Oufir, Mouhssin; Leroux, Alejandro; Krauth-Siegel, R Luise; Becker, Katja; Kaiser, Marcel; Brun, Reto; Hamburger, Matthias; Adams, Michael

    2013-11-15

    In mice cynaropicrin (CYN) potently inhibits the proliferation of Trypanosoma brucei-the causative agent of Human African Trypanosomiasis-by a so far unknown mechanism. We hypothesized that CYNs α,β-unsaturated methylene moieties act as Michael acceptors for glutathione (GSH) and trypanothione (T(SH)2), the main low molecular mass thiols essential for unique redox metabolism of these parasites. The analysis of this putative mechanism and the effects of CYN on enzymes of the T(SH)2 redox metabolism including trypanothione reductase, trypanothione synthetase, glutathione-S-transferase, and ornithine decarboxylase are shown. A two step extraction protocol with subsequent UPLC-MS/MS analysis was established to quantify intra-cellular CYN, T(SH)2, GSH, as well as GS-CYN and T(S-CYN)2 adducts in intact T. b. rhodesiense cells. Within minutes of exposure to CYN, the cellular GSH and T(SH)2 pools were entirely depleted, and the parasites entered an apoptotic stage and died. CYN also showed inhibition of the ornithine decarboxylase similar to the positive control eflornithine. Significant interactions with the other enzymes involved in the T(SH)2 redox metabolism were not observed. Alongside many other biological activities sesquiterpene lactones including CYN have shown antitrypanosomal effects, which have been postulated to be linked to formation of Michael adducts with cellular nucleophiles. Here the interaction of CYN with biological thiols in a cellular system in general, and with trypanosomal T(SH)2 redox metabolism in particular, thus offering a molecular explanation for the antitrypanosomal activity is demonstrated. At the same time, the study provides a novel extraction and analysis protocol for components of the trypanosomal thiol metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. NASA Redox system development project status

    NASA Technical Reports Server (NTRS)

    Nice, A. W.

    1981-01-01

    NASA-Redox energy storage systems developed for solar power applications and utility load leveling applications are discussed. The major objective of the project is to establish the technology readiness of Redox energy storage for transfer to industry for product development and commercialization by industry. The approach is to competitively contract to design, build, and test Redox systems progressively from preprototype to prototype multi-kW and megawatt systems and conduct supporting technology advancement tasks. The Redox electrode and membrane are fully adequate for multi-kW solar related applications and the viability of the Redox system technology as demonstrated for multi-kW solar related applications. The status of the NASA Redox Storage System Project is described along with the goals and objectives of the project elements.

  16. Engineering redox balance through cofactor systems.

    PubMed

    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.

  17. Redox flow batteries having multiple electroactive elements

    SciTech Connect

    Wang, Wei; Li, Liyu; Yang, Zhenguo

    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.

  18. Redox State of Cytochromes in Frozen Yeast Cells Probed by Resonance Raman Spectroscopy.

    PubMed

    Okotrub, Konstantin A; Surovtsev, Nikolay V

    2015-12-01

    Cryopreservation is a well-established technique used for the long-term storage of biological materials whose biological activity is effectively stopped under low temperatures (suspended animation). Since most biological methods do not work in a low-temperature frozen environment, the mechanism and details of the depression of cellular activity in the frozen state remain largely uncharacterized. In this work, we propose, to our knowledge, a new approach to study the downregulation of the redox activity of cytochromes b and c in freezing yeast cells in a contactless, label-free manner. Our approach is based on cytochrome photobleaching effects observed in the resonance Raman spectra of live cells. Photoinduced and native redox reactions that contributed to the photobleaching rate were studied over a wide temperature range (from -173 to +25 °C). We found that ice formation influences both the rate of cytochrome redox reactions and the balance between the reduced and oxidized cytochromes. We demonstrate that the temperature dependence of native redox reaction rates can be well described by the thermal activation law with an apparent energy of 32.5 kJ/mol, showing that the redox reaction rate is ∼10(15) times slower at liquid nitrogen temperature than at room temperature. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  19. Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress.

    PubMed

    Sies, Helmut

    2017-04-01

    Hydrogen peroxide emerged as major redox metabolite operative in redox sensing, signaling and redox regulation. Generation, transport and capture of H 2 O 2 in biological settings as well as their biological consequences can now be addressed. The present overview focuses on recent progress on metabolic sources and sinks of H 2 O 2 and on the role of H 2 O 2 in redox signaling under physiological conditions (1-10nM), denoted as oxidative eustress. Higher concentrations lead to adaptive stress responses via master switches such as Nrf2/Keap1 or NF-κB. Supraphysiological concentrations of H 2 O 2 (>100nM) lead to damage of biomolecules, denoted as oxidative distress. Three questions are addressed: How can H 2 O 2 be assayed in the biological setting? What are the metabolic sources and sinks of H 2 O 2 ? What is the role of H 2 O 2 in redox signaling and oxidative stress? Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. [Redox Molecular Imaging Using ReMI].

    PubMed

    Hyodo, Fuminori; Ito, Shinji; Utsumi, Hideo

    2015-01-01

    Tissue redox status is one of the most important parameters to maintain homeostasis in the living body. Numerous redox reactions are involved in metabolic processes, such as energy production in the mitochondrial electron transfer system. A variety of intracellular molecules such as reactive oxygen species, glutathione, thioredoxins, NADPH, flavins, and ascorbic acid may contribute to the overall redox status in tissues. Breakdown of redox balance may lead to oxidative stress and can induce many pathological conditions such as cancer, neurological disorders, and aging. Therefore imaging of tissue redox status and monitoring antioxidant levels in living organisms can be useful in the diagnosis of disease states and assessment of treatment response. In vivo redox molecular imaging technology such as electron spin resonance imaging (ESRI), magnetic resonance imaging (MRI), and dynamic nuclear polarization (DNP)-MRI (redox molecular imaging; ReMI) is emerging as a viable redox status imaging modality. This review focuses on the application of magnetic resonance technologies using MRI or DNP-MRI and redox-sensitive contrast agents.

  1. Zinc and the modulation of redox homeostasis

    PubMed Central

    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

  2. Clinically Evaluated Cancer Drugs Inhibiting Redox Signaling.

    PubMed

    Kirkpatrick, D Lynn; Powis, Garth

    2017-02-20

    There are a number of redox-active anticancer agents currently in development based on the premise that altered redox homeostasis is necessary for cancer cell's survival. Recent Advances: This review focuses on the relatively few agents that target cellular redox homeostasis to have entered clinical trial as anticancer drugs. The success rate of redox anticancer drugs has been disappointing compared to other classes of anticancer agents. This is due, in part, to our incomplete understanding of the functions of the redox targets in normal and cancer tissues, leading to off-target toxicities and low therapeutic indexes of the drugs. The field also lags behind in the use biomarkers and other means to select patients who are most likely to respond to redox-targeted therapy. If we wish to derive clinical benefit from agents that attack redox targets, then the future will require a more sophisticated understanding of the role of redox targets in cancer and the increased application of personalized medicine principles for their use. Antioxid. Redox Signal. 26, 262-273.

  3. Disulfide proteome yields a detailed understanding of redox regulations: a model study of thioredoxin-linked reactions in seed germination.

    PubMed

    Yano, Hiroyuki; Kuroda, Masaharu

    2006-01-01

    Accumulating evidence suggests that redox regulations play important roles in a broad spectrum of biological processes. Recently, Yano et al. developed a disulfide proteome technique that comprehensively visualizes redox change in proteins. In this paper, using the disulfide proteome, we examined rice bran and identified fragments of embryo-specific protein and dienelactone hydrolase as putative targets of thioredoxin. Also, monitoring of the endogenous and recombinant effects of thioredoxin on rice bran proteins and supporting in vivo observations propose a mechanism of redox regulation in seed germination, in which thioredoxin activates cysteine protease with a concurrent unfolding of its substrate, the embryo-specific protein. Our findings suggest that thioredoxin controls the lifetime of specific proteins effectively by regulating the redox reactions coordinately. The model study demonstrates that the disulfide proteome technique is useful not only for identifying targets of thioredoxin, but also for clarify the detailed mechanism of redox regulation.

  4. Redox-dependent transcriptional regulation.

    PubMed

    Liu, Hongjun; Colavitti, Renata; Rovira, Ilsa I; Finkel, Toren

    2005-11-11

    Reactive oxygen species contribute to the pathogenesis of a number of disparate disorders including tissue inflammation, heart failure, hypertension, and atherosclerosis. In response to oxidative stress, cells activate expression of a number of genes, including those required for the detoxification of reactive molecules as well as for the repair and maintenance of cellular homeostasis. In many cases, these induced genes are regulated by transcription factors whose structure, subcellular localization, or affinity for DNA is directly or indirectly regulated by the level of oxidative stress. This review summarizes the recent progress on how cellular redox status can regulate transcription-factor activity and the implications of this regulation for cardiovascular disease.

  5. Method for producing redox shuttles

    DOEpatents

    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.

  6. Electrical Microengineering of Redox Enzymes

    DTIC Science & Technology

    1994-03-31

    coating applied to the electrode 41 to prevent lose of mediator graphite foil potassium -~0.02a 0.03  electrolyte wus dioxane with 15% 42...hexacyanoferrats(ll)d aqueous buffer carbon fiber’ none h 40-5000 biotin/avidin complex used to obtain a 43 surface layer of HRP Pt organic metal, potassium ...OFFICE OF NAVAL RESEARCH AD-A279 015 FINAL REPORT FOR CONTRACT NOOO 14-91 -J- 1656 R&T CODE 413h007---05 ELECTRICAL MICROENGINEERING OF REDOX ENZYMES

  7. Chromium electrodes for REDOX cells

    NASA Technical Reports Server (NTRS)

    Jalan, V.; Reid, M. A.; Charleston, A. (Inventor)

    1984-01-01

    An improved electrode having a gold coating for use in the anode compartment of a REDOX cell is described. The anode fluid utilizes a chromic/chromous couple. A carbon felt is soaked in methanol, rinsed in water, dried and then heated in KOH after which it is again washed in deionized water and dried. The felt is then moistened with a methanol water solution containing chloroauric acid and is stored in a dark place while still in contact with the gold-containing solution. After all the gold-containing solution is absorbed in the felt, the latter is dried by heat and then heat treated at a substantially greater temperature. The felt is then suitable for use as an electrode and is wetted with water or up to two molar HCl prior to installation in a REDOX cell. The novelty of the invention lies in the use of KOH for cleaning the felt and the use of alcohol as a carrier for the gold together with the heat treating procedure.

  8. Method for characterization of the redox condition of cementitious materials

    DOEpatents

    Almond, Philip M.; Langton, Christine A.; Stefanko, David B.

    2015-12-22

    Disclosed are methods for determining the redox condition of cementitious materials. The methods are leaching methods that utilize an in situ redox indicator that is present in the cementitious materials as formed. The in situ redox indicator leaches from cementitious material and, when the leaching process is carried out under anaerobic conditions can be utilized to determine the redox condition of the material. The in situ redox indicator can exhibit distinct characteristics in the leachate depending upon the redox condition of the indicator.

  9. Development of redox-sensitive red fluorescent proteins for imaging redox dynamics in cellular compartments.

    PubMed

    Fan, Yichong; Ai, Hui-wang

    2016-04-01

    We recently reported a redox-sensitive red fluorescent protein, rxRFP1, which is one of the first genetically encoded red-fluorescent probes for general redox states in living cells. As individual cellular compartments have different basal redox potentials, we hereby describe a group of rxRFP1 mutants, showing different midpoint redox potentials for detection of redox dynamics in various subcellular domains, such as mitochondria, the cell nucleus, and endoplasmic reticulum (ER). When these redox probes were expressed and subcellularly localized in human embryonic kidney (HEK) 293 T cells, they responded to membrane-permeable oxidants and reductants. In addition, a mitochondrially localized rxRFP1 mutant, Mito-rxRFP1.1, was used to detect mitochondrial oxidative stress induced by doxorubicin-a widely used cancer chemotherapy drug. Our work has expanded the fluorescent protein toolkit with new research tools for studying compartmentalized redox dynamics and oxidative stress under various pathophysiological conditions.

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

    PubMed

    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.

  11. Screening of redox couples and electrode materials

    NASA Technical Reports Server (NTRS)

    Giner, J.; Swette, L.; Cahill, K.

    1976-01-01

    Electrochemical parameters of selected redox couples that might be potentially promising for application in bulk energy storage systems were investigated. This was carried out in two phases: a broad investigation of the basic characteristics and behavior of various redox couples, followed by a more limited investigation of their electrochemical performance in a redox flow reactor configuration. In the first phase of the program, eight redox couples were evaluated under a variety of conditions in terms of their exchange current densities as measured by the rotating disk electrode procedure. The second phase of the program involved the testing of four couples in a redox reactor under flow conditions with a varity of electrode materials and structures.

  12. Breast Cancer: A Molecular and Redox Snapshot.

    PubMed

    Raman, Deepika; Foo, Chuan Han Jonathan; Clement, Marie-Veronique; Pervaiz, Shazib

    2016-08-20

    Breast cancer is a unique disease characterized by heterogeneous cell populations causing roadblocks in therapeutic medicine, owing to its complex etiology and primeval understanding of the biology behind its genesis, progression, and sustenance. Globocan statistics indicate over 1.7 million new breast cancer diagnoses in 2012, accounting for 25% of all cancer morbidities. Despite these dismal statistics, the introduction of molecular gene signature platforms, progressive therapeutic approaches in diagnosis, and management of breast cancer has led to more effective treatment strategies and control measures concurrent with an equally reassuring decline in the mortality rate. However, an enormous body of research in this area is requisite as high mortality associated with metastatic and/or drug refractory tumors continues to present a therapeutic challenge. Despite advances in systemic chemotherapy, the median survival of patients harboring metastatic breast cancers continues to be below 2 years. Hence, a massive effort to scrutinize and evaluate chemotherapeutics on the basis of the molecular classification of these cancers is undertaken with the objective to devise more attractive and feasible approaches to treat breast cancers and improve patients' quality of life. This review aims to summarize the current understanding of the biology of breast cancer as well as challenges faced in combating breast cancer, with special emphasis on the current battery of treatment strategies. We will also try and gain perspective from recent encounters on novel findings responsible for the progression and metastatic transformation of breast cancer cells in an endeavor to develop more targeted treatment options. Antioxid. Redox Signal. 25, 337-370.

  13. Antioxidants as therapeutics in the intensive care unit: Have we ticked the redox boxes?

    PubMed

    Margaritelis, Nikos V

    2016-09-01

    Critically ill patients are under oxidative stress and antioxidant administration reasonably emerged as a promising approach to combat the aberrant redox homeostasis in this patient cohort. However, the results of the antioxidant treatments in the intensive care unit are conflicting and inconclusive. The main objective of the present review is to highlight some inherent, yet widely overlooked redox-related issues about the equivocal effectiveness of antioxidants in the intensive care unit, beyond methodological considerations. In particular, the discrepancy in the literature partially stems from: (1) the largely unspecified role of reactive species in disease onset and progression, (2) our fragmentary understanding on the interplay between inflammation and oxidative stress, (3) the complex spatiotemporal specificity of in vivo redox biology, (4) the pleiotropic effects of antioxidants and (5) the divergent effects of antioxidants according to the temporal administration pattern. In addition, two novel and sophisticated practices with promising pre-clinical results are presented: (1) the selective neutralization of reactive species in key organelles after they are formed (i.e., in mitochondria) and (2) the targeted complete inhibition of dominant reactive species sources (i.e., NADPH oxidases). Finally, the reductive potential of NADPH as a key pharmacological target for redox therapies is rationalized. In light of the above, the recontextualization of knowledge from basic redox biology to translational medicine seems imperative to perform more realistic in vivo studies in the fast-growing field of critical care pharmacology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

    PubMed Central

    Miao, Lu; Holley, Aaron K.; Zhao, Yanming; St. Clair, William H.

    2014-01-01

    Abstract Significance: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency. Recent Advances: Ionizing radiation (IR)–generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from cell death to development of radioresistance. Critical Issues: Tumors are heterogeneous and dynamic communication occurs between stromal and prostate cancer cells, and complicated redox-regulated mechanisms exist in the tumor microenvironment. Thus, antioxidant and anti-inflammatory strategies should be carefully evaluated for each patient at different stages of the disease to maximize therapeutic benefits while minimizing unintended side effects. Future Directions: Compared with normal cells, tumor cells are usually under higher oxidative stress and secrete more proinflammatory mediators. Thus, redox status is often less adaptive in tumor cells than in their normal counterparts. This difference can be exploited in a search for new cancer therapeutics and treatment regimes that selectively activate cell death pathways in tumor cells with minimal unintended consequences in terms of chemo- and radio-resistance in tumor cells and toxicity in normal tissues. Antioxid. Redox Signal. 20, 1481–1500. PMID:24093432

  15. Electrically rechargeable REDOX flow cell

    NASA Technical Reports Server (NTRS)

    Thaller, L. H. (Inventor)

    1976-01-01

    A bulk energy storage system is designed with an electrically rechargeable reduction-oxidation (REDOX) cell divided into two compartments by a membrane, each compartment containing an electrode. An anode fluid is directed through the first compartment at the same time that a cathode fluid is directed through the second compartment. Means are provided for circulating the anode and cathode fluids, and the electrodes are connected to an intermittent or non-continuous electrical source, which when operating, supplies current to a load as well as to the cell to recharge it. Ancillary circuitry is provided for disconnecting the intermittent source from the cell at prescribed times and for circulating the anode and cathode fluids according to desired parameters and conditions.

  16. HMGB1 redox during sepsis.

    PubMed

    Abdulmahdi, Wasan; Patel, Devika; Rabadi, May M; Azar, Tala; Jules, Edson; Lipphardt, Mark; Hashemiyoon, Rameen; Ratliff, Brian B

    2017-10-01

    During sepsis, the alarmin HMGB1 is released from tissues and promotes systemic inflammation that results in multi-organ damage, with the kidney particularly susceptible to injury. The severity of inflammation and pro-damage signaling mediated by HMGB1 appears to be dependent on the alarmin's redox state. Therefore, we examined HMGB1 redox in kidney cells during sepsis. Using intravital microscopy, CellROX labeling of kidneys in live mice indicated increased ROS generation in the kidney perivascular endothelium and tubules during lipopolysaccharide (LPS)-induced sepsis. Subsequent CellROX and MitoSOX labeling of LPS-stressed endothelial and kidney proximal tubule cells demonstrated increased ROS generation in these cells as sepsis worsens. Consequently, HMGB1 oxidation increased in the cytoplasm of kidney cells during its translocation from the nucleus to the circulation, with the degree of oxidation dependent on the severity of sepsis, as measured in in vivo mouse samples using a thiol assay and mass spectrometry (LC-MS/MS). The greater the oxidation of HMGB1, the greater the ability of the alarmin to stimulate pro-inflammatory cyto-/chemokine release (measured by Luminex Multiplex) and alter mitochondrial ATP generation (Luminescent ATP Detection Assay). Administration of glutathione and thioredoxin inhibitors to cell cultures enhanced HMGB1 oxidation during sepsis in endothelial and proximal tubule cells, respectively. In conclusion, as sepsis worsens, ROS generation and HMGB1 oxidation increases in kidney cells, which enhances HMGB1's pro-inflammatory signaling. Conversely, the glutathione and thioredoxin systems work to maintain the protein in its reduced state. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

    PubMed Central

    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

  18. Redox subpopulations and the risk of cancer progression: a new method for characterizing redox heterogeneity

    NASA Astrophysics Data System (ADS)

    Xu, He N.; Li, Lin Z.

    2016-02-01

    It has been shown that a malignant tumor is akin to a complex organ comprising of various cell populations including tumor cells that are genetically, metabolically and functionally different. Our redox imaging data have demonstrated intra-tumor redox heterogeneity in all mouse xenografts derived from human melanomas, breast, prostate, and colon cancers. Based on the signals of NADH and oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and their ratio, i.e., the redox ratio, which is an indicator of mitochondrial metabolic status, we have discovered several distinct redox subpopulations in xenografts of breast tumors potentially recapitulating functional/metabolic heterogeneity within the tumor. Furthermore, xenografts of breast tumors with higher metastatic potential tend to have a redox subpopulation whose redox ratio is significantly different from that of tumors with lower metastatic potential and usually have a bi-modal distribution of the redox ratio. The redox subpopulations from human breast cancer samples can also be very complex with multiple subpopulations as determined by fitting the redox ratio histograms with multi- Gaussian functions. In this report, we present a new method for identifying the redox subpopulations within individual breast tumor xenografts and human breast tissues, which may be used to differentiate between breast cancer and normal tissue and among breast cancer with different risks of progression.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2016-12-14

    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.

  1. Biological Relevance of Free Radicals and Nitroxides.

    PubMed

    Prescott, Christopher; Bottle, Steven E

    2017-06-01

    Nitroxides are stable, kinetically-persistent free radicals which have been successfully used in the study and intervention of oxidative stress, a critical issue pertaining to cellular health which results from an imbalance in the levels of damaging free radicals and redox-active species in the cellular environment. This review gives an overview of some of the biological processes that produce radicals and other reactive oxygen species with relevance to oxidative stress, and then discusses interactions of nitroxides with these species in terms of the use of nitroxides as redox-sensitive probes and redox-active therapeutic agents.

  2. Organelle redox autonomy during environmental stress.

    PubMed

    Bratt, Avishay; Rosenwasser, Shilo; Meyer, Andreas; Fluhr, Robert

    2016-09-01

    Oxidative stress is generated in plants because of inequalities in the rate of reactive oxygen species (ROS) generation and scavenging. The subcellular redox state under various stress conditions was assessed using the redox reporter roGFP2 targeted to chloroplastic, mitochondrial, peroxisomal and cytosolic compartments. In parallel, the vitality of the plant was measured by ion leakage. Our results revealed that during certain physiological stress conditions the changes in roGFP2 oxidation are comparable to application of high concentrations of exogenous H2 O2 . Under each stress, particular organelles were affected. Conditions of extended dark stress, or application of elicitor, impacted chiefly on the status of peroxisomal redox state. In contrast, conditions of drought or high light altered the status of mitochondrial or chloroplast redox state, respectively. Amalgamation of the results from diverse environmental stresses shows cases of organelle autonomy as well as multi-organelle oxidative change. Importantly, organelle-specific oxidation under several stresses proceeded cell death as measured by ion leakage, suggesting early roGFP oxidation as predictive of cell death. The measurement of redox state in multiple compartments enables one to look at redox state connectivity between organelles in relation to oxidative stress as well as assign a redox fingerprint to various types of stress conditions. © 2016 John Wiley & Sons Ltd.

  3. Oxidative stress, thiols, and redox profiles.

    PubMed

    Harris, Craig; Hansen, Jason M

    2012-01-01

    Oxidative stress has been recognized as a contributing factor in the toxicity of a large number of developmental toxicants. Traditional definitions of oxidative stress state that a shift in the balance between reduced and oxidized biomolecules within cells, in favor of the latter, result in changes that are deleterious to vital cell functions and can culminate in malformations and death. The glutathione (GSH)/glutathione disulfide (GSSG) redox couple has been the traditional marker of choice for characterization of oxidative stress because of its high concentrations and direct roles as antioxidant and cellular protectant. Steady state depletion of GSH through conjugation, oxidation, or export has often been reported as the sole criteria for invoking oxidative stress and a myriad of associated deleterious consequences. Numerous other, mostly qualitative, observations have also been reported to suggest oxidative stress has occurred but it is not always clear how well they reflect the state of a cell or its functions. Our emerging understanding of redox signaling and the roles of reactive oxygen species (ROS), thiols, oxidant molecules, and cellular antioxidants, all acting as second messengers, has prompted a redefinition of oxidative stress based on changes in the real posttranslational protein thiol modifications that are central to redox regulation and control. Thiol-based redox couples such as GSH/GSSG, cysteine/cystine (cys/cySS), thioredoxin-reduced/thioredoxin-oxidized (TRX(red)/TRX(ox)) form independent signaling nodes that selectively regulate developmental events and are closely linked to changes in intracellular redox potentials. Accurate assessment of the consequences of increased free radicals in developing conceptuses should best be made using a battery of measurements including the quantitative assessment of intracellular redox potential, ROS, redox status of biomolecules, and induced changes in specific redox signaling nodes. Methods are presented for

  4. Bifunctional redox tagging of carbon nanoparticles

    NASA Astrophysics Data System (ADS)

    Poon, Jeffrey; Batchelor-McAuley, Christopher; Tschulik, Kristina; Palgrave, Robert G.; Compton, Richard G.

    2015-01-01

    Despite extensive work on the controlled surface modification of carbon with redox moieties, to date almost all available methodologies involve complex chemistry and are prone to the formation of polymerized multi-layer surface structures. Herein, the facile bifunctional redox tagging of carbon nanoparticles (diameter 27 nm) and its characterization is undertaken using the industrial dye Reactive Blue 2. The modification route is demonstrated to be via exceptionally strong physisorption. The modified carbon is found to exhibit both well-defined oxidative and reductive voltammetric redox features which are quantitatively interpreted. The method provides a generic approach to monolayer modifications of carbon and carbon nanoparticle surfaces.

  5. Redox polymer electrodes for advanced batteries

    DOEpatents

    Gregg, Brian A.; Taylor, A. Michael

    1998-01-01

    Advanced batteries having a long cycle lifetime are provided. More specifically, the present invention relates to electrodes made from redox polymer films and batteries in which either the positive electrode, the negative electrode, or both, comprise redox polymers. Suitable redox polymers for this purpose include pyridyl or polypyridyl complexes of transition metals like iron, ruthenium, osmium, chromium, tungsten and nickel; porphyrins (either free base or metallo derivatives); phthalocyanines (either free base or metallo derivatives); metal complexes of cyclams, such as tetraazacyclotetradecane; metal complexes of crown ethers and metallocenes such as ferrocene, cobaltocene and ruthenocene.

  6. Redox polymer electrodes for advanced batteries

    DOEpatents

    Gregg, B.A.; Taylor, A.M.

    1998-11-24

    Advanced batteries having a long cycle lifetime are provided. More specifically, the present invention relates to electrodes made from redox polymer films and batteries in which either the positive electrode, the negative electrode, or both, comprise redox polymers. Suitable redox polymers for this purpose include pyridyl or polypyridyl complexes of transition metals like iron, ruthenium, osmium, chromium, tungsten and nickel; porphyrins (either free base or metallo derivatives); phthalocyanines (either free base or metallo derivatives); metal complexes of cyclams, such as tetraazacyclotetradecane; metal complexes of crown ethers and metallocenes such as ferrocene, cobaltocene and ruthenocene. 2 figs.

  7. Electrochemical cell for rebalancing REDOX flow system

    NASA Technical Reports Server (NTRS)

    Thaller, L. H. (Inventor)

    1979-01-01

    An electrically rechargeable REDOX cell or battery system including one of more rebalancing cells is described. Each rebalancing cell is divided into two chambers by an ion permeable membrane. The first chamber is fed with gaseous hydrogen and a cathode fluid which is circulated through the cathode chamber of the REDOX cell is also passed through the second chamber of the rebalancing cell. Electrochemical reactions take place on the surface of insert electrodes in the first and second chambers to rebalance the electrochemical capacity of the anode and cathode fluids of the REDOX system.

  8. Direct measurement of electron transfer distance decay constants of single redox proteins by electrochemical tunneling spectroscopy.

    PubMed

    Artés, Juan M; Díez-Pérez, Ismael; Sanz, Fausto; Gorostiza, Pau

    2011-03-22

    We present a method to measure directly and at the single-molecule level the distance decay constant that characterizes the rate of electron transfer (ET) in redox proteins. Using an electrochemical tunneling microscope under bipotentiostatic control, we obtained current−distance spectroscopic recordings of individual redox proteins confined within a nanometric tunneling gap at a well-defined molecular orientation. The tunneling current decays exponentially, and the corresponding decay constant (β) strongly supports a two-step tunneling ET mechanism. Statistical analysis of decay constant measurements reveals differences between the reduced and oxidized states that may be relevant to the control of ET rates in enzymes and biological electron transport chains.

  9. Redox sensor proteins for highly sensitive direct imaging of intracellular redox state.

    PubMed

    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.

  10. High-Temperature Controlled Redox Crystallization Studies

    NASA Technical Reports Server (NTRS)

    Williams, R. J.

    1985-01-01

    The crystallization of silicates containing redox sensitive ions (e.g., Fe, Ti, Ce) must be performed under controlled and known redox conditions in order to obtain the maximum scientific benefit from experimental study. Furthermore, many compositions crystallize dense phases which settle during ground-based experiments. This settling influences the texture and chemical evolution of the crystallizing system. The purpose of this investigation is to develop a test system in which controlled redox experiments can be performed in the microgravity environment. The system will use solid ceramic oxygen electrolyte cells for control, measurements, and production of the required redox conditions. A preliminary design for a prototype is developed, the electrolyte and furnace tested, and a tentative protocol for experiment developed. The control parameter is to be established and a laboratory prototype built.

  11. Redox flow cell energy storage systems

    NASA Technical Reports Server (NTRS)

    Thaller, L. H.

    1979-01-01

    The redox flow cell energy storage system being developed by NASA for use in remote power systems and distributed storage installations for electric utilities is presented. The system under consideration is an electrochemical storage device which utilizes the oxidation and reduction of two fully soluble redox couples (acidified chloride solutions of chromium and iron) as active electrode materials separated by a highly selective ion exchange membrane. The reactants are contained in large storage tanks and pumped through a stack of redox flow cells where the electrochemical reactions take place at porous carbon felt electrodes. Redox equipment has allowed the incorporation of state of charge readout, stack voltage control and system capacity maintenance (rebalance) devices to regulate cells in a stack jointly. A 200 W, 12 V system with a capacity of about 400 Wh has been constructed, and a 2 kW, 10kWh system is planned.

  12. High energy density redox flow device

    DOEpatents

    Chiang, Yet-Ming; Carter, W. Craig; Ho, Bryan Y; Duduta, Mihai; Limthongkul, Pimpa

    2014-05-13

    Redox flow devices are described in which at least one of the positive electrode or negative electrode-active materials is a semi-solid or is a condensed ion-storing electroactive material, and in which at least one of the electrode-active materials is transported to and from an assembly at which the electrochemical reaction occurs, producing electrical energy. The electronic conductivity of the semi-solid is increased by the addition of conductive particles to suspensions and/or via the surface modification of the solid in semi-solids (e.g., by coating the solid with a more electron conductive coating material to increase the power of the device). High energy density and high power redox flow devices are disclosed. The redox flow devices described herein can also include one or more inventive design features. In addition, inventive chemistries for use in redox flow devices are also described.

  13. Polyarene mediators for mediated redox flow battery

    DOEpatents

    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.

  14. Glutathione and redox signaling in substance abuse.

    PubMed

    Uys, Joachim D; Mulholland, Patrick J; Townsend, Danyelle M

    2014-07-01

    Throughout the last couple decades, the cause and consequences of substance abuse has expanded to identify the underlying neurobiological signaling mechanisms associated with addictive behavior. Chronic use of drugs, such as cocaine, methamphetamine and alcohol leads to the formation of oxidative or nitrosative stress (ROS/RNS) and changes in glutathione and redox homeostasis. Of importance, redox-sensitive post-translational modifications on cysteine residues, such as S-glutathionylation and S-nitrosylation could impact on the structure and function of addiction related signaling proteins. In this commentary, we evaluate the role of glutathione and redox signaling in cocaine-, methamphetamine- and alcohol addiction and conclude by discussing the possibility of targeting redox pathways for the therapeutic intervention of these substance abuse disorders. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Redox storage systems for solar applications

    NASA Technical Reports Server (NTRS)

    Hagedorn, N. H.; Thaller, L. H.

    1980-01-01

    The NASA Redox energy storage system is described. The system is based on soluble aqueous iron and chromium chloride redox couples. The needed technology advances in the two elements (electrodes and membranes) that are key to its technological feasibility have been achieved and system development has begun. The design, construction, and test of a 1 kilowatt system integrated with a solar photovoltaic array is discussed.

  16. Biofabricated film with enzymatic and redox-capacitor functionalities to harvest and store electrons.

    PubMed

    Liba, Benjamin D; Kim, Eunkyoung; Martin, Alexandra N; Liu, Yi; Bentley, William E; Payne, Gregory F

    2013-03-01

    Exciting opportunities in bioelectronics will be facilitated by materials that can bridge the chemical logic of biology and the digital logic of electronics. Here we report the fabrication of a dual functional hydrogel film that can harvest electrons from its chemical environment and store these electrons by switching the film's redox-state. The hydrogel scaffold was formed by the anodic deposition of the aminopolysaccharide chitosan. Electron-harvesting function was conferred by co-depositing the enzyme glucose dehydrogenase (GDH) with chitosan. GDH catalyzes the transfer of electrons from glucose to the soluble redox-shuttle NADP(+). Electron-storage function was conferred by the redox-active food phenolic chlorogenic acid (CA) that was enzymatically grafted to the chitosan scaffold using tyrosinase. The grafted CA undergoes redox-cycling reactions with NADPH resulting in the net transfer of electrons to the film where they are stored in the reduced state of CA. The individual and dual functionalities of these films were demonstrated experimentally. There are three general conclusions from this proof-of-concept study. First, enzymatically-grafted catecholic moieties confer redox-capacitor function to the chitosan scaffold. Second, biological materials (i.e. chitosan and CA) and mechanisms (i.e. tyrosinase-mediated grafting) allow the reagentless fabrication of functional films that should be environmentally-friendly, safe and potentially even edible. Finally, the film's ability to mediate the transfer of electrons from a biological metabolite to an electrode suggests an approach to bridge the chemical logic of biology with the digital logic of electronics.

  17. Membranes for redox flow battery applications.

    PubMed

    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.

  18. Redox Proteomics Applied to the Thiol Secretome.

    PubMed

    Ghezzi, Pietro; Chan, Philippe

    2017-03-01

    Secreted proteins are important both as signaling molecules and potential biomarkers. Recent Advances: Protein can undergo different types of oxidation, both in physiological conditions or under oxidative stress. Several redox proteomics techniques have been successfully applied to the identification of glutathionylated proteins, an oxidative post-translational modification consisting in the formation of a mixed disulfide between a protein cysteine and glutathione. Redox proteomics has also been used to study other forms of protein oxidation. Because of the highest proportion of free cysteines in the cytosol, redox proteomics of protein thiols has focused, so far, on intracellular proteins. However, plasma proteins, such as transthyretin and albumin, have been described as glutathionylated or cysteinylated. The present review discusses the redox state of protein cysteines in relation to their cellular distribution. We describe the various approaches used to detect secreted glutathionylated proteins, the only thiol modification studied so far in secreted proteins, and the specific problems presented in the study of the secretome. This review focusses on glutathionylated proteins secreted under inflammatory conditions and that may act as soluble mediators (cytokines). Future studies on the redox secretome (including other forms of oxidation) might identify new soluble mediators and biomarkers of oxidative stress. Antioxid. Redox Signal. 26, 299-312.

  19. Membranes for Redox Flow Battery Applications

    PubMed Central

    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

  20. Dynamic Redox Regulation of IL-4 Signaling.

    PubMed

    Dwivedi, Gaurav; Gran, Margaret A; Bagchi, Pritha; Kemp, Melissa L

    2015-11-01

    Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation.

  1. Dynamic Redox Regulation of IL-4 Signaling

    PubMed Central

    Dwivedi, Gaurav; Gran, Margaret A.; Bagchi, Pritha; Kemp, Melissa L.

    2015-01-01

    Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation. PMID:26562652

  2. In Vivo Detection of Reactive Oxygen Species and Redox Status in Caenorhabditis elegans.

    PubMed

    Braeckman, Bart P; Smolders, Arne; Back, Patricia; De Henau, Sasha

    2016-10-01

    Due to its large families of redox-active enzymes, genetic amenability, and complete transparency, the nematode Caenorhabditis elegans has the potential to become an important model for the in vivo study of redox biology. The recent development of several genetically encoded ratiometric reactive oxygen species (ROS) and redox sensors has revolutionized the quantification and precise localization of ROS and redox signals in living organisms. Only few exploratory studies have applied these sensors in C. elegans and undoubtedly much remains to be discovered in this model. As a follow-up to our recent findings that the C. elegans somatic gonad uses superoxide and hydrogen peroxide (H2O2) signals to communicate with the germline, we here analyze the patterns of H2O2 inside the C. elegans germline. Despite the advantages of genetically encoded ROS and redox sensors over classic chemical sensors, still several general as well as C. elegans-specific issues need to be addressed. The major concerns for the application of these sensors in C. elegans are (i) decreased vitality of some reporter strains, (ii) interference of autofluorescent compartments with the sensor signal, and (iii) the use of immobilization methods that do not influence the worm's redox physiology. We propose that several of the current issues may be solved by designing reporter strains carrying single copies of codon-optimized sensors. Preferably, these sensors should have their emission wavelengths in the red region, where autofluorescence is absent. Worm analysis could be optimized using four-dimensional ratiometric fluorescence microscopy of worms immobilized in microfluidic chips. Antioxid. Redox Signal. 25, 577-592.

  3. Redox regulation of mitochondrial proteins and proteomes by cysteine thiol switches.

    PubMed

    Nietzel, Thomas; Mostertz, Jörg; Hochgräfe, Falko; Schwarzländer, Markus

    2017-03-01

    Mitochondria are hotspots of cellular redox biochemistry. Respiration as a defining mitochondrial function is made up of a series of electron transfers that are ultimately coupled to maintaining the proton motive force, ATP production and cellular energy supply. The individual reaction steps involved require tight control and flexible regulation to maintain energy and redox balance in the cell under fluctuating demands. Redox regulation by thiol switching has been a long-standing candidate mechanism to support rapid adjustment of mitochondrial protein function at the posttranslational level. Here we review recent advances in our understanding of cysteine thiol switches in the mitochondrial proteome with a focus on their operation in vivo. We assess the conceptual basis for thiol switching in mitochondria and discuss to what extent insights gained from in vitro studies may be valid in vivo, considering thermodynamic, kinetic and structural constraints. We compare functional proteomic approaches that have been used to assess mitochondrial protein thiol switches, including thioredoxin trapping, redox difference gel electrophoresis (redoxDIGE), isotope-coded affinity tag (OxICAT) and iodoacetyl tandem mass tag (iodoTMT) labelling strategies. We discuss conditions that may favour active thiol switching in mitochondrial proteomes in vivo, and appraise recent advances in dissecting their impact using combinations of in vivo redox sensing and quantitative redox proteomics. Finally we focus on four central facets of mitochondrial biology, aging, carbon metabolism, energy coupling and electron transport, exemplifying the current emergence of a mechanistic understanding of mitochondrial regulation by thiol switching in living plants and animals. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  4. Integrated redox proteomics and metabolomics of mitochondria to identify mechanisms of cd toxicity.

    PubMed

    Go, Young-Mi; Roede, James R; Orr, Michael; Liang, Yongliang; Jones, Dean P

    2014-05-01

    Cadmium (Cd) exposure contributes to human diseases affecting liver, kidney, lung, and other organ systems, but mechanisms underlying the pleotropic nature of these toxicities are poorly understood. Cd accumulates in humans from dietary, environmental (including cigarette smoke), and occupational sources, and has a twenty-year biologic half-life. Our previous mouse and cell studies showed that environmental low-dose Cd exposure altered protein redox states resulting in stimulation of inflammatory signaling and disruption of the actin cytoskeleton system, suggesting that Cd could impact multiple mechanisms of disease. In the current study, we investigated the effects of acute Cd exposure on the redox proteome and metabolome of mouse liver mitochondria to gain insight into associated toxicological mechanisms and functions. We analyzed redox states of liver mitochondrial proteins by redox proteomics using isotope coded affinity tag (ICAT) combined mass spectrometry. Redox ICAT identified 2687 cysteine-containing peptides (peptidyl Cys) of which 1667 peptidyl Cys (657 proteins) were detected in both control and Cd-exposed samples. Of these, 46% (1247 peptidyl Cys, 547 proteins) were oxidized by Cd more than 1.5-fold relative to controls. Bioinformatics analysis using MetaCore software showed that Cd affected 86 pathways, including 24 Cys in proteins functioning in branched chain amino acid (BCAA) and 14 Cys in proteins functioning in fatty acid (acylcarnitine/carnitine) metabolism. Consistently, high-resolution metabolomics data showed that Cd treatment altered levels of BCAA and carnitine metabolites. Together, these results show that mitochondrial protein redox and metabolites are targets in Cd-induced hepatotoxicity. The results further indicate that redox proteomics and metabolomics can be used in an integrated systems approach to investigate complex disease mechanisms.

  5. Electronic control of gene expression and cell behaviour in Escherichia coli through redox signalling

    NASA Astrophysics Data System (ADS)

    Tschirhart, Tanya; Kim, Eunkyoung; McKay, Ryan; Ueda, Hana; Wu, Hsuan-Chen; Pottash, Alex Eli; Zargar, Amin; Negrete, Alejandro; Shiloach, Joseph; Payne, Gregory F.; Bentley, William E.

    2017-01-01

    The ability to interconvert information between electronic and ionic modalities has transformed our ability to record and actuate biological function. Synthetic biology offers the potential to expand communication `bandwidth' by using biomolecules and providing electrochemical access to redox-based cell signals and behaviours. While engineered cells have transmitted molecular information to electronic devices, the potential for bidirectional communication stands largely untapped. Here we present a simple electrogenetic device that uses redox biomolecules to carry electronic information to engineered bacterial cells in order to control transcription from a simple synthetic gene circuit. Electronic actuation of the native transcriptional regulator SoxR and transcription from the PsoxS promoter allows cell response that is quick, reversible and dependent on the amplitude and frequency of the imposed electronic signals. Further, induction of bacterial motility and population based cell-to-cell communication demonstrates the versatility of our approach and potential to drive intricate biological behaviours.

  6. Effect of Redox Conditions on Bacterial Community Structure in Baltic Sea Sediments with Contrasting Phosphorus Fluxes

    PubMed Central

    Steenbergh, Anne K.; Bodelier, Paul L. E.; Slomp, Caroline P.; Laanbroek, Hendrikus J.

    2014-01-01

    Phosphorus release from sediments can exacerbate the effect of eutrophication in coastal marine ecosystems. The flux of phosphorus from marine sediments to the overlying water is highly dependent on the redox conditions at the sediment-water interface. Bacteria are key players in the biological processes that release or retain phosphorus in marine sediments. To gain more insight in the role of bacteria in phosphorus release from sediments, we assessed the effect of redox conditions on the structure of bacterial communities. To do so, we incubated surface sediments from four sampling sites in the Baltic Sea under oxic and anoxic conditions and analyzed the fingerprints of the bacterial community structures in these incubations and the original sediments. This paper describes the effects of redox conditions, sampling station, and sample type (DNA, RNA, or whole-cell sample) on bacterial community structure in sediments. Redox conditions explained only 5% of the variance in community structure, and bacterial communities from contrasting redox conditions showed considerable overlap. We conclude that benthic bacterial communities cannot be classified as being typical for oxic or anoxic conditions based on community structure fingerprints. Our results suggest that the overall structure of the benthic bacterial community has only a limited impact on benthic phosphate fluxes in the Baltic Sea. PMID:24667801

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

    PubMed Central

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

    2015-01-01

    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. PMID:25720653

  8. Effect of redox conditions on bacterial community structure in Baltic Sea sediments with contrasting phosphorus fluxes.

    PubMed

    Steenbergh, Anne K; Bodelier, Paul L E; Slomp, Caroline P; Laanbroek, Hendrikus J

    2014-01-01

    Phosphorus release from sediments can exacerbate the effect of eutrophication in coastal marine ecosystems. The flux of phosphorus from marine sediments to the overlying water is highly dependent on the redox conditions at the sediment-water interface. Bacteria are key players in the biological processes that release or retain phosphorus in marine sediments. To gain more insight in the role of bacteria in phosphorus release from sediments, we assessed the effect of redox conditions on the structure of bacterial communities. To do so, we incubated surface sediments from four sampling sites in the Baltic Sea under oxic and anoxic conditions and analyzed the fingerprints of the bacterial community structures in these incubations and the original sediments. This paper describes the effects of redox conditions, sampling station, and sample type (DNA, RNA, or whole-cell sample) on bacterial community structure in sediments. Redox conditions explained only 5% of the variance in community structure, and bacterial communities from contrasting redox conditions showed considerable overlap. We conclude that benthic bacterial communities cannot be classified as being typical for oxic or anoxic conditions based on community structure fingerprints. Our results suggest that the overall structure of the benthic bacterial community has only a limited impact on benthic phosphate fluxes in the Baltic Sea.

  9. Redox Regulation of the Superoxide Dismutases SOD3 and SOD2 in the Pulmonary Circulation.

    PubMed

    Hernandez-Saavedra, Daniel; Swain, Kalin; Tuder, Rubin; Petersen, Steen V; Nozik-Grayck, Eva

    2017-01-01

    When evaluating the role of redox-regulating signaling in pulmonary vascular diseases, it is intriguing to consider the modulation of key antioxidant enzymes like superoxide dismutase (SOD) because SOD isoforms are regulated by redox reactions, and, in turn, modulate downstream redox sensitive processes. The emerging field of redox biology is built upon understanding the regulation and consequences of tightly controlled and specific reduction-oxidation reactions that are critical for diverse cellular processes including cell signaling. Of relevance, both the site of production of specific reactive oxygen and nitrogen species and the site of the antioxidant defenses are highly compartmentalized within the cell. For example, superoxide is generated during oxidative phosphorylation in the mitochondria as well as by a number of enzymatic sources within the cytosol and at the cell membrane. In the pulmonary circulation, these sources include the mitochondrial electron transport chain, NADPH oxidases (NOX1-4, Duox1,2), nitric oxide synthases, and xanthine oxidase; this important topic has been thoroughly reviewed recently [1]. In parallel with these different cellular sites of superoxide production, the three SOD isoforms are also specifically localized to the cytosol (SOD1), mitochondria (SOD2) or extracellular compartment (SOD3). This chapter focuses on the role of redox mechanisms regulating SOD2 and SOD3, with an emphasis on these processes in the setting of pulmonary hypertension.

  10. Interaction between heavy metals and thiol-linked redox reactions in germination.

    PubMed

    Smiri, M; Chaoui, A; Ferjani, E E

    2010-09-15

    Thioredoxin (TRX) proteins perform important biological functions in cells by changing the redox state of proteins via dithiol disulfide exchange. Several systems are able to control the activity, stability, and correct folding of enzymes through dithiol/disulfide isomerization reactions including the enzyme protein disulfide-isomerase, the glutathione-dependent glutaredoxin system, and the thioredoxin systems. Plants have devised sophisticated mechanisms to cope with biotic and abiotic stresses imposed by their environment. Among these mechanisms, those collectively referred to as redox reactions induced by endogenous systems. This is of agronomical importance since a better knowledge of the involved mechanisms can offer novel means for crop protection. In the plant life cycle, the seed and seedling stages are key developmental stages conditioning the final yield of crops. Both are very sensitive to heavy metal stress. Plant redox reactions are principally studied on adult plant organs and there is only very scarce informations about the onset of redox regulation at the level of seed germination. In the here presented study, we discussed the importance of redox proteins in plant cell metabolism and defence. Special focus is given to TRX, which are involved in detoxification of ROS and also to their targets.

  11. An Unconventional Redox Cross Claisen Condensation-Aromatization of 4-Hydroxyprolines with Ketones.

    PubMed

    Tang, Mi; Sun, Rengwei; Li, Hao; Yu, Xinhong; Wang, Wei

    2017-08-18

    Reaction of α-amino acids, particularly prolines and their derivatives with carbonyl compounds via decarboxylative redox process, is a viable strategy for synthesis of structurally diverse nitrogen centered heterocyclics. In these processes, the decarboxylation is the essential driving force for the processes. The realization of the redox process without decarboxylation may offer an opportunity to explore new reactions. Herein, we report the discovery of an unprecedented redox Claisen-type condensation aromatization cascade reaction of 4-substituted 4-hydroxyproline and its esters with unreactive ketones. We found that the use of propionic acid as a catalyst and a co-solvent can change the reaction course. The commonly observed redox decarboxylation and aldol condensation reactions are significantly minimized. Moreover, unreactive ketones can effectively participate in the Claisen condensation reaction. The new reactivity enables a redox cyclization via an unconventional Claisen-type condensation reaction of in situ formed enamine intermediates from ketone precursors with 4-substituted 4-hydroxyproline and its esters as electrophilic acylation partners. Under the reaction conditions, the cascade process proceeds highly regio- and stereoselectively to afford highly synthetically and biologically valued cis-2,3-dihydro-1H-pyrrolizin-1-ones with a broad substrate scope in efficient 'one-pot' operation, whereas such structures generally require multiple steps.

  12. Corynebacterium diphtheriae methionine sulfoxide reductase a exploits a unique mycothiol redox relay mechanism.

    PubMed

    Tossounian, Maria-Armineh; Pedre, Brandán; Wahni, Khadija; Erdogan, Huriye; Vertommen, Didier; Van Molle, Inge; Messens, Joris

    2015-05-01

    Methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in proteins and play a pivotal role in cellular redox signaling. We have unraveled the redox relay mechanisms of methionine sulfoxide reductase A of the pathogen Corynebacterium diphtheriae (Cd-MsrA) and shown that this enzyme is coupled to two independent redox relay pathways. Steady-state kinetics combined with mass spectrometry of Cd-MsrA mutants give a view of the essential cysteine residues for catalysis. Cd-MsrA combines a nucleophilic cysteine sulfenylation reaction with an intramolecular disulfide bond cascade linked to the thioredoxin pathway. Within this cascade, the oxidative equivalents are transferred to the surface of the protein while releasing the reduced substrate. Alternatively, MsrA catalyzes methionine sulfoxide reduction linked to the mycothiol/mycoredoxin-1 pathway. After the nucleophilic cysteine sulfenylation reaction, MsrA forms a mixed disulfide with mycothiol, which is transferred via a thiol disulfide relay mechanism to a second cysteine for reduction by mycoredoxin-1. With x-ray crystallography, we visualize two essential intermediates of the thioredoxin relay mechanism and a cacodylate molecule mimicking the substrate interactions in the active site. The interplay of both redox pathways in redox signaling regulation forms the basis for further research into the oxidative stress response of this pathogen. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. A redox-based mechanism for nitric oxide-induced inhibition of DNA synthesis in human vascular smooth muscle cells

    PubMed Central

    Bundy, Ruth E; Marczin, Nándor; Chester, Adrian H; Yacoub, Magdi

    2000-01-01

    The current study explored potential redox mechanisms of nitric oxide (NO)-induced inhibition of DNA synthesis in cultured human and rat aortic smooth muscle cells.Exposure to S-nitrosothiols, DETA-NONOate and NO itself inhibited ongoing DNA synthesis and S phase progression in a concentration-dependent manner, as measured by thymidine incorporation and flow cytometry. Inhibition by NO donors occurred by release of NO, as detected by chemiluminescence and judged by the effects of NO scavengers, haemoglobin and cPTIO.Co-incubation with redox compounds, N-acetyl-L-cysteine, glutathione and L-ascorbic acid prevented NO inhibition of DNA synthesis. These observations suggest that redox agents may alternatively attenuate NO bioactivity extracellularly, interfere with intracellular actions of NO on the DNA synthesis machinery or restore DNA synthesis after established inhibition by NO.Recovery of DNA synthesis after inhibition by NO was similar with and without redox agents suggesting that augmented restoration of DNA synthesis is an unlikely mechanism to explain redox regulation.Study of extracellular interactions revealed that all redox agents potentiated S-nitrosothiol decomposition and NO release.Examination of intracellular NO bioactivity showed that as opposed to attenuation of NO inhibition of DNA synthesis by redox agents, there was no inhibition (potentiation in the presence of ascorbic acid) of soluble guanylate cyclase (sGC) activation judged by cyclic GMP accumulation in rat cells.These data provide evidence that NO-induced inhibition of ongoing DNA synthesis is sensitive to redox environment. Redox processes might protect the DNA synthesis machinery from inhibition by NO, in the setting of augmented liberation of biologically active NO from NO donors. PMID:10742309

  14. Selenium- and tellurium-containing multifunctional redox agents as biochemical redox modulators with selective cytotoxicity.

    PubMed

    Jamier, Vincent; Ba, Lalla A; Jacob, Claus

    2010-09-24

    Various human diseases, including different types of cancer, are associated with a disturbed intracellular redox balance and oxidative stress (OS). The past decade has witnessed the emergence of redox-modulating compounds able to utilize such pre-existing disturbances in the redox state of sick cells for therapeutic advantage. Selenium- and tellurium-based agents turn the oxidizing redox environment present in certain cancer cells into a lethal cocktail of reactive species that push these cells over a critical redox threshold and ultimately kill them through apoptosis. This kind of toxicity is highly selective: normal, healthy cells remain largely unaffected, since changes to their naturally low levels of oxidizing species produce little effect. To further improve selectivity, multifunctional sensor/effector agents are now required that recognize the biochemical signature of OS in target cells. The synthesis of such compounds provides interesting challenges for chemistry in the future.

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

    PubMed

    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.

  16. Impact of hydroquinone used as a redox effector model on potential denitrification, microbial activity and redox condition of a cultivable soil.

    PubMed

    Perotti, Elda B R

    2015-01-01

    In this microcosm study, we analyzed the effect produced by hydroquinone on the expression of soil biological denitrification, in relation to the redox state of the soil, both in terms of intensity factor (Eh') and capacity factor (amount of oxidized or reduced compounds). The supplementation of an Argiudoll soil with hydroquinone decreased the soil apparent reduction potential (Eh') and soil dehydrogenase activity (formazan production from tetrazolium chloride reduction; redox capacity factor), the relationship between both factors being highly significative, r=0.99 (p<0.001). The bacterial population (measured by colony forming units) increased, and the production of N2O was greater (p<0.001) at 200 and 400μg/g dry soil doses. Furthermore, there was an inverse relationship between soil dehydrogenase activity and the number of bacteria (r=-0.82; p<0.05), increased denitrification activity and changes in the CO2/N2O ratio value. These results suggest that hydroquinone at supplemented doses modified the soil redox state and the functional structure of the microbial population. Acetate supplementation on soil with hydroquinone, to ensure the availability of an energy source for microbial development, confirmed the tendency of the results obtained with the supplementation of hydroquinone alone. The differences observed at increased doses of hydroquinone might be explained by differences on the hydroquinone redox species between treatments. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Transport of gadolinium- and arsenic-based pharmaceuticals in saturated soil under various redox conditions.

    PubMed

    Menahem, Adi; Dror, Ishai; Berkowitz, Brian

    2016-02-01

    The release of pharmaceuticals and personal care products (PPCPs) to the soil-water environment necessitates understanding of PPCP transport behavior under conditions that account for dynamic flow and varying redox states. This study investigates the transport of two organometallic PPCPs, Gd-DTPA and roxarsone (arsenic compound) and their metal salts (Gd(NO3)3, AsNaO2); Gd-DTPA is used widely as a contrasting agent for MRI, while roxarsone is applied extensively as a food additive in the broiler poultry industry. Here, we present column experiments using sand and Mediterranean red sandy clay soil, performed under several redox conditions. The metal salts were almost completely immobile. In contrast, transport of Gd-DTPA and roxarsone was affected by the soil type. Roxarsone was also affected by the different redox conditions, showing delayed breakthrough curves as the redox potential became more negative due to biological activity (chemically-strong reducing conditions did not affect the transport). Mechanisms that include adsorptive retardation for aerobic and nitrate-reducing conditions, and non-adsorptive retardation for iron-reducing, sulfate-reducing and biologically-strong reducing conditions, are suggested to explain the roxarsone behavior. Gd-DTPA is found to be a stable complex, with potential for high mobility in groundwater systems, whereas roxarsone transport through groundwater systems is affected by redox environments, demonstrating high mobility under aerobic and nitrate-reducing conditions and delayed transport under iron-reducing, sulfate-reducing and biologically-strong reducing conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Redox Homeostasis in Pancreatic β Cells

    PubMed Central

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

    2012-01-01

    We reviewed mechanisms that determine reactive oxygen species (redox) homeostasis, redox information signaling and metabolic/regulatory function of autocrine insulin signaling in pancreatic β cells, and consequences of oxidative stress and dysregulation of redox/information signaling for their dysfunction. We emphasize the role of mitochondrion in β cell molecular physiology and pathology, including the antioxidant role of mitochondrial uncoupling protein UCP2. Since in pancreatic β cells pyruvate cannot be easily diverted towards lactate dehydrogenase for lactate formation, the respiration and oxidative phosphorylation intensity are governed by the availability of glucose, leading to a certain ATP/ADP ratio, whereas in other cell types, cell demand dictates respiration/metabolism rates. Moreover, we examine the possibility that type 2 diabetes mellitus might be considered as an inevitable result of progressive self-accelerating oxidative stress and concomitantly dysregulated information signaling in peripheral tissues as well as in pancreatic β cells. It is because the redox signaling is inherent to the insulin receptor signaling mechanism and its impairment leads to the oxidative and nitrosative stress. Also emerging concepts, admiting participation of redox signaling even in glucose sensing and insulin release in pancreatic β cells, fit in this view. For example, NADPH has been firmly established to be a modulator of glucose-stimulated insulin release. PMID:23304259

  19. Redox Signaling Mechanisms in Nervous System Development.

    PubMed

    Olguín-Albuerne, Mauricio; Morán, Julio

    2018-06-20

    Numerous studies have demonstrated the actions of reactive oxygen species (ROS) as regulators of several physiological processes. In this study, we discuss how redox signaling mechanisms operate to control different processes such as neuronal differentiation, oligodendrocyte differentiation, dendritic growth, and axonal growth. Recent Advances: Redox homeostasis regulates the physiology of neural stem cells (NSCs). Notably, the neuronal differentiation process of NSCs is determined by a change toward oxidative metabolism, increased levels of mitochondrial ROS, increased activity of NADPH oxidase (NOX) enzymes, decreased levels of Nrf2, and differential regulation of different redoxins. Furthermore, during the neuronal maturation processes, NOX and MICAL produce ROS to regulate cytoskeletal dynamics, which control the dendritic and axonal growth, as well as the axonal guidance. The redox homeostasis changes are, in part, attributed to cell metabolism and compartmentalized production of ROS, which is regulated, sensed, and transduced by different molecules such as thioredoxins, glutaredoxins, peroxiredoxins, and nucleoredoxin to control different signaling pathways in different subcellular regions. The study of how these elements cooperatively act is essential for the understanding of nervous system development, as well as the application of regenerative therapies that recapitulate these processes. The information about these topics in the last two decades leads us to the conclusion that the role of ROS signaling in development of the nervous system is more important than it was previously believed and makes clear the importance of exploring in more detail the mechanisms of redox signaling. Antioxid. Redox Signal. 28, 1603-1625.

  20. NASA Redox Storage System Development Project

    NASA Technical Reports Server (NTRS)

    Hagedorn, N. H.

    1984-01-01

    The Redox Storage System Technology Project was jointly supported by the U.S. Department of Energy and NASA. The objectives of the project were to develop the Redox flow battery concept and to probe its technical and economic viability. The iron and chromium redox couples were selected as the reactants. Membranes and electrodes were developed for the original mode of operating at 25 C with the reactants separated by an ion-exchange membrane. Analytical capabilities and system-level operating concepts were developed and verified in a 1-kW, 13-kWh preprototype system. A subsequent change was made in operating mode, going to 65 C and using mixed reactants. New membranes and a new electrode catalyst were developed, resulting in single cell operation as high as 80 mA/sq cm with energy efficiencies greater than 80 percent. Studies indicate a likely system cost of about $75/kWh. Standard Oil of Ohio (Sohio) has undertaken further development of the Redox system. An exclusive patent license was obtained from NASA by Sohio. Transfer of Redox technology to Sohio is supported by the NASA Technology Utilization Office.

  1. Mitochondrial Redox Signaling and Tumor Progression.

    PubMed

    Chen, Yuxin; Zhang, Haiqing; Zhou, Huanjiao Jenny; Ji, Weidong; Min, Wang

    2016-03-25

    Cancer cell can reprogram their energy production by switching mitochondrial oxidative phosphorylation to glycolysis. However, mitochondria play multiple roles in cancer cells, including redox regulation, reactive oxygen species (ROS) generation, and apoptotic signaling. Moreover, these mitochondrial roles are integrated via multiple interconnected metabolic and redox sensitive pathways. Interestingly, mitochondrial redox proteins biphasically regulate tumor progression depending on cellular ROS levels. Low level of ROS functions as signaling messengers promoting cancer cell proliferation and cancer invasion. However, anti-cancer drug-initiated stress signaling could induce excessive ROS, which is detrimental to cancer cells. Mitochondrial redox proteins could scavenger basal ROS and function as "tumor suppressors" or prevent excessive ROS to act as "tumor promoter". Paradoxically, excessive ROS often also induce DNA mutations and/or promotes tumor metastasis at various stages of cancer progression. Targeting redox-sensitive pathways and transcriptional factors in the appropriate context offers great promise for cancer prevention and therapy. However, the therapeutics should be cancer-type and stage-dependent.

  2. Synergistic oxygen atom transfer by ruthenium complexes with non-redox metal ions.

    PubMed

    Lv, Zhanao; Zheng, Wenrui; Chen, Zhuqi; Tang, Zhiming; Mo, Wanling; Yin, Guochuan

    2016-07-28

    Non-redox metal ions can affect the reactivity of active redox metal ions in versatile biological and heterogeneous oxidation processes; however, the intrinsic roles of these non-redox ions still remain elusive. This work demonstrates the first example of the use of non-redox metal ions as Lewis acids to sharply improve the catalytic oxygen atom transfer efficiency of a ruthenium complex bearing the classic 2,2'-bipyridine ligand. In the absence of Lewis acid, the oxidation of ruthenium(ii) complex by PhI(OAc)2 generates the Ru(iv)[double bond, length as m-dash]O species, which is very sluggish for olefin epoxidation. When Ru(bpy)2Cl2 was tested as a catalyst alone, only 21.2% of cyclooctene was converted, and the yield of 1,2-epoxycyclooctane was only 6.7%. As evidenced by electronic absorption spectra and EPR studies, both the oxidation of Ru(ii) by PhI(OAc)2 and the reduction of Ru(iv)[double bond, length as m-dash]O by olefin are kinetically slow. However, adding non-redox metal ions such as Al(iii) can sharply improve the oxygen transfer efficiency of the catalyst to 100% conversion with 89.9% yield of epoxide under identical conditions. Through various spectroscopic characterizations, an adduct of Ru(iv)[double bond, length as m-dash]O with Al(iii), Ru(iv)[double bond, length as m-dash]O/Al(iii), was proposed to serve as the active species for epoxidation, which in turn generated a Ru(iii)-O-Ru(iii) dimer as the reduced form. In particular, both the oxygen transfer from Ru(iv)[double bond, length as m-dash]O/Al(iii) to olefin and the oxidation of Ru(iii)-O-Ru(iii) back to the active Ru(iv)[double bond, length as m-dash]O/Al(iii) species in the catalytic cycle can be remarkably accelerated by adding a non-redox metal, such as Al(iii). These results have important implications for the role played by non-redox metal ions in catalytic oxidation at redox metal centers as well as for the understanding of the redox mechanism of ruthenium catalysts in the oxygen atom

  3. Editing disulphide bonds: error correction using redox currencies.

    PubMed

    Ito, Koreaki

    2010-01-01

    The disulphide bond-introducing enzyme of bacteria, DsbA, sometimes oxidizes non-native cysteine pairs. DsbC should rearrange the resulting incorrect disulphide bonds into those with correct connectivity. DsbA and DsbC receive oxidizing and reducing equivalents, respectively, from respective redox components (quinones and NADPH) of the cell. Two mechanisms of disulphide bond rearrangement have been proposed. In the redox-neutral 'shuffling' mechanism, the nucleophilic cysteine in the DsbC active site forms a mixed disulphide with a substrate and induces disulphide shuffling within the substrate part of the enzyme-substrate complex, followed by resolution into a reduced enzyme and a disulphide-rearranged substrate. In the 'reduction-oxidation' mechanism, DsbC reduces those substrates with wrong disulphides so that DsbA can oxidize them again. In this issue of Molecular Microbiology, Berkmen and his collaborators show that a disulphide reductase, TrxP, from an anaerobic bacterium can substitute for DsbC in Escherichia coli. They propose that the reduction-oxidation mechanism of disulphide rearrangement can indeed operate in vivo. An implication of this work is that correcting errors in disulphide bonds can be coupled to cellular metabolism and is conceptually similar to the proofreading processes observed with numerous synthesis and maturation reactions of biological macromolecules.

  4. Transduction of Redox Signaling by Electrophile-Protein Reactions

    PubMed Central

    Rudolph, Tanja K.; Freeman, Bruce A.

    2014-01-01

    Over the last 50 years, the posttranslational modification (PTM) of proteins has emerged as a central mechanism for cells to regulate metabolism, growth, differentiation, cell-cell interactions, and immune responses. By influencing protein structure and function, PTM leads to a multiplication of proteome diversity. Redox-dependent PTMs, mediated by environmental and endogenously generated reactive species, induce cell signaling responses and can have toxic effects in organisms. PTMs induced by the electrophilic by-products of redox reactions most frequently occur at protein thiols; other nucleophilic amino acids serve as less favorable targets. Advances in mass spectrometry and affinity-chemistry strategies have improved the detection of electrophile-induced protein modifications both in vitro and in vivo and have revealed a high degree of amino acid and protein selectivity of electrophilic PTM. The identification of biological targets of electrophiles has motivated further study of the functional impact of various PTM reactions on specific signaling pathways and how this might affect organisms. PMID:19797270

  5. REDOX IMAGING OF THE p53-DEPENDENT MITOCHONDRIAL REDOX STATE IN COLON CANCER EX VIVO

    PubMed Central

    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

  6. Lipogenesis and Redox Balance in Nitrogen-Fixing Pea Bacteroids

    PubMed Central

    Terpolilli, Jason J.; Masakapalli, Shyam K.; Karunakaran, Ramakrishnan; Webb, Isabel U. C.; Green, Rob; Watmough, Nicholas J.; Kruger, Nicholas J.; Ratcliffe, R. George

    2016-01-01

    ABSTRACT Within legume root nodules, rhizobia differentiate into bacteroids that oxidize host-derived dicarboxylic acids, which is assumed to occur via the tricarboxylic acid (TCA) cycle to generate NAD(P)H for reduction of N2. Metabolic flux analysis of laboratory-grown Rhizobium leguminosarum showed that the flux from [13C]succinate was consistent with respiration of an obligate aerobe growing on a TCA cycle intermediate as the sole carbon source. However, the instability of fragile pea bacteroids prevented their steady-state labeling under N2-fixing conditions. Therefore, comparative metabolomic profiling was used to compare free-living R. leguminosarum with pea bacteroids. While the TCA cycle was shown to be essential for maximal rates of N2 fixation, levels of pyruvate (5.5-fold reduced), acetyl coenzyme A (acetyl-CoA; 50-fold reduced), free coenzyme A (33-fold reduced), and citrate (4.5-fold reduced) were much lower in bacteroids. Instead of completely oxidizing acetyl-CoA, pea bacteroids channel it into both lipid and the lipid-like polymer poly-β-hydroxybutyrate (PHB), the latter via a type III PHB synthase that is active only in bacteroids. Lipogenesis may be a fundamental requirement of the redox poise of electron donation to N2 in all legume nodules. Direct reduction by NAD(P)H of the likely electron donors for nitrogenase, such as ferredoxin, is inconsistent with their redox potentials. Instead, bacteroids must balance the production of NAD(P)H from oxidation of acetyl-CoA in the TCA cycle with its storage in PHB and lipids. IMPORTANCE Biological nitrogen fixation by symbiotic bacteria (rhizobia) in legume root nodules is an energy-expensive process. Within legume root nodules, rhizobia differentiate into bacteroids that oxidize host-derived dicarboxylic acids, which is assumed to occur via the TCA cycle to generate NAD(P)H for reduction of N2. However, direct reduction of the likely electron donors for nitrogenase, such as ferredoxin, is inconsistent

  7. Lipogenesis and Redox Balance in Nitrogen-Fixing Pea Bacteroids.

    PubMed

    Terpolilli, Jason J; Masakapalli, Shyam K; Karunakaran, Ramakrishnan; Webb, Isabel U C; Green, Rob; Watmough, Nicholas J; Kruger, Nicholas J; Ratcliffe, R George; Poole, Philip S

    2016-10-15

    Within legume root nodules, rhizobia differentiate into bacteroids that oxidize host-derived dicarboxylic acids, which is assumed to occur via the tricarboxylic acid (TCA) cycle to generate NAD(P)H for reduction of N2 Metabolic flux analysis of laboratory-grown Rhizobium leguminosarum showed that the flux from [(13)C]succinate was consistent with respiration of an obligate aerobe growing on a TCA cycle intermediate as the sole carbon source. However, the instability of fragile pea bacteroids prevented their steady-state labeling under N2-fixing conditions. Therefore, comparative metabolomic profiling was used to compare free-living R. leguminosarum with pea bacteroids. While the TCA cycle was shown to be essential for maximal rates of N2 fixation, levels of pyruvate (5.5-fold reduced), acetyl coenzyme A (acetyl-CoA; 50-fold reduced), free coenzyme A (33-fold reduced), and citrate (4.5-fold reduced) were much lower in bacteroids. Instead of completely oxidizing acetyl-CoA, pea bacteroids channel it into both lipid and the lipid-like polymer poly-β-hydroxybutyrate (PHB), the latter via a type III PHB synthase that is active only in bacteroids. Lipogenesis may be a fundamental requirement of the redox poise of electron donation to N2 in all legume nodules. Direct reduction by NAD(P)H of the likely electron donors for nitrogenase, such as ferredoxin, is inconsistent with their redox potentials. Instead, bacteroids must balance the production of NAD(P)H from oxidation of acetyl-CoA in the TCA cycle with its storage in PHB and lipids. Biological nitrogen fixation by symbiotic bacteria (rhizobia) in legume root nodules is an energy-expensive process. Within legume root nodules, rhizobia differentiate into bacteroids that oxidize host-derived dicarboxylic acids, which is assumed to occur via the TCA cycle to generate NAD(P)H for reduction of N2 However, direct reduction of the likely electron donors for nitrogenase, such as ferredoxin, is inconsistent with their redox

  8. Role of antioxidants in redox regulation of diabetic cardiovascular complications.

    PubMed

    Turan, Belma

    2010-12-01

    Cardiovascular dysfunction is leading cause for the mortality of diabetic individuals, in part due to a specific cardiomyopathy, and due to altered endothelial dependent/independent vascular reactivity. Cardiovascular complications result from multiple parameters including glucotoxicity, lipotoxicity, fibrosis and mitochondrial uncoupling. Oxidative stress arises from an imbalance between the production of reactive oxygen and nitrogen species (ROS and RNS) and the capability of biological system to readily detoxify reactive intermediates. Several studies have reported beneficial effects of a therapy with antioxidant agents, including trace elements and other antioxidants, against the cardiovascular system dysfunction due to the diabetes. Antioxidants act through different mechanisms to prevent oxidant-induced cell damages acting either directly or indirectly. They can reduce the generation of ROS, scavenge ROS, or interfere with ROS-induced alterations. Modulating mitochondrial activity is an important possibility to control ROS production. Hence, the use of PPARα agonist to reduce fatty acid oxidation and of trace elements such as selenium as antioxidant and other antioxidants such as vitamins E and C, contribute to the prevention of diabetes-induced cardiovascular dysfunction. The paradigm that, inhibiting the overproduction of superoxides and peroxides would prevent cardiac dysfunction in diabetes has been difficult to verify using conventional antioxidants like vitamins E and C. That led to use of catalytic antioxidants such as SOD/CAT mimetics. Hence, well-tuned, balanced and responsive antioxidant defence systems are vital for proper prevention against diabetic damage. Myocardial cell death is observed in the hearts of diabetic patients and animal models; however, its importance in the development of diabetic cardiomyopathy is not completely understood. This review aims to summarize our present knowledge on various strategies to control oxidative stress and

  9. Carbon Redox-Polymer-Gel Hybrid Supercapacitors.

    PubMed

    Vlad, A; Singh, N; Melinte, S; Gohy, J-F; Ajayan, P M

    2016-02-26

    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.

  10. Carbon Redox-Polymer-Gel Hybrid Supercapacitors

    PubMed Central

    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

  11. Compromised redox homeostasis, altered nitroso–redox balance, and therapeutic possibilities in atrial fibrillation

    PubMed Central

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

    2016-01-01

    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. PMID:26786158

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

    PubMed

    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.

  13. Redox metabolites signal polymicrobial biofilm development via the NapA oxidative stress cascade in Aspergillus

    PubMed Central

    Zheng, He; Kim, Jaekuk; Liew, Mathew; Yan, John K.; Herrera, Oscar; Bok, JinWoo; Kelleher, Neil L.; Keller, Nancy P.; Wang, Yun

    2014-01-01

    Summary Background Filamentous fungi and bacteria form mixed-species biofilms in nature and diverse clinical contexts. They secrete a wealth of redox-active small molecule secondary metabolites, which are traditionally viewed as toxins that inhibit growth of competing microbes. Results Here we report that these “toxins” can act as interspecies signals, affecting filamentous fungal development via oxidative stress regulation. Specifically, in co-culture biofilms, Pseudomonas aeruginosa phenazine-derived metabolites differentially modulated Aspergillus fumigatus development, shifting from weak vegetative growth to induced asexual sporulation (conidiation) along a decreasing phenazine gradient. The A. fumigatus morphological shift correlated with the production of phenazine radicals and concomitant reactive oxygen species (ROS) production generated by phenazine redox cycling. Phenazine conidiation signaling was conserved in the genetic model A. nidulans, and mediated by NapA, a homolog of AP-1-like bZIP transcription factor, which is essential for the response to oxidative stress in humans, yeast, and filamentous fungi. Expression profiling showed phenazine treatment induced a NapA-dependent response of the global oxidative stress metabolome including the thioredoxin, glutathione and NADPH-oxidase systems. Conidiation induction in A. nidulans by another microbial redox-active secondary metabolite, gliotoxin, also required NapA. Conclusions This work highlights that microbial redox metabolites are key signals for sporulation in filamentous fungi, which are communicated through an evolutionarily conserved eukaryotic stress response pathway. It provides a foundation for interspecies signaling in environmental and clinical biofilms involving bacteria and filamentous fungi. PMID:25532893

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

    PubMed

    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

    2016-08-05

    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). © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Fate of Pharmaceuticals and Personal Care Products (PPCPs) in Saturated Soil Under Various Redox Conditions

    NASA Astrophysics Data System (ADS)

    Dror, I.; Menahem, A.; Berkowitz, B.

    2014-12-01

    The growing use of PPCPs results in their increasing release to the aquatic environment. Consequently, understanding the fate of PPCPs under environmentally relevant conditions that account for dynamic flow and varying redox states is critical. In this study, the transport of two organometallic PPCPs, Gd-DTPA and Roxarsone (As complex) and their metal salts (Gd(NO3)3, AsNaO2), is investigated. The former is used widely as a contrasting agent for MRI, while the latter is applied extensively as a food additive in the broiler poultry industry. Both of these compounds are excreted from the body, almost unchanged chemically. Gadolinium complexes are not fully eliminated in wastewater treatment and can reach groundwater via irrigation with treated wastewater; Roxarsone can enter groundwater via leaching from manure used as fertilizer. Studies have shown that the transport of PPCPs in groundwater is affected by environmental conditions such as redox states, pH, and soil type. For this study, column experiments using sand or Mediterranean red sandy clay soil were performed under several redox conditions: aerobic, nitrate-reducing, iron-reducing, sulfate-reducing, methanogenic, and very strongly chemical reducing. Batch experiments to determine adsorption isotherms were also performed for the complexes and metal salts. We found that Gd-DTPA transport was affected by the soil type and was not affected by the redox conditions. In contrast, Roxarsone transport was affected mainly by the different redox conditions, showing delayed breakthrough curves as the conditions became more biologically reduced (strong chemical reducing conditions did not affect the transport). We also observed that the metal salts show essentially no transport while the organic complexes display much faster breakthrough. The results suggest that transport of these PPCPs through soil and groundwater is determined by the redox conditions, as well as by soil type and the form of the applied metal (as salt

  16. Redox regulation and pro-oxidant reactions in the physiology of circadian systems.

    PubMed

    Méndez, Isabel; Vázquez-Martínez, Olivia; Hernández-Muñoz, Rolando; Valente-Godínez, Héctor; Díaz-Muñoz, Mauricio

    2016-05-01

    Rhythms of approximately 24 h are pervasive in most organisms and are known as circadian. There is a molecular circadian clock in each cell sustained by a feedback system of interconnected "clock" genes and transcription factors. In mammals, the timing system is formed by a central pacemaker, the suprachiasmatic nucleus, in coordination with a collection of peripheral oscillators. Recently, an extensive interconnection has been recognized between the molecular circadian clock and the set of biochemical pathways that underlie the bioenergetics of the cell. A principle regulator of metabolic networks is the flow of electrons between electron donors and acceptors. The concomitant reduction and oxidation (redox) reactions directly influence the balance between anabolic and catabolic processes. This review summarizes and discusses recent findings concerning the mutual and dynamic interactions between the molecular circadian clock, redox reactions, and redox signaling. The scope includes the regulatory role played by redox coenzymes (NAD(P)+/NAD(P)H, GSH/GSSG), reactive oxygen species (superoxide anion, hydrogen peroxide), antioxidants (melatonin), and physiological events that modulate the redox state (feeding condition, circadian rhythms) in determining the timing capacity of the molecular circadian clock. In addition, we discuss a purely metabolic circadian clock, which is based on the redox enzymes known as peroxiredoxins and is present in mammalian red blood cells and in other biological systems. Both the timing system and the metabolic network are key to a better understanding of widespread pathological conditions such as the metabolic syndrome, obesity, and diabetes. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  17. Metabolic Impact of Redox Cofactor Perturbations on the Formation of Aroma Compounds in Saccharomyces cerevisiae

    PubMed Central

    Sanchez, Isabelle; Dequin, Sylvie; Camarasa, Carole

    2015-01-01

    Redox homeostasis is a fundamental requirement for the maintenance of metabolism, energy generation, and growth in Saccharomyces cerevisiae. The redox cofactors NADH and NADPH are among the most highly connected metabolites in metabolic networks. Changes in their concentrations may induce widespread changes in metabolism. Redox imbalances were achieved with a dedicated biological tool overexpressing native NADH-dependent or engineered NADPH-dependent 2,3-butanediol dehydrogenase, in the presence of acetoin. We report that targeted perturbation of the balance of cofactors (NAD+/NADH or, to a lesser extent, NADP+/NADPH) significantly affected the production of volatile compounds. In most cases, variations in the redox state of yeasts modified the formation of all compounds from the same biochemical pathway (isobutanol, isoamyl alcohol, and their derivatives) or chemical class (ethyl esters), irrespective of the cofactors. These coordinated responses were found to be closely linked to the impact of redox status on the availability of intermediates of central carbon metabolism. This was the case for α-keto acids and acetyl coenzyme A (acetyl-CoA), which are precursors for the synthesis of many volatile compounds. We also demonstrated that changes in the availability of NADH selectively affected the synthesis of some volatile molecules (e.g., methionol, phenylethanol, and propanoic acid), reflecting the specific cofactor requirements of the dehydrogenases involved in their formation. Our findings indicate that both the availability of precursors from central carbon metabolism and the accessibility of reduced cofactors contribute to cell redox status modulation of volatile compound formation. PMID:26475113

  18. Redox Non-Innocence of Nitrosobenzene at Nickel

    DOE PAGES

    Kundu, Subrata; Stieber, S. Chantal; Ferrier, Maryline Ghislaine; ...

    2016-08-22

    Nitrosobenzene (PhNO) serves as a stable analogue of nitroxyl (HNO), a biologically relevant, redox-active nitric oxide derivative. Capture of nitrosobenzene at the electrondeficient β-diketiminato nickel(I) complex [ iPr 2NN F6]Ni results in reduction of the PhNO ligand to a (PhNO) ./ ⁻ species coordinated to a square planar Ni II center in [ iPr 2NN F6]Ni(η 2- ONPh). Ligand centered reduction leads to the (PhNO) -2 moiety bound to Ni II supported by XAS studies. Ultimately, systematic investigation of structure–reactivity patterns of (PhNO) ./ ⁻ and (PhNO) 2- ligands reveals parallels with superoxo (O 2) ./ ⁻ and peroxo (Omore » 2) 2- ligands, respectively, and forecasts reactivity patterns of the more transient HNO ligand.« less

  19. Introduction to the Thematic Minireview Series: Redox metabolism and signaling.

    PubMed

    Banerjee, Ruma

    2017-10-13

    Life on oxygen predisposes cells to reactive oxygen species (ROS) generation by electron slippage in the electron transfer chain. Aerobic metabolism also generates superoxide (O 2 ̇̄ ) and hydrogen peroxide (H 2 O 2 ) as bona fide products in reactions involving 1- or 2-electron reduction of O 2 Although often viewed as dangerous, ROS are now recognized as important messengers in redox signaling pathways. A delicate balance between needed versus excessive ROS production distinguishes health from an array of disease states. A collection of provocative reviews in this thematic series discusses the relative importance of mitochondrial sites for ROS production, ROS signaling-mediated regulation of cellular stress responses and thermogenesis, and how O 2 deficiency leads to metabolic reprograming in cancer. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Biogeochemical Barriers: Redox Behavior of Metals and Metalloids

    EPA Science Inventory

    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...

  1. Redox Modulation of Flavin and Tyrosine Determines Photoinduced Proton-coupled Electron Transfer and Photoactivation of BLUF Photoreceptors

    PubMed Central

    Mathes, Tilo; van Stokkum, Ivo H. M.; Stierl, Manuela; Kennis, John T. M.

    2012-01-01

    Photoinduced electron transfer in biological systems, especially in proteins, is a highly intriguing matter. Its mechanistic details cannot be addressed by structural data obtained by crystallography alone because this provides only static information on a given redox system. In combination with transient spectroscopy and site-directed manipulation of the protein, however, a dynamic molecular picture of the ET process may be obtained. In BLUF (blue light sensors using FAD) photoreceptors, proton-coupled electron transfer between a tyrosine and the flavin cofactor is the key reaction to switch from a dark-adapted to a light-adapted state, which corresponds to the biological signaling state. Particularly puzzling is the fact that, although the various naturally occurring BLUF domains show little difference in the amino acid composition of the flavin binding pocket, the reaction rates of the forward reaction differ quite largely from a few ps up to several hundred ps. In this study, we modified the redox potential of the flavin/tyrosine redox pair by site-directed mutagenesis close to the flavin C2 carbonyl and fluorination of the tyrosine, respectively. We provide information on how changes in the redox potential of either reaction partner significantly influence photoinduced proton-coupled electron transfer. The altered redox potentials allowed us furthermore to experimentally describe an excited state charge transfer intermediately prior to electron transfer in the BLUF photocycle. Additionally, we show that the electron transfer rate directly correlates with the quantum yield of signaling state formation. PMID:22833672

  2. Redox-Directed Cancer Therapeutics: Molecular Mechanisms and Opportunities

    PubMed Central

    2009-01-01

    Abstract Redox dysregulation originating from metabolic alterations and dependence on mitogenic and survival signaling through reactive oxygen species represents a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics. This review will present an update on drug discovery, target identification, and mechanisms of action of experimental redox chemotherapeutics with a focus on pro- and antioxidant redox modulators now in advanced phases of preclinal and clinical development. Recent research indicates that numerous oncogenes and tumor suppressor genes exert their functions in part through redox mechanisms amenable to pharmacological intervention by redox chemotherapeutics. The pleiotropic action of many redox chemotherapeutics that involves simultaneous modulation of multiple redox sensitive targets can overcome cancer cell drug resistance originating from redundancy of oncogenic signaling and rapid mutation. Moreover, some redox chemotherapeutics may function according to the concept of synthetic lethality (i.e., drug cytotoxicity is confined to cancer cells that display loss of function mutations in tumor suppressor genes or upregulation of oncogene expression). The impressive number of ongoing clinical trials that examine therapeutic performance of novel redox drugs in cancer patients demonstrates that redox chemotherapy has made the crucial transition from bench to bedside. Antioxid. Redox Signal. 11, 3013–3069. PMID:19496700

  3. Redox regulation in cancer stem cells

    USDA-ARS?s Scientific Manuscript database

    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...

  4. Redox Aspects of Chaperones in Cardiac Function

    PubMed Central

    Penna, Claudia; Sorge, Matteo; Femminò, Saveria; Pagliaro, Pasquale; Brancaccio, Mara

    2018-01-01

    Molecular chaperones are stress proteins that allow the correct folding or unfolding as well as the assembly or disassembly of macromolecular cellular components. Changes in expression and post-translational modifications of chaperones have been linked to a number of age- and stress-related diseases including cancer, neurodegeneration, and cardiovascular diseases. Redox sensible post-translational modifications, such as S-nitrosylation, glutathionylation and phosphorylation of chaperone proteins have been reported. Redox-dependent regulation of chaperones is likely to be a phenomenon involved in metabolic processes and may represent an adaptive response to several stress conditions, especially within mitochondria, where it impacts cellular bioenergetics. These post-translational modifications might underlie the mechanisms leading to cardioprotection by conditioning maneuvers as well as to ischemia/reperfusion injury. In this review, we discuss this topic and focus on two important aspects of redox-regulated chaperones, namely redox regulation of mitochondrial chaperone function and cardiac protection against ischemia/reperfusion injury. PMID:29615920

  5. TXNIP links redox circuitry to glucose control.

    PubMed

    Muoio, Deborah M

    2007-06-01

    Thioredoxin-interacting protein (TXNIP) binds and inhibits the reducing activity of thioredoxin. A new study (Parikh et al., 2007) implicates this redox rheostat as a negative regulator of peripheral glucose metabolism in humans. Investigators combined human physiology, genomic screening, and cell-based genetic studies to highlight TNXIP as a potential culprit in the pathogenesis of type 2 diabetes.

  6. Redox flow cell energy storage systems

    NASA Technical Reports Server (NTRS)

    Thaller, L. H.

    1979-01-01

    NASA-Redox systems are electrochemical storage devices that use two fully soluble Redox couples, anode and cathode fluids, as active electrode materials separated by a highly selective ion exchange membrane. The reactants are contained in large storage tanks and pumped through a stack of Redox flow cells where the electrochemical reactions (reduction and oxidation) take place at porous carbon felt electrodes. A string or stack of these power producing cells is connected in series in a bipolar manner. Redox energy storage systems promise to be inexpensive and possess many features that provide for flexible design, long life, high reliability and minimal operation and maintenance costs. These features include independent sizing of power and storage capacity requirements and inclusion within the cell stack of a cell that monitors the state of charge of the system as a whole, and a rebalance cell which permits continuous correction to be made for minor side reactions that would tend to result in the anode fluid and cathode fluids becoming electrochemically out of balance. These system features are described and discussed.

  7. NRF2: Translating the Redox Code

    PubMed Central

    Tummala, Krishna S.; Kottakis, Filippos; Bardeesy, Nabeel

    2016-01-01

    Cancer requires mechanisms to mitigate reactive oxygen species (ROS) generated during rapid growth, such as induction of the antioxidant transcription factor, Nrf2. However, the targets of ROS-mediated cytotoxicity are unclear. Recent studies in pancreatic cancer show that redox control by Nrf2 prevents cysteine oxidation of the mRNA translational machinery, thereby supporting efficient protein synthesis. PMID:27555347

  8. Mitochondrial Energy and Redox Signaling in Plants

    PubMed Central

    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

  9. Bimetallic redox synergy in oxidative palladium catalysis.

    PubMed

    Powers, David C; Ritter, Tobias

    2012-06-19

    Polynuclear transition metal complexes, which are embedded in the active sites of many metalloenzymes, are responsible for effecting a diverse array of oxidation reactions in nature. The range of chemical transformations remains unparalleled in the laboratory. With few noteworthy exceptions, chemists have primarily focused on mononuclear transition metal complexes in developing homogeneous catalysis. Our group is interested in the development of carbon-heteroatom bond-forming reactions, with a particular focus on identifying reactions that can be applied to the synthesis of complex molecules. In this context, we have hypothesized that bimetallic redox chemistry, in which two metals participate synergistically, may lower the activation barriers to redox transformations relevant to catalysis. In this Account, we discuss redox chemistry of binuclear Pd complexes and examine the role of binuclear intermediates in Pd-catalyzed oxidation reactions. Stoichiometric organometallic studies of the oxidation of binuclear Pd(II) complexes to binuclear Pd(III) complexes and subsequent C-X reductive elimination from the resulting binuclear Pd(III) complexes have confirmed the viability of C-X bond-forming reactions mediated by binuclear Pd(III) complexes. Metal-metal bond formation, which proceeds concurrently with oxidation of binuclear Pd(II) complexes, can lower the activation barrier for oxidation. We also discuss experimental and theoretical work that suggests that C-X reductive elimination is also facilitated by redox cooperation of both metals during reductive elimination. The effect of ligand modification on the structure and reactivity of binuclear Pd(III) complexes will be presented in light of the impact that ligand structure can exert on the structure and reactivity of binuclear Pd(III) complexes. Historically, oxidation reactions similar to those discussed here have been proposed to proceed via mononuclear Pd(IV) intermediates, and the hypothesis of mononuclear Pd

  10. The Redox Stress Hypothesis of Aging

    PubMed Central

    Sohal, Rajindar S.; Orr, William C.

    2011-01-01

    The main objective of this review is to examine the role of the endogenous reactive oxygen/nitrogen species (ROS) in the aging process. Until relatively recently, ROS were considered to be potentially toxic by-products of aerobic metabolism, which, if not eliminated, may inflict structural damage on various macromolecules. Accrual of such damage over time was postulated to be responsible for the physiological deterioration in the post-reproductive phase of life and eventually the death of the organism. This “structural damage-based oxidative stress” hypothesis has received support from the age-associated increases in the rates of ROS production and the steady-state amounts of oxidized macromolecules; however, there are increasing indications that structural damage alone is insufficient to satisfactorily explain the age-associated functional losses. The level of oxidative damage, accrued during aging, often does not match the magnitude of functional losses. Although experimental augmentations of antioxidant defenses tend to enhance resistance to induced oxidative stress, such manipulations are generally ineffective in the extension of life span of long-lived strains of animals. More recently, in a major conceptual shift, ROS have been found to be physiologically vital for signal transduction, gene regulation and redox regulation, among others, implying that their complete elimination would be harmful. An alternative notion, advocated here, termed “redox stress hypothesis”, proposes that aging-associated functional losses are primarily caused by a progressive pro-oxidizing shift in the redox state of the cells, which leads to the over-oxidation of redox-sensitive protein thiols and the consequent disruption of the redox-regulated signaling mechanisms. PMID:22080087

  11. Gel-based methods in redox proteomics.

    PubMed

    Charles, Rebecca; Jayawardhana, Tamani; Eaton, Philip

    2014-02-01

    The key to understanding the full significance of oxidants in health and disease is the development of tools and methods that allow the study of proteins that sense and transduce changes in cellular redox. Oxidant-reactive deprotonated thiols commonly operate as redox sensors in proteins and a variety of methods have been developed that allow us to monitor their oxidative modification. This outline review specifically focuses on gel-based methods used to detect, quantify and identify protein thiol oxidative modifications. The techniques we discuss fall into one of two broad categories. Firstly, methods that allow oxidation of thiols in specific proteins or the global cellular pool to be monitored are discussed. These typically utilise thiol-labelling reagents that add a reporter moiety (e.g. affinity tag, fluorophore, chromophore), in which loss of labelling signifies oxidation. Secondly, we outline methods that allow specific thiol oxidation states of proteins (e.g. S-sulfenylation, S-nitrosylation, S-thionylation and interprotein disulfide bond formation) to be investigated. A variety of different gel-based methods for identifying thiol proteins that are sensitive to oxidative modifications have been developed. These methods can aid the detection and quantification of thiol redox state, as well as identifying the sensor protein. By understanding how cellular redox is sensed and transduced to a functional effect by protein thiol redox sensors, this will help us better appreciate the role of oxidants in health and disease. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. An overview of mechanisms of redox signaling.

    PubMed

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

    2014-08-01

    A principal characteristic of redox signaling is that it involves an oxidation-reduction reaction or covalent adduct formation between the sensor signaling protein and second messenger. Non-redox signaling may involve alteration of the second messenger as in hydrolysis of GTP by G proteins, modification of the signaling protein as in farnesylation, or simple non-covalent binding of an agonist or second messenger. The chemistry of redox signaling is reviewed here. Specifically we have described how among the so-called reactive oxygen species, only hydroperoxides clearly fit the role of a second messenger. Consideration of reaction kinetics and cellular location strongly suggests that for hydroperoxides, particular protein cysteines are the targets and that the requirements for redox signaling is that these cysteines are in microenvironments in which the cysteine is ionized to the thiolate, and a proton can be donated to form a leaving group. The chemistry described here is the same as occurs in the cysteine and selenocysteine peroxidases that are generally considered the primary defense against oxidative stress. But, these same enzymes can also act as the sensors and transducer for signaling. Conditions that would allow specific signaling by peroxynitrite and superoxide are also defined. Signaling by other electrophiles, which includes lipid peroxidation products, quinones formed from polyphenols and other metabolites also involves reaction with specific protein thiolates. Again, kinetics and location are the primary determinants that provide specificity required for physiological signaling although enzymatic catalysis is not likely involved. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System". Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Redox proteomics for the assessment of redox-related posttranslational regulation in plants.

    PubMed

    Mock, Hans-Peter; Dietz, Karl-Josef

    2016-08-01

    The methodological developments of in vivo and in vitro protein labeling and subsequent detection enable sensitive and specific detection of redox modifications. Such methods are presently applied to diverse cells and tissues, subproteomes and developmental as well as environmental conditions. The chloroplast proteome is particularly suitable for such kind of studies, because redox regulation of chloroplast proteins is well established, many plastid proteins are abundant, redox network components have been inventoried in great depth, and functional consequences explored. Thus the repertoire of redox-related posttranslational modifications on the one hand side and their abundance on the other pose a challenge for the near future to understand their contribution to physiological regulation. The various posttranslational redox modifications are introduced, followed by a description of the available proteomics methods. The significance of the redox-related posttranslational modification is exemplarily worked out using established examples from photosynthesis. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. Copyright © 2016. Published by Elsevier B.V.

  14. Dual redox catalysts for oxygen reduction and evolution reactions: towards a redox flow Li-O2 battery.

    PubMed

    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.

  15. Redox Bulk Energy Storage System Study, Volume 1

    NASA Technical Reports Server (NTRS)

    Ciprios, G.; Erskine, W., Jr.; Grimes, P. G.

    1977-01-01

    Opportunities were found for electrochemical energy storage devices in the U.S. electric utility industry. Application requirements for these devices were defined, including techno-economic factors. A new device, the Redox storage battery was analyzed. The Redox battery features a decoupling of energy storage and power conversion functions. General computer methods were developed to simulate Redox system operations. These studies showed that the Redox system is potentially attractive if certain performance goals can be achieved. Pathways for reducing the cost of the Redox system were identified.

  16. Imaging dynamic redox processes with genetically encoded probes.

    PubMed

    Ezeriņa, Daria; Morgan, Bruce; Dick, Tobias P

    2014-08-01

    Redox signalling plays an important role in many aspects of physiology, including that of the cardiovascular system. Perturbed redox regulation has been associated with numerous pathological conditions; nevertheless, the causal relationships between redox changes and pathology often remain unclear. Redox signalling involves the production of specific redox species at specific times in specific locations. However, until recently, the study of these processes has been impeded by a lack of appropriate tools and methodologies that afford the necessary redox species specificity and spatiotemporal resolution. Recently developed genetically encoded fluorescent redox probes now allow dynamic real-time measurements, of defined redox species, with subcellular compartment resolution, in intact living cells. Here we discuss the available genetically encoded redox probes in terms of their sensitivity and specificity and highlight where uncertainties or controversies currently exist. Furthermore, we outline major goals for future probe development and describe how progress in imaging methodologies will improve our ability to employ genetically encoded redox probes in a wide range of situations. This article is part of a special issue entitled "Redox Signalling in the Cardiovascular System." Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Characterization of redox conditions in groundwater contaminant plumes

    NASA Astrophysics Data System (ADS)

    Christensen, Thomas H.; Bjerg, Poul L.; Banwart, Steven A.; Jakobsen, Rasmus; Heron, Gorm; Albrechtsen, Hans-Jørgen

    2000-10-01

    Evaluation of redox conditions in groundwater pollution plumes is often a prerequisite for understanding the behaviour 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 cases have been reported. No standardised or generally accepted approach exists. Slow electrode kinetics and the common lack of internal equilibrium of redox processes in pollution plumes make, with a few exceptions, direct electrochemical measurement and rigorous interpretation of redox potentials dubious, if not erroneous. Several other approaches have been used in addressing redox conditions in pollution plumes: redox-sensitive compounds in groundwater samples, hydrogen concentrations in groundwater, concentrations of volatile fatty acids in groundwater, sediment characteristics and microbial tools, such as MPN counts, PLFA biomarkers and redox bioassays. This paper reviews the principles behind the different approaches, summarizes methods used and evaluates the approaches based on the experience from the reported applications.

  18. Mesoporous tungsten oxynitride as electrocatalyst for promoting redox reactions of vanadium redox couple and performance of vanadium redox flow battery

    NASA Astrophysics Data System (ADS)

    Lee, Wonmi; Jo, Changshin; Youk, Sol; Shin, Hun Yong; Lee, Jinwoo; Chung, Yongjin; Kwon, Yongchai

    2018-01-01

    For enhancing the performance of vanadium redox flow battery (VRFB), a sluggish reaction rate issue of V2+/V3+ redox couple evaluated as the rate determining reaction should be addressed. For doing that, mesoporous tungsten oxide (m-WO3) and oxyniride (m-WON) structures are proposed as the novel catalysts, while m-WON is gained by NH3 heat treatment of m-WO3. Their specific surface area, crystal structure, surface morphology and component analysis are measured using BET, XRD, TEM and XPS, while their catalytic activity for V2+/V3+ redox reaction is electrochemically examined. As a result, the m-WON shows higher peak current, smaller peak potential difference, higher electron transfer rate constant and lower charge transfer resistance than other catalysts, like the m-WO3, WO3 nanoparticle and mesoporous carbon, proving that it is superior catalyst. Regarding the charge-discharge curve tests, the VRFB single cell employing the m-WON demonstrates high voltage and energy efficiencies, high specific capacity and low capacity loss rate. The excellent results of m-WON are due to the reasons like (i) reduced energy band gap, (ii) reaction familiar surface functional groups and (ii) greater electronegativity.

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

    PubMed

    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.

  20. Cost projections for Redox Energy storage systems

    NASA Technical Reports Server (NTRS)

    Michaels, K.; Hall, G.

    1980-01-01

    A preliminary design and system cost analysis was performed for the redox energy storage system. A conceptual design and cost estimate was prepared for each of two energy applications: (1) electric utility 100-MWh requirement (10-MW for ten hours) for energy storage for utility load leveling application, and (2) a 500-kWh requirement (10-kW for 50 hours) for use with a variety of residential or commercial applications, including stand alone solar photovoltaic systems. The conceptual designs were based on cell performance levels, system design parameters, and special material costs. These data were combined with estimated thermodynamic and hydraulic analysis to provide preliminary system designs. Results indicate that the redox cell stack to be amenable to mass production techniques with a relatively low material cost.

  1. The Chemistry of Redox-Flow Batteries.

    PubMed

    Noack, Jens; Roznyatovskaya, Nataliya; Herr, Tatjana; Fischer, Peter

    2015-08-17

    The development of various redox-flow batteries for the storage of fluctuating renewable energy has intensified in recent years because of their peculiar ability to be scaled separately in terms of energy and power, and therefore potentially to reduce the costs of energy storage. This has resulted in a considerable increase in the number of publications on redox-flow batteries. This was a motivation to present a comprehensive and critical overview of the features of this type of batteries, focusing mainly on the chemistry of electrolytes and introducing a thorough systematic classification to reveal their potential for future development. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Proteostasis and REDOX state in the heart.

    PubMed

    Christians, Elisabeth S; Benjamin, Ivor J

    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.

  3. Proteostasis and REDOX state in the heart

    PubMed Central

    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

  4. NRF2: Translating the Redox Code.

    PubMed

    Tummala, Krishna S; Kottakis, Filippos; Bardeesy, Nabeel

    2016-10-01

    Cancer requires mechanisms to mitigate reactive oxygen species (ROS) generated during rapid growth, such as induction of the antioxidant transcription factor, Nrf2. However, the targets of ROS-mediated cytotoxicity are unclear. Recent studies in pancreatic cancer show that redox control by Nrf2 prevents cysteine oxidation of the mRNA translational machinery, thereby supporting efficient protein synthesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Redox Indicator Mice Stably Expressing Genetically Encoded Neuronal roGFP: Versatile Tools to Decipher Subcellular Redox Dynamics in Neuropathophysiology.

    PubMed

    Wagener, Kerstin C; Kolbrink, Benedikt; Dietrich, Katharina; Kizina, Kathrin M; Terwitte, Lukas S; Kempkes, Belinda; Bao, Guobin; Müller, Michael

    2016-07-01

    Reactive oxygen species (ROS) and downstream redox alterations not only mediate physiological signaling but also neuropathology. For long, ROS/redox imaging was hampered by a lack of reliable probes. Genetically encoded redox sensors overcame this gap and revolutionized (sub)cellular redox imaging. Yet, the successful delivery of sensor-coding DNA, which demands transfection/transduction of cultured preparations or stereotaxic microinjections of each subject, remains challenging. By generating transgenic mice, we aimed to overcome limiting cultured preparations, circumvent surgical interventions, and to extend effectively redox imaging to complex and adult preparations. Our redox indicator mice widely express Thy1-driven roGFP1 (reduction-oxidation-sensitive green fluorescent protein 1) in neuronal cytosol or mitochondria. Negative phenotypic effects of roGFP1 were excluded and its proper targeting and functionality confirmed. Redox mapping by ratiometric wide-field imaging reveals most oxidizing conditions in CA3 neurons. Furthermore, mitochondria are more oxidized than cytosol. Cytosolic and mitochondrial roGFP1s reliably report cell endogenous redox dynamics upon metabolic challenge or stimulation. Fluorescence lifetime imaging yields stable, but marginal, response ranges. We therefore developed automated excitation ratiometric 2-photon imaging. It offers superior sensitivity, spatial resolution, and response dynamics. Redox indicator mice enable quantitative analyses of subcellular redox dynamics in a multitude of preparations and at all postnatal stages. This will uncover cell- and compartment-specific cerebral redox signals and their defined alterations during development, maturation, and aging. Cross-breeding with other disease models will reveal molecular details on compartmental redox homeostasis in neuropathology. Combined with ratiometric 2-photon imaging, this will foster our mechanistic understanding of cellular redox signals in their full complexity

  6. Redox Indicator Mice Stably Expressing Genetically Encoded Neuronal roGFP: Versatile Tools to Decipher Subcellular Redox Dynamics in Neuropathophysiology

    PubMed Central

    Wagener, Kerstin C.; Kolbrink, Benedikt; Dietrich, Katharina; Kizina, Kathrin M.; Terwitte, Lukas S.; Kempkes, Belinda; Bao, Guobin

    2016-01-01

    Abstract Aims: Reactive oxygen species (ROS) and downstream redox alterations not only mediate physiological signaling but also neuropathology. For long, ROS/redox imaging was hampered by a lack of reliable probes. Genetically encoded redox sensors overcame this gap and revolutionized (sub)cellular redox imaging. Yet, the successful delivery of sensor-coding DNA, which demands transfection/transduction of cultured preparations or stereotaxic microinjections of each subject, remains challenging. By generating transgenic mice, we aimed to overcome limiting cultured preparations, circumvent surgical interventions, and to extend effectively redox imaging to complex and adult preparations. Results: Our redox indicator mice widely express Thy1-driven roGFP1 (reduction–oxidation-sensitive green fluorescent protein 1) in neuronal cytosol or mitochondria. Negative phenotypic effects of roGFP1 were excluded and its proper targeting and functionality confirmed. Redox mapping by ratiometric wide-field imaging reveals most oxidizing conditions in CA3 neurons. Furthermore, mitochondria are more oxidized than cytosol. Cytosolic and mitochondrial roGFP1s reliably report cell endogenous redox dynamics upon metabolic challenge or stimulation. Fluorescence lifetime imaging yields stable, but marginal, response ranges. We therefore developed automated excitation ratiometric 2-photon imaging. It offers superior sensitivity, spatial resolution, and response dynamics. Innovation and Conclusion: Redox indicator mice enable quantitative analyses of subcellular redox dynamics in a multitude of preparations and at all postnatal stages. This will uncover cell- and compartment-specific cerebral redox signals and their defined alterations during development, maturation, and aging. Cross-breeding with other disease models will reveal molecular details on compartmental redox homeostasis in neuropathology. Combined with ratiometric 2-photon imaging, this will foster our mechanistic understanding

  7. Pyridine nucleotides in regulation of cell death and survival by redox and non-redox reactions.

    PubMed

    Novak Kujundžić, Renata; Žarković, Neven; Gall Trošelj, Koraljka

    2014-01-01

    Changes of the level and ratios of pyridine nucleotides determine metabolism- dependent cellular redox status and the activity of poly(ADP-ribose) polymerases (PARPs) and sirtuins, thereby influencing several processes closely related to cell survival and death. Pyridine nucleotides participate in numerous metabolic reactions whereby their net cellular level remains constant, but the ratios of NAD+/NADP+ and NADH/NADPH oscillate according to metabolic changes in response to diverse stress signals. In non-redox reactions, NAD+ is degraded and quickly, afterward, resynthesized in the NAD+ salvage pathway, unless overwhelming activation of PARP-1 consumes NAD+ to the point of no return, when the cell can no longer generate enough ATP to accommodate NAD+ resynthesis. The activity of PARP-1 is mandatory for the onset of cytoprotective autophagy on sublethal stress signals. It has become increasingly clear that redox status, largely influenced by the metabolism-dependent composition of the pyridine nucleotides pool, plays an important role in the synthesis of pro-apoptotic and anti-apoptotic sphingolipids. Awareness of the involvement of the prosurvival sphingolipid, sphingosine-1-phosphate, in transition from inflammation to malignant transformation has recently emerged. Here, the participation of pyridine nucleotides in redox and non-redox reactions, sphingolipid metabolism, and their role in cell fate decisions is reviewed.

  8. Membrane development for vanadium redox flow batteries.

    PubMed

    Schwenzer, Birgit; Zhang, Jianlu; Kim, Soowhan; Li, Liyu; Liu, Jun; Yang, Zhenguo

    2011-10-17

    Large-scale energy storage has become the main bottleneck for increasing the percentage of renewable energy in our electricity grids. Redox flow batteries are considered to be among the best options for electricity storage in the megawatt range and large demonstration systems have already been installed. Although the full technological potential of these systems has not been reached yet, currently the main problem hindering more widespread commercialization is the high cost of redox flow batteries. Nafion, as the preferred membrane material, is responsible for about 11% of the overall cost of a 1 MW/8 MWh system. Therefore, in recent years two main membrane related research threads have emerged: 1) chemical and physical modification of Nafion membranes to optimize their properties with regard to vanadium redox flow battery (VRFB) application; and 2) replacement of the Nafion membranes with different, less expensive materials. This review summarizes the underlying basic scientific issues associated with membrane use in VRFBs and presents an overview of membrane-related research approaches aimed at improving the efficiency of VRFBs and making the technology cost-competitive. Promising research strategies and materials are identified and suggestions are provided on how materials issues could be overcome.

  9. Redox Regulation in Amyotrophic Lateral Sclerosis

    PubMed Central

    Parakh, Sonam; Spencer, Damian M.; Halloran, Mark A.; Soo, Kai Y.; Atkin, Julie D.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS. PMID:23533690

  10. Retractions. Antioxidants and Redox Signaling (ARS).

    PubMed

    2012-04-01

    Due to the recent findings of an investigation led by the U.S. Office of Research Integrity, and as a direct result of the falsification and manipulation of data in the articles listed below, Antioxidants and Redox Signaling (ARS) is officially retracting the following published papers, authored by Dipak K. Das. 1. Malik G, Gorbounov N, Das S, Gurusamy N, Otani H, Maulik N, Goswami S, Das DK. Ischemic preconditioning triggers nuclear translocation of thioredoxin and its interaction with Ref-1 potentiating a survival signal through the PI-3-kinase-Akt pathway. Antioxid Redox Signal 8:2101-2109, 2006. 2. Muinck ED, Nagy N, Tirziu D, Murakami M, Gurusamy N, Goswami SK, Ghatpande S, Engelman RM, Simons M, Das DK. Protection against myocardial ischemia-reperfusion injury by the angiogenic Masterswitch protein PR 39 gene therapy: the roles of HIF1alpha stabilization and FGFR1 signaling. Antioxid Redox Signal 9:437-445, 2007. These actions reinforce the high standards to which ARS is committed.

  11. A redox-mediated Kemp eliminase

    NASA Astrophysics Data System (ADS)

    Li, Aitao; Wang, Binju; Ilie, Adriana; Dubey, Kshatresh D.; Bange, Gert; Korendovych, Ivan V.; Shaik, Sason; Reetz, Manfred T.

    2017-03-01

    The acid/base-catalysed Kemp elimination of 5-nitro-benzisoxazole forming 2-cyano-4-nitrophenol has long served as a design platform of enzymes with non-natural reactions, providing new mechanistic insights in protein science. Here we describe an alternative concept based on redox catalysis by P450-BM3, leading to the same Kemp product via a fundamentally different mechanism. QM/MM computations show that it involves coordination of the substrate's N-atom to haem-Fe(II) with electron transfer and concomitant N-O heterolysis liberating an intermediate having a nitrogen radical moiety Fe(III)-N. and a phenoxyl anion. Product formation occurs by bond rotation and H-transfer. Two rationally chosen point mutations cause a notable increase in activity. The results shed light on the prevailing mechanistic uncertainties in human P450-catalysed metabolism of the immunomodulatory drug leflunomide, which likewise undergoes redox-mediated Kemp elimination by P450-BM3. Other isoxazole-based pharmaceuticals are probably also metabolized by a redox mechanism. Our work provides a basis for designing future artificial enzymes.

  12. Endosomal Redox Signaling in the Antiphospholipid Syndrome.

    PubMed

    Lackner, Karl J; Manukyan, Davit; Müller-Calleja, Nadine

    2017-04-01

    It is well established that the antiphospholipid syndrome (APS) is caused by antiphospholipid antibodies (aPL). While several underlying mechanisms have been described in the past, many open questions remain. Here, we will review data on endosomal signaling and, in particular, redox signaling in APS. Endosomal redox signaling has been implicated in several cellular processes including signaling of proinflammatory cytokines. We have shown that certain aPL can activate endosomal NADPH-oxidase (NOX) in several cell types followed by induction of proinflammatory and procoagulant cellular responses in vitro. Involvement of endosomes in aPL signaling has also been reported by others. In wild-type mice but not in NOX-deficient mice, aPL accelerate venous thrombus formation underscoring the relevance of endosomal NOX. Furthermore, hydroxychloroquine (HCQ) inhibits activation of endosomal NOX and prevents thrombus formation in aPL-treated mice. Endosomal redox signaling is an important novel mechanism involved in APS pathogenesis. This makes endosomes a potential target for future treatment approaches of APS.

  13. Measurement of redox potential in nanoecotoxicological investigations.

    PubMed

    Tantra, Ratna; Cackett, Alex; Peck, Roger; Gohil, Dipak; Snowden, Jacqueline

    2012-01-01

    Redox potential has been identified by the Organisation for Economic Co-operation and Development (OECD) as one of the parameters that should be investigated for the testing of manufactured nanomaterials. There is still some ambiguity concerning this parameter, i.e., as to what and how to measure, particularly when in a nanoecotoxicological context. In this study the redox potentials of six nanomaterials (either zinc oxide (ZnO) or cerium oxide (CeO(2))) dispersions were measured using an oxidation-reduction potential (ORP) electrode probe. The particles under testing differed in terms of their particle size and dispersion stability in deionised water and in various ecotox media. The ORP values of the various dispersions and how they fluctuate relative to each other are discussed. Results show that the ORP values are mainly governed by the type of liquid media employed, with little contributions from the nanoparticles. Seawater was shown to have reduced the ORP value, which was attributed to an increase in the concentration of reducing agents such as sulphites or the reduction of dissolved oxygen concentration. The lack of redox potential value contribution from the particles themselves is thought to be due to insufficient interaction of the particles at the Pt electrode of the ORP probe.

  14. Measurement of Redox Potential in Nanoecotoxicological Investigations

    PubMed Central

    Tantra, Ratna; Cackett, Alex; Peck, Roger; Gohil, Dipak; Snowden, Jacqueline

    2012-01-01

    Redox potential has been identified by the Organisation for Economic Co-operation and Development (OECD) as one of the parameters that should be investigated for the testing of manufactured nanomaterials. There is still some ambiguity concerning this parameter, i.e., as to what and how to measure, particularly when in a nanoecotoxicological context. In this study the redox potentials of six nanomaterials (either zinc oxide (ZnO) or cerium oxide (CeO2)) dispersions were measured using an oxidation-reduction potential (ORP) electrode probe. The particles under testing differed in terms of their particle size and dispersion stability in deionised water and in various ecotox media. The ORP values of the various dispersions and how they fluctuate relative to each other are discussed. Results show that the ORP values are mainly governed by the type of liquid media employed, with little contributions from the nanoparticles. Seawater was shown to have reduced the ORP value, which was attributed to an increase in the concentration of reducing agents such as sulphites or the reduction of dissolved oxygen concentration. The lack of redox potential value contribution from the particles themselves is thought to be due to insufficient interaction of the particles at the Pt electrode of the ORP probe. PMID:22131988

  15. Tailoring partially reduced graphene oxide as redox mediator for enhanced biotransformation of iopromide under methanogenic and sulfate-reducing conditions.

    PubMed

    Toral-Sánchez, Eduardo; Rangel-Mendez, J Rene; Ascacio Valdés, Juan A; Aguilar, Cristóbal N; Cervantes, Francisco J

    2017-01-01

    This work reports the first successful application of graphene oxide (GO) and partially reduced GO (rGO) as redox mediator (RM) to increase the biotransformation of the recalcitrant iodinated contrast medium, iopromide (IOP). Results showed that GO-based materials promoted up to 5.5 and 2.8-fold faster biotransformation of IOP by anaerobic sludge under methanogenic and sulfate-reducing conditions, respectively. Correlation between the extent of reduction of GO and its redox-mediating capacity was demonstrated, which was reflected in faster removal and greater extent of biotransformation of IOP. Further analysis indicated that the biotransformation pathway of IOP involved multiple reactions including deiodination, decarboxylation, demethylation, dehydration and N-dealkylation. GO-based materials could be strategically tailored and integrated in biological treatment systems to effectively enhance the redox conversion of recalcitrant pollutants commonly found in wastewater treatment systems and industrial effluents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Trapped in the coordination sphere: Nitrate ion transfer driven by the cerium(III/IV) redox couple

    DOE PAGES

    Ellis, Ross J.; Bera, Mrinal K.; Reinhart, Benjamin; ...

    2016-11-07

    Redox-driven ion transfer between phases underpins many biological and technological processes, including industrial separation of ions. Here we investigate the electrochemical transfer of nitrate anions between oil and water phases, driven by the reduction and oxidation of cerium coordination complexes in oil phases. We find that the coordination environment around the cerium cation has a pronounced impact on the overall redox potential, particularly with regard to the number of coordinated nitrate anions. Our results suggest a new fundamental mechanism for tuning ion transfer between phases; by 'trapping' the migrating ion inside the coordination sphere of a redox-active complex. Here, thismore » presents a new route for controlling anion transfer in electrochemically-driven separation applications.« less

  17. Hypoxic Signaling and the Cellular Redox Tumor Environment Determine Sensitivity to MTH1 Inhibition.

    PubMed

    Bräutigam, Lars; Pudelko, Linda; Jemth, Ann-Sofie; Gad, Helge; Narwal, Mohit; Gustafsson, Robert; Karsten, Stella; Carreras Puigvert, Jordi; Homan, Evert; Berndt, Carsten; Berglund, Ulrika Warpman; Stenmark, Pål; Helleday, Thomas

    2016-04-15

    Cancer cells are commonly in a state of redox imbalance that drives their growth and survival. To compensate for oxidative stress induced by the tumor redox environment, cancer cells upregulate specific nononcogenic addiction enzymes, such as MTH1 (NUDT1), which detoxifies oxidized nucleotides. Here, we show that increasing oxidative stress in nonmalignant cells induced their sensitization to the effects of MTH1 inhibition, whereas decreasing oxidative pressure in cancer cells protected against inhibition. Furthermore, we purified zebrafish MTH1 and solved the crystal structure of MTH1 bound to its inhibitor, highlighting the zebrafish as a relevant tool to study MTH1 biology. Delivery of 8-oxo-dGTP and 2-OH-dATP to zebrafish embryos was highly toxic in the absence of MTH1 activity. Moreover, chemically or genetically mimicking activated hypoxia signaling in zebrafish revealed that pathologic upregulation of the HIF1α response, often observed in cancer and linked to poor prognosis, sensitized embryos to MTH1 inhibition. Using a transgenic zebrafish line, in which the cellular redox status can be monitored in vivo, we detected an increase in oxidative pressure upon activation of hypoxic signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine protected embryos with activated hypoxia signaling against MTH1 inhibition, suggesting that the aberrant redox environment likely causes sensitization. In summary, MTH1 inhibition may offer a general approach to treat cancers characterized by deregulated hypoxia signaling or redox imbalance. Cancer Res; 76(8); 2366-75. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Redox-mediated dissolution of paramagnetic nanolids to achieve a smart theranostic system.

    PubMed

    Wang, Aifei; Guo, Mingyi; Wang, Nan; Zhao, Jianyun; Qi, Wenxiu; Muhammad, Faheem; Chen, Liang; Guo, Yingjie; Nguyen, Nam-Trung; Zhu, Guangshan

    2014-05-21

    Manganese oxide (Mn3O4) nanoparticles have recently emerged as a promising T1 contrast agent. In this study, for the first time, we demonstrated an interaction of Mn3O4 with a biological system, and found redox sensitive behavior of these paramagnetic nanoparticles in intracellular reducing environment. Inspired by these findings, we for the first time used this interaction for some therapeutic advantages and designed a versatile mesoporous silica based nanotheranostic system to realize redox-activated enhanced magnetic resonance imaging and responsive anticancer drug delivery. Contrary to previous reports, we firstly prepared high quality amine terminated hydrophilic Mn3O4 nanolids, without using multistep ligand exchange strategies. The resulting water stable and small-sized Mn3O4 nanolids were subsequently used as nanolids to cap drug loaded nanochannels of a porous carrier. Exposure to highly prevalent intracellular reducing environment resulted in the steady-state dissolution of these nanolids and attained an intelligent drug release. Furthermore, the redox receptive dissolution of paramagnetic Mn3O4 nanolids into Mn(2+) in turn increases the T1 signal to twofold, providing an added opportunity to even track the feedback of therapy. This study, in addition to simultaneously realizing drug delivery and imaging, also provides a new insight into the fate and interaction of manganese oxide nanoparticles with components of biological systems.

  19. Celebrating Professor Britton Chance (1913-2010), a founding father of redox sciences.

    PubMed

    Ohnishi, Tomoko; Zweier, Jay L

    2011-12-01

    Renowned great scientist and redox pioneer, Dr. Britton Chance, closed his 97 years of legendary life on November 16, 2010. He was the Eldridge Reeves Johnson emeritus professor of biophysics, physical chemistry, and radiologic physics at the University of Pennsylvania. He achieved fame as a prominent biophysicist and developer of highly innovative biomedical instrumentation. His scientific career stretched over almost one century and he achieved many scientific and engineering breakthroughs throughout his long prolific career. The advances that he and his colleagues achieved led to great strides in our understanding of biology and disease. He was among the first scientists to recognize the importance of free radicals and reactive oxygen species in mitochondrial metabolism and cells as well as to map pathways of redox biology and signaling. Dr. Chance served as a pioneer and inspiration to generations of researchers in the fields of redox biochemistry, metabolism, and disease. He will be missed by all of us in the research community but will live on through his monumental scientific accomplishments, the novel instrumentation he developed, as well as the many scientists whom he trained and influenced.

  20. Organelle Redox of CF and CFTR-Corrected Airway Epithelia

    PubMed Central

    Schwarzer, Christian; Illek, Beate; Suh, Jung H.; Remington, S. James; Fischer, Horst; Machen, Terry E.

    2014-01-01

    In cystic fibrosis reduced CFTR function may alter redox properties of airway epithelial cells. Redox-sensitive GFP (roGFP1) and imaging microscopy were used to measure redox potentials of cytosol, ER, mitochondria and cell surface of cystic fibrosis nasal epithelial cells and CFTR-corrected cells. We also measured glutathione and cysteine thiol redox states in cell lysates and apical fluids to provide coverage over a range of redox potentials and environments that might be affected by CFTR. As measured with roGFP1, redox potentials at the cell surface (~ -207 ±8 mV) and in the ER (~ -217 ±1 mV) and rates of regulation of the apical fluid and ER lumen following DTT treatment were similar for CF and CFTR-corrected cells. CF and CFTR-corrected cells had similar redox potentials in mitochondria (-344 ±9 mV) and cytosol (-322 ±7 mV). Oxidation of carboxy-dichlorodihydrofluoresceindiacetate and of apical Amplex Red occurred at equal rates in CF and CFTR-corrected cells. Glutathione and cysteine redox couples in cell lysates and apical fluid were equal in CF and CFTR-corrected cells. These quantitative estimates of organelle redox potentials combined with apical and cell measurements using small molecule couples confirmed there were no differences in redox properties of CF and CFTR-corrected cells. PMID:17603939

  1. Surface Redox Chemistry of Immobilized Nanodiamond: Effects of Particle Size and Electrochemical Environment

    NASA Astrophysics Data System (ADS)

    Gupta, S.; McDonald, B.; Carrizosa, S. B.

    2017-07-01

    The size of the diamond particle is tailored to nanoscale (nanodiamond, ND), and the ND surface is engineered targeting specific (electrochemical and biological) applications. In this work, we investigated the complex surface redox chemistry of immobilized ND layer on conductive boron-doped diamond electrode with a broad experimental parameter space such as particle size (nano versus micron), scan rate, pH (cationic/acidic versus anionic/basic), electrolyte KCl concentration (four orders of magnitude), and redox agents (neutral and ionic). We reported on the significant enhancement of ionic currents while recording reversible oxidation of neutral ferrocene methanol (FcMeOH) by almost one order of magnitude than traditional potassium ferricyanide (K3Fe(CN)6) redox agent. The current enhancement is inversely related to ND particle diameter in the following order: 1 μm << 1000 nm < 100 nm < 10 nm ≤ 5 nm < 2 nm. We attribute the current enhancement to concurrent electrocatalytic processes, i.e. the electron transfer between redox probes and electroactive surface functional (e.g. hydroxyl, carboxyl, epoxy) moieties and the electron transfer mediated by adsorbed FcMeOH+ (or Fe(CN) 6 3+ ) ions onto ND surface. The first process is pH dependent since it depends upon ND surface functionalities for which the electron transfer is coupled to proton transfer. The adsorption mediated process is observed most apparently at slower scan rates owing to self-exchange between adsorbed FcMeOH+ ions and FcMeOH redox agent molecules in diffusion-limited bulk electrolyte solution. Alternatively, it is hypothesized that the surface functionality and defect sites ( sp 2-bonded C shell and unsaturated bonds) give rise to surface electronic states with energies within the band gap (midgap states) in undoped ND. These surface states serve as electron donors (and acceptors) depending upon their bonding (and antibonding) character and, therefore, they can support electrocatalytic redox

  2. An UV-vis spectroelectrochemical approach for rapid detection of phenazines and exploration of their redox characteristics.

    PubMed

    Chen, Wei; Liu, Xiao-Yang; Qian, Chen; Song, Xiang-Ning; Li, Wen-Wei; Yu, Han-Qing

    2015-02-15

    Phenazines are widely distributed in the environment and play an important role in various biological processes to facilitate microbial metabolism and electron transfer. In this work, an efficient and reliable spectroelectrochemical method is developed to quantitatively detect 1-hydroxyphenazine (1-OHPZ), a representative phenazine, and explore its redox characteristics. This approach is based on the sensitive absorption change of 1-OHPZ in response to its changes under redox state in rapid electrochemical reduction. The redox reaction of 1-OHPZ in aqueous solution is a proton-coupled electron transfer process, with a reversible one-step 2e(-)/2H(+) transfer reaction. This spectroelectrochemical approach exhibits good linear response covering two magnitudes to 1-OHPZ with a detection limit of 0.48µM, and is successfully applied to detect 1-OHPZ from a mixture of phenazines produced by Pseudomonas aeruginosa cultures. This method might also be applicable in exploring the abundance and redox processes of a wide range of other redox-active molecules in natural and engineered environments. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Neutral Red and Ferroin as Reversible and Rapid Redox Materials for Redox Flow Batteries.

    PubMed

    Hong, Jeehoon; Kim, Ketack

    2018-06-11

    Neutral red and ferroin are used as redox indicators (RINs) in potentiometric titrations. The rapid response and reversibility that are prerequisites for RINs are also desirable properties for the active materials in redox flow batteries (RFBs). This study describes the electrochemical properties of ferroin and neutral red as a redox pair. The rapid reaction rates of the RINs allow a cell to run at a rate of 4 C with 89 % capacity retention after the 100 th  cycle. The diffusion coefficients, electrode reaction rates, and solubilities of the RINs were determined. The electron-transfer rate constants of ferroin and neutral red are 0.11 and 0.027 cm s -1 , respectively, which are greater than those of the components of all-vanadium and Zn/Br 2 cells. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Computational design of molecules for an all-quinone redox flow battery.

    PubMed

    Er, Süleyman; Suh, Changwon; Marshak, Michael P; Aspuru-Guzik, Alán

    2015-02-01

    Inspired by the electron transfer properties of quinones in biological systems, we recently showed that quinones are also very promising electroactive materials for stationary energy storage applications. Due to the practically infinite chemical space of organic molecules, the discovery of additional quinones or other redox-active organic molecules for energy storage applications is an open field of inquiry. Here, we introduce a high-throughput computational screening approach that we applied to an accelerated study of a total of 1710 quinone (Q) and hydroquinone (QH 2 ) ( i.e. , two-electron two-proton) redox couples. We identified the promising candidates for both the negative and positive sides of organic-based aqueous flow batteries, thus enabling an all-quinone battery. To further aid the development of additional interesting electroactive small molecules we also provide emerging quantitative structure-property relationships.

  5. Reversible Stabilization of Vesicles: Redox-Responsive Polymer Nanocontainers for Intracellular Delivery.

    PubMed

    de Vries, Wilke C; Grill, David; Tesch, Matthias; Ricker, Andrea; Nüsse, Harald; Klingauf, Jürgen; Studer, Armido; Gerke, Volker; Ravoo, Bart Jan

    2017-08-01

    We present the self-assembly of redox-responsive polymer nanocontainers comprising a cyclodextrin vesicle core and a thin reductively cleavable polymer shell anchored via host-guest recognition on the vesicle surface. The nanocontainers are of uniform size, show high stability, and selectively respond to a mild reductive trigger as revealed by dynamic light scattering, transmission electron microscopy, atomic force microscopy, a quantitative thiol assay, and fluorescence spectroscopy. Live cell imaging experiments demonstrate a specific redox-responsive release and cytoplasmic delivery of encapsulated hydrophilic payloads, such as the pH-probe pyranine, and the fungal toxin phalloidin. Our results show the high potential of these stimulus-responsive nanocontainers for cell biological applications requiring a controlled delivery. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. In vivo ROS and redox potential fluorescent detection in plants: Present approaches and future perspectives.

    PubMed

    Ortega-Villasante, Cristina; Burén, Stefan; Barón-Sola, Ángel; Martínez, Flor; Hernández, Luis E

    2016-10-15

    Reactive oxygen species (ROS) are metabolic by-products in aerobic organisms including plants. Endogenously produced ROS act as cellular messengers and redox regulators involved in several plant biological processes, but excessive accumulation of ROS cause oxidative stress and cell damage. Understanding ROS signalling and stress responses requires precise imaging and quantification of local, subcellular and global ROS dynamics with high selectivity, sensitivity, and spatiotemporal resolution. Several fluorescent vital dyes have been tested so far, which helped to provide relevant spatially resolved information of oxidative stress dynamics in plants subjected to harmful environmental conditions. However, certain plant characteristics, such as high background fluorescence of plant tissues in vivo and antioxidant mechanisms, can interfere with ROS detection. The development of improved small-molecule fluorescent dyes and protein-based ROS sensors targeted to subcellular compartments will enable in vivo monitoring of ROS and redox changes in photosynthetic organisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Redox-Active vs Redox-Innocent: A Comparison of Uranium Complexes Containing Diamine Ligands.

    PubMed

    Pattenaude, Scott A; Mullane, Kimberly C; Schelter, Eric J; Ferrier, Maryline G; Stein, Benjamin W; Bone, Sharon E; Lezama Pacheco, Juan S; Kozimor, Stosh A; Fanwick, Phillip E; Zeller, Matthias; Bart, Suzanne C

    2018-05-11

    Uranium complexes ( Mes DAE) 2 U(THF) (1-DAE) and Cp 2 U( Mes DAE) (2-DAE) ( Mes DAE = [ArN-CH 2 CH 2 -NAr]; Ar = 2,4,6-trimethylphenyl (Mes)), bearing redox-innocent diamide ligands, have been synthesized and characterized for a full comparison with previously published, redox-active diimine complexes, ( Mes DAB Me ) 2 U(THF) (1-DAB) and Cp 2 U( Mes DAB Me ) (2-DAB) ( Mes DAB Me = [ArN═C(Me)C(Me)═NAr]; Ar = Mes). These redox-innocent analogues maintain an analogous steric environment to their redox-active ligand counterparts to facilitate a study aimed at determining the differing electronic behavior around the uranium center. Structural analysis by X-ray crystallography showed 1-DAE and 2-DAE have a structural environment very similar to 1-DAB and 2-DAB, respectively. The main difference occurs with coordination of the ene-backbone to the uranium center in the latter species. Electronic absorption spectroscopy reveals these new DAE complexes are nearly identical to each other. X-ray absorption spectroscopy suggests all four species contain +4 uranium ions. The data also indicates that there is an electronic difference between the bis(diamide)-THF uranium complexes as opposed to those that only contain one diamide and two cyclopentadienyl rings. Finally, magnetic measurements reveal that all complexes display temperature-dependent behavior consistent with uranium(IV) ions that do not include ligand radicals. Overall, this study determines that there is no significant bonding difference between the redox-innocent and redox-active ligand frameworks on uranium. Furthermore, there are no data to suggest covalent bonding character using the latter ligand framework on uranium, despite what is known for transition metals.

  8. Redox properties of structural Fe in clay minerals: 3. Relationships between smectite redox and structural properties.

    PubMed

    Gorski, Christopher A; Klüpfel, Laura E; Voegelin, Andreas; Sander, Michael; Hofstetter, Thomas B

    2013-01-01

    Structural Fe in clay minerals is an important redox-active species in many pristine and contaminated environments as well as in engineered systems. Understanding the extent and kinetics of redox reactions involving Fe-bearing clay minerals has been challenging due to the inability to relate structural Fe(2+)/Fe(total) fractions to fundamental redox properties, such as reduction potentials (EH). Here, we overcame this challenge by using mediated electrochemical reduction (MER) and oxidation (MEO) to characterize the fraction of redox-active structural Fe (Fe(2+)/Fe(total)) in smectites over a wide range of applied EH-values (-0.6 V to +0.6 V). We examined Fe(2+)/Fe(total )- EH relationships of four natural Fe-bearing smectites (SWy-2, SWa-1, NAu-1, NAu-2) in their native, reduced, and reoxidized states and compared our measurements with spectroscopic observations and a suite of mineralogical properties. All smectites exhibited unique Fe(2+)/Fe(total) - EH relationships, were redox active over wide EH ranges, and underwent irreversible electron transfer induced structural changes that were observable with X-ray absorption spectroscopy. Variations among the smectite Fe(2+)/Fe(total) - EH relationships correlated well with both bulk and molecular-scale properties, including Fe(total) content, layer charge, and quadrupole splitting values, suggesting that multiple structural parameters determined the redox properties of smectites. The Fe(2+)/Fe(total) - EH relationships developed for these four commonly studied clay minerals may be applied to future studies interested in relating the extent of structural Fe reduction or oxidation to EH-values.

  9. Nanostructured Electrocatalysts for All-Vanadium Redox Flow Batteries.

    PubMed

    Park, Minjoon; Ryu, Jaechan; Cho, Jaephil

    2015-10-01

    Vanadium redox reactions have been considered as a key factor affecting the energy efficiency of the all-vanadium redox flow batteries (VRFBs). This redox reaction determines the reaction kinetics of whole cells. However, poor kinetic reversibility and catalytic activity towards the V(2+)/V(3+) and VO(2+)/VO2(+) redox couples on the commonly used carbon substrate limit broader applications of VRFBs. Consequently, modified carbon substrates have been extensively investigated to improve vanadium redox reactions. In this Focus Review, recent progress on metal- and carbon-based nanomaterials as an electrocatalyst for VRFBs is discussed in detail, without the intention to provide a comprehensive review on the whole components of the system. Instead, the focus is mainly placed on the redox chemistry of vanadium ions at a surface of various metals, different dimensional carbons, nitrogen-doped carbon nanostructures, and metal-carbon composites. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

    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

  11. Sepiapterin Reductase Mediates Chemical Redox Cycling in Lung Epithelial Cells*

    PubMed Central

    Yang, Shaojun; Jan, Yi-Hua; Gray, Joshua P.; Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2013-01-01

    In the lung, chemical redox cycling generates highly toxic reactive oxygen species that can cause alveolar inflammation and damage to the epithelium, as well as fibrosis. In this study, we identified a cytosolic NADPH-dependent redox cycling activity in mouse lung epithelial cells as sepiapterin reductase (SPR), an enzyme important for the biosynthesis of tetrahydrobiopterin. Human SPR was cloned and characterized. In addition to reducing sepiapterin, SPR mediated chemical redox cycling of bipyridinium herbicides and various quinones; this activity was greatest for 1,2-naphthoquinone followed by 9,10-phenanthrenequinone, 1,4-naphthoquinone, menadione, and 2,3-dimethyl-1,4-naphthoquinone. Whereas redox cycling chemicals inhibited sepiapterin reduction, sepiapterin had no effect on redox cycling. Additionally, inhibitors such as dicoumarol, N-acetylserotonin, and indomethacin blocked sepiapterin reduction, with no effect on redox cycling. Non-redox cycling quinones, including benzoquinone and phenylquinone, were competitive inhibitors of sepiapterin reduction but noncompetitive redox cycling inhibitors. Site-directed mutagenesis of the SPR C-terminal substrate-binding site (D257H) completely inhibited sepiapterin reduction but had minimal effects on redox cycling. These data indicate that SPR-mediated reduction of sepiapterin and redox cycling occur by distinct mechanisms. The identification of SPR as a key enzyme mediating chemical redox cycling suggests that it may be important in generating cytotoxic reactive oxygen species in the lung. This activity, together with inhibition of sepiapterin reduction by redox-active chemicals and consequent deficiencies in tetrahydrobiopterin, may contribute to tissue injury. PMID:23640889

  12. Involvement of Redox State in the Aging of Drosophila melanogaster

    PubMed Central

    Radyuk, Svetlana N.; Sohal, Rajindar S.

    2013-01-01

    Abstract Significance: The main objective of this review was to provide an exposition of investigations, conducted in Drosophila melanogaster, on the role of reactive oxygen species and redox state in the aging process. While early transgenic studies did not clearly support the validity of the oxidative stress hypothesis of aging, predicated on the accumulation of structural damage, they spawned a broader search for redox-related effects that might impact the aging process. Recent Advances: Initial evidence implicating the thiol redox state as a possible causative factor in aging has been obtained in Drosophila. Overexpression of genes, such as GCL, G6PD, Prx2, and Prx5, which are involved in the maintenance of thiol redox homeostasis, has strong positive effects on longevity. Further, the depletion of peroxiredoxin activity in the mitochondria through the double knockdown of Prx5 and Prx3 not only results in a redox crisis but also elicits a rapid aging phenotype. Critical Issues: Herein, we summarize the present status of knowledge about the main components of the machinery controlling thiol redox homeostasis and describe how age-related redox fluctuations might impact aging more acutely through disruption of the redox-sensitive signaling mechanisms rather than via the simple accumulation of structural damage. Future Directions: Based on these initial insights into the plausible impact of redox fluctuations on redox signaling, future studies should focus on the pathways that have been explicitly implicated in aging, such as insulin signaling, TOR, and JNK/FOXO, with particular attention to elements that are redox sensitive. Antioxid. Redox Signal. 19, 788–803. PMID:23458359

  13. Redox homeostasis: The Golden Mean of healthy living

    PubMed Central

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

    2016-01-01

    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

  14. Redox active polymers and colloidal particles for flow batteries

    SciTech Connect

    Gavvalapalli, Nagarjuna; Moore, Jeffrey S.; Rodriguez-Lopez, Joaquin

    The invention provides a redox flow battery comprising a microporous or nanoporous size-exclusion membrane, wherein one cell of the battery contains a redox-active polymer dissolved in the non-aqueous solvent or a redox-active colloidal particle dispersed in the non-aqueous solvent. The redox flow battery provides enhanced ionic conductivity across the electrolyte separator and reduced redox-active species crossover, thereby improving the performance and enabling widespread utilization. Redox active poly(vinylbenzyl ethylviologen) (RAPs) and redox active colloidal particles (RACs) were prepared and were found to be highly effective redox species. Controlled potential bulk electrolysis indicates that 94-99% of the nominal charge on different RAPsmore » is accessible and the electrolysis products are stable upon cycling. The high concentration attainable (>2.0 M) for RAPs in common non-aqueous battery solvents, their electrochemical and chemical reversibility, and their hindered transport across porous separators make them attractive materials for non-aqueous redox flow batteries based on size-selectivity.« less

  15. Biogeochemical redox processes and their impact on contaminant dynamics

    USGS Publications Warehouse

    Borch, Thomas; Kretzschmar, Ruben; Kappler, Andreas; Van Cappellen, Philippe; Ginder-Vogel, Matthew; Campbell, Kate M.

    2010-01-01

    Life and element cycling on Earth is directly related to electron transfer (or redox) reactions. An understanding of biogeochemical redox processes is crucial for predicting and protecting environmental health and can provide new opportunities for engineered remediation strategies. Energy can be released and stored by means of redox reactions via the oxidation of labile organic carbon or inorganic compounds (electron donors) by microorganisms coupled to the reduction of electron acceptors including humic substances, iron-bearing minerals, transition metals, metalloids, and actinides. Environmental redox processes play key roles in the formation and dissolution of mineral phases. Redox cycling of naturally occurring trace elements and their host minerals often controls the release or sequestration of inorganic contaminants. Redox processes control the chemical speciation, bioavailability, toxicity, and mobility of many major and trace elements including Fe, Mn, C, P, N, S, Cr, Cu, Co, As, Sb, Se, Hg, Tc, and U. Redox-active humic substances and mineral surfaces can catalyze the redox transformation and degradation of organic contaminants. In this review article, we highlight recent advances in our understanding of biogeochemical redox processes and their impact on contaminant fate and transport, including future research needs.

  16. Redox Signaling and Persistent Pulmonary Hypertension of the Newborn.

    PubMed

    Sharma, Megha; Afolayan, Adeleye J

    2017-01-01

    Reactive oxygen species (ROS) are redox-signaling molecules that are critically involved in regulating endothelial cell functions, host defense, aging, and cellular adaptation. Mitochondria are the major sources of ROS and important sources of redox signaling in pulmonary circulation. It is becoming increasingly evident that increased mitochondrial oxidative stress and aberrant signaling through redox-sensitive pathways play a direct causative role in the pathogenesis of many cardiopulmonary disorders including persistent pulmonary hypertension of the newborn (PPHN). This chapter highlights redox signaling in endothelial cells, antioxidant defense mechanism, cell responses to oxidative stress, and their contributions to disease pathogenesis.

  17. Redox Pioneer: Professor Stuart A. Lipton

    PubMed Central

    2013-01-01

    Abstract Professor Stuart A. Lipton Stuart A. Lipton, M.D., Ph.D. is recognized here as a Redox Pioneer because of his publication of four articles that have been cited more than 1000 times, and 96 reports which have been cited more than 100 times. In the redox field, Dr. Lipton is best known for his work on the regulation by S-nitrosylation of the NMDA-subtype of neuronal glutamate receptor, which provided early evidence for in situ regulation of protein activity by S-nitrosylation and a prototypic model of allosteric control by this post-translational modification. Over the past several years, Lipton's group has pioneered the discovery of aberrant protein nitrosylation that may contribute to a number of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (Lou Gehrig's disease). In particular, the phenotypic effects of rare genetic mutations may be understood to be enhanced or mimicked by nitrosative (and oxidative) modifications of cysteines and thereby help explain common sporadic forms of disease. Thus, Lipton has contributed in a major way to the understanding that nitrosative stress may result from modifications of specific proteins and may operate in conjunction with genetic mutation to create disease phenotype. Lipton (collaborating with Jonathan S. Stamler) has also employed the concept of targeted S-nitrosylation to produce novel neuroprotective drugs that act at allosteric sites in the NMDA receptor. Lipton has won a number of awards, including the Ernst Jung Prize in Medicine, and is an elected fellow of the AAAS. Antioxid. Redox Signal. 19, 757–764. PMID:23815466

  18. Redox-mediated quorum sensing in plants.

    PubMed

    Fuller, Alexandra W; Young, Phoebe; Pierce, B Daniel; Kitson-Finuff, Jamie; Jain, Purvi; Schneider, Karl; Lazar, Stephen; Taran, Olga; Palmer, Andrew G; Lynn, David G

    2017-01-01

    The rhizosphere, the narrow zone of soil around plant roots, is a complex network of interactions between plants, bacteria, and a variety of other organisms. The absolute dependence on host-derived signals, or xenognosins, to regulate critical developmental checkpoints for host commitment in the obligate parasitic plants provides a window into the rhizosphere's chemical dynamics. These sessile intruders use H2O2 in a process known as semagenesis to chemically modify the mature root surfaces of proximal host plants and generate p-benzoquinones (BQs). The resulting redox-active signaling network regulates the spatial and temporal commitments necessary for host attachment. Recent evidence from non-parasites, including Arabidopsis thaliana, establishes that reactive oxygen species (ROS) production regulates similar redox circuits related to root recognition, broadening xenognosins' role beyond the parasites. Here we compare responses to the xenognosin dimethoxybenzoquinone (DMBQ) between the parasitic plant Striga asiatica and the non-parasitic A. thaliana. Exposure to DMBQ simulates the proximity of a mature root surface, stimulating an increase in cytoplasmic Ca2+ concentration in both plants, but leads to remarkably different phenotypic responses in the parasite and non-parasite. In S. asiatica, DMBQ induces development of the host attachment organ, the haustorium, and decreases ROS production at the root tip, while in A. thaliana, ROS production increases and further growth of the root tip is arrested. Obstruction of Ca2+ channels and the addition of antioxidants both lead to a decrease in the DMBQ response in both parasitic and non-parasitic plants. These results are consistent with Ca2+ regulating the activity of NADPH oxidases, which in turn sustain the autocatalytic production of ROS via an external quinone/hydroquinone redox cycle. Mechanistically, this chemistry is similar to black and white photography with the emerging dynamic reaction-diffusion network

  19. Chiral Redox-Active Isosceles Triangles

    DOE PAGES

    Nalluri, Siva Krishna Mohan; Liu, Zhichang; Wu, Yilei; ...

    2016-04-12

    Designing small-molecule organic redox-active materials, with potential applications in energy storage, has received considerable interest of late. Herein, we report on the synthesis, characterization, and application of two rigid chiral triangles, each of which consist of non-identical pyromellitic diimide (PMDI) and naphthalene diimide (NDI)-based redox-active units. 1H and 13C NMR spectroscopic investigations in solution confirm the lower symmetry (C2 point group) associated with these two isosceles triangles. Single-crystal X-ray diffraction analyses reveal their rigid triangular prism-like geometries. Unlike previously investigated equilateral triangle containing three identical NDI subunits, both isosceles triangles do not choose to form one-dimensional supramolecular nanotubes by dintmore » of [C–H···O] interaction-driven columnar stacking. The rigid isosceles triangle, composed of one NDI and two PMDI subunits, forms—in the presence of N,N-dimethylformamide—two different types of intermolecular NDI–NDI and NDI–PMDI π–π stacked dimers with opposite helicities in the solid state. Cyclic voltammetry reveals that both isosceles triangles can accept reversibly up to six electrons. Continuous-wave electron paramagnetic resonance and electron–nuclear double-resonance spectroscopic investigations, supported by density functional theory calculations, on the single-electron reduced radical anions of the isosceles triangles confirm the selective sharing of unpaired electrons among adjacent redox-active NDI subunit(s) within both molecules. The isosceles triangles have been employed as electrode-active materials in organic rechargeable lithium-ion batteries. The evaluation of the structure–performance relationships of this series of diimide-based triangles reveals that the increase in the number of NDI subunits, replacing PMDI ones, within the molecules improves the electrochemical cell performance of the batteries.« less

  20. Redox-iodometry: a new potentiometric method.

    PubMed

    Gottardi, Waldemar; Pfleiderer, Jörg

    2005-07-01

    A new iodometric method for quantifying aqueous solutions of iodide-oxidizing and iodine-reducing substances, as well as plain iodine/iodide solutions, is presented. It is based on the redox potential of said solutions after reaction with iodide (or iodine) of known initial concentration. Calibration of the system and calculations of unknown concentrations was performed on the basis of developed algorithms and simple GWBASIC-programs. The method is distinguished by a short analysis time (2-3 min) and a simple instrumentation consisting of pH/mV meter, platinum and reference electrodes. In general the feasible concentration range encompasses 0.1 to 10(-6) mol/L, although it goes down to 10(-8) mol/L (0.001 mg Cl2/L) for oxidants like active chlorine compounds. The calculated imprecision and inaccuracy of the method were found to be 0.4-0.9% and 0.3-0.8%, respectively, resulting in a total error of 0.5-1.2%. Based on the experiments, average imprecisions of 1.0-1.5% at c(Ox)>10(-5) M, 1.5-3% at 10(-5) to 10(-7) M, and 4-7% at <10(-7) M were found. Redox-iodometry is a simple, precise, and time-saving substitute for the more laborious and expensive iodometric titration method, which, like other well-established colorimetric procedures, is clearly outbalanced at low concentrations; this underlines the practical importance of redox-iodometry.

  1. Performance Mapping Studies in Redox Flow Cells

    NASA Technical Reports Server (NTRS)

    Hoberecht, M. A.; Thaller, L. H.

    1981-01-01

    Pumping power requirements in any flow battery system constitute a direct parasitic energy loss. It is therefore useful to determine the practical lower limit for reactant flow rates. Through the use of a theoretical framework based on electrochemical first principles, two different experimental flow mapping techniques were developed to evaluate and compare electrodes as a function of flow rate. For the carbon felt electrodes presently used in NASA-Lewis Redox cells, a flow rate 1.5 times greater than the stoichiometric rate seems to be the required minimum.

  2. Electronic Tongue Containing Redox and Conductivity Sensors

    NASA Technical Reports Server (NTRS)

    Buehler, Martin

    2007-01-01

    The Electronic Tongue (E-tongue 2) is an assembly of sensors for measuring concentrations of metal ions and possibly other contaminants in water. Potential uses for electronic tongues include monitoring the chemical quality of water in a variety of natural, industrial, and laboratory settings, and detecting micro-organisms indirectly by measuring microbially influenced corrosion. The device includes a heater, a temperature sensor, an oxidation/reduction (redox) sensor pair, an electrical sensor, an array of eight galvanic cells, and eight ion-specific electrodes.

  3. Rebalancing electrolytes in redox flow battery systems

    DOEpatents

    Chang, On Kok; Pham, Ai Quoc

    2014-12-23

    Embodiments of redox flow battery rebalancing systems include a system for reacting an unbalanced flow battery electrolyte with a rebalance electrolyte in a first reaction cell. In some embodiments, the rebalance electrolyte may contain ferrous iron (Fe.sup.2+) which may be oxidized to ferric iron (Fe.sup.3+) in the first reaction cell. The reducing ability of the rebalance reactant may be restored in a second rebalance cell that is configured to reduce the ferric iron in the rebalance electrolyte back into ferrous iron through a reaction with metallic iron.

  4. Redox shuttles for lithium ion batteries

    DOEpatents

    Weng, Wei; Zhang, Zhengcheng; Amine, Khalil

    2014-11-04

    Compounds may have general Formula IVA or IVB. ##STR00001## where, R.sup.8, R.sup.9, R.sup.10, and R.sup.11 are each independently selected from H, F, Cl, Br, CN, NO.sub.2, alkyl, haloalkyl, and alkoxy groups; X and Y are each independently O, S, N, or P; and Z' is a linkage between X and Y. Such compounds may be used as redox shuttles in electrolytes for use in electrochemical cells, batteries and electronic devices.

  5. Fe-V redox flow batteries

    DOEpatents

    Li, Liyu; Kim, Soowhan; Yang, Zhenguo; Wang, Wei; Zhang, Jianlu; Chen, Baowei; Nie, Zimin; Xia, Guanguang

    2014-07-08

    A redox flow battery having a supporting solution that includes Cl.sup.- anions is characterized by an anolyte having V.sup.2+ and V.sup.3+ in the supporting solution, a catholyte having Fe.sup.2+ and Fe.sup.3+ in the supporting solution, and a membrane separating the anolyte and the catholyte. The anolyte and catholyte can have V cations and Fe cations, respectively, or the anolyte and catholyte can each contain both V and Fe cations in a mixture. Furthermore, the supporting solution can contain a mixture of SO.sub.4.sup.2- and Cl.sup.- anions.

  6. Aqueous electrolytes for redox flow battery systems

    SciTech Connect

    Liu, Tianbiao; Li, Bin; Wei, Xiaoliang

    An aqueous redox flow battery system includes an aqueous catholyte and an aqueous anolyte. The aqueous catholyte may comprise (i) an optionally substituted thiourea or a nitroxyl radical compound and (ii) a catholyte aqueous supporting solution. The aqueous anolyte may comprise (i) metal cations or a viologen compound and (ii) an anolyte aqueous supporting solution. The catholyte aqueous supporting solution and the anolyte aqueous supporting solution independently may comprise (i) a proton source, (ii) a halide source, or (iii) a proton source and a halide source.

  7. Redox polymer mediation for enzymatic biofuel cells

    NASA Astrophysics Data System (ADS)

    Gallaway, Joshua

    Mediated biocatalytic cathodes prepared from the oxygen-reducing enzyme laccase and redox-conducting osmium hydrogels were characterized for use as cathodes in enzymatic biofuel cells. A series of osmium-based redox polymers was synthesized with redox potentials spanning the range from 0.11 V to 0.85 V (SHE), and the resulting biocatalytic electrodes were modeled to determine reaction kinetic constants using the current response, measured osmium concentration, and measured apparent electron diffusion. As in solution-phase systems, the bimolecular rate constant for mediation was found to vary greatly with mediator potential---from 250 s-1M-1 when mediator and enzyme were close in potential to 9.4 x 10 4 s-1M-1 when this overpotential was large. Optimum mediator potential for a cell operating with a non-limiting platinum anode and having no mass transport limitation from bulk solution was found to be 0.66 V (SHE). Redox polymers were synthesized under different concentrations, producing osmium variation. An increase from 6.6% to 7.2% osmium increased current response from 1.2 to 2.1 mA/cm2 for a planar film in 40°C oxygen-saturated pH 4 buffer, rotating at 900 rpm. These results translated to high surface area electrodes, nearly doubling current density to 13 mA/cm2, the highest to date for such an electrode. The typical fungal laccase from Trametes versicolor was replaced by a bacterially-expressed small laccase from Streptomyces coelicolor, resulting in biocatalytic films that reduced oxygen at increased pH, with full functionality at pH 7, producing 1.5 mA/cm 2 in planar configuration. Current response was biphasic with pH, matching the activity profile of the free enzyme in solution. The mediated enzyme electrode system was modeled with respect to apparent electron diffusion, mediator concentration, and transport of oxygen from bulk solution, all of which are to some extent controlled by design. Each factor was found to limit performance in certain circumstances

  8. Redox regulation of mammalian sperm capacitation

    PubMed Central

    O’Flaherty, Cristian

    2015-01-01

    Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS) that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P) H for sperm capacitation. Peroxiredoxins (PRDXs) are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility. PMID:25926608

  9. Redox interventions to increase exercise performance

    PubMed Central

    2015-01-01

    Abstract Skeletal muscle continually produces reactive oxygen species (ROS) and nitric oxide (NO) derivatives. Both oxidant cascades have complex effects on muscle contraction, metabolic function and tissue perfusion. Strenuous exercise increases oxidant production by muscle, limiting performance during endurance exercise tasks. Conversely, redox interventions that modulate ROS or NO activity have the potential to improve performance. Antioxidants have long been known to buffer ROS activity and lessen oxidative perturbations during exercise. The capacity to enhance human performance varies among antioxidant categories. Vitamins, provitamins and nutriceuticals often blunt oxidative changes at the biochemical level but do not enhance performance. In contrast, reduced thiol donors have been shown to delay fatigue or increase endurance under a variety of experimental conditions. Dietary nitrate supplementation has recently emerged as a second redox strategy for increasing endurance. Purified nitrate salts and nitrate‐rich foods, notably beetroot and beetroot juice, are reported to lessen the oxygen cost of exercise, increase efficiency, and enhance performance during endurance tasks. These findings are exciting but enigmatic since nitrate per se has little bioactivity and cannot be converted to NO by mammalian cells. Overall, the available data suggest exercise endurance can be augmented by redox‐active supplements, either reduced thiol donors or dietary nitrates. These findings have clear implications for athletes seeking a competitive edge. More importantly, interventions that increase endurance may benefit individuals whose physical activity is limited by illness, ageing, or frailty. PMID:26584644

  10. Redox driven conductance changes for resistive memory

    NASA Astrophysics Data System (ADS)

    Shoute, Lian C. T.; Pekas, Nikola; Wu, Yiliang; McCreery, Richard L.

    2011-03-01

    The relationship between bias-induced redox reactions and resistance switching is considered for memory devices containing TiO2 or a conducting polymer in "molecular heterojunctions" consisting of thin (2-25 nm) films of covalently bonded molecules, polymers, and oxides. Raman spectroscopy was used to monitor changes in the oxidation state of polythiophene in Au/P3HT/SiO2/Au devices, and it was possible to directly determine the formation and stability of the conducting polaron state of P3HT by applied bias pulses [P3HT = poly(3-hexyl thiophene)]. Polaron formation was strongly dependent on junction composition, particularly on the interfaces between the polymer, oxide, and electrodes. In all cases, trace water was required for polaron formation, leading to the proposal that water reduction acts as a redox counter-reaction to polymer oxidation. Polaron stability was longest for the case of a direct contact between Au and SiO2, implying that catalytic water reduction at the Au surface generated hydroxide ions which stabilized the cationic polaron. The spectroscopic information about the dependence of polaron stability on device composition will be useful for designing and monitoring resistive switching memory based on conducting polymers, with or without TiO2 present.

  11. Copper redox chemistry of plant frataxins.

    PubMed

    Sánchez, Manu; Palacios, Òscar; Buchensky, Celeste; Sabio, Laura; Gomez-Casati, Diego Fabian; Pagani, Maria Ayelen; Capdevila, Mercè; Atrian, Silvia; Dominguez-Vera, Jose M

    2018-03-01

    The presence of a conserved cysteine residue in the C-terminal amino acid sequences of plant frataxins differentiates these frataxins from those of other kingdoms and may be key in frataxin assembly and function. We report a full study on the ability of Arabidopsis (AtFH) and Zea mays (ZmFH-1 and ZmFH-2) frataxins to assemble into disulfide-bridged dimers by copper-driven oxidation and to revert to monomers by chemical reduction. We monitored the redox assembly-disassembly process by electrospray ionization mass spectrometry, electrophoresis, UV-Vis spectroscopy, and fluorescence measurements. We conclude that plant frataxins AtFH, ZmFH-1 and ZmFH-2 are oxidized by Cu 2+ and exhibit redox cysteine monomer - cystine dimer interexchange. Interestingly, the tendency to interconvert is not the same for each protein. Through yeast phenotypic rescue experiments, we show that plant frataxins are important for plant survival under conditions of excess copper, indicating that these proteins might be involved in copper metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Mitochondrial Redox Dysfunction and Environmental Exposures

    PubMed Central

    Caito, Samuel W.

    2015-01-01

    Abstract Significance: Mitochondria are structurally and biochemically diverse, even within a single type of cell. Protein complexes localized to the inner mitochondrial membrane synthesize ATP by coupling electron transport and oxidative phosphorylation. The organelles produce reactive oxygen species (ROS) from mitochondrial oxygen and ROS can, in turn, alter the function and expression of proteins used for aerobic respiration by post-translational and transcriptional regulation. Recent Advances: New interest is emerging not only into the roles of mitochondria in disease development and progression but also as a target for environmental toxicants. Critical Issues: Dysregulation of respiration has been linked to cell death and is a major contributor to acute neuronal trauma, peripheral diseases, as well as chronic neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Future Directions: Here, we discuss the mechanisms underlying the sensitivity of the mitochondrial respiratory complexes to redox modulation, as well as examine the effects of environmental contaminants that have well-characterized mitochondrial toxicity. The contaminants discussed in this review are some of the most prevalent and potent environmental contaminants that have been linked to neurological dysfunction, altered cellular respiration, and oxidation. Antioxid. Redox Signal. 23, 578–595. PMID:25826672

  13. Fluorescent in vivo imaging of reactive oxygen species and redox potential in plants.

    PubMed

    Ortega-Villasante, Cristina; Burén, Stefan; Blázquez-Castro, Alfonso; Barón-Sola, Ángel; Hernández, Luis E

    2018-04-05

    Reactive oxygen species (ROS) are by-products of aerobic metabolism, and excessive production can result in oxidative stress and cell damage. In addition, ROS function as cellular messengers, working as redox regulators in a multitude of biological processes. Understanding ROS signalling and stress responses requires methods for precise imaging and quantification to monitor local, subcellular and global ROS dynamics with high selectivity, sensitivity and spatiotemporal resolution. In this review, we summarize the present knowledge for in vivo plant ROS imaging and detection, using both chemical probes and fluorescent protein-based biosensors. Certain characteristics of plant tissues, for example high background autofluorescence in photosynthetic organs and the multitude of endogenous antioxidants, can interfere with ROS and redox potential detection, making imaging extra challenging. Novel methods and techniques to measure in vivo plant ROS and redox changes with better selectivity, accuracy, and spatiotemporal resolution are therefore desirable to fully acknowledge the remarkably complex plant ROS signalling networks. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Recapitulating the Structural Evolution of Redox Regulation in Adenosine 5'-Phosphosulfate Kinase from Cyanobacteria to Plants.

    PubMed

    Herrmann, Jonathan; Nathin, David; Lee, Soon Goo; Sun, Tony; Jez, Joseph M

    2015-10-09

    In plants, adenosine 5'-phosphosulfate (APS) kinase (APSK) is required for reproductive viability and the production of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a sulfur donor in specialized metabolism. Previous studies of the APSK from Arabidopsis thaliana (AtAPSK) identified a regulatory disulfide bond formed between the N-terminal domain (NTD) and a cysteine on the core scaffold. This thiol switch is unique to mosses, gymnosperms, and angiosperms. To understand the structural evolution of redox control of APSK, we investigated the redox-insensitive APSK from the cyanobacterium Synechocystis sp. PCC 6803 (SynAPSK). Crystallographic analysis of SynAPSK in complex with either APS and a non-hydrolyzable ATP analog or APS and sulfate revealed the overall structure of the enzyme, which lacks the NTD found in homologs from mosses and plants. A series of engineered SynAPSK variants reconstructed the structural evolution of the plant APSK. Biochemical analyses of SynAPSK, SynAPSK H23C mutant, SynAPSK fused to the AtAPSK NTD, and the fusion protein with the H23C mutation showed that the addition of the NTD and cysteines recapitulated thiol-based regulation. These results reveal the molecular basis for structural changes leading to the evolution of redox control of APSK in the green lineage from cyanobacteria to plants. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Inhibition of Ape1 Redox Activity Promotes Odonto/osteogenic Differentiation of Dental Papilla Cells.

    PubMed

    Chen, Tian; Liu, Zhi; Sun, Wenhua; Li, Jingyu; Liang, Yan; Yang, Xianrui; Xu, Yang; Yu, Mei; Tian, Weidong; Chen, Guoqing; Bai, Ding

    2015-12-07

    Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth, and this process is performed by odontoblasts. Dental papilla cells (DPCs), as the progenitor cells of odontoblasts, undergo the odontogenic differentiation regulated by multiple cytokines and paracrine signal molecules. Ape1 is a perfect paradigm of the function complexity of a biological macromolecule with two major functional regions for DNA repair and redox regulation, respectively. To date, it remains unclear whether Ape1 can regulate the dentinogenesis in DPCs. In the present study, we firstly examed the spatio-temporal expression of Ape1 during tooth germ developmental process, and found the Ape1 expression was initially high and then gradually reduced along with the tooth development. Secondly, the osteo/odontogenic differentiation capacity of DPCs was up-regulated when treated with either Ape1-shRNA or E3330 (a specific inhibitor of the Ape1 redox function), respectively. Moreover, we found that the canonical Wnt signaling pathway was activated in this process, and E3330 reinforced-osteo/odontogenic differentiation capacity was suppressed by Dickkopf1 (DKK1), a potent antagonist of canonical Wnt signaling pathway. Taken together, we for the first time showed that inhibition of Ape1 redox regulation could promote the osteo/odontogenic differentiation capacity of DPCs via canonical Wnt signaling pathway.

  16. Redox Stimulation of Human THP-1 Monocytes in Response to Cold Physical Plasma.

    PubMed

    Bekeschus, Sander; Schmidt, Anke; Bethge, Lydia; Masur, Kai; von Woedtke, Thomas; Hasse, Sybille; Wende, Kristian

    2016-01-01

    In plasma medicine, cold physical plasma delivers a delicate mixture of reactive components to cells and tissues. Recent studies suggested a beneficial role of cold plasma in wound healing. Yet, the biological processes related to the redox modulation via plasma are not fully understood. We here used the monocytic cell line THP-1 as a model to test their response to cold plasma in vitro. Intriguingly, short term plasma treatment stimulated cell growth. Longer exposure only modestly compromised cell viability but apparently supported the growth of cells that were enlarged in size and that showed enhanced metabolic activity. A significantly increased mitochondrial content in plasma treated cells supported this notion. On THP-1 cell proteome level, we identified an increase of protein translation with key regulatory proteins being involved in redox regulation (hypoxia inducible factor 2α), differentiation (retinoic acid signaling and interferon inducible factors), and cell growth (Yin Yang 1). Regulation of inflammation is a key element in many chronic diseases, and we found a significantly increased expression of the anti-inflammatory heme oxygenase 1 (HMOX1) and of the neutrophil attractant chemokine interleukin-8 (IL-8). Together, these results foster the view that cold physical plasma modulates the redox balance and inflammatory processes in wound related cells.

  17. Characterization of Mammalian Selenoprotein O: A Redox-Active Mitochondrial Protein

    PubMed Central

    Yim, Sun Hee; Gladyshev, Vadim N.; Lee, Seung-Rock

    2014-01-01

    Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein. PMID:24751718

  18. Characterization of mammalian selenoprotein o: a redox-active mitochondrial protein.

    PubMed

    Han, Seong-Jeong; Lee, Byung Cheon; Yim, Sun Hee; Gladyshev, Vadim N; Lee, Seung-Rock

    2014-01-01

    Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein.

  19. Redox reactions and weak buffering capacity lead to acidification in the Chesapeake Bay.

    PubMed

    Cai, Wei-Jun; Huang, Wei-Jen; Luther, George W; Pierrot, Denis; Li, Ming; Testa, Jeremy; Xue, Ming; Joesoef, Andrew; Mann, Roger; Brodeur, Jean; Xu, Yuan-Yuan; Chen, Baoshan; Hussain, Najid; Waldbusser, George G; Cornwell, Jeffrey; Kemp, W Michael

    2017-08-28

    The combined effects of anthropogenic and biological CO 2 inputs may lead to more rapid acidification in coastal waters compared to the open ocean. It is less clear, however, how redox reactions would contribute to acidification. Here we report estuarine acidification dynamics based on oxygen, hydrogen sulfide (H 2 S), pH, dissolved inorganic carbon and total alkalinity data from the Chesapeake Bay, where anthropogenic nutrient inputs have led to eutrophication, hypoxia and anoxia, and low pH. We show that a pH minimum occurs in mid-depths where acids are generated as a result of H 2 S oxidation in waters mixed upward from the anoxic depths. Our analyses also suggest a large synergistic effect from river-ocean mixing, global and local atmospheric CO 2 uptake, and CO 2 and acid production from respiration and other redox reactions. Together they lead to a poor acid buffering capacity, severe acidification and increased carbonate mineral dissolution in the USA's largest estuary.The potential contribution of redox reactions to acidification in coastal waters is unclear. Here, using measurements from the Chesapeake Bay, the authors show that pH minimum occurs at mid-depths where acids are produced via hydrogen sulfide oxidation in waters mixed upward from anoxic depths.

  20. Redox regulation of electrophilic signaling by reactive persulfides in cardiac cells.

    PubMed

    Nishida, Motohiro; Nishimura, Akiyuki; Matsunaga, Tetsuro; Motohashi, Hozumi; Kasamatsu, Shingo; Akaike, Takaaki

    2017-08-01

    Maintaining a redox balance by means of precisely controlled systems that regulate production, and elimination, and metabolism of electrophilic substances (electrophiles) is essential for normal cardiovascular function. Electrophilic signaling is mainly regulated by endogenous electrophiles that are generated from reactive oxygen species, nitric oxide, and the derivative reactive species of nitric oxide during stress responses, as well as by exogenous electrophiles including compounds in foods and environmental pollutants. Among electrophiles formed endogenously, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive persulfide species such as cysteine persulfides and polysulfides that are endogenously produced in cells are likely to be involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cardiovascular physiology and pathophysiology. In our review, we focus on the redox-dependent regulation of electrophilic signaling via reduction and metabolism of electrophiles by reactive persulfides in cardiac cells, and we include suggestions for a new therapeutic strategy for cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Peripheral artery disease, redox signaling, oxidative stress - Basic and clinical aspects.

    PubMed

    Steven, Sebastian; Daiber, Andreas; Dopheide, Jörn F; Münzel, Thomas; Espinola-Klein, Christine

    2017-08-01

    Reactive oxygen and nitrogen species (ROS and RNS, e.g. H 2 O 2 , nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. At higher concentrations, ROS and RNS lead to oxidative stress and oxidative damage of biomolecules (e.g. via formation of peroxynitrite, fenton chemistry). Peripheral artery disease (PAD) is characterized by severe ischemic conditions in the periphery leading to intermittent claudication and critical limb ischemia (end stage). It is well known that redox biology and oxidative stress play an important role in this setting. We here discuss the major pathways of oxidative stress and redox signaling underlying the disease progression with special emphasis on the contribution of inflammatory processes. We also highlight therapeutic strategies comprising pharmacological (e.g. statins, angiotensin-converting enzyme inhibitors, phosphodiesterase inhibition) and non-pharmacological (e.g. exercise) interventions. Both of these strategies induce potent indirect antioxidant and anti-inflammatory mechanisms that may contribute to an improvement of PAD associated complications and disease progression by removing excess formation of ROS and RNS (e.g. by ameliorating primary complications such as hyperlipidemia and hypertension) as well as the normalization of the inflammatory phenotype suppressing the progression of atherosclerosis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Reduction potentials of heterometallic manganese–oxido cubane complexes modulated by redox-inactive metals

    PubMed Central

    Tsui, Emily Y.; Agapie, Theodor

    2013-01-01

    Understanding the effect of redox-inactive metals on the properties of biological and heterogeneous water oxidation catalysts is important both fundamentally and for improvement of future catalyst designs. In this work, heterometallic manganese–oxido cubane clusters [MMn3O4] (M = Sr2+, Zn2+, Sc3+, Y3+) structurally relevant to the oxygen-evolving complex (OEC) of photosystem II were prepared and characterized. The reduction potentials of these clusters and other related mixed metal manganese–tetraoxido complexes are correlated with the Lewis acidity of the apical redox-inactive metal in a manner similar to a related series of heterometallic manganese–dioxido clusters. The redox potentials of the [SrMn3O4] and [CaMn3O4] clusters are close, which is consistent with the observation that the OEC is functional only with one of these two metals. Considering our previous studies of [MMn3O2] moieties, the present results with more structurally accurate models of the OEC ([MMn3O4]) suggest a general relationship between the reduction potentials of heterometallic oxido clusters and the Lewis acidities of incorporated cations that applies to diverse structural motifs. These findings support proposals that one function of calcium in the OEC is to modulate the reduction potential of the cluster to allow electron transfer. PMID:23744039

  3. Signaling Pathways Regulating Redox Balance in Cancer Metabolism

    PubMed Central

    De Santis, Maria Chiara; Porporato, Paolo Ettore; Martini, Miriam; Morandi, Andrea

    2018-01-01

    The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells’ demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions. PMID:29740540

  4. Signaling Pathways Regulating Redox Balance in Cancer Metabolism.

    PubMed

    De Santis, Maria Chiara; Porporato, Paolo Ettore; Martini, Miriam; Morandi, Andrea

    2018-01-01

    The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells' demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions.

  5. Exogenous antioxidants—Double-edged swords in cellular redox state

    PubMed Central

    Bohn, Torsten

    2010-01-01

    The balance between oxidation and antioxidation is believed to be critical in maintaining healthy biological systems. Under physiological conditions, the human antioxidative defense system including e.g., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and others, allows the elimination of excess reactive oxygen species (ROS) including, among others superoxide anions (O2.-), hydroxyl radicals (OH.), alkoxyl radicals (RO.) and peroxyradicals (ROO.). However, our endogenous antioxidant defense systems are incomplete without exogenous originating reducing compounds such as vitamin C, vitamin E, carotenoids and polyphenols, playing an essential role in many antioxidant mechanisms in living organisms. Therefore, there is continuous demand for exogenous antioxidants in order to prevent oxidative stress, representing a disequilibrium redox state in favor of oxidation. However, high doses of isolated compounds may be toxic, owing to prooxidative effects at high concentrations or their potential to react with beneficial concentrations of ROS normally present at physiological conditions that are required for optimal cellular functioning. This review aims to examine the double-edged effects of dietary originating antioxidants with a focus on the most abundant compounds, especially polyphenols, vitamin C, vitamin E and carotenoids. Different approaches to enrich our body with exogenous antioxidants such as via synthetic antioxidants, diets rich in fruits and vegetables and taking supplements will be reviewed and experimental and epidemiological evidences discussed, highlighting that antioxidants at physiological doses are generally safe, exhibiting interesting health beneficial effects. PMID:20972369

  6. The carbon cycle and associated redox processes through time

    PubMed Central

    Hayes, John M; Waldbauer, Jacob R

    2006-01-01

    Earth's biogeochemical cycle of carbon delivers both limestones and organic materials to the crust. In numerous, biologically catalysed redox reactions, hydrogen, sulphur, iron, and oxygen serve prominently as electron donors and acceptors. The progress of these reactions can be reconstructed from records of variations in the abundance of 13C in sedimentary carbonate minerals and organic materials. Because the crust is always receiving new CO2 from the mantle and a portion of it is being reduced by photoautotrophs, the carbon cycle has continuously released oxidizing power. Most of it is represented by Fe3+ that has accumulated in the crust or been returned to the mantle via subduction. Less than 3% of the estimated, integrated production of oxidizing power since 3.8 Gyr ago is represented by O2 in the atmosphere and dissolved in seawater. The balance is represented by sulphate. The accumulation of oxidizing power can be estimated from budgets summarizing inputs of mantle carbon and rates of organic-carbon burial, but levels of O2 are only weakly and indirectly coupled to those phenomena and thus to carbon-isotopic records. Elevated abundances of 13C in carbonate minerals ca 2.3 Gyr old, in particular, are here interpreted as indicating the importance of methanogenic bacteria in sediments rather than increased burial of organic carbon. PMID:16754608

  7. Redox-inactive metal ions promoted the catalytic reactivity of non-heme manganese complexes towards oxygen atom transfer.

    PubMed

    Choe, Cholho; Yang, Ling; Lv, Zhanao; Mo, Wanling; Chen, Zhuqi; Li, Guangxin; Yin, Guochuan

    2015-05-21

    Redox-inactive metal ions can modulate the reactivity of redox-active metal ions in a variety of biological and chemical oxidations. Many synthetic models have been developed to help address the elusive roles of these redox-inactive metal ions. Using a non-heme manganese(II) complex as the model, the influence of redox-inactive metal ions as a Lewis acid on its catalytic efficiency in oxygen atom transfer was investigated. In the absence of redox-inactive metal ions, the manganese(II) catalyst is very sluggish, for example, in cyclooctene epoxidation, providing only 9.9% conversion with 4.1% yield of epoxide. However, addition of 2 equiv. of Al(3+) to the manganese(II) catalyst sharply improves the epoxidation, providing up to 97.8% conversion with 91.4% yield of epoxide. EPR studies of the manganese(II) catalyst in the presence of an oxidant reveal a 16-line hyperfine structure centered at g = 2.0, clearly indicating the formation of a mixed valent di-μ-oxo-bridged diamond core, Mn(III)-(μ-O)2-Mn(IV). The presence of a Lewis acid like Al(3+) causes the dissociation of this diamond Mn(III)-(μ-O)2-Mn(IV) core to form monomeric manganese(iv) species which is responsible for improved epoxidation efficiency. This promotional effect has also been observed in other manganese complexes bearing various non-heme ligands. The findings presented here have provided a promising strategy to explore the catalytic reactivity of some di-μ-oxo-bridged complexes by adding non-redox metal ions to in situ dissociate those dimeric cores and may also provide clues to understand the mechanism of methane monooxygenase which has a similar diiron diamond core as the intermediate.

  8. Redox regulation of neuronal voltage-gated calcium channels.

    PubMed

    Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

    2014-08-20

    Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain.

  9. Redox-Active Separators for Lithium-Ion Batteries.

    PubMed

    Wang, Zhaohui; Pan, Ruijun; Ruan, Changqing; Edström, Kristina; Strømme, Maria; Nyholm, Leif

    2018-03-01

    A bilayered cellulose-based separator design is presented that can enhance the electrochemical performance of lithium-ion batteries (LIBs) via the inclusion of a porous redox-active layer. The proposed flexible redox-active separator consists of a mesoporous, insulating nanocellulose fiber layer that provides the necessary insulation between the electrodes and a porous, conductive, and redox-active polypyrrole-nanocellulose layer. The latter layer provides mechanical support to the nanocellulose layer and adds extra capacity to the LIBs. The redox-active separator is mechanically flexible, and no internal short circuits are observed during the operation of the LIBs, even when the redox-active layer is in direct contact with both electrodes in a symmetric lithium-lithium cell. By replacing a conventional polyethylene separator with a redox-active separator, the capacity of the proof-of-concept LIB battery containing a LiFePO 4 cathode and a Li metal anode can be increased from 0.16 to 0.276 mA h due to the capacity contribution from the redox-active separator. As the presented redox-active separator concept can be used to increase the capacities of electrochemical energy storage systems, this approach may pave the way for new types of functional separators.

  10. "JCE" Classroom Activity #111: Redox Reactions in Three Representations

    ERIC Educational Resources Information Center

    Nieves, Edgardo L. Ortiz; Barreto, Reizelie; Medina, Zuleika

    2012-01-01

    This activity introduces students to the concept of reduction-oxidation (redox) reactions. To help students obtain a thorough understanding of redox reactions, the concept is explored at three levels: macroscopic, submicroscopic, and symbolic. In this activity, students perform hands-on investigations of the three levels as they work at different…

  11. All biology is computational biology.

    PubMed

    Markowetz, Florian

    2017-03-01

    Here, I argue that computational thinking and techniques are so central to the quest of understanding life that today all biology is computational biology. Computational biology brings order into our understanding of life, it makes biological concepts rigorous and testable, and it provides a reference map that holds together individual insights. The next modern synthesis in biology will be driven by mathematical, statistical, and computational methods being absorbed into mainstream biological training, turning biology into a quantitative science.

  12. Redox-Based Regulation of Bacterial Development and Behavior.

    PubMed

    Sporer, Abigail J; Kahl, Lisa J; Price-Whelan, Alexa; Dietrich, Lars E P

    2017-06-20

    Severe changes in the environmental redox potential, and resulting alterations in the oxidation states of intracellular metabolites and enzymes, have historically been considered negative stressors, requiring responses that are strictly defensive. However, recent work in diverse organisms has revealed that more subtle changes in the intracellular redox state can act as signals, eliciting responses with benefits beyond defense and detoxification. Changes in redox state have been shown to influence or trigger chromosome segregation, sporulation, aerotaxis, and social behaviors, including luminescence as well as biofilm establishment and dispersal. Connections between redox state and complex behavior allow bacteria to link developmental choices with metabolic state and coordinate appropriate responses. Promising future directions for this area of study include metabolomic analysis of species- and condition-dependent changes in metabolite oxidation states and elucidation of the mechanisms whereby the redox state influences circadian regulation.

  13. Energy storage device including a redox-enhanced electrolyte

    DOEpatents

    Stucky, Galen; Evanko, Brian; Parker, Nicholas; Vonlanthen, David; Auston, David; Boettcher, Shannon; Chun, Sang-Eun; Ji, Xiulei; Wang, Bao; Wang, Xingfeng; Chandrabose, Raghu Subash

    2017-08-08

    An electrical double layer capacitor (EDLC) energy storage device is provided that includes at least two electrodes and a redox-enhanced electrolyte including two redox couples such that there is a different one of the redox couples for each of the electrodes. When charged, the charge is stored in Faradaic reactions with the at least two redox couples in the electrolyte and in a double-layer capacitance of a porous carbon material that comprises at least one of the electrodes, and a self-discharge of the energy storage device is mitigated by at least one of electrostatic attraction, adsorption, physisorption, and chemisorption of a redox couple onto the porous carbon material.

  14. Cancer drug resistance: redox resetting renders a way

    PubMed Central

    Xie, Na; Nice, Edouard C.; Zhang, Haiyuan; Huang, Canhua; Lei, Yunlong

    2016-01-01

    Disruption of redox homeostasis is a crucial factor in the development of drug resistance, which is a major problem facing current cancer treatment. Compared with normal cells, tumor cells generally exhibit higher levels of reactive oxygen species (ROS), which can promote tumor progression and development. Upon drug treatment, some tumor cells can undergo a process of ‘Redox Resetting’ to acquire a new redox balance with higher levels of ROS accumulation and stronger antioxidant systems. Evidence has accumulated showing that the ‘Redox Resetting’ enables cancer cells to become resistant to anticancer drugs by multiple mechanisms, including increased rates of drug efflux, altered drug metabolism and drug targets, activated prosurvival pathways and inefficient induction of cell death. In this article, we provide insight into the role of ‘Redox Resetting’ on the emergence of drug resistance that may contribute to pharmacological modulation of resistance. PMID:27057637

  15. Incorporating redox processes improves prediction of carbon and nutrient cycling and greenhouse gas emission

    NASA Astrophysics Data System (ADS)

    Tang, Guoping; Zheng, Jianqiu; Yang, Ziming; Graham, David; Gu, Baohua; Mayes, Melanie; Painter, Scott; Thornton, Peter

    2016-04-01

    Among the coupled thermal, hydrological, geochemical, and biological processes, redox processes play major roles in carbon and nutrient cycling and greenhouse gas (GHG) emission. Increasingly, mechanistic representation of redox processes is acknowledged as necessary for accurate prediction of GHG emission in the assessment of land-atmosphere interactions. Simple organic substrates, Fe reduction, microbial reactions, and the Windermere Humic Aqueous Model (WHAM) were added to a reaction network used in the land component of an Earth system model. In conjunction with this amended reaction network, various temperature response functions used in ecosystem models were assessed for their ability to describe experimental observations from incubation tests with arctic soils. Incorporation of Fe reduction reactions improves the prediction of the lag time between CO2 and CH4 accumulation. The inclusion of the WHAM model enables us to approximately simulate the initial pH drop due to organic acid accumulation and then a pH increase due to Fe reduction without parameter adjustment. The CLM4.0, CENTURY, and Ratkowsky temperature response functions better described the observations than the Q10 method, Arrhenius equation, and ROTH-C. As electron acceptors between O2 and CO2 (e.g., Fe(III), SO42-) are often involved, our results support inclusion of these redox reactions for accurate prediction of CH4 production and consumption. Ongoing work includes improving the parameterization of organic matter decomposition to produce simple organic substrates, examining the influence of redox potential on methanogenesis under thermodynamically favorable conditions, and refining temperature response representation near the freezing point by additional model-experiment iterations. We will use the model to describe observed GHG emission at arctic and tropical sites.

  16. Selective Targeting of the Cysteine Proteome by Thioredoxin and Glutathione Redox Systems

    PubMed Central

    Go, Young-Mi; Roede, James R.; Walker, Douglas I.; Duong, Duc M.; Seyfried, Nicholas T.; Orr, Michael; Liang, Yongliang; Pennell, Kurt D.; Jones, Dean P.

    2013-01-01

    Thioredoxin (Trx) and GSH are the major thiol antioxidants protecting cells from oxidative stress-induced cytotoxicity. Redox states of Trx and GSH have been used as indicators of oxidative stress. Accumulating studies suggest that Trx and GSH redox systems regulate cell signaling and metabolic pathways differently and independently during diverse stressful conditions. In the current study, we used a mass spectrometry-based redox proteomics approach to test responses of the cysteine (Cys) proteome to selective disruption of the Trx- and GSH-dependent systems. Auranofin (ARF) was used to inhibit Trx reductase without detectable oxidation of the GSH/GSSG couple, and buthionine sulfoximine (BSO) was used to deplete GSH without detectable oxidation of Trx1. Results for 606 Cys-containing peptides (peptidyl Cys) showed that 36% were oxidized more than 1.3-fold by ARF, whereas BSO-induced oxidation of peptidyl Cys was only 10%. Mean fold oxidation of these peptides was also higher by ARF than BSO treatment. Analysis of potential functional pathways showed that ARF oxidized peptides associated with glycolysis, cytoskeleton remodeling, translation and cell adhesion. Of 60 peptidyl Cys oxidized due to depletion of GSH, 41 were also oxidized by ARF and included proteins of translation and cell adhesion but not glycolysis or cytoskeletal remodeling. Studies to test functional correlates showed that pyruvate kinase activity and lactate levels were decreased with ARF but not BSO, confirming the effects on glycolysis-associated proteins are sensitive to oxidation by ARF. These data show that the Trx system regulates a broader range of proteins than the GSH system, support distinct function of Trx and GSH in cellular redox control, and show for the first time in mammalian cells selective targeting peptidyl Cys and biological pathways due to deficient function of the Trx system. PMID:23946468

  17. Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling.

    PubMed

    Brand, Martin D

    2016-11-01

    and have important roles in redox signaling (e.g. hypoxic signaling and ER-stress) and in causing oxidative damage in a variety of biological contexts. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Biological Agents

    MedlinePlus

    ... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

  19. The decay of Redox-stress Response Capacity is a substantive characteristic of aging: Revising the redox theory of aging.

    PubMed

    Meng, Jiao; Lv, Zhenyu; Qiao, Xinhua; Li, Xiaopeng; Li, Yazi; Zhang, Yuying; Chen, Chang

    2017-04-01

    Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals. In response to paraquat stress, young individuals generated more ROS and activated signaling pathways including p-ERK, p-AKT and p-AMPKα/β. After the initial response, young individuals then promoted NRF2 translocation and induced additional antioxidant enzymes and higher expression of phase II enzymes, including SOD, CAT, GPX, HO-1, GSTP-1and others, to maintain redox homeostasis. Moreover, young individuals also demonstrated a better ability to degrade damaged proteins by up-regulating the expression of chaperones and improving proteasome activity. Based on these data, we propose a new concept "Redox-stress Response Capacity (RRC)", which suggests cells or organisms are capable of generating dynamic redox responses to activate cellular signaling and maintain cellular homeostasis. The decay of RRC is the substantive characteristic of aging, which gives a new understand of the redox theory of aging. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Electrolytes Based on TEMPO–Co Tandem Redox Systems Outperform Single Redox Systems in Dye‐sensitized Solar Cells

    PubMed Central

    Cong, Jiayan; Hao, Yan; Boschloo, Gerrit

    2014-01-01

    Abstract A new TEMPO–Co tandem redox system with TEMPO and Co(bpy)3 2+/3+ has been investigated for the use in dye‐sensitized solar cells (DSSCs). A large open‐circuit voltage (V OC) increase, from 862 mV to 965 mV, was observed in the tandem redox system, while the short‐circuit current density (J SC) was maintained. The conversion efficiency was observed to increase from 7.1 % for cells containing the single Co(bpy)3 2+/3+ redox couple, to 8.4 % for cells containing the TEMPO–Co tandem redox system. The reason for the increase in V OC and overall efficiency is ascribed to the involvement of partial regeneration of the sensitizing dye molecules by TEMPO. This assumption can be verified through the observed much faster regeneration dynamics exhibited in the presence of the tandem system. Using the tandem redox system, the faster recombination problem of the single TEMPO redox couple is resolved and the mass‐transport of the metal‐complex‐based electrolyte is also improved. This TEMPO–Co tandem system is so far the most effienct tandem redox electrolyte reported not involving iodine. The current results show a promising future for tandem system as replacements for single redox systems in electrolytes for DSSCs. PMID:25504818

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

    PubMed Central

    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

  2. High energy density redox flow device

    DOEpatents

    Chiang, Yet-Ming; Carter, William Craig; Duduta, Mihai; Limthongkul, Pimpa

    2014-05-13

    Redox flow devices are described including a positive electrode current collector, a negative electrode current collector, and an ion-permeable membrane separating said positive and negative current collectors, positioned and arranged to define a positive electroactive zone and a negative electroactive zone; wherein at least one of said positive and negative electroactive zone comprises a flowable semi-solid composition comprising ion storage compound particles capable of taking up or releasing said ions during operation of the cell, and wherein the ion storage compound particles have a polydisperse size distribution in which the finest particles present in at least 5 vol % of the total volume, is at least a factor of 5 smaller than the largest particles present in at least 5 vol % of the total volume.

  3. An electrochemical rebalance cell for Redox systems

    NASA Technical Reports Server (NTRS)

    Acevedo, J. C.; Stalnaker, D. K.

    1983-01-01

    An electrochemical rebalance cell for maintaining electrochemical balance, at the system level, of the acidified aqueous iron chloride and chromium chloride reactant solutions in the redox energy storage system was constructed and evaluated. The electrochemical reaction for the cathode is Fe(+3) + e(-) yields Fe(+2), and that for the anode is 1/2H2 yields H(+) + e(-). The iron (carbon felt) electrode and the hydrogen (platinized carbon) electrode are separated by an anion exchange membrane. The performance of the rebalance cell is discussed as well as the assembly of a single rebalance cell and multicell stacks. Various cell configurations were tested and the results are presented and discussed. The rebalance cell was also used to demonstrate its ability, as a preparative tool, for making high purity solutions of soluble reduced metal ionic species. Preparations of titanium, copper, vanadium and chromium ions in acidified solutions were evaluated.

  4. High energy density redox flow device

    DOEpatents

    Chiang, Yet -Ming; Carter, W. Craig; Duduta, Mihai; Limthongkul, Pimpa

    2015-10-06

    Redox flow devices are described including a positive electrode current collector, a negative electrode current collector, and an ion-permeable membrane separating said positive and negative current collectors, positioned and arranged to define a positive electroactive zone and a negative electroactive zone; wherein at least one of said positive and negative electroactive zone comprises a flowable semi-solid composition comprising ion storage compound particles capable of taking up or releasing said ions during operation of the cell, and wherein the ion storage compound particles have a polydisperse size distribution in which the finest particles present in at least 5 vol % of the total volume, is at least a factor of 5 smaller than the largest particles present in at least 5 vol % of the total volume.

  5. Iron-sulfide redox flow batteries

    DOEpatents

    Xia, Guanguang; Yang, Zhenguo; Li, Liyu; Kim, Soowhan; Liu, Jun; Graff, Gordon L

    2016-06-14

    Iron-sulfide redox flow battery (RFB) systems can be advantageous for energy storage, particularly when the electrolytes have pH values greater than 6. Such systems can exhibit excellent energy conversion efficiency and stability and can utilize low-cost materials that are relatively safer and more environmentally friendly. One example of an iron-sulfide RFB is characterized by a positive electrolyte that comprises Fe(III) and/or Fe(II) in a positive electrolyte supporting solution, a negative electrolyte that comprises S.sup.2- and/or S in a negative electrolyte supporting solution, and a membrane, or a separator, that separates the positive electrolyte and electrode from the negative electrolyte and electrode.

  6. Iron-sulfide redox flow batteries

    DOEpatents

    Xia, Guan-Guang; Yang, Zhenguo; Li, Liyu; Kim, Soowhan; Liu, Jun; Graff, Gordon L

    2013-12-17

    Iron-sulfide redox flow battery (RFB) systems can be advantageous for energy storage, particularly when the electrolytes have pH values greater than 6. Such systems can exhibit excellent energy conversion efficiency and stability and can utilize low-cost materials that are relatively safer and more environmentally friendly. One example of an iron-sulfide RFB is characterized by a positive electrolyte that comprises Fe(III) and/or Fe(II) in a positive electrolyte supporting solution, a negative electrolyte that comprises S.sup.2- and/or S in a negative electrolyte supporting solution, and a membrane, or a separator, that separates the positive electrolyte and electrode from the negative electrolyte and electrode.

  7. Inflammatory and redox reactions in colorectal carcinogenesis.

    PubMed

    Guina, Tina; Biasi, Fiorella; Calfapietra, Simone; Nano, Mario; Poli, Giuseppe

    2015-03-01

    It has been established that there is a relationship between chronic inflammation and cancer development. The constant colonic inflammation typical of inflammatory bowel diseases is now considered a risk factor for colorectal carcinoma (CRC) development. The inflammatory network of signaling molecules is also required during the late phases of carcinogenesis, to enable cancer cells to survive and to metastasize. Oxidative reactions are an integral part of the inflammatory response, and are generally associated with CRC development. However, when the malignant phenotype is acquired, increased oxidative status induces antioxidant defenses in cancer cells, favoring their aggressiveness. This contradictory behavior of cancer cells toward redox status is of great significance for potential anticancer therapies. This paper summarizes the essential background information relating to the molecules involved in regulating oxidative stress and inflammation during carcinogenesis. Understanding more of their function in CRC stages might provide the foundation for future developments in CRC treatment. © 2015 New York Academy of Sciences.

  8. Redox signaling in pathophysiology of hypertension.

    PubMed

    Majzunova, Miroslava; Dovinova, Ima; Barancik, Miroslav; Chan, Julie Y H

    2013-09-18

    Reactive oxygen species (ROS) are products of normal cellular metabolism and derive from various sources in different cellular compartments. Oxidative stress resultant from imbalance between ROS generation and antioxidant defense mechanisms is important in pathogenesis of cardiovascular diseases, such as hypertension, heart failure, atherosclerosis, diabetes, and cardiac hypertrophy. In this review we focus on hypertension and address sources of cellular ROS generation, mechanisms involved in regulation of radical homeostasis, superoxide dismutase isoforms in pathophysiology of hypertension; as well as radical intracellular signaling and phosphorylation processes in proteins of the affected cardiovascular tissues. Finally, we discuss the transcriptional factors involved in redox-sensitive gene transcription and antioxidant response, as well as their roles in hypertension.

  9. Redox signaling in pathophysiology of hypertension

    PubMed Central

    2013-01-01

    Reactive oxygen species (ROS) are products of normal cellular metabolism and derive from various sources in different cellular compartments. Oxidative stress resultant from imbalance between ROS generation and antioxidant defense mechanisms is important in pathogenesis of cardiovascular diseases, such as hypertension, heart failure, atherosclerosis, diabetes, and cardiac hypertrophy. In this review we focus on hypertension and address sources of cellular ROS generation, mechanisms involved in regulation of radical homeostasis, superoxide dismutase isoforms in pathophysiology of hypertension; as well as radical intracellular signaling and phosphorylation processes in proteins of the affected cardiovascular tissues. Finally, we discuss the transcriptional factors involved in redox-sensitive gene transcription and antioxidant response, as well as their roles in hypertension. PMID:24047403

  10. Hybrid anodes for redox flow batteries

    DOEpatents

    Wang, Wei; Xiao, Jie; Wei, Xiaoliang; Liu, Jun; Sprenkle, Vincent L.

    2015-12-15

    RFBs having solid hybrid electrodes can address at least the problems of active material consumption, electrode passivation, and metal electrode dendrite growth that can be characteristic of traditional batteries, especially those operating at high current densities. The RFBs each have a first half cell containing a first redox couple dissolved in a solution or contained in a suspension. The solution or suspension can flow from a reservoir to the first half cell. A second half cell contains the solid hybrid electrode, which has a first electrode connected to a second electrode, thereby resulting in an equipotential between the first and second electrodes. The first and second half cells are separated by a separator or membrane.

  11. High energy density redox flow device

    SciTech Connect

    Carter, W. Craig; Chiang, Yet-Ming; Duduta, Mihai

    2017-04-04

    Redox flow devices are described including a positive electrode current collector, a negative electrode current collector, and an ion-permeable membrane separating said positive and negative current collectors, positioned and arranged to define a positive electroactive zone and a negative electroactive zone; wherein at least one of said positive and negative electroactive zone comprises a flowable semi-solid composition comprising ion storage compound particles capable of taking up or releasing said ions during operation of the cell, and wherein the ion storage compound particles have a polydisperse size distribution in which the finest particles present in at least 5 vol % ofmore » the total volume, is at least a factor of 5 smaller than the largest particles present in at least 5 vol % of the total volume.« less

  12. Cellular Senescence, Neurological Function, and Redox State.

    PubMed

    Maciel-Barón, Luis Ángel; Moreno-Blas, Daniel; Morales-Rosales, Sandra Lizbeth; González-Puertos, Viridiana Yazmín; López-Díazguerrero, Norma Edith; Torres, Claudio; Castro-Obregón, Susana; Königsberg, Mina

    2018-06-20

    Cellular senescence, characterized by permanent cell cycle arrest, has been extensively studied in mitotic cells such as fibroblasts. However, senescent cells have also been observed in the brain. Even though it is recognized that cellular energetic metabolism and redox homeostasis are perturbed in the aged brain and neurodegenerative diseases (NDDs), it is still unknown which alterations in the overall physiology can stimulate cellular senescence induction and their relationship with the former events. Recent Advances: Recent findings have shown that during prolonged inflammatory and pathologic events, the blood-brain barrier could be compromised and immune cells might enter the brain; this fact along with the brain's high oxygen dependence might result in oxidative damage to macromolecules and therefore senescence induction. Thus, cellular senescence in different brain cell types is revised here. Most information related to cellular senescence in the brain has been obtained from research in glial cells since it has been assumed that the senescent phenotype is a feature exclusive to mitotic cells. Nevertheless, neurons with senescence hallmarks have been observed in old mouse brains. Therefore, although this is a controversial topic in the field, here we summarize and integrate the observations from several studies and propose that neurons indeed senesce. It is still unknown which alterations in the overall metabolism can stimulate senescence induction in the aged brain, what are the mechanisms and signaling pathways, and what is their relationship to NDD development. The understanding of these processes will expose new targets to intervene age-associated pathologies.-Antioxid. Redox Signal. 28, 1704-1723.

  13. Lung extracellular matrix and redox regulation.

    PubMed

    Watson, Walter H; Ritzenthaler, Jeffrey D; Roman, Jesse

    2016-08-01

    Pulmonary fibrosis affects millions worldwide and, even though there has been a significant investment in understanding the processes involved in wound healing and maladaptive repair, a complete understanding of the mechanisms responsible for lung fibrogenesis eludes us, and interventions capable of reversing or halting disease progression are not available. Pulmonary fibrosis is characterized by the excessive expression and uncontrolled deposition of extracellular matrix (ECM) proteins resulting in erosion of the tissue structure. Initially considered an 'end-stage' process elicited after injury, these events are now considered pathogenic and are believed to contribute to the course of the disease. By interacting with integrins capable of signal transduction and by influencing tissue mechanics, ECM proteins modulate processes ranging from cell adhesion and migration to differentiation and growth factor expression. In doing so, ECM proteins help orchestrate complex developmental processes and maintain tissue homeostasis. However, poorly controlled deposition of ECM proteins promotes inflammation, fibroproliferation, and aberrant differentiation of cells, and has been implicated in the pathogenesis of pulmonary fibrosis, atherosclerosis and cancer. Considering their vital functions, ECM proteins are the target of investigation, and oxidation-reduction (redox) reactions have emerged as important regulators of the ECM. Oxidative stress invariably accompanies lung disease and promotes ECM expression directly or through the overproduction of pro-fibrotic growth factors, while affecting integrin binding and activation. In vitro and in vivo investigations point to redox reactions as targets for intervention in pulmonary fibrosis and related disorders, but studies in humans have been disappointing probably due to the narrow impact of the interventions tested, and our poor understanding of the factors that regulate these complex reactions. This review is not meant to

  14. Redox-regulated growth factor survival signaling.

    PubMed

    Woolley, John F; Corcoran, Aoife; Groeger, Gillian; Landry, William D; Cotter, Thomas G

    2013-11-20

    Once the thought of as unwanted byproducts of cellular respiration in eukaryotes, reactive oxygen species (ROS) have been shown to facilitate essential physiological roles. It is now understood that ROS are critical mediators of intracellular signaling. Control of signal transduction downstream of growth factor receptors by ROS is a complex process whose details are only recently coming to light. Indeed, recent evidence points to control of signal propagation by ROS at multiple levels in the typical cascade. Growth factor stimulation activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Noxs) at the membrane, producing superoxide in the extracellular matrix, which is catalyzed to the membrane-permeable hydrogen peroxide (H2O2) that mediates intracellular signaling events. The potential for H2O2, however, to disrupt cellular functions by damaging proteins and nucleic acids demands that its levels are kept in check by receptor-associated peroxiredoxins. This interplay of Nox and peroxiredoxin activity moderates levels of H2O2 sufficiently to modify signaling partners locally. Among the best studied of these partners are redox-controlled phosphatases that are inactivated by H2O2. Phosphatases regulate signal propagation downstream of receptors, and thus their inactivation allows a further level of control. Transmission of information further downstream to targets such as transcription factors, themselves regulated by ROS, completes this pathway. Thus, signal propagation or attenuation can be dictated by ROS at multiple points. Given the complex nature of these processes, we envisage the emerging trends in the field of redox signaling in the context of growth factor stimulation.

  15. Lung extracellular matrix and redox regulation

    PubMed Central

    Watson, Walter H.; Ritzenthaler, Jeffrey D.; Roman, Jesse

    2016-01-01

    Pulmonary fibrosis affects millions worldwide and, even though there has been a significant investment in understanding the processes involved in wound healing and maladaptive repair, a complete understanding of the mechanisms responsible for lung fibrogenesis eludes us, and interventions capable of reversing or halting disease progression are not available. Pulmonary fibrosis is characterized by the excessive expression and uncontrolled deposition of extracellular matrix (ECM) proteins resulting in erosion of the tissue structure. Initially considered an ‘end-stage’ process elicited after injury, these events are now considered pathogenic and are believed to contribute to the course of the disease. By interacting with integrins capable of signal transduction and by influencing tissue mechanics, ECM proteins modulate processes ranging from cell adhesion and migration to differentiation and growth factor expression. In doing so, ECM proteins help orchestrate complex developmental processes and maintain tissue homeostasis. However, poorly controlled deposition of ECM proteins promotes inflammation, fibroproliferation, and aberrant differentiation of cells, and has been implicated in the pathogenesis of pulmonary fibrosis, atherosclerosis and cancer. Considering their vital functions, ECM proteins are the target of investigation, and oxidation–reduction (redox) reactions have emerged as important regulators of the ECM. Oxidative stress invariably accompanies lung disease and promotes ECM expression directly or through the overproduction of pro-fibrotic growth factors, while affecting integrin binding and activation. In vitro and in vivo investigations point to redox reactions as targets for intervention in pulmonary fibrosis and related disorders, but studies in humans have been disappointing probably due to the narrow impact of the interventions tested, and our poor understanding of the factors that regulate these complex reactions. This review is not meant to

  16. Polyoxometalate active charge-transfer material for mediated redox flow battery

    DOEpatents

    Anderson, Travis Mark; Hudak, Nicholas; Staiger, Chad; Pratt, Harry

    2017-01-17

    Redox flow batteries including a half-cell electrode chamber coupled to a current collecting electrode are disclosed herein. In a general embodiment, a separator is coupled to the half-cell electrode chamber. The half-cell electrode chamber comprises a first redox-active mediator and a second redox-active mediator. The first redox-active mediator and the second redox-active mediator are circulated through the half-cell electrode chamber into an external container. The container includes an active charge-transfer material. The active charge-transfer material has a redox potential between a redox potential of the first redox-active mediator and a redox potential of the second redox-active mediator. The active charge-transfer material is a polyoxometalate or derivative thereof. The redox flow battery may be particularly useful in energy storage solutions for renewable energy sources and for providing sustained power to an electrical grid.

  17. A multi-electron redox mediator for redox-targeting lithium-sulfur flow batteries

    NASA Astrophysics Data System (ADS)

    Li, Guochun; Yang, Liuqing; Jiang, Xi; Zhang, Tianran; Lin, Haibin; Yao, Qiaofeng; Lee, Jim Yang

    2018-02-01

    The lithium-sulfur flow battery (LSFB) is a new addition to the rechargeable lithium flow batteries (LFBs) where sulfur or a sulfur compound is used as the cathode material against the lithium anode. We report here our evaluation of an organic sulfide - dimethyl trisulfide (DMTS), as 1) a catholyte of a LFB and 2) a multi-electron redox mediator for discharging and charging a solid sulfur cathode without any conductive additives. The latter configuration is also known as the redox-targeting lithium-sulfur flow battery (RTLSFB). The LFB provides an initial discharge capacity of 131.5 mAh g-1DMTS (1.66 A h L-1), which decreases to 59 mAh g-1DMTS (0.75 A h L-1) after 40 cycles. The RTLSFB delivers a significantly higher application performance - initial discharge capacity of 1225.3 mAh g-1sulfur (3.83 A h L-1), for which 1030.9 mAh g-1sulfur (3.23 A h L-1) is still available after 40 cycles. The significant increase in the discharge and charge duration of the LFB after sulfur addition indicates that DMTS is better used as a redox mediator in a RTLSFB than as a catholyte in a LFB.

  18. Arteriovenous oscillations of the redox potential: Is the redox state influencing blood flow?

    PubMed

    Poznanski, Jaroslaw; Szczesny, Pawel; Pawlinski, Bartosz; Mazurek, Tomasz; Zielenkiewicz, Piotr; Gajewski, Zdzislaw; Paczek, Leszek

    2017-09-01

    Studies on the regulation of human blood flow revealed several modes of oscillations with frequencies ranging from 0.005 to 1 Hz. Several mechanisms were proposed that might influence these oscillations, such as the activity of vascular endothelium, the neurogenic activity of vessel wall, the intrinsic activity of vascular smooth muscle, respiration, and heartbeat. These studies relied typically on non-invasive techniques, for example, laser Doppler flowmetry. Oscillations of biochemical markers were rarely coupled to blood flow. The redox potential difference between the artery and the vein was measured by platinum electrodes placed in the parallel homonymous femoral artery and the femoral vein of ventilated anesthetized pigs. Continuous measurement at 5 Hz sampling rate using a digital nanovoltmeter revealed fluctuating signals with three basic modes of oscillations: ∼ 1, ∼ 0.1 and ∼ 0.01 Hz. These signals clearly overlap with reported modes of oscillations in blood flow, suggesting coupling of the redox potential and blood flow. The amplitude of the oscillations associated with heart action was significantly smaller than for the other two modes, despite the fact that heart action has the greatest influence on blood flow. This finding suggests that redox potential in blood might be not a derivative but either a mediator or an effector of the blood flow control system.

  19. Electrochemical study of quinone redox cycling: A novel application of DNA-based biosensors for monitoring biochemical reactions.

    PubMed

    Ensafi, Ali A; Jamei, Hamid Reza; Heydari-Bafrooei, Esmaeil; Rezaei, B

    2016-10-01

    This paper presents the results of an experimental investigation of voltammetric and impedimetric DNA-based biosensors for monitoring biological and chemical redox cycling reactions involving free radical intermediates. The concept is based on associating the amounts of radicals generated with the electrochemical signals produced, using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). For this purpose, a pencil graphite electrode (PGE) modified with multiwall carbon nanotubes and poly-diallydimethlammonium chloride decorated with double stranded fish sperm DNA was prepared to detect DNA damage induced by the radicals generated from a redox cycling quinone (i.e., menadione (MD; 2-methyl-1,4-naphthoquinone)). Menadione was employed as a model compound to study the redox cycling of quinones. A direct relationship was found between free radical production and DNA damage. The relationship between MD-induced DNA damage and free radical generation was investigated in an attempt to identify the possible mechanism(s) involved in the action of MD. Results showed that DPV and EIS were appropriate, simple and inexpensive techniques for the quantitative and qualitative comparisons of different reducing reagents. These techniques may be recommended for monitoring DNA damages and investigating the mechanisms involved in the production of redox cycling compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Flavin redox bifurcation as a mechanism for controlling the direction of electron flow during extracellular electron transfer.

    PubMed

    Okamoto, Akihiro; Hashimoto, Kazuhito; Nealson, Kenneth H

    2014-10-06

    The iron-reducing bacterium Shewanella oneidensis MR-1 has a dual directional electronic conduit involving 40 heme redox centers in flavin-binding outer-membrane c-type cytochromes (OM c-Cyts). While the mechanism for electron export from the OM c-Cyts to an anode is well understood, how the redox centers in OM c-Cyts take electrons from a cathode has not been elucidated at the molecular level. Electrochemical analysis of live cells during switching from anodic to cathodic conditions showed that altering the direction of electron flow does not require gene expression or protein synthesis, but simply redox potential shift about 300 mV for a flavin cofactor interacting with the OM c-Cyts. That is, the redox bifurcation of the riboflavin cofactor in OM c-Cyts switches the direction of electron conduction in the biological conduit at the cell-electrode interface to drive bacterial metabolism as either anode or cathode catalysts. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Proteome-wide Light/Dark Modulation of Thiol Oxidation in Cyanobacteria Revealed by Quantitative Site-specific Redox Proteomics*

    PubMed Central

    Guo, Jia; Nguyen, Amelia Y.; Dai, Ziyu; Su, Dian; Gaffrey, Matthew J.; Moore, Ronald J.; Jacobs, Jon M.; Monroe, Matthew E.; Smith, Richard D.; Koppenaal, David W.; Pakrasi, Himadri B.; Qian, Wei-Jun

    2014-01-01

    Reversible protein thiol oxidation is an essential regulatory mechanism of photosynthesis, metabolism, and gene expression in photosynthetic organisms. Herein, we present proteome-wide quantitative and site-specific profiling of in vivo thiol oxidation modulated by light/dark in the cyanobacterium Synechocystis sp. PCC 6803, an oxygenic photosynthetic prokaryote, using a resin-assisted thiol enrichment approach. Our proteomic approach integrates resin-assisted enrichment with isobaric tandem mass tag labeling to enable site-specific and quantitative measurements of reversibly oxidized thiols. The redox dynamics of ∼2,100 Cys-sites from 1,060 proteins under light, dark, and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (a photosystem II inhibitor) conditions were quantified. In addition to relative quantification, the stoichiometry or percentage of oxidation (reversibly oxidized/total thiols) for ∼1,350 Cys-sites was also quantified. The overall results revealed broad changes in thiol oxidation in many key biological processes, including photosynthetic electron transport, carbon fixation, and glycolysis. Moreover, the redox sensitivity along with the stoichiometric data enabled prediction of potential functional Cys-sites for proteins of interest. The functional significance of redox-sensitive Cys-sites in NADP-dependent glyceraldehyde-3-phosphate dehydrogenase, peroxiredoxin (AhpC/TSA family protein Sll1621), and glucose 6-phosphate dehydrogenase was further confirmed with site-specific mutagenesis and biochemical studies. Together, our findings provide significant insights into the broad redox regulation of photosynthetic organisms. PMID:25118246

  2. Redox-mediated dissolution of paramagnetic nanolids to achieve a smart theranostic system

    NASA Astrophysics Data System (ADS)

    Wang, Aifei; Guo, Mingyi; Wang, Nan; Zhao, Jianyun; Qi, Wenxiu; Muhammad, Faheem; Chen, Liang; Guo, Yingjie; Nguyen, Nam-Trung; Zhu, Guangshan

    2014-04-01

    Manganese oxide (Mn3O4) nanoparticles have recently emerged as a promising T1 contrast agent. In this study, for the first time, we demonstrated an interaction of Mn3O4 with a biological system, and found redox sensitive behavior of these paramagnetic nanoparticles in intracellular reducing environment. Inspired by these findings, we for the first time used this interaction for some therapeutic advantages and designed a versatile mesoporous silica based nanotheranostic system to realize redox-activated enhanced magnetic resonance imaging and responsive anticancer drug delivery. Contrary to previous reports, we firstly prepared high quality amine terminated hydrophilic Mn3O4 nanolids, without using multistep ligand exchange strategies. The resulting water stable and small-sized Mn3O4 nanolids were subsequently used as nanolids to cap drug loaded nanochannels of a porous carrier. Exposure to highly prevalent intracellular reducing environment resulted in the steady-state dissolution of these nanolids and attained an intelligent drug release. Furthermore, the redox receptive dissolution of paramagnetic Mn3O4 nanolids into Mn2+ in turn increases the T1 signal to twofold, providing an added opportunity to even track the feedback of therapy. This study, in addition to simultaneously realizing drug delivery and imaging, also provides a new insight into the fate and interaction of manganese oxide nanoparticles with components of biological systems.Manganese oxide (Mn3O4) nanoparticles have recently emerged as a promising T1 contrast agent. In this study, for the first time, we demonstrated an interaction of Mn3O4 with a biological system, and found redox sensitive behavior of these paramagnetic nanoparticles in intracellular reducing environment. Inspired by these findings, we for the first time used this interaction for some therapeutic advantages and designed a versatile mesoporous silica based nanotheranostic system to realize redox-activated enhanced magnetic resonance

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

    PubMed

    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.

  4. Antioxidant enzymes as redox-based biomarkers: a brief review

    PubMed Central

    Yang, Hee-Young; Lee, Tae-Hoon

    2015-01-01

    The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins. Redox regulators with antioxidant properties related to active mediators, cellular organelles, and the surrounding environments are all connected within a network and are involved in diseases related to redox imbalance including cancer, ischemia/reperfusion injury, neurodegenerative diseases, as well as normal aging. In this review, we will briefly look at the selected aspects of oxidative thiol modification in antioxidant enzymes and thiol oxidation in proteins affected by redox control of antioxidant enzymes and their relation to disease. [BMB Reports 2015; 48(4): 200-208] PMID:25560698

  5. Characterization and redox regulation of Plasmodium falciparum methionine adenosyltransferase.

    PubMed

    Pretzel, Jette; Gehr, Marina; Eisenkolb, Maike; Wang, Lihui; Fritz-Wolf, Karin; Rahlfs, Stefan; Becker, Katja; Jortzik, Esther

    2016-12-01

    As a methyl group donor for biochemical reactions, S-adenosylmethionine plays a central metabolic role in most organisms. Depletion of S-adenosylmethionine has downstream effects on polyamine metabolism and methylation reactions, and is an effective way to combat pathogenic microorganisms such as malaria parasites. Inhibition of both the methylation cycle and polyamine synthesis strongly affects Plasmodium falciparum growth. Despite its central position in the methylation cycle, not much is currently known about P. falciparum methionine adenosyltransferase (PfalMAT). Notably, however, PfalMAT has been discussed as a target of different redox regulatory modifications. Modulating the redox state of critical cysteine residues is a way to regulate enzyme activity in different pathways in response to changes in the cellular redox state. In the present study, we optimized an assay for detailed characterization of enzymatic activity and redox regulation of PfalMAT. While the presence of reduced thioredoxin increases the activity of the enzyme, it was found to be inhibited upon S-glutathionylation and S-nitrosylation. A homology model and site-directed mutagenesis studies revealed a contribution of the residues Cys52, Cys113 and Cys187 to redox regulation of PfalMAT by influencing its structure and activity. This phenomenon connects cellular S-adenosylmethionine synthesis to the redox state of PfalMAT and therefore to the cellular redox homeostasis. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  6. Imaging Redox State in Mouse Muscles of Different Ages.

    PubMed

    Moon, Lily; Frederick, David W; Baur, Joseph A; Li, Lin Z

    2017-01-01

    Aging is the greatest risk factor for many diseases. Intracellular concentrations of nicotinamide adenine dinucleotide (NAD + ) and the NAD + -coupled redox state have been proposed to moderate many aging-related processes, yet the specific mechanisms remain unclear. The concentration of NAD + falls with age in skeletal muscle, yet there is no consensus on whether aging will increase or decrease the redox potential of NAD + /NADH. Oxidized flavin groups (Fp) (e.g. FAD, i.e., flavin adenine dinucleotide, contained in flavoproteins) and NADH are intrinsic fluorescent indicators of oxidation and reduction status of tissue, respectively. The redox ratio, i.e., the ratio of Fp to NADH, may be a surrogate indicator of the NAD + /NADH redox potential. In this study we used the Chance redox scanner (NADH/Fp fluorescence imaging at low temperature) to investigate the effect of aging on the redox state of mitochondria in skeletal muscles. The results showed that there are borderline significant differences in nominal concentrations of Fp and NADH, but not in the redox ratio s when comparing 3.5-month and 13-month old muscles of mice (n = 6). It may be necessary to increase the number of muscle samples and study mice of more advanced age.

  7. Antioxidant enzymes as redox-based biomarkers: a brief review.

    PubMed

    Yang, Hee-Young; Lee, Tae-Hoon

    2015-04-01

    The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins. Redox regulators with antioxidant properties related to active mediators, cellular organelles, and the surrounding environments are all connected within a network and are involved in diseases related to redox imbalance including cancer, ischemia/reperfusion injury, neurodegenerative diseases, as well as normal aging. In this review, we will briefly look at the selected aspects of oxidative thiol modification in antioxidant enzymes and thiol oxidation in proteins affected by redox control of antioxidant enzymes and their relation to disease.

  8. Redox mechanisms in hepatic chronic wound healing and fibrogenesis

    PubMed Central

    Novo, Erica; Parola, Maurizio

    2008-01-01

    Reactive oxygen species (ROS) generated within cells or, more generally, in a tissue environment, may easily turn into a source of cell and tissue injury. Aerobic organisms have developed evolutionarily conserved mechanisms and strategies to carefully control the generation of ROS and other oxidative stress-related radical or non-radical reactive intermediates (that is, to maintain redox homeostasis), as well as to 'make use' of these molecules under physiological conditions as tools to modulate signal transduction, gene expression and cellular functional responses (that is, redox signalling). However, a derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, can play a significant role in the pathogenesis of major human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis. This review has been designed to first offer a critical introduction to current knowledge in the field of redox research in order to introduce readers to the complexity of redox signalling and redox homeostasis. This will include ready-to-use key information and concepts on ROS, free radicals and oxidative stress-related reactive intermediates and reactions, sources of ROS in mammalian cells and tissues, antioxidant defences, redox sensors and, more generally, the major principles of redox signalling and redox-dependent transcriptional regulation of mammalian cells. This information will serve as a basis of knowledge to introduce the role of ROS and other oxidative stress-related intermediates in contributing to essential events, such as the induction of cell death, the perpetuation of chronic inflammatory responses, fibrogenesis and much more, with a major focus on hepatic chronic wound healing and liver fibrogenesis. PMID:19014652

  9. Naphthalene SOA: redox activity and naphthoquinone gas-particle partitioning

    NASA Astrophysics Data System (ADS)

    McWhinney, R. D.; Zhou, S.; Abbatt, J. P. D.

    2013-10-01

    Chamber secondary organic aerosol (SOA) from low-NOx photooxidation of naphthalene by hydroxyl radical was examined with respect to its redox cycling behaviour using the dithiothreitol (DTT) assay. Naphthalene SOA was highly redox-active, consuming DTT at an average rate of 118 ± 14 pmol per minute per μg of SOA material. Measured particle-phase masses of the major previously identified redox active products, 1,2- and 1,4-naphthoquinone, accounted for only 21 ± 3% of the observed redox cycling activity. The redox-active 5-hydroxy-1,4-naphthoquinone was identified as a new minor product of naphthalene oxidation, and including this species in redox activity predictions increased the predicted DTT reactivity to 30 ± 5% of observations. These results suggest that there are substantial unidentified redox-active SOA constituents beyond the small quinones that may be important toxic components of these particles. A gas-to-SOA particle partitioning coefficient was calculated to be (7.0 ± 2.5) × 10-4 m3 μg-1 for 1,4-naphthoquinone at 25 °C. This value suggests that under typical warm conditions, 1,4-naphthoquinone is unlikely to contribute strongly to redox behaviour of ambient particles, although further work is needed to determine the potential impact under conditions such as low temperatures where partitioning to the particle is more favourable. Also, higher order oxidation products that likely account for a substantial fraction of the redox cycling capability of the naphthalene SOA are likely to partition much more strongly to the particle phase.

  10. Redox Regulation of Neuronal Voltage-Gated Calcium Channels

    PubMed Central

    Jevtovic-Todorovic, Vesna

    2014-01-01

    Abstract Significance: Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Recent Advances: Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. Critical Issues: A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Future Directions: Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain. Antioxid. Redox Signal. 21, 880–891. PMID:24161125

  11. An Excel Workbook for Identifying Redox Processes in Ground Water

    USGS Publications Warehouse

    Jurgens, Bryant C.; McMahon, Peter B.; Chapelle, Francis H.; Eberts, Sandra M.

    2009-01-01

    The reduction/oxidation (redox) condition of ground water affects the concentration, transport, and fate of many anthropogenic and natural contaminants. The redox state of a ground-water sample is defined by the dominant type of reduction/oxidation reaction, or redox process, occurring in the sample, as inferred from water-quality data. However, because of the difficulty in defining and applying a systematic redox framework to samples from diverse hydrogeologic settings, many regional water-quality investigations do not attempt to determine the predominant redox process in ground water. Recently, McMahon and Chapelle (2008) devised a redox framework that was applied to a large number of samples from 15 principal aquifer systems in the United States to examine the effect of redox processes on water quality. This framework was expanded by Chapelle and others (in press) to use measured sulfide data to differentiate between iron(III)- and sulfate-reducing conditions. These investigations showed that a systematic approach to characterize redox conditions in ground water could be applied to datasets from diverse hydrogeologic settings using water-quality data routinely collected in regional water-quality investigations. This report describes the Microsoft Excel workbook, RedoxAssignment_McMahon&Chapelle.xls, that assigns the predominant redox process to samples using the framework created by McMahon and Chapelle (2008) and expanded by Chapelle and others (in press). Assignment of redox conditions is based on concentrations of dissolved oxygen (O2), nitrate (NO3-), manganese (Mn2+), iron (Fe2+), sulfate (SO42-), and sulfide (sum of dihydrogen sulfide [aqueous H2S], hydrogen sulfide [HS-], and sulfide [S2-]). The logical arguments for assigning the predominant redox process to each sample are performed by a program written in Microsoft Visual Basic for Applications (VBA). The program is called from buttons on the main worksheet. The number of samples that can be analyzed

  12. Redox flow cell development and demonstration project, calendar year 1977

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Research and development on the redox flow cell conducted from January 1, 1977, to December 31, 1977, are described in this report. The major focus of the effort during 1977 was the key technology issues that directly influence the fundamental feasibility of the overall redox concept. These issues were the development of a suitable ion exchange membrane for the system, the screening and study of candidate redox couples to achieve optimum cell performance, and the carrying out of systems analysis and modeling to develop system performance goals and cost estimates.

  13. Clostridium thermocellum DSM 1313 transcriptional responses to redox perturbation

    DOE PAGES

    Sander, Kyle B.; Wilson, Charlotte M.; M. Rodriquez, Jr.; ...

    2015-12-12

    Clostridium thermocellum is a promising consolidated bioprocessing candidate organism capable of directly converting lignocellulosic biomass to ethanol. Current ethanol yields, productivities, and growth inhibitions are industrial deployment impediments for commodity fuel production by this bacterium. Redox imbalance under certain conditions and in engineered strains may contribute to incomplete substrate utilization and may direct fermentation products to undesirable overflow metabolites. As a result, towards a better understanding of redox metabolism in C. thermocellum, we established continuous growth conditions and analyzed global gene expression during addition of two stress chemicals (methyl viologen and hydrogen peroxide) which changed the fermentation redox potential.

  14. Study to establish cost projections for production of Redox chemicals

    NASA Technical Reports Server (NTRS)

    Walther, J. F.; Greco, C. C.; Rusinko, R. N.; Wadsworth, A. L., III

    1982-01-01

    A cost study of four proposed manufacturing processes for redox chemicals for the NASA REDOX Energy Storage System yielded favorable selling prices in the range $0.99 to $1.91/kg of chromic chloride, anhydrous basis, including ferrous chloride. The prices corresponded to specific energy storage costs from under $9 to $17/kWh. A refined and expanded cost analysis of the most favored process yielded a price estimate corresponding to a storage cost of $11/kWh. The findings supported the potential economic viability of the NASA REDOX system.

  15. The Redox Flow System for solar photovoltaic energy storage

    NASA Technical Reports Server (NTRS)

    Odonnell, P.; Gahn, R. F.; Pfeiffer, W.

    1976-01-01

    The interfacing of a Solar Photovoltaic System and a Redox Flow System for storage was workable. The Redox Flow System, which utilizes the oxidation-reduction capability of two redox couples, in this case iron and titanium, for its storage capacity, gave a relatively constant output regardless of solar activity so that a load could be run continually day and night utilizing the sun's energy. One portion of the system was connected to a bank of solar cells to electrochemically charge the solutions, while a separate part of the system was used to electrochemically discharge the stored energy.

  16. Glutathione redox potential in the mitochondrial intermembrane space is linked to the cytosol and impacts the Mia40 redox state

    PubMed Central

    Kojer, Kerstin; Bien, Melanie; Gangel, Heike; Morgan, Bruce; Dick, Tobias P; Riemer, Jan

    2012-01-01

    Glutathione is an important mediator and regulator of cellular redox processes. Detailed knowledge of local glutathione redox potential (EGSH) dynamics is critical to understand the network of redox processes and their influence on cellular function. Using dynamic oxidant recovery assays together with EGSH-specific fluorescent reporters, we investigate the glutathione pools of the cytosol, mitochondrial matrix and intermembrane space (IMS). We demonstrate that the glutathione pools of IMS and cytosol are dynamically interconnected via porins. In contrast, no appreciable communication was observed between the glutathione pools of the IMS and matrix. By modulating redox pathways in the cytosol and IMS, we find that the cytosolic glutathione reductase system is the major determinant of EGSH in the IMS, thus explaining a steady-state EGSH in the IMS which is similar to the cytosol. Moreover, we show that the local EGSH contributes to the partially reduced redox state of the IMS oxidoreductase Mia40 in vivo. Taken together, we provide a comprehensive mechanistic picture of the IMS redox milieu and define the redox influences on Mia40 in living cells. PMID:22705944

  17. Redox Control and Hydrogen Production in Sediment Caps Using Carbon Cloth Electrodes

    PubMed Central

    Sun, Mei; Yan, Fei; Zhang, Ruiling; Reible, Danny D.; Lowry, Gregory V.; Gregory, Kelvin B.

    2010-01-01

    Sediment caps that degrade contaminants can improve their ability to contain contaminants relative to sand and sorbent-amended caps, but few methods to enhance contaminant degradation in sediment caps are available. The objective of this study was to determine if, carbon electrodes emplaced within a sediment cap at poised potential could create a redox gradient and provide electron donor for the potential degradation of contaminants. In a simulated sediment cap overlying sediment from the Anacostia River (Washington, DC), electrochemically induced redox gradients were developed within 3 days and maintained over the period of the test (~100 days). Hydrogen and oxygen were produced by water electrolysis at the electrode surfaces and may serve as electron donor and acceptor for contaminant degradation. Electrochemical and geochemical factors that may influence hydrogen production were studied. Hydrogen production displayed zero order kinetics with ~75% coulombic efficiency and rates were proportional to the applied potential between 2.5V to 5V and not greatly affected by pH. Hydrogen production was promoted by increasing ionic strength and in the presence of natural organic matter. Graphite electrode-stimulated degradation of tetrachlorobenzene in a batch reactor was dependent on applied voltage and production of hydrogen to a concentration above the threshold for biological dechlorination. These findings suggest that electrochemical reactive capping can potentially be used to create “reactive” sediments caps capable of promoting chemical or biological transformations of contaminants within the cap. PMID:20879761

  18. Redox signaling regulated by an electrophilic cyclic nucleotide and reactive cysteine persulfides.

    PubMed

    Fujii, Shigemoto; Sawa, Tomohiro; Nishida, Motohiro; Ihara, Hideshi; Ida, Tomoaki; Motohashi, Hozumi; Akaike, Takaaki

    2016-04-01

    Reactive oxygen (oxidant) and free radical species are known to cause nonspecific damage of various biological molecules. The oxidant toxicology is developing an emerging concept of the physiological functions of reactive oxygen species in cell signaling regulation. Redox signaling is precisely modulated by endogenous electrophilic substances that are generated from reactive oxygen species during cellular oxidative stress responses. Among diverse electrophilic molecular species that are endogenously generated, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a unique second messenger whose formation, signaling, and metabolism in cells was recently clarified. Most important, our current studies revealed that reactive cysteine persulfides that are formed abundantly in cells are critically involved in the metabolism of 8-nitro-cGMP. Modern redox biology involves frontiers of cell research and stem cell research; medical and clinical investigations of infections, cancer, metabolic syndrome, aging, and neurodegenerative diseases; and other fields. 8-Nitro-cGMP-mediated signaling and metabolism in cells may therefore be potential targets for drug development, which may lead to discovery of new therapeutic agents for many diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Modelling sulfamethoxazole degradation under different redox conditions

    NASA Astrophysics Data System (ADS)

    Sanchez-Vila, X.; Rodriguez-Escales, P.

    2015-12-01

    Sulfamethoxazole (SMX) is a low adsorptive, polar, sulfonamide antibiotic, widely present in aquatic environments. Degradation of SMX in subsurface porous media is spatially and temporally variable, depending on various environmental factors such as in situ redox potential, availability of nutrients, local soil characteristics, and temperature. It has been reported that SMX is better degraded under anoxic conditions and by co-metabolism processes. In this work, we first develop a conceptual model of degradation of SMX under different redox conditions (denitrification and iron reducing conditions), and second, we construct a mathematical model that allows reproducing different experiments of SMX degradation reported in the literature. The conceptual model focuses on the molecular behavior and contemplates the formation of different metabolites. The model was validated using the experimental data from Barbieri et al. (2012) and Mohatt et al. (2011). It adequately reproduces the reversible degradation of SMX under the presence of nitrite as an intermediate product of denitrification. In those experiments degradation was mediated by the transient formation of a diazonium cation, which was considered responsible of the substitution of the amine radical by a nitro radical, forming the 4-nitro-SMX. The formation of this metabolite is a reversible process, so that once the concentration of nitrite was back to zero due to further advancement of denitrification, the concentration of SMX was fully recovered. The forward reaction, formation of 4-nitro SMX, was modeled considering a kinetic of second order, whereas the backward reaction, dissociation of 4-nitro-SMX back to the original compound, could be modeled with a first order degradation reaction. Regarding the iron conditions, SMX was degraded due to the oxidation of iron (Fe2+), which was previously oxidized from goethite due to the degradation of a pool of labile organic carbon. As the oxidation of iron occurred on the

  20. Iron Analysis by Redox Titration. A General Chemistry Experiment.

    ERIC Educational Resources Information Center

    Kaufman, Samuel; DeVoe, Howard

    1988-01-01

    Describes a simplified redox method for total iron analysis suitable for execution in a three-hour laboratory period by general chemistry students. Discusses materials, procedures, analyses, and student performance. (CW)

  1. Organic non-aqueous cation-based redox flow batteries

    SciTech Connect

    Zhang, Lu; Huang, Jinhua; Burrell, Anthony

    The present invention provides a non-aqueous redox flow battery comprising a negative electrode immersed in a non-aqueous liquid negative electrolyte, a positive electrode immersed in a non-aqueous liquid positive electrolyte, and a cation-permeable separator (e.g., a porous membrane, film, sheet, or panel) between the negative electrolyte from the positive electrolyte. During charging and discharging, the electrolytes are circulated over their respective electrodes. The electrolytes each comprise an electrolyte salt (e.g., a lithium or sodium salt), a transition-metal free redox reactant, and optionally an electrochemically stable organic solvent. Each redox reactant is selected from an organic compound comprising a conjugated unsaturatedmore » moiety, a boron cluster compound, and a combination thereof. The organic redox reactant of the positive electrolyte comprises a tetrafluorohydroquinone ether compound or a tetrafluorocatechol ether compound.« less

  2. E-tongue 2 REDOX response to heavy metals

    NASA Technical Reports Server (NTRS)

    Buehler, M. G.; Kuhlman, G. M.; Kounaves, S. P.

    2002-01-01

    E-Tongue 2 an array of electrochemical sensors including REDOX electrodes for Cylic Voltammetry and Anodic Stripping Voltammetry measurements, Galvanic cells for corrosion measurements, and Ion Selective Electrodes.

  3. Redox shuttles for overcharge protection of lithium batteries

    DOEpatents

    Amine, Khalil; Chen, Zonghai; Wang, Qingzheng

    2010-12-14

    The present invention is generally related to electrolytes containing novel redox shuttles for overcharge protection of lithium-ion batteries. The redox shuttles are capable of thousands hours of overcharge tolerance and have a redox potential at about 3-5.5 V vs. Li and particularly about 4.4-4.8 V vs. Li. Accordingly, in one aspect the invention provides electrolytes comprising an alkali metal salt; a polar aprotic solvent; and a redox shuttle additive that is an aromatic compound having at least one aromatic ring with four or more electronegative substituents, two or more oxygen atoms bonded to the aromatic ring, and no hydrogen atoms bonded to the aromatic ring; and wherein the electrolyte solution is substantially non-aqueous. Further there are provided electrochemical devices employing the electrolyte and methods of making the electrolyte.

  4. Applications of biochar in redox-mediated reactions.

    PubMed

    Yuan, Yong; Bolan, Nanthi; Prévoteau, Antonin; Vithanage, Meththika; Biswas, Jayanta Kumar; Ok, Yong Sik; Wang, Hailong

    2017-12-01

    Biochar is chemically more reduced and reactive than the original feedstock biomass. Graphite regions, functional groups, and redox-active metals in biochar contribute to its redox characteristics. While the functional groups such as phenolic species in biochar are the main electron donating moieties (i.e., reducers), the quinones and polycondensed aromatic functional groups are the components accepting electrons (oxidants). The redox capacity of biochar depends on feedstock properties and pyrolysis conditions. This paper aims to review and summarize the various synthesis techniques for biochars and the methods for probing their redox characteristics. We review the abiotic and microbial applications of biochars as electron donors, electron acceptors, or electron shuttles for pollutant degradation, metal(loid)s (im)mobilization, nutrient transformation, and discuss the underlying mechanisms. Furthermore, knowledge gaps that exist in the exploration and differentiation of the electron transfer mechanisms involving biochars are also identified. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Redox signaling in the cardiomyocyte: From physiology to failure.

    PubMed

    Santos, Celio X C; Raza, Sadaf; Shah, Ajay M

    2016-05-01

    The specific effect of oxygen and reactive oxygen species (ROS) in mediating post-translational modification of protein targets has emerged as a key mechanism regulating signaling components, a process termed redox signaling. ROS act in the post-translational modification of multiple target proteins including receptors, kinases, phosphatases, ion channels and transcription factors. Both O2 and ROS are major source of electrons in redox reactions in aerobic organisms. Because the heart has the highest O2 consumption among body organs, it is not surprising that redox signaling is central to heart function and pathophysiology. In this article, we review some of the main cardiac redox signaling pathways and their roles in the cardiomyocyte and in heart failure, with particular focus on the specific molecular targets of ROS in the heart. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Extracellular Matrix and Redox Signaling in Cellular Responses to Stress.

    PubMed

    Roberts, David D

    2017-10-20

    Cells in multicellular organisms communicate extensively with neighboring cells and distant organs using a variety of secreted proteins and small molecules. Cells also reside in a structural extracellular matrix (ECM), and changes in its composition, mechanical properties, and post-translational modifications provide additional layers of communication. This Forum addresses emerging mechanisms by which redox signaling controls and is controlled by changes in the ECM, focusing on the roles of matricellular proteins. These proteins engage specific cell surface signaling receptors, integrins, and proteoglycans to regulate the biosynthesis and catabolism of redox signaling molecules and the activation of their signal transducers. These signaling pathways, in turn, regulate the composition of ECM and its function. Covalent post-translational modifications of ECM by redox molecules further regulate its structure and function. Recent studies of acute injuries and chronic disease have identified important pathophysiological roles for this cross-talk and new therapeutic opportunities. Antioxid. Redox Signal. 27, 771-773.

  7. The Hallmarks of Cancer from a Redox Perspective.

    PubMed

    Hornsveld, Marten; Dansen, Tobias B

    2016-08-20

    For a healthy cell to turn into a cancer cell and grow out to become a tumor, it needs to undergo a series of complex changes and acquire certain traits, summarized as "The Hallmarks of Cancer." These hallmarks can all be regarded as the result of altered signal transduction cascades and an understanding of these cascades is essential for cancer treatment. Redox signaling is a long overlooked form of signal transduction that proceeds through the reversible oxidation of cysteines in proteins and that uses hydrogen peroxide as a second messenger. In this article, we provide examples that show that redox signaling is involved in the regulation of proteins and signaling cascades that play roles in every hallmark of cancer. An understanding of how redox signaling and "classical" signal transduction are intertwined could hold promising strategies for cancer therapy in the future. Antioxid. Redox Signal. 25, 300-325.

  8. Directly amplified redox sensor for on-chip chemical analysis

    NASA Astrophysics Data System (ADS)

    Takahashi, Sou; Futagawa, Masato; Ishida, Makoto; Sawada, Kazuaki

    2014-03-01

    In recent years, many groups have studied redox sensors for chemical analysis. A redox sensor has certain powerful advantages, such as its ability to detect multiple ions inside the sensing area, and its ability to measure concentrations of materials by using voltage and current signals. However, the output current signal of a redox sensor decreases when either concentration or sensing area decreases. Therefore, we propose the use of an amplified redox sensor (ARS) for measuring small current signals. The proposed sensor consists of a working electrode combined with a bipolar transistor. In this study, we fabricated an ARS sensor and performed low-concentration measurements using current signal amplification with an integrated bipolar transistor. The sensor chip successfully detected a potassium ferricyanide (K3[Fe(CN)6]) concentration of as low as 10 µM using cyclic voltammetry.

  9. Redox Transformations of Arsenic Oxyanions in Periphyton Communities

    PubMed Central

    Kulp, Thomas R.; Hoeft, Shelley E.; Oremland, Ronald S.

    2004-01-01

    Periphyton (Cladophora sp.) samples from a suburban stream lacking detectable dissolved As were able to reduce added As(V) to As(III) when incubated under anoxic conditions and, conversely, oxidized added As(III) to As(V) with aerobic incubation. Both types of activity were abolished in autoclaved controls, thereby demonstrating its biological nature. The reduction of As(V) was inhibited by chloramphenicol, indicating that it required the synthesis of new protein. Nitrate also inhibited As(V) reduction, primarily because it served as a preferred electron acceptor to which the periphyton community was already adapted. However, part of the inhibition was also caused by microbial reoxidation of As(III) linked to nitrate. Addition of [14C]glucose to anoxic samples resulted in the production of 14CO2, suggesting that the observed As(V) reduction was a respiratory process coupled to the oxidation of organic matter. The population density of As(V)-reducing bacteria within the periphyton increased with time and with the amount of As(V) added, reaching values as high as ∼106 cells ml−1 at the end of the incubation. This indicated that dissimilatory As(V) reduction in these populations was linked to growth. However, As(V)-respiring bacteria were found to be present, albeit at lower numbers (∼102 ml−1), in freshly sampled periphyton. These results demonstrate the presence of a bacterial population within the periphyton communities that is capable of two key arsenic redox transformations that were previously studied in As-contaminated environments, which suggests that these processes are widely distributed in nature. This assumption was reinforced by experiments with estuarine samples of Cladophora sericea in which we detected a similar capacity for anaerobic As(V) reduction and aerobic As(III) oxidation. PMID:15528502

  10. Redox transformations of arsenic oxyanions in periphyton communities

    USGS Publications Warehouse

    Kulp, T.R.; Hoeft, S.E.; Oremland, R.S.

    2004-01-01

    Periphyton (Cladophora sp.) samples from a suburban stream lacking detectable dissolved As were able to reduce added As(V) to As(III) when incubated under anoxic conditions and, conversely, oxidized added As(III) to As(V) with aerobic incubation. Both types of activity were abolished in autoclaved controls, thereby demonstrating its biological nature. The reduction of As(V) was inhibited by chloramphenicol, indicating that it required the synthesis of new protein. Nitrate also inhibited As(V) reduction, primarily because it served as a preferred electron acceptor to which the periphyton community was already adapted. However, part of the inhibition was also caused by microbial reoxidation of As(III) linked to nitrate. Addition of [ 14C]glucose to anoxic samples resulted in the production of 14CO2, suggesting that the observed As(V) reduction was a respiratory process coupled to the oxidation of organic matter. The population density of As(V)-reducing bacteria within the periphyton increased with time and with the amount of As(V) added, reaching values as high as ???106 cells ml-1 at the end of the incubation. This indicated that dissimilatory As(V) reduction in these populations was linked to growth. However, As(V)-respiring bacteria were found to be present, albeit at lower numbers (???102 ml-1), in freshly sampled periphyton. These results demonstrate the presence of a bacterial population within the periphyton communities that is capable of two key arsenic redox transformations that were previously studied in As-contaminated environments, which suggests that these processes are widely distributed in nature. This assumption was reinforced by experiments with estuarine samples of Cladophora sericea in which we detected a similar capacity for anaerobic As(V) reduction and aerobic As(III) oxidation.

  11. Redox processes and water quality of selected principal aquifer systems

    USGS Publications Warehouse

    McMahon, P.B.; Chapelle, F.H.

    2008-01-01

    Reduction/oxidation (redox) conditions in 15 principal aquifer (PA) systems of the United States, and their impact on several water quality issues, were assessed from a large data base collected by the National Water-Quality Assessment Program of the USGS. The logic of these assessments was based on the observed ecological succession of electron acceptors such as dissolved oxygen, nitrate, and sulfate and threshold concentrations of these substrates needed to support active microbial metabolism. Similarly, the utilization of solid-phase electron acceptors such as Mn(IV) and Fe(III) is indicated by the production of dissolved manganese and iron. An internally consistent set of threshold concentration criteria was developed and applied to a large data set of 1692 water samples from the PAs to assess ambient redox conditions. The indicated redox conditions then were related to the occurrence of selected natural (arsenic) and anthropogenic (nitrate and volatile organic compounds) contaminants in ground water. For the natural and anthropogenic contaminants assessed in this study, considering redox conditions as defined by this framework of redox indicator species and threshold concentrations explained many water quality trends observed at a regional scale. An important finding of this study was that samples indicating mixed redox processes provide information on redox heterogeneity that is useful for assessing common water quality issues. Given the interpretive power of the redox framework and given that it is relatively inexpensive and easy to measure the chemical parameters included in the framework, those parameters should be included in routine water quality monitoring programs whenever possible.

  12. Hydrologic influence on redox dynamics in estuarine environments

    NASA Astrophysics Data System (ADS)

    Michael, H. A.; Kim, K. H.; Guimond, J. A.; Heiss, J.; Ullman, W. J.; Seyfferth, A.

    2017-12-01

    Redox conditions in coastal aquifers control reactions that impact nutrient cycling, contaminant release, and carbon budgets, with implications for water resources and ecosystem health. Hydrologic changes can shift redox boundaries and inputs of reactants, especially in dynamic coastal systems subject to fluctuations on tidal, lunar, and longer timescales. We present two examples of redox shifts in estuarine systems in Delaware, USA: a beach aquifer and a saltmarsh. Beach aquifers are biogeochemical hot spots due to mixing between fresh groundwater and infiltrating seawater. At Cape Henlopen, DE, geochemical measurements identified reactions in the intertidal aquifer that include cycling of carbon, nitrogen, iron, and sulfur. Measurements and modeling illustrate that redox potential as well as the locations of redox reactions shift on tidal to seasonal timescales and in response to changing beach and aquifer properties, impacting overall rates of reactions such as denitrification that reduces N loads to coastal waters. In the St. Jones National Estuarine Research Reserve, tidal fluctuations in channels cause periodic groundwater-surface water exchange, water table movement, and intermittent flooding that varies spatially across the saltmarsh. These changes create shifts in redox potential that are greatest near channels and in the top 20 cm of sediments. The magnitude of redox change depends on hydrologic setting (near channels or in marsh interior), hydrologic conditions (tidal stage, seasonal shifts), as well as prevalence of macropores created by crab burrows that change seasonally with crab activity. These shifts correspond to changes in porewater chemistry that have implications for nutrient cycling and carbon export to the ocean. Understanding hydrologic influence on redox geochemistry is critical for predicting how these systems and their ecosystem services may change in the future in response to anthropogenic and climate change.

  13. Redox flow cell development and demonstration project, calendar year 1976

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The major focus of the effort was the key technology issues that directly influence the fundamental feasibility of the overall redox concept. These issues were the development of a suitable semipermeable separator membrane for the system, the screening and study of candidate redox couples to achieve optimum cell performance, and the carrying out of systems analysis and modeling to develop system performance goals and cost estimates.

  14. Method and apparatus for rebalancing a redox flow cell system

    NASA Technical Reports Server (NTRS)

    Gahn, Randall F. (Inventor)

    1986-01-01

    A rebalance cell is provided for a REDOX electrochemical system of the type having anode and cathode fluids which are aqueous HCl solutions with two metal species in each. The rebalance cell has a cathode compartment and a chlorine compartment separated by an ion permeable membrane. By applying an electrical potential to the rebalance cell while circulating cathode fluid through the cathode compartment and while circulating an identical fluid through the chlorine compartment, any significant imbalance of the REDOX system is prevented.

  15. Preparation of redox polymer cathodes for thin film rechargeable batteries

    DOEpatents

    Skotheim, T.A.; Lee, H.S.; Okamoto, Yoshiyuki.

    1994-11-08

    The present invention relates to the manufacture of thin film solid state electrochemical devices using composite cathodes comprising a redox polymer capable of undergoing oxidation and reduction, a polymer solid electrolyte and conducting carbon. The polymeric cathode material is formed as a composite of radiation crosslinked polymer electrolytes and radiation crosslinked redox polymers based on polysiloxane backbones with attached organosulfur side groups capable of forming sulfur-sulfur bonds during electrochemical oxidation.

  16. Method and apparatus for rebalancing a REDOX flow cell system

    NASA Technical Reports Server (NTRS)

    Gahn, R. F. (Inventor)

    1985-01-01

    A rebalance cell is provided for a REDOX electrochemical system of the type with anode and cathode fluids which are aqueous HC1 solutions with two metal species in each. The rebalance cell has a cathode compartment and a chlorine compartment separated by an ion permeable membrane. By applying an electrical potential to the rebalance cell while circulating cathode fluid through the cathode compartment and while circulating an identical fluid through the chlorine compartment, any significant imbalance of the REDOX system is prevented.

  17. Differentiating cancerous from normal breast tissue by redox imaging

    NASA Astrophysics Data System (ADS)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2015-02-01

    Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (p<0.05) and the redox ratio Fp/(NADH+Fp) was about 27% higher in the cancerous tissues than in the normal ones (p<0.05). Our findings suggest that the redox state could differentiate between cancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

  18. Complexation Key to a pH Locked Redox Reaction

    ERIC Educational Resources Information Center

    Rizvi, Masood Ahmad; Dangat, Yuvraj; Shams, Tahir; Khan, Khaliquz Zaman

    2016-01-01

    An unfavorable pH can block a feasible electron transfer for a pH dependent redox reaction. In this experiment, a series of potentiometric titrations demonstrate the sequential loss in feasibility of iron(II) dichromate redox reaction over a pH range of 0-4. The pH at which this reaction failed to occur was termed as a pH locked reaction. The…

  19. Fe-phyllosilicate redox cycling organisms from a redox transition zone in Hanford 300 Area sediments.

    PubMed

    Benzine, Jason; Shelobolina, Evgenya; Xiong, Mai Yia; Kennedy, David W; McKinley, James P; Lin, Xueju; Roden, Eric E

    2013-01-01

    Microorganisms capable of reducing or oxidizing structural iron (Fe) in Fe-bearing phyllosilicate minerals were enriched and isolated from a subsurface redox transition zone at the Hanford 300 Area site in eastern Washington, USA. Both conventional and in situ "i-chip" enrichment strategies were employed. One Fe(III)-reducing Geobacter (G. bremensis strain R1, Deltaproteobacteria) and six Fe(II) phyllosilicate-oxidizing isolates from the Alphaproteobacteria (Bradyrhizobium japonicum strains 22, is5, and in8p8), Betaproteobacteria (Cupriavidus necator strain A5-1, Dechloromonas agitata strain is5), and Actinobacteria (Nocardioides sp. strain in31) were recovered. The G. bremensis isolate grew by oxidizing acetate with the oxidized form of NAu-2 smectite as the electron acceptor. The Fe(II)-oxidizers grew by oxidation of chemically reduced smectite as the energy source with nitrate as the electron acceptor. The Bradyrhizobium isolates could also carry out aerobic oxidation of biotite. This is the first report of the recovery of a Fe(II)-oxidizing Nocardioides, and to date only one other Fe(II)-oxidizing Bradyrhizobium is known. The 16S rRNA gene sequences of the isolates were similar to ones found in clone libraries from Hanford 300 sediments and groundwater, suggesting that such organisms may be present and active in situ. Whole genome sequencing of the isolates is underway, the results of which will enable comparative genomic analysis of mechanisms of extracellular phyllosilicate Fe redox metabolism, and facilitate development of techniques to detect the presence and expression of genes associated with microbial phyllosilicate Fe redox cycling in sediments.

  20. Fe-phyllosilicate redox cycling organisms from a redox transition zone in Hanford 300 Area sediments

    PubMed Central

    Benzine, Jason; Xiong, Mai Yia; Kennedy, David W.; McKinley, James P.; Lin, Xueju; Roden, Eric E.

    2013-01-01

    Microorganisms capable of reducing or oxidizing structural iron (Fe) in Fe-bearing phyllosilicate minerals were enriched and isolated from a subsurface redox transition zone at the Hanford 300 Area site in eastern Washington, USA. Both conventional and in situ “i-chip” enrichment strategies were employed. One Fe(III)-reducing Geobacter (G. bremensis strain R1, Deltaproteobacteria) and six Fe(II) phyllosilicate-oxidizing isolates from the Alphaproteobacteria (Bradyrhizobium japonicum strains 22, is5, and in8p8), Betaproteobacteria (Cupriavidus necator strain A5-1, Dechloromonas agitata strain is5), and Actinobacteria (Nocardioides sp. strain in31) were recovered. The G. bremensis isolate grew by oxidizing acetate with the oxidized form of NAu-2 smectite as the electron acceptor. The Fe(II)-oxidizers grew by oxidation of chemically reduced smectite as the energy source with nitrate as the electron acceptor. The Bradyrhizobium isolates could also carry out aerobic oxidation of biotite. This is the first report of the recovery of a Fe(II)-oxidizing Nocardioides, and to date only one other Fe(II)-oxidizing Bradyrhizobium is known. The 16S rRNA gene sequences of the isolates were similar to ones found in clone libraries from Hanford 300 sediments and groundwater, suggesting that such organisms may be present and active in situ. Whole genome sequencing of the isolates is underway, the results of which will enable comparative genomic analysis of mechanisms of extracellular phyllosilicate Fe redox metabolism, and facilitate development of techniques to detect the presence and expression of genes associated with microbial phyllosilicate Fe redox cycling in sediments. PMID:24379809

  1. Genetic and biochemical investigations of the role of MamP in redox control of iron biomineralization in Magnetospirillum magneticum.

    PubMed

    Jones, Stephanie R; Wilson, Tiffany D; Brown, Margaret E; Rahn-Lee, Lilah; Yu, Yi; Fredriksen, Laura L; Ozyamak, Ertan; Komeili, Arash; Chang, Michelle C Y

    2015-03-31

    Magnetotactic bacteria have evolved complex subcellular machinery to construct linear chains of magnetite nanocrystals that allow the host cell to sense direction. Each mixed-valent iron nanoparticle is mineralized from soluble iron within a membrane-encapsulated vesicle termed the magnetosome, which serves as a specialized compartment that regulates the iron, redox, and pH environment of the growing mineral. To dissect the biological components that control this process, we have carried out a genetic and biochemical study of proteins proposed to function in iron mineralization. In this study, we show that the redox sites of c-type cytochromes of the Magnetospirillum magneticum AMB-1 magnetosome island, MamP and MamT, are essential to their physiological function and that ablation of one or both heme motifs leads to loss of function, suggesting that their ability to carry out redox chemistry in vivo is important. We also develop a method to heterologously express fully heme-loaded MamP from AMB-1 for in vitro biochemical studies, which show that its Fe(III)-Fe(II) redox couple is set at an unusual potential (-89 ± 11 mV) compared with other related cytochromes involved in iron reduction or oxidation. Despite its low reduction potential, it remains competent to oxidize Fe(II) to Fe(III) and mineralize iron to produce mixed-valent iron oxides. Finally, in vitro mineralization experiments suggest that Mms mineral-templating peptides from AMB-1 can modulate the iron redox chemistry of MamP.

  2. Electron transfer and docking between cytochrome cd1 nitrite reductase and different redox partners - A comparative study.

    PubMed

    Pedroso, Humberto A; Silveira, Célia M; Almeida, Rui M; Almeida, Ana; Besson, Stéphane; Moura, Isabel; Moura, José J G; Almeida, M Gabriela

    2016-09-01

    Cytochrome cd1 nitrite reductases (cd1NiRs) catalyze the reduction of nitrite to nitric oxide in denitrifying bacteria, such as Marinobacter hydrocarbonoclasticus. Previous work demonstrated that the enzymatic activity depends on a structural pre-activation triggered by the entry of electrons through the electron transfer (ET) domain, which houses a heme c center. The catalytic activity of M. hydrocarbonoclasticus cd1NiR (Mhcd1NiR) was tested by mediated electrochemistry, using small ET proteins and chemical redox mediators. The rate of enzymatic reaction depends on the nature of the redox partner, with cytochrome (cyt) c552 providing the highest value. In situations where cyt c552 is replaced by either a biological (cyt c from horse heart) or a chemical mediator the catalytic response was only observed at very low scan rates, suggesting that the intermolecular ET rate is much slower. Molecular docking simulations with the 3D model structure of Mhcd1NiR and cyt c552 or cyt c showed that hydrophobic interactions favor the formation of complexes where the heme c domain of the enzyme is the principal docking site. However, only in the case of cyt c552 the preferential areas of contact and Fe-Fe distances between heme c groups of the redox partners allow establishing competent ET pathways. The coupling of the enzyme with chemical redox mediators was also found not to be energetically favorable. These results indicate that although low activity functional complexes can be formed between Mhcd1NiR and different types of redox mediators, efficient ET is only observed with the putative physiological electron donor cyt c552. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Wine consumption and intestinal redox homeostasis.

    PubMed

    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.

  4. Redox chemistry in the phosphorus biogeochemical cycle

    NASA Astrophysics Data System (ADS)

    Pasek, Matthew A.; Sampson, Jacqueline M.; Atlas, Zachary

    2014-10-01

    The element phosphorus (P) controls growth in many ecosystems as the limiting nutrient, where it is broadly considered to reside as pentavalent P in phosphate minerals and organic esters. Exceptions to pentavalent P include phosphine-PH3-a trace atmospheric gas, and phosphite and hypophosphite, P anions that have been detected recently in lightning strikes, eutrophic lakes, geothermal springs, and termite hindguts. Reduced oxidation state P compounds include the phosphonates, characterized by C-P bonds, which bear up to 25% of total organic dissolved phosphorus. Reduced P compounds have been considered to be rare; however, the microbial ability to use reduced P compounds as sole P sources is ubiquitous. Here we show that between 10% and 20% of dissolved P bears a redox state of less than +5 in water samples from central Florida, on average, with some samples bearing almost as much reduced P as phosphate. If the quantity of reduced P observed in the water samples from Florida studied here is broadly characteristic of similar environments on the global scale, it accounts well for the concentration of atmospheric phosphine and provides a rationale for the ubiquity of phosphite utilization genes in nature. Phosphine is generated at a quantity consistent with thermodynamic equilibrium established by the disproportionation reaction of reduced P species. Comprising 10-20% of the total dissolved P inventory in Florida environments, reduced P compounds could hence be a critical part of the phosphorus biogeochemical cycle, and in turn may impact global carbon cycling and methanogenesis.

  5. Wine consumption and intestinal redox homeostasis

    PubMed Central

    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

  6. Redox Conditions Among the Terrestrial Planets

    NASA Technical Reports Server (NTRS)

    Jones, J. H.

    2004-01-01

    Early solar system conditions should have been extremely reducing. The redox state of the early solar nebula was determined by the H2O/H2 of the gas, which is calculated (based on solar composition) to have been about IW-5. At high temperature under such conditions, ferrous iron would exist only as a trace element in silicates and the most common type of chondritic material should have been enstatite chondrites. The observation that E-chondrites form only a subset of the chondrite suite and that the terrestrial planets (Earth, Moon, Mars, Venus, 4 Vesta) contain ferrous and ferric iron as major and minor elements, respectively, implies that either most chondritic materials formed under conditions that were not solar or that early-formed metals oxidized at low temperature, producing FeO. For example, equilibrated ordinary chondrites (by definition, common chondritic materials), by their phase assemblage of olivine, orthopyroxene and metal, must fall not far from the QFI (Quartz-Fayalite-Iron) oxygen buffer. The QFI buffer is about IW-0.5 and, as we shall see, this fo2 is close to that inferred for many materials in the inner solar system.

  7. Redox State of the Neoarchean Earth Environment

    NASA Technical Reports Server (NTRS)

    Zerkle, Aubrey L.; Claire, Mark W.; Domagal-Goldman, Shawn; Farquhar, James; Poulton, Simon W.

    2011-01-01

    A Titan-like organic haze has been hypothesized for Earth's atmosphere prior to widespread surface oxygenation approx.2.45 billion years ago (Ga). We present a high-resolution record of quadruple sulfur isotopes, carbon isotopes, and Fe speciation from the approx.2.65-2.5 Ga Ghaap Group, South Africa, which suggest a linkage between organic haze and the biogeochemical cycling of carbon, sulfur, oxygen, and iron on the Archean Earth. These sediments provide evidence for oxygen production in microbial mats and localized oxygenation of surface waters. However, this oxygen production occurred under a reduced atmosphere which existed in multiple distinct redox states that correlate to changes in carbon and sulfur isotopes. The data are corroborated by photochemical model results that suggest bi-stable transitions between organic haze and haze-free atmospheric conditions in the Archean. These geochemical correlations also extend to other datasets, indicating that variations in the character of anomalous sulfur fractionation could provide insight into the role of carbon-bearing species in the reducing Archean atmosphere.

  8. Electrode redox reactions with polarizable molecules.

    PubMed

    Matyushov, Dmitry V

    2018-04-21

    A theory of redox reactions involving electron transfer between a metal electrode and a polarizable molecule in solution is formulated. Both the existence of molecular polarizability and its ability to change due to electron transfer distinguish this problem from classical theories of interfacial electrochemistry. When the polarizability is different between the oxidized and reduced states, the statistics of thermal fluctuations driving the reactant over the activation barrier becomes non-Gaussian. The problem of electron transfer is formulated as crossing of two non-parabolic free energy surfaces. An analytical solution for these free energy surfaces is provided and the activation barrier of electrode electron transfer is given in terms of two reorganization energies corresponding to the oxidized and reduced states of the molecule in solution. The new non-Gaussian theory is, therefore, based on two theory parameters in contrast to one-parameter Marcus formulation for electrode reactions. The theory, which is consistent with the Nernst equation, predicts asymmetry between the cathodic and anodic branches of the electrode current. They show different slopes at small electrode overpotentials and become curved at larger overpotentials. However, the curvature of the Tafel plot is reduced compared to the Marcus-Hush model and approaches the empirical Butler-Volmer form with different transfer coefficients for the anodic and cathodic currents.

  9. Electrode redox reactions with polarizable molecules

    NASA Astrophysics Data System (ADS)

    Matyushov, Dmitry V.

    2018-04-01

    A theory of redox reactions involving electron transfer between a metal electrode and a polarizable molecule in solution is formulated. Both the existence of molecular polarizability and its ability to change due to electron transfer distinguish this problem from classical theories of interfacial electrochemistry. When the polarizability is different between the oxidized and reduced states, the statistics of thermal fluctuations driving the reactant over the activation barrier becomes non-Gaussian. The problem of electron transfer is formulated as crossing of two non-parabolic free energy surfaces. An analytical solution for these free energy surfaces is provided and the activation barrier of electrode electron transfer is given in terms of two reorganization energies corresponding to the oxidized and reduced states of the molecule in solution. The new non-Gaussian theory is, therefore, based on two theory parameters in contrast to one-parameter Marcus formulation for electrode reactions. The theory, which is consistent with the Nernst equation, predicts asymmetry between the cathodic and anodic branches of the electrode current. They show different slopes at small electrode overpotentials and become curved at larger overpotentials. However, the curvature of the Tafel plot is reduced compared to the Marcus-Hush model and approaches the empirical Butler-Volmer form with different transfer coefficients for the anodic and cathodic currents.

  10. Redox Flow Batteries, Hydrogen and Distributed Storage.

    PubMed

    Dennison, C R; Vrubel, Heron; Amstutz, Véronique; Peljo, Pekka; Toghill, Kathryn E; Girault, Hubert H

    2015-01-01

    Social, economic, and political pressures are causing a shift in the global energy mix, with a preference toward renewable energy sources. In order to realize widespread implementation of these resources, large-scale storage of renewable energy is needed. Among the proposed energy storage technologies, redox flow batteries offer many unique advantages. The primary limitation of these systems, however, is their limited energy density which necessitates very large installations. In order to enhance the energy storage capacity of these systems, we have developed a unique dual-circuit architecture which enables two levels of energy storage; first in the conventional electrolyte, and then through the formation of hydrogen. Moreover, we have begun a pilot-scale demonstration project to investigate the scalability and technical readiness of this approach. This combination of conventional energy storage and hydrogen production is well aligned with the current trajectory of modern energy and mobility infrastructure. The combination of these two means of energy storage enables the possibility of an energy economy dominated by renewable resources.

  11. Scaling Behavior in Mitochondrial Redox Fluctuations

    PubMed Central

    Ramanujan, V. Krishnan; Biener, Gabriel; Herman, Brian A.

    2006-01-01

    Scale-invariant long-range correlations have been reported in fluctuations of time-series signals originating from diverse processes such as heart beat dynamics, earthquakes, and stock market data. The common denominator of these apparently different processes is a highly nonlinear dynamics with competing forces and distinct feedback species. We report for the first time an experimental evidence for scaling behavior in NAD(P)H signal fluctuations in isolated mitochondria and intact cells isolated from the liver of a young (5-month-old) mouse. Time-series data were collected by two-photon imaging of mitochondrial NAD(P)H fluorescence and signal fluctuations were quantitatively analyzed for statistical correlations by detrended fluctuation analysis and spectral power analysis. Redox [NAD(P)H / NAD(P)+] fluctuations in isolated mitochondria and intact liver cells were found to display nonrandom, long-range correlations. These correlations are interpreted as arising due to the regulatory dynamics operative in Krebs' cycle enzyme network and electron transport chain in the mitochondria. This finding may provide a novel basis for understanding similar regulatory networks that govern the nonequilibrium properties of living cells. PMID:16565066

  12. The Chloroplast ATP Synthase Features the Characteristic Redox Regulation Machinery

    PubMed Central

    Sunamura, Ei-Ichiro; Kim, Yusung; Konno, Hiroki

    2013-01-01

    Abstract Significance: Regulation of the activity of the chloroplast ATP synthase is largely accomplished by the chloroplast thioredoxin system, the main redox regulation system in chloroplasts, which is directly coupled to the photosynthetic reaction. We review the current understanding of the redox regulation system of the chloroplast ATP synthase. Recent Advances: The thioredoxin-targeted portion of the ATP synthase consists of two cysteines located on the central axis subunit γ. The redox state of these two cysteines is under the influence of chloroplast thioredoxin, which directly controls rotation during catalysis by inducing a conformational change in this subunit. The molecular mechanism of redox regulation of the chloroplast ATP synthase has recently been determined. Critical Issues: Regulation of the activity of the chloroplast ATP synthase is critical in driving efficiency into the ATP synthesis reaction in chloroplasts. Future Directions: The molecular architecture of the chloroplast ATP synthase, which confers redox regulatory properties requires further investigation, in light of the molecular structure of the enzyme complex as well as the physiological significance of the regulation system. Antioxid. Redox Signal. 19, 1846–1854. PMID:23145525

  13. Coupling desalination and energy storage with redox flow electrodes.

    PubMed

    Hou, Xianhua; Liang, Qian; Hu, Xiaoqiao; Zhou, Yu; Ru, Qiang; Chen, Fuming; Hu, Shejun

    2018-06-26

    Both freshwater shortage and energy crisis are global issues. Herein, we present a double-function system of faradaic desalination and a redox flow battery consisting of VCl3|NaI redox flow electrodes and a feed stream. The system has a nominal cell potential (E0 = +0.79 V). During the discharge process, the salt ions in the feed are extracted by the redox reaction of the flow electrodes, which is indicated by salt removal. Stable and reversible salt removal capacity and electricity can be achieved up to 30 cycles. The energy consumption is as low as 10.27 kJ mol-1 salt. The energy efficiency is as high as 50% in the current aqueous redox flow battery. With energy recovery, the desalination energy consumption decreases greatly to 5.38 kJ mol-1; this is the lowest reported value to date. This "redox flow battery desalination generator" can be operated in a voltage range of 0.3-1.1 V. Our research provides a novel method for obtaining energy-saving desalination and redox flow batteries.

  14. Redox-Assisted Protein Folding Systems in Eukaryotic Parasites

    PubMed Central

    Haque, Saikh Jaharul; Majumdar, Tanmay

    2012-01-01

    Abstract Significance: The cysteine (Cys) residues of proteins play two fundamentally important roles. They serve as sites of post-translational redox modifications as well as influence the conformation of the protein through the formation of disulfide bonds. Recent Advances: Redox-related and redox-associated protein folding in protozoan parasites has been found to be a major mode of regulation, affecting myriad aspects of the parasitic life cycle, host-parasite interactions, and the disease pathology. Available genome sequences of various parasites have begun to complement the classical biochemical and enzymological studies of these processes. In this article, we summarize the reversible Cys disulfide (S-S) bond formation in various classes of strategically important parasitic proteins, and its structural consequence and functional relevance. Critical Issues: Molecular mechanisms of folding remain under-studied and often disconnected from functional relevance. Future Directions: The clinical benefit of redox research will require a comprehensive characterization of the various isoforms and paralogs of the redox enzymes and their concerted effect on the structure and function of the specific parasitic client proteins. Antioxid. Redox Signal. 17, 674–683. PMID:22122448

  15. Squaraine dyes as efficient coupling bridges between triarylamine redox centres.

    PubMed

    Völker, Sebastian F; Renz, Manuel; Kaupp, Martin; Lambert, Christoph

    2011-12-09

    Various indolenine squarylium dyes with additional electron-donating amine redox centres have been synthesised and their redox chemistry has been studied. A combination of cyclic voltammetry, spectro-electrochemistry and DFT calculations has been used to characterise the electronic structure of the mono-, di- and, in one case, trications. All monocations still retain the cyanine-like, delocalised character due to the relatively low redox potential of the squaraine bridge and are therefore compounds of Robin-Day class III. Thus we extended previous studies on organic mixed-valence systems by using the indolenine squaraine moiety as very electron-rich bridge between two electron-donating amine redox centres to provoke a strong coupling between the additional redox centres. We synthesised TA3, which has an N-N distance of 26 bonds between the triarylamine redox centres and is to our knowledge the longest bis(triarylamine) radical cation that is completely delocalised. We furthermore show that altering the symmetry of a squaraine dye by substitution of a squaric ring oxygen atom by a dicyanomethylene group has a direct impact on the optical properties of the monocations. In case of the dications, it turned out that the energetically most stable state of dianisylamine-substituted squaraines is an anti-ferromagnetically coupled open-shell singlet state. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Electrochemistry of redox-active self-assembled monolayers

    PubMed Central

    Eckermann, Amanda L.; Feld, Daniel J.; Shaw, Justine A.; Meade, Thomas J.

    2010-01-01

    Redox-active self-assembled monolayers (SAMs) provide an excellent platform for investigating electron transfer kinetics. Using a well-defined bridge, a redox center can be positioned at a fixed distance from the electrode and electron transfer kinetics probed using a variety of electrochemical techniques. Cyclic voltammetry, AC voltammetry, electrochemical impedance spectroscopy, and chronoamperometry are most commonly used to determine the rate of electron transfer of redox-activated SAMs. A variety of redox species have been attached to SAMs, and include transition metal complexes (e.g., ferrocene, ruthenium pentaammine, osmium bisbipyridine, metal clusters) and organic molecules (e.g., galvinol, C60). SAMs offer an ideal environment to study the outer-sphere interactions of redox species. The composition and integrity of the monolayer and the electrode material influence the electron transfer kinetics and can be investigated using electrochemical methods. Theoretical models have been developed for investigating SAM structure. This review discusses methods and monolayer compositions for electrochemical measurements of redox-active SAMs. PMID:20563297

  17. Thiol-redox signaling, dopaminergic cell death, and Parkinson's disease.

    PubMed

    Garcia-Garcia, Aracely; Zavala-Flores, Laura; Rodriguez-Rocha, Humberto; Franco, Rodrigo

    2012-12-15

    Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta, which has been widely associated with oxidative stress. However, the mechanisms by which redox signaling regulates cell death progression remain elusive. Early studies demonstrated that depletion of glutathione (GSH), the most abundant low-molecular-weight thiol and major antioxidant defense in cells, is one of the earliest biochemical events associated with PD, prompting researchers to determine the role of oxidative stress in dopaminergic cell death. Since then, the concept of oxidative stress has evolved into redox signaling, and its complexity is highlighted by the discovery of a variety of thiol-based redox-dependent processes regulating not only oxidative damage, but also the activation of a myriad of signaling/enzymatic mechanisms. GSH and GSH-based antioxidant systems are important regulators of neurodegeneration associated with PD. In addition, thiol-based redox systems, such as peroxiredoxins, thioredoxins, metallothioneins, methionine sulfoxide reductases, transcription factors, as well as oxidative modifications in protein thiols (cysteines), including cysteine hydroxylation, glutathionylation, and nitrosylation, have been demonstrated to regulate dopaminergic cell loss. In this review, we summarize major advances in the understanding of the role of thiol-redox signaling in dopaminergic cell death in experimental PD. Future research is still required to clearly understand how integrated thiol-redox signaling regulates the activation of the cell death machinery, and the knowledge generated should open new avenues for the design of novel therapeutic approaches against PD.

  18. Lipid Raft Redox Signaling: Molecular Mechanisms in Health and Disease

    PubMed Central

    Zhou, Fan; Katirai, Foad

    2011-01-01

    Abstract Lipid rafts, the sphingolipid and cholesterol-enriched membrane microdomains, are able to form different membrane macrodomains or platforms upon stimulations, including redox signaling platforms, which serve as a critical signaling mechanism to mediate or regulate cellular activities or functions. In particular, this raft platform formation provides an important driving force for the assembling of NADPH oxidase subunits and the recruitment of other related receptors, effectors, and regulatory components, resulting, in turn, in the activation of NADPH oxidase and downstream redox regulation of cell functions. This comprehensive review attempts to summarize all basic and advanced information about the formation, regulation, and functions of lipid raft redox signaling platforms as well as their physiological and pathophysiological relevance. Several molecular mechanisms involving the formation of lipid raft redox signaling platforms and the related therapeutic strategies targeting them are discussed. It is hoped that all information and thoughts included in this review could provide more comprehensive insights into the understanding of lipid raft redox signaling, in particular, of their molecular mechanisms, spatial-temporal regulations, and physiological, pathophysiological relevances to human health and diseases. Antioxid. Redox Signal. 15, 1043–1083. PMID:21294649

  19. Principles in redox signaling: from chemistry to functional significance.

    PubMed

    Bindoli, Alberto; Rigobello, Maria Pia

    2013-05-01

    Reactive oxygen and nitrogen species are currently considered not only harmful byproducts of aerobic respiration but also critical mediators of redox signaling. The molecules and the chemical principles sustaining the network of cellular redox regulated processes are described. Special emphasis is placed on hydrogen peroxide (H(2)O(2)), now considered as acting as a second messenger, and on sulfhydryl groups, which are the direct targets of the oxidant signal. Cysteine residues of some proteins, therefore, act as sensors of redox conditions and are oxidized in a reversible reaction. In particular, the formation of sulfenic acid and disulfide, the initial steps of thiol oxidation, are described in detail. The many cell pathways involved in reactive oxygen species formation are reported. Central to redox signaling processes are the glutathione and thioredoxin systems controlling H(2)O(2) levels and, hence, the thiol/disulfide balance. Lastly, some of the most important redox-regulated processes involving specific enzymes and organelles are described. The redox signaling area of research is rapidly expanding, and future work will examine new pathways and clarify their importance in cellular pathophysiology.

  20. Modulation of Chlamydomonas reinhardtii flagellar motility by redox poise

    PubMed Central

    Wakabayashi, Ken-ichi; King, Stephen M.

    2006-01-01

    Redox-based regulatory systems are essential for many cellular activities. Chlamydomonas reinhardtii exhibits alterations in motile behavior in response to different light conditions (photokinesis). We hypothesized that photokinesis is signaled by variations in cytoplasmic redox poise resulting from changes in chloroplast activity. We found that this effect requires photosystem I, which generates reduced NADPH. We also observed that photokinetic changes in beat frequency and duration of the photophobic response could be obtained by altering oxidative/reductive stress. Analysis of reactivated cell models revealed that this redox poise effect is mediated through the outer dynein arms (ODAs). Although the global redox state of the thioredoxin-related ODA light chains LC3 and LC5 and the redox-sensitive Ca2+-binding subunit of the docking complex DC3 did not change upon light/dark transitions, we did observe significant alterations in their interactions with other flagellar components via mixed disulfides. These data indicate that redox poise directly affects ODAs and suggest that it may act in the control of flagellar motility. PMID:16754958

  1. Reply to 'Comment on kinetic modeling of microbially-driven redox chemistry of subsurface environments: coupling transport, microbial metabolism and geochemistry' by J. Griffioen

    NASA Astrophysics Data System (ADS)

    Hunter, K. S.; Van Cappellen, P.

    2000-01-01

    Our paper, 'Kinetic modeling of microbially-driven redox chemistry of subsurface environments: coupling transport, microbial metabolism and geochemistry' (Hunter et al., 1998), presents a theoretical exploration of biogeochemical reaction networks and their importance to the biogeochemistry of groundwater systems. As with any other model, the kinetic reaction-transport model developed in our paper includes only a subset of all physically, biologically and chemically relevant processes in subsurface environments. It considers aquifer systems where the primary energy source driving microbial activity is the degradation of organic matter. In addition to the primary biodegradation pathways of organic matter (i.e. respiration and fermentation), the redox chemistry of groundwaters is also affected by reactions not directly involving organic matter oxidation. We refer to the latter as secondary reactions. By including secondary redox reactions which consume reduced reaction products (e.g., Mn2+, FeS, H2S), and in the process compete with microbial heterotrophic populations for available oxidants (i.e. O2, NO3-, Mn(IV), Fe(III), SO42-), we predict spatio-temporal distributions of microbial activity which differ significantly from those of models which consider only the biodegradation reactions. That is, the secondary reactions have a significant impact on the distributions of the rates of heterotrophic and chemolithotrophic metabolic pathways. We further show that secondary redox reactions, as well as non-redox reactions, significantly influence the acid-base chemistry of groundwaters. The distributions of dissolved inorganic redox species along flowpaths, however, are similar in simulations with and without secondary reactions (see Figs. 3(b) and 7(b) in Hunter et al., 1998), indicating that very different biogeochemical reaction dynamics may lead to essentially the same chemical redox zonation of a groundwater system.

  2. Biological oscillations: Fluorescence monitoring by confocal microscopy

    NASA Astrophysics Data System (ADS)

    Chattoraj, Shyamtanu; Bhattacharyya, Kankan

    2016-09-01

    Fluctuations play a vital role in biological systems. Single molecule spectroscopy has recently revealed many new kinds of fluctuations in biological molecules. In this account, we focus on structural fluctuations of an antigen-antibody complex, conformational dynamics of a DNA quadruplex, effects of taxol on dynamics of microtubules, intermittent red-ox oscillations at different organelles in a live cell (mitochondria, lipid droplets, endoplasmic reticulum and cell membrane) and stochastic resonance in gene silencing. We show that there are major differences in these dynamics between a cancer cell and the corresponding non-cancer cell.

  3. Biological Filters.

    ERIC Educational Resources Information Center

    Klemetson, S. L.

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. The review is concerned with biological filters, and it covers: (1) trickling filters; (2) rotating biological contractors; and (3) miscellaneous reactors. A list of 14 references is also presented. (HM)

  4. Playing with Cardiac “Redox Switches”: The “HNO Way” to Modulate Cardiac Function

    PubMed Central

    Tocchetti, Carlo G.; Stanley, Brian A.; Murray, Christopher I.; Sivakumaran, Vidhya; Donzelli, Sonia; Mancardi, Daniele; Pagliaro, Pasquale; Gao, Wei Dong; van Eyk, Jennifer; Kass, David A.; Wink, David A.

    2011-01-01

    Abstract The nitric oxide (NO•) sibling, nitroxyl or nitrosyl hydride (HNO), is emerging as a molecule whose pharmacological properties include providing functional support to failing hearts. HNO also preconditions myocardial tissue, protecting it against ischemia-reperfusion injury while exerting vascular antiproliferative actions. In this review, HNO's peculiar cardiovascular assets are discussed in light of its unique chemistry that distinguish HNO from NO• as well as from reactive oxygen and nitrogen species such as the hydroxyl radical and peroxynitrite. Included here is a discussion of the possible routes of HNO formation in the myocardium and its chemical targets in the heart. HNO has been shown to have positive inotropic/lusitropic effects under normal and congestive heart failure conditions in animal models. The mechanistic intricacies of the beneficial cardiac effects of HNO are examined in cellular models. In contrast to β-receptor/cyclic adenosine monophosphate/protein kinase A-dependent enhancers of myocardial performance, HNO uses its “thiophylic” nature as a vehicle to interact with redox switches such as cysteines, which are located in key components of the cardiac electromechanical machinery ruling myocardial function. Here, we will briefly review new features of HNO's cardiovascular effects that when combined with its positive inotropic/lusitropic action may render HNO donors an attractive addition to the current therapeutic armamentarium for treating patients with acutely decompensated congestive heart failure. Antioxid. Redox Signal. 14, 1687–1698. PMID:21235349

  5. Biological properties

    Treesearch

    Rebecca E. Ibach

    2005-01-01

    There are numerous biological degradations that wood is exposed to in various environments. Biological damage occurs when a log, sawn product, or final product is not stored, handled, or designed properly. Biological organisms, such as bacteria, mold, stain, decay fungi, insects, and marine borers, depend heavily on temperature and moisture conditions to grow. A higher...

  6. Redox electrodeposition polymers: adaptation of the redox potential of polymer-bound Os complexes for bioanalytical applications.

    PubMed

    Guschin, Dmitrii A; Castillo, John; Dimcheva, Nina; Schuhmann, Wolfgang

    2010-10-01

    The design of polymers carrying suitable ligands for coordinating Os complexes in ligand exchange reactions against labile chloro ligands is a strategy for the synthesis of redox polymers with bound Os centers which exhibit a wide variation in their redox potential. This strategy is applied to polymers with an additional variation of the properties of the polymer backbone with respect to pH-dependent solubility, monomer composition, hydrophilicity etc. A library of Os-complex-modified electrodeposition polymers was synthesized and initially tested with respect to their electron-transfer ability in combination with enzymes such as glucose oxidase, cellobiose dehydrogenase, and PQQ-dependent glucose dehydrogenase entrapped during the pH-induced deposition process. The different polymer-bound Os complexes in a library containing 50 different redox polymers allowed the statistical evaluation of the impact of an individual ligand to the overall redox potential of an Os complex. Using a simple linear regression algorithm prediction of the redox potential of Os complexes becomes feasible. Thus, a redox polymer can now be designed to optimally interact in electron-transfer reactions with a selected enzyme.

  7. Regulatory mechanisms of thiol-based redox sensors: lessons learned from structural studies on prokaryotic redox sensors.

    PubMed

    Lee, Sang Jae; Kim, Dong-Gyun; Lee, Kyu-Yeon; Koo, Ji Sung; Lee, Bong-Jin

    2018-05-17

    Oxidative stresses, such as reactive oxygen species, reactive electrophilic species, reactive nitrogen species, and reactive chlorine species, can damage cellular components, leading to cellular malfunction and death. In response to oxidative stress, bacteria have evolved redox-responsive sensors that enable them to simultaneously monitor and eradicate potential oxidative stress. Specifically, redox-sensing transcription regulators react to oxidative stress by means of modifying the thiol groups of cysteine residues, functioning as part of an efficient survival mechanism for many bacteria. In general, oxidative molecules can induce changes in the three-dimensional structures of redox sensors, which, in turn, affects the transcription of specific genes in detoxification pathways and defense mechanisms. Moreover, pathogenic bacteria utilize these redox sensors for adaptation and to evade subsequent oxidative attacks from host immune defense. For this reason, the redox sensors of pathogenic bacteria are potential antibiotic targets. Understanding the regulatory mechanisms of thiol-based redox sensors in bacteria will provide insight and knowledge into the discovery of new antibiotics.

  8. Redox potential - field measurements - meassured vs. expected values

    NASA Astrophysics Data System (ADS)

    Stavělová, Monika; Kovář, Martin

    2016-04-01

    Oxidation and reduction (redox) potential is an important and theoretically very well defined parameter and can be calculated accurately. Its value is determinative for management of many electrochemical processes, chemical redox technologies as well as biotechnologies. To measure the redox value that would correspond with the accuracy level of theoretical calculations in field or operational conditions is however nearly impossible. Redox is in practice measured using combined argentochloride electrode with subsequent value conversion to standard hydrogen electrode (EH). Argentochloride electrode does not allow for precise calibration. Prior to the measurement the accuracy of measurement of particular electrode can only be verified in comparative/control solution with value corresponding with oxic conditions (25°C: +220 mV argentochloride electrode, i.e.. +427 mV after conversion to EH). A commercial product of stabile comparative solution for anoxic conditions is not available and therefore not used in every day practice - accuracy of negative redox is not verified. In this presentation results of two tests will be presented: a) monitoring during dynamic groundwater sampling from eight monitoring wells at a site contaminated by chlorinated ethenes (i.e. post-oxic to anoxic conditions) and b) laboratory test of groundwater contaminated by arsenic from two sites during reaction with highly oxidized compounds of iron (ferrates) - i.e. strongly oxic conditions. In both tests a simultaneous measurement by four argentochloride electrodes was implemented - all four electrodes were prior to the test maintained expertly. The redox values of testing electrodes in a comparative solution varied by max. 6 mV. The redox values measured by four electrodes in both anoxic and oxic variant varied by tens to a hundred mV, while with growing time of test the variance of measured redox values increased in both oxic and anoxic variant. Therefore the interpretation of measured redox

  9. Redox and non-redox mechanism of in vitro cyclooxygenase inhibition by natural quinones.

    PubMed

    Landa, Premysl; Kutil, Zsofia; Temml, Veronika; Vuorinen, Anna; Malik, Jan; Dvorakova, Marcela; Marsik, Petr; Kokoska, Ladislav; Pribylova, Marie; Schuster, Daniela; Vanek, Tomas

    2012-03-01

    In this study, ten anthra-, nine naphtho-, and five benzoquinone compounds of natural origin and five synthetic naphthoquinones were assessed, using an enzymatic in vitro assay, for their potential to inhibit cyclooxygenase-1 and -2 (COX-1 and COX-2), the key enzymes of the arachidonic acid cascade. IC₅₀ values comparable with COX reference inhibitor indomethacin were recorded for several quinones (primin, alkannin, diospyrin, juglone, 7-methyljuglone, and shikonin). For some of the compounds, we suggest the redox potential of quinones as the mechanism responsible for in vitro COX inhibition because of the quantitative correlation with their pro-oxidant effect. Structure-relationship activity studies revealed that the substitutions at positions 2 and 5 play the key roles in the COX inhibitory and pro-oxidant actions of naphthoquinones. In contrast, the redox mechanism alone could not explain the activity of primin, embelin, alkannin, and diospyrin. For these four quinones, molecular modeling suggested similar binding modes as for conventional nonsteroidal anti-inflammatory drugs (NSAIDs). © Georg Thieme Verlag KG Stuttgart · New York.

  10. A Membrane‐Free Redox Flow Battery with Two Immiscible Redox Electrolytes

    PubMed Central

    Navalpotro, Paula; Palma, Jesus; Anderson, Marc

    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 and where vanadium is replaced by organic molecules. We show that the biphasic system formed by one acidic solution and one ionic liquid, both containing quinoyl species, behaves as a reversible battery without any membrane. This proof‐of‐concept of a membrane‐free battery has an open circuit voltage of 1.4 V with a high theoretical energy density of 22.5 Wh L−1, and is able to deliver 90 % of its theoretical capacity while showing excellent long‐term performance (coulombic efficiency of 100 % and energy efficiency of 70 %). PMID:28658538

  11. Redox-Flow Batteries: From Metals to Organic Redox-Active Materials.

    PubMed

    Winsberg, Jan; Hagemann, Tino; Janoschka, Tobias; Hager, Martin D; Schubert, Ulrich S

    2017-01-16

    Research on redox-flow batteries (RFBs) is currently experiencing a significant upturn, stimulated by the growing need to store increasing quantities of sustainably generated electrical energy. RFBs are promising candidates for the creation of smart grids, particularly when combined with photovoltaics and wind farms. To achieve the goal of "green", safe, and cost-efficient energy storage, research has shifted from metal-based materials to organic active materials in recent years. This Review presents an overview of various flow-battery systems. Relevant studies concerning their history are discussed as well as their development over the last few years from the classical inorganic, to organic/inorganic, to RFBs with organic redox-active cathode and anode materials. Available technologies are analyzed in terms of their technical, economic, and environmental aspects; the advantages and limitations of these systems are also discussed. Further technological challenges and prospective research possibilities are highlighted. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  12. A Membrane-Free Redox Flow Battery with Two Immiscible Redox Electrolytes.

    PubMed

    Navalpotro, Paula; Palma, Jesus; Anderson, Marc; Marcilla, Rebeca

    2017-10-02

    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 and where vanadium is replaced by organic molecules. We show that the biphasic system formed by one acidic solution and one ionic liquid, both containing quinoyl species, behaves as a reversible battery without any membrane. This proof-of-concept of a membrane-free battery has an open circuit voltage of 1.4 V with a high theoretical energy density of 22.5 Wh L -1 , and is able to deliver 90 % of its theoretical capacity while showing excellent long-term performance (coulombic efficiency of 100 % and energy efficiency of 70 %). © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  13. The dipole moment of the electron carrier adrenodoxin is not critical for redox partner interaction and electron transfer.

    PubMed

    Hannemann, Frank; Guyot, Arnaud; Zöllner, Andy; Müller, Jürgen J; Heinemann, Udo; Bernhardt, Rita

    2009-07-01

    Dipole moments of proteins arise from helical dipoles, hydrogen bond networks and charged groups at the protein surface. High protein dipole moments were suggested to contribute to the electrostatic steering between redox partners in electron transport chains of respiration, photosynthesis and steroid biosynthesis, although so far experimental evidence for this hypothesis was missing. In order to probe this assumption, we changed the dipole moment of the electron transfer protein adrenodoxin and investigated the influence of this on protein-protein interactions and electron transfer. In bovine adrenodoxin, the [2Fe-2S] ferredoxin of the adrenal glands, a dipole moment of 803 Debye was calculated for a full-length adrenodoxin model based on the Adx(4-108) and the wild type adrenodoxin crystal structures. Large distances and asymmetric distribution of the charged residues in the molecule mainly determine the observed high value. In order to analyse the influence of the resulting inhomogeneous electric field on the biological function of this electron carrier the molecular dipole moment was systematically changed. Five recombinant adrenodoxin mutants with successively reduced dipole moment (from 600 to 200 Debye) were analysed for their redox properties, their binding affinities to the redox partner proteins and for their function during electron transfer-dependent steroid hydroxylation. None of the mutants, not even the quadruple mutant K6E/K22Q/K24Q/K98E with a dipole moment reduced by about 70% showed significant changes in the protein function as compared with the unmodified adrenodoxin demonstrating that neither the formation of the transient complex nor the biological activity of the electron transfer chain of the endocrine glands was affected. This is the first experimental evidence that the high dipole moment observed in electron transfer proteins is not involved in electrostatic steering among the proteins in the redox chain.

  14. "Unexpected" behaviour of the internal resistance of a vanadium redox flow battery

    NASA Astrophysics Data System (ADS)

    Rudolph, S.; Schröder, U.; Bayanov, I. M.; Hage-Packhäuser, S.

    2016-02-01

    This article presents the results of experimental and theoretical studies of energy losses owing to the internal resistance of vanadium redox flow batteries (VRFBs). A dependence of the internal cell resistance (ICR) on the electric current was measured and calculated. During the cyclic operation of a test battery, the internal resistance was halved by increasing the electric current from 3 A to 9 A. This is due to a strongly non-linear dependence of an over-potential of the electrochemical reactions on the current density. However, the energy efficiency does not increase due to a squared dependence of the energy losses on the increasing electric current. The energy efficiency of the test battery versus the electric current was measured and simulated. The deviation between the simulation results and experimental data is less than ±3.5%.

  15. Redox Regulation of Methionine Aminopeptidase 2 Activity*

    PubMed Central

    Chiu, Joyce; Wong, Jason W. H.; Hogg, Philip J.

    2014-01-01

    Protein translation is initiated with methionine in eukaryotes, and the majority of proteins have their N-terminal methionine removed by methionine aminopeptidases (MetAP1 and MetAP2) prior to action. Methionine removal can be important for protein function, localization, or stability. No mechanism of regulation of MetAP activity has been identified. MetAP2, but not MetAP1, contains a single Cys228-Cys448 disulfide bond that has an −RHStaple configuration and links two β-loop structures, which are hallmarks of allosteric disulfide bonds. From analysis of crystal structures and using mass spectrometry and activity assays, we found that the disulfide bond exists in oxidized and reduced states in the recombinant enzyme. The disulfide has a standard redox potential of −261 mV and is efficiently reduced by the protein reductant, thioredoxin, with a rate constant of 16,180 m−1 s−1. The MetAP2 disulfide bond also exists in oxidized and reduced states in glioblastoma tumor cells, and stressing the cells by oxygen or glucose deprivation results in more oxidized enzyme. The Cys228-Cys448 disulfide is at the rim of the active site and is only three residues distant from the catalytic His231, which suggested that cleavage of the bond would influence substrate hydrolysis. Indeed, oxidized and reduced isoforms have different catalytic efficiencies for hydrolysis of MetAP2 peptide substrates. These findings indicate that MetAP2 is post-translationally regulated by an allosteric disulfide bond, which controls substrate specificity and catalytic efficiency. PMID:24700462

  16. Cardiovascular Redox and Ox Stress Proteomics

    PubMed Central

    Kumar, Vikas; Calamaras, Timothy Dean; Haeussler, Dagmar; Colucci, Wilson Steven; Cohen, Richard Alan; McComb, Mark Errol; Pimentel, David

    2012-01-01

    Abstract Significance: Oxidative post-translational modifications (OPTMs) have been demonstrated as contributing to cardiovascular physiology and pathophysiology. These modifications have been identified using antibodies as well as advanced proteomic methods, and the functional importance of each is beginning to be understood using transgenic and gene deletion animal models. Given that OPTMs are involved in cardiovascular pathology, the use of these modifications as biomarkers and predictors of disease has significant therapeutic potential. Adequate understanding of the chemistry of the OPTMs is necessary to determine what may occur in vivo and which modifications would best serve as biomarkers. Recent Advances: By using mass spectrometry, advanced labeling techniques, and antibody identification, OPTMs have become accessible to a larger proportion of the scientific community. Advancements in instrumentation, database search algorithms, and processing speed have allowed MS to fully expand on the proteome of OPTMs. In addition, the role of enzymatically reversible OPTMs has been further clarified in preclinical models. Critical Issues: The identification of OPTMs suffers from limitations in analytic detection based on the methodology, instrumentation, sample complexity, and bioinformatics. Currently, each type of OPTM requires a specific strategy for identification, and generalized approaches result in an incomplete assessment. Future Directions: Novel types of highly sensitive MS instrumentation that allow for improved separation and detection of modified proteins and peptides have been crucial in the discovery of OPTMs and biomarkers. To further advance the identification of relevant OPTMs in advanced search algorithms, standardized methods for sample processing and depository of MS data will be required. Antioxid. Redox Signal. 17, 1528–1559. PMID:22607061

  17. Redox regulation, gene expression and longevity.

    PubMed

    Honda, Yoko; Tanaka, Masashi; Honda, Shuji

    2010-07-01

    Lifespan can be lengthened by genetic and environmental modifications. Study of these might provide valuable insights into the mechanism of aging. Low doses of radiation and short-term exposure to heat and high concentrations of oxygen prolong the lifespan of the nematode Caenorhabditis elegans. These might be caused by adaptive responses to harmful environmental conditions. Single-gene mutations have been found to extend lifespan in C. elegans, Drosophila and mice. So far, the best-characterized system is the C. elegans mutant in the daf-2, insulin/IGF-I receptor gene that is the component of the insulin/IGF-I signaling pathway. The mutant animals live twice as long as the wild type. The insulin/IGF-I signaling pathway regulates the activity of DAF-16, a FOXO transcription factor. However, the unified explanation for the function of DAF-16 transcription targets in the lifespan extension is not yet fully established. As both of the Mn superoxide dismutase (MnSOD) isoforms (sod-2 and sod-3) are found to be targets of DAF-16, we attempted to assess their functions in regulating lifespan and oxidative stress responsivity. We show that the double deletions of sod-2 and sod-3 genes induced oxidative-stress sensitivity but do not shorten lifespan in the daf-2 mutant background, indicating that oxidative stress is not necessarily a limiting factor for longevity. Furthermore, the deletion in the sod-3 gene lengthens lifespan in the daf-2 mutant. We conclude that the MnSOD systems in C. elegans fine-tune the insulin/IGF-I-signaling based regulation of longevity by acting not as anti-oxidants but as physiological-redox-signaling modulators.

  18. Redox regulation in metabolic programming and inflammation.

    PubMed

    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

  19. Accelerated redox reaction between chromate and phenolic pollutants during freezing.

    PubMed

    Ju, Jinjung; Kim, Jaesung; Vetráková, Ľubica; Seo, Jiwon; Heger, Dominik; Lee, Changha; Yoon, Ho-Il; Kim, Kitae; Kim, Jungwon

    2017-05-05

    The redox reaction between 4-chlorophenol (4-CP) and chromate (Cr(VI)) (i.e., the simultaneous oxidation of 4-CP by Cr(VI) and reduction of Cr(VI) by 4-CP) in ice (i.e., at -20°C) was compared with the corresponding reaction in water (i.e., at 25°C). The redox conversion of 4-CP/Cr(VI), which was negligible in water, was significantly accelerated in ice. This accelerated redox conversion of 4-CP/Cr(VI) in ice is ascribed to the freeze concentration effect occurring during freezing, which excludes solutes (i.e., 4-CP and Cr(VI)) and protons from the ice crystals and subsequently concentrates them in the liquid brine. The concentrations of Cr(VI) and protons in the liquid brine were confirmed by measuring the optical image and the UV-vis absorption spectra of cresol red (CR) as a pH indicator of frozen solution. The redox conversion of 4-CP/Cr(VI) was observed in water when the concentrations of 4-CP/protons or Cr(VI)/protons increased by 100/1000-fold. These results corroborate the freeze concentration effect as the reason for the accelerated redox conversion of 4-CP/Cr(VI) in ice. The redox conversion of various phenolic pollutants/Cr(VI) and 4-CP/Cr(VI) in real wastewater was successfully achieved in ice, which verifies the environmental relevance and importance of freezing-accelerated redox conversion of phenolic pollutants/Cr(VI) in cold regions. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Redox Fluctuations Increase the Contribution of Lignin to Soil Respiration

    NASA Astrophysics Data System (ADS)

    Hall, S. J.; Silver, W. L.; Timokhin, V.; Hammel, K.

    2014-12-01

    Lignin mineralization represents a critical flux in the terrestrial carbon (C) cycle, yet little is known about mechanisms and environmental factors controlling lignin breakdown in mineral soils. Hypoxia has long been thought to suppress lignin decomposition, yet variation in oxygen (O2) availability in surface soils accompanying moisture fluctuations could potentially stimulate this process by generating reactive oxygen species via coupled biotic and abiotic iron (Fe) redox cycling. Here, we tested the impact of redox fluctuations on lignin breakdown in humid tropical forest soils during ten-week laboratory incubations. We used synthetic lignins labeled with 13C in either of two positions (aromatic methoxyl and propyl Cβ) to provide highly sensitive and specific measures of lignin mineralization not previously employed in soils. Four-day redox fluctuations increased the percent contribution of methoxyl C to soil respiration, and cumulative methoxyl C mineralization was equivalent under static aerobic and fluctuating redox conditions despite lower total C mineralization in the latter treatment. Contributions of the highly stable Cβ to mineralization were also equivalent in static aerobic and fluctuating redox treatments during periods of O2 exposure, and nearly doubled in the fluctuating treatment after normalizing to cumulative O2 exposure. Oxygen fluctuations drove substantial net Fe reduction and oxidation, implying that reactive oxygen species generated during abiotic Fe oxidation likely contributed to the elevated contribution of lignin to C mineralization. Iron redox cycling provides a mechanism for lignin breakdown in soils that experience conditions unfavorable for canonical lignin-degrading organisms, and provides a potential mechanism for lignin depletion in soil organic matter during late-stage decomposition. Thus, close couplings between soil moisture, redox fluctuations, and lignin breakdown provide potential a link between climate variability and

  1. Extracellular redox state regulates features associated with prostate cancer cell invasion.

    PubMed

    Chaiswing, Luksana; Zhong, Weixiong; Cullen, Joseph J; Oberley, Larry W; Oberley, Terry D

    2008-07-15

    We have examined the possible role of extracellular reduction-oxidation (redox) state in regulation of biological/biochemical features associated with prostate cancer cell invasion. DU145, PC-3, and RWPE1-derived human prostate cancer (WPE1-NB26) cell lines were used for the present in vitro analysis. Increasing levels of nitric oxide using S-nitroso-N-acetylpenicillamine resulted in a decrease in cell invasion ability, whereas increasing levels of extracellular superoxide radical (O(2)(*-)) using xanthine/xanthine oxidase resulted in an increase in cell invasion ability in these three cell lines. WPE1-NB26 cells exhibited an increased glutathione/glutathione disulfide ratio in the medium in comparison with RWPE1 cells (immortalized but nonmalignant prostate epithelial cells), suggesting an alteration of extracellular redox state of WPE1-NB26 cells. We hypothesized that O(2)(*-) production at or near the plasma membrane or in the adjacent extracellular matrix at least partially regulated prostate cancer cell invasion. Using adenovirus-mediated extracellular superoxide dismutase (EC-SOD) gene transduction to enzymatically decrease O(2)(*-) levels, we showed that in the presence of heparin, adenovirus EC-SOD gene transduction resulted in an increase in the expression of EC-SOD outside the cells with resultant inhibition of cell invasion ability. This inhibition correlated with reduced metalloproteinase [matrix metalloproteinase (MMP) 2/membrane type 1-MMP] activities and increased levels of extracellular nitrite. Our results suggest a prominent role of extracellular redox status in regulation of cell invasion, which may provide opportunities for therapeutic interventions.

  2. Uranium biogeochemistry across the redox transition zone of a permanently stratified fjord: Framvaren, Norway

    USGS Publications Warehouse

    Swarzenski, P.W.; McKee, B.A.; Skei, J.M.; Todd, J.F.

    1999-01-01

    During August 1995, the vertical concentration profile of dissolved and particulate uranium exhibited strong non-conservative characteristics in the upper 30 m of Framvaren Fjord. There was a pronounced peak in both particulate (> 0.2 ??m; 1.09 nM) and dissolved (< 0.2 ??m; 17.06 nM) uranium in the finely stratified waters at the O2/H2S interface which is positioned well within the euphotic zone at about 20-21 m. Such concentration maxima at the redox boundary are also observed for dissolved organic carbon (DEC), Sr and Ba. Dissolved U levels seen in the water column from 18 m down to 30 m exceeded the high salinity (salinity = 35) U concentrations (13.63 ?? 0.84 nM; Chen, J.H., Edwards, R.L., Wasserburg, G.L., 1986. 238U, 234U and 232Th in seawater. Earth Planet Sci. Lett. 80, 241-251.) observed uniformly in the open ocean. A prolific population of S microbes (e.g., Chromatium, Chlorobium sp.) flourishes at the O2/H2S interface. The source of elevated U at the redox boundary must be due to microbial uptake and subsequent release processes rather than dilution from oceanic uranium. Uranium oxidation state determinations in waters from 1, 22 and 30 m depth reveal that reduced U(IV) is not present in significant abundance, and that the chemical and/or biological reduction of hexavalent uranium is largely inhibited. Our results suggest that U and other trace constituents such as DOC, Sr, Ba, Fe(II), Mn(II) are greatly modified by direct and indirect microbial transformation reactions which are most concentrated across the redox transition zone in Framvaren Fjord.

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

    PubMed

    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. Sulfur Radical-Induced Redox Modifications in Proteins: Analysis and Mechanistic Aspects.

    PubMed

    Schöneich, Christian

    2017-03-10

    The sulfur-containing amino acids cysteine (Cys) and methionine (Met) are prominent protein targets of redox modification during conditions of oxidative stress. Here, two-electron pathways have received widespread attention, in part due to their role in signaling processes. However, Cys and Met are equally prone to one-electron pathways, generating intermediary radicals and/or radial ions. These radicals/radical ions can generate various reaction products that are not commonly monitored in redox proteomic studies, but they may be relevant for the fate of proteins during oxidative stress. Recent Advances: Time-resolved kinetic studies and product analysis have expanded our mechanistic understanding of radical reaction pathways of sulfur-containing amino acids. These reactions are now studied in some detail for Met and Cys in proteins, and homocysteine (Hcy) chemically linked to proteins, and the role of protein radical reactions in physiological processes is evolving. Radical-derived products from Cys, Hcy, and Met can react with additional amino acids in proteins, leading to secondary protein modifications, which are potentially remote from initial points of radical attack. These products may contain intra- and intermolecular cross-links, which may lead to protein aggregation. Protein sequence and conformation will have a significant impact on the formation of such products, and a thorough understanding of reaction mechanisms and specifically how protein structure influences reaction pathways will be critical for identification and characterization of novel reaction products. Future studies must evaluate the biological significance of novel reaction products that are derived from radical reactions of sulfur-containing amino acids. Antioxid. Redox Signal. 26, 388-405.

  5. Molecular Orbital Principles of Oxygen-Redox Battery Electrodes.

    PubMed

    Okubo, Masashi; Yamada, Atsuo

    2017-10-25

    Lithium-ion batteries are key energy-storage devices for a sustainable society. The most widely used positive electrode materials are LiMO 2 (M: transition metal), in which a redox reaction of M occurs in association with Li + (de)intercalation. Recent developments of Li-excess transition-metal oxides, which deliver a large capacity of more than 200 mAh/g using an extra redox reaction of oxygen, introduce new possibilities for designing higher energy density lithium-ion batteries. For better engineering using this fascinating new chemistry, it is necessary to achieve a full understanding of the reaction mechanism by gaining knowledge on the chemical state of oxygen. In this review, a summary of the recent advances in oxygen-redox battery electrodes is provided, followed by a systematic demonstration of the overall electronic structures based on molecular orbitals with a focus on the local coordination environment around oxygen. We show that a π-type molecular orbital plays an important role in stabilizing the oxidized oxygen that emerges upon the charging process. Molecular orbital principles are convenient for an atomic-level understanding of how reversible oxygen-redox reactions occur in bulk, providing a solid foundation toward improved oxygen-redox positive electrode materials for high energy-density batteries.

  6. Anionic Redox Chemistry in Polysulfide Electrode Materials for Rechargeable Batteries.

    PubMed

    Grayfer, Ekaterina D; Pazhetnov, Egor M; Kozlova, Mariia N; Artemkina, Sofya B; Fedorov, Vladimir E

    2017-12-22

    Classical Li-ion battery technology is based on the insertion of lithium ions into cathode materials involving metal (cationic) redox reactions. However, this vision is now being reconsidered, as many new-generation electrode materials with enhanced reversible capacities operate through combined cationic and anionic (non-metal) reversible redox processes or even exclusively through anionic redox transformations. Anionic participation in the redox reactions is observed in materials with more pronounced covalency, which is less typical for oxides, but quite common for phosphides or chalcogenides. In this Concept, we would like to draw the reader's attention to this new idea, especially, as it applies to transition-metal polychalcogenides, such as FeS 2 , VS 4 , TiS 3 , NbS 3 , TiS 4 , MoS 3 , etc., in which the key role is played by the (S-S) 2- /2 S 2- redox reaction. The exploration and better understanding of the anion-driven chemistry is important for designing advanced materials for battery and other energy-related applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Vegetarian diets and public health: biomarker and redox connections.

    PubMed

    Benzie, Iris F F; Wachtel-Galor, Sissi

    2010-11-15

    Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.

  8. TEMPOL increases NAD(+) and improves redox imbalance in obese mice.

    PubMed

    Yamato, Mayumi; Kawano, Kimika; Yamanaka, Yuki; Saiga, Misako; Yamada, Ken-Ichi

    2016-08-01

    Continuous energy conversion is controlled by reduction-oxidation (redox) processes. NAD(+) and NADH represent an important redox couple in energy metabolism. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) is a redox-cycling nitroxide that promotes the scavenging of several reactive oxygen species (ROS) and is reduced to hydroxylamine by NADH. TEMPOL is also involved in NAD(+) production in the ascorbic acid-glutathione redox cycle. We utilized the chemical properties of TEMPOL to investigate the effects of antioxidants and NAD(+)/NADH modulators on the metabolic imbalance in obese mice. Increases in the NAD(+)/NADH ratio by TEMPOL ameliorated the metabolic imbalance when combined with a dietary intervention, changing from a high-fat diet to a normal diet. Plasma levels of the superoxide marker dihydroethidium were higher in mice receiving the dietary intervention compared with a control diet, but were normalized with TEMPOL consumption. These findings provide novel insights into redox regulation in obesity. Copyright © 2016. Published by Elsevier B.V.

  9. Redox-responsive theranostic nanoplatforms based on inorganic nanomaterials.

    PubMed

    Han, Lu; Zhang, Xiao-Yong; Wang, Yu-Long; Li, Xi; Yang, Xiao-Hong; Huang, Min; Hu, Kun; Li, Lu-Hai; Wei, Yen

    2017-08-10

    Spurred on by advances in materials chemistry and nanotechnology, scientists have developed many novel nanopreparations for cancer diagnosis and therapy. To treat complex malignant tumors effectively, multifunctional nanomedicines with targeting ability, imaging properties and controlled drug release behavior should be designed and exploited. The therapeutic efficiency of loaded drugs can be dramatically improved using redox-responsive nanoplatforms which can sense the differences in the redox status of tumor tissues and healthy ones. Redox-sensitive nanocarriers can be constructed from both organic and inorganic nanomaterials; however, at present, drug delivery nanovectors progressively lean towards inorganic nanomaterials because of their facile synthesis/modification and their unique physicochemical properties. In this review, we focus specifically on the preparation and application of redox-sensitive nanosystems based on mesoporous silica nanoparticles (MSNs), carbon nanomaterials, magnetic nanoparticles, gold nanomaterials and other inorganic nanomaterials. We discuss relevant examples of redox-sensitive nanosystems in each category. Finally, we discuss current challenges and future strategies from the aspect of material design and practical application. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Systemic Redox Imbalance in Chronic Kidney Disease: A Systematic Review

    PubMed Central

    Kaltsatou, Antonia; Jamurtas, Athanasios Z.; Koutedakis, Yiannis; Stefanidis, Ioannis; Sakkas, Giorgos K.

    2016-01-01

    Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue damage. However, it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD. PMID:27563376

  11. Anticancer activity of metal complexes: involvement of redox processes.

    PubMed

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

    2011-08-15

    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.

  12. Recent developments in organic redox flow batteries: A critical review

    NASA Astrophysics Data System (ADS)

    Leung, P.; Shah, A. A.; Sanz, L.; Flox, C.; Morante, J. R.; Xu, Q.; Mohamed, M. R.; Ponce de León, C.; Walsh, F. C.

    2017-08-01

    Redox flow batteries (RFBs) have emerged as prime candidates for energy storage on the medium and large scales, particularly at the grid scale. The demand for versatile energy storage continues to increase as more electrical energy is generated from intermittent renewable sources. A major barrier in the way of broad deployment and deep market penetration is the use of expensive metals as the active species in the electrolytes. The use of organic redox couples in aqueous or non-aqueous electrolytes is a promising approach to reducing the overall cost in long-term, since these materials can be low-cost and abundant. The performance of such redox couples can be tuned by modifying their chemical structure. In recent years, significant developments in organic redox flow batteries has taken place, with the introduction of new groups of highly soluble organic molecules, capable of providing a cell voltage and charge capacity comparable to conventional metal-based systems. This review summarises the fundamental developments and characterization of organic redox flow batteries from both the chemistry and materials perspectives. The latest advances, future challenges and opportunities for further development are discussed.

  13. Optical imaging the redox status change during cell apoptosis

    NASA Astrophysics Data System (ADS)

    Su, Ting; Zhang, Zhihong; Lin, Juqiang; Luo, Qingming

    2007-02-01

    Many cellular events involve the alteration in redox equilibrium, globally or locally. In many cases, excessive reactive oxygen species (ROS) production is the underlying cause. Several green fluoresecence protein based indicators are constructed to measure redox status in cells, e.g, rxYFP and roGFPs, which allow real time detection. reduction and oxidization-sensitive GFP (RoGFPs) are more useful due to ratiometric variation by excitation, making the measurement more accurate. Utilizing one of those roGFPs called roGFP1, we establish a mitochondrial redox state probing platform in HeLa cells with laser scan confocal microscopy (LSCM) as detection system. Control experiments confirmed that our platform could produce stable ratiometric values, which made the data more accurately reflect the real environmental changes of redox status that roGFP1 probed. Using exogenous H IIO II and DTT, we evaluated the reactivity and reversibility of roGFP1. The minimal hydrogen peroxide concentration that roGFP1 could show detectable ratiometric changes in our system was about 200μM. Preliminarily applying our platform to exploring the redox status during apoptosis, we observed an increase in ratiometric, suggesting an excessive ROS production.

  14. Redox Polypharmacology as an Emerging Strategy to Combat Malarial Parasites.

    PubMed

    Sidorov, Pavel; Desta, Israel; Chessé, Matthieu; Horvath, Dragos; Marcou, Gilles; Varnek, Alexandre; Davioud-Charvet, Elisabeth; Elhabiri, Mourad

    2016-06-20

    3-Benzylmenadiones are potent antimalarial agents that are thought to act through their 3-benzoylmenadione metabolites as redox cyclers of two essential targets: the NADPH-dependent glutathione reductases (GRs) of Plasmodium-parasitized erythrocytes and methemoglobin. Their physicochemical properties were characterized in a coupled assay using both targets and modeled with QSPR predictive tools built in house. The substitution pattern of the west/east aromatic parts that controls the oxidant character of the electrophore was highlighted and accurately predicted by QSPR models. The effects centered on the benz(o)yl chain, induced by drug bioactivation, markedly influenced the oxidant character of the reduced species through a large anodic shift of the redox potentials that correlated with the redox cycling of both targets in the coupled assay. Our approach demonstrates that the antimalarial activity of 3-benz(o)ylmenadiones results from a subtle interplay between bioactivation, fine-tuned redox properties, and interactions with crucial targets of P. falciparum. Plasmodione and its analogues give emphasis to redox polypharmacology, which constitutes an innovative approach to antimalarial therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin

    PubMed Central

    Henkens, Robert; Alayash, Abdu I.; Banerjee, Sambuddha; Crumbliss, Alvin L.

    2013-01-01

    Abstract Significance: The broad classes of O2-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O2-binding functions. Recent Advances: The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. Critical Issues: An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. Future Directions: This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes. Antioxid. Redox Signal. 18, 2298–2313. PMID:23198874

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

    PubMed Central

    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

  17. The chloroplast ATP synthase features the characteristic redox regulation machinery.

    PubMed

    Hisabori, Toru; Sunamura, Ei-Ichiro; Kim, Yusung; Konno, Hiroki

    2013-11-20

    Regulation of the activity of the chloroplast ATP synthase is largely accomplished by the chloroplast thioredoxin system, the main redox regulation system in chloroplasts, which is directly coupled to the photosynthetic reaction. We review the current understanding of the redox regulation system of the chloroplast ATP synthase. The thioredoxin-targeted portion of the ATP synthase consists of two cysteines located on the central axis subunit γ. The redox state of these two cysteines is under the influence of chloroplast thioredoxin, which directly controls rotation during catalysis by inducing a conformational change in this subunit. The molecular mechanism of redox regulation of the chloroplast ATP synthase has recently been determined. Regulation of the activity of the chloroplast ATP synthase is critical in driving efficiency into the ATP synthesis reaction in chloroplasts. The molecular architecture of the chloroplast ATP synthase, which confers redox regulatory properties requires further investigation, in light of the molecular structure of the enzyme complex as well as the physiological significance of the regulation system.

  18. Synthesis and characterization of redox-active fe