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Redox Biology May 2021In the open metabolic system, redox-related signaling requires continuous monitoring and fine-tuning of the steady-state redox set point. The ongoing oxidative... (Review)
Review
In the open metabolic system, redox-related signaling requires continuous monitoring and fine-tuning of the steady-state redox set point. The ongoing oxidative metabolism is a persistent challenge, denoted as oxidative eustress, which operates within a physiological range that has been called the 'Homeodynamic Space', the 'Goldilocks Zone' or the 'Golden Mean'. Spatiotemporal control of redox signaling is achieved by compartmentalized generation and removal of oxidants. The cellular landscape of HO, the major redox signaling molecule, is characterized by orders-of-magnitude concentration differences between organelles. This concentration pattern is mirrored by the pattern of oxidatively modified proteins, exemplified by S-glutathionylated proteins. The review presents the conceptual background for short-term (non-transcriptional) and longer-term (transcriptional/translational) homeostatic mechanisms of stress and stress responses. The redox set point is a variable moving target value, modulated by circadian rhythm and by external influence, summarily denoted as exposome, which includes nutrition and lifestyle factors. Emerging fields of cell-specific and tissue-specific redox regulation in physiological settings are briefly presented, including new insight into the role of oxidative eustress in embryonal development and lifespan, skeletal muscle and exercise, sleep-wake rhythm, and the function of the nervous system with aspects leading to psychobiology.
Topics: Homeostasis; Hydrogen Peroxide; Oxidants; Oxidation-Reduction; Oxidative Stress
PubMed: 33657525
DOI: 10.1016/j.redox.2021.101867 -
Handbook of Experimental Pharmacology 2021A number of diseases and conditions have been associated with prolonged or persistent exposure to non-physiological levels of reactive oxygen species (ROS). Similarly,... (Review)
Review
A number of diseases and conditions have been associated with prolonged or persistent exposure to non-physiological levels of reactive oxygen species (ROS). Similarly, ROS underproduction due to loss-of-function mutations in superoxide or hydrogen peroxide (HO)-generating enzymes is a risk factor or causative for certain diseases. However, ROS are required for basic cell functions; in particular the diffusible second messenger HO that serves as signaling molecule in redox processes. This activity sets HO apart from highly reactive oxygen radicals and influences the approach to drug discovery, clinical utility, and therapeutic intervention. Here we review the chemical and biological fundamentals of ROS with emphasis on HO as a signaling conduit and initiator of redox relays and propose an integrated view of physiological versus non-physiological reactive species. Therapeutic interventions that target persistently altered ROS levels should include both selective inhibition of a specific source of primary ROS and careful consideration of a targeted pro-oxidant approach, an avenue that is still underdeveloped. Both strategies require attention to redox dynamics in complex cellular systems, integration of the overall spatiotemporal cellular environment, and target validation to yield effective and safe therapeutics. The only professional primary ROS producers are NADPH oxidases (NOX1-5, DUOX1-2). Many other enzymes, e.g., xanthine oxidase (XO), monoamine oxidases (MAO), lysyl oxidases (LO), lipoxygenase (LOX), and cyclooxygenase (COX), produce superoxide and HO secondary to their primary metabolic function. Superoxide is too reactive to disseminate, but HO is diffusible, only limited by adjacent PRDXs or GPXs, and can be apically secreted and imported into cells through aquaporin (AQP) channels. HO redox signaling includes oxidation of the active site thiol in protein tyrosine phosphatases, which will inhibit their activity and thereby increase tyrosine phosphorylation on target proteins. Essential functions include the oxidative burst by NOX2 as antimicrobial innate immune response; gastrointestinal NOX1 and DUOX2 generating low HO concentrations sufficient to trigger antivirulence mechanisms; and thyroidal DUOX2 essential for providing HO reduced by TPO to oxidize iodide to an iodinating form which is then attached to tyrosyls in TG. Loss-of-function (LoF) variants in TPO or DUOX2 cause congenital hypothyroidism and LoF variants in the NOX2 complex chronic granulomatous disease.
Topics: Hydrogen Peroxide; NADPH Oxidases; Oxidants; Oxidation-Reduction; Physiological Phenomena; Reactive Oxygen Species
PubMed: 32767144
DOI: 10.1007/164_2020_380 -
Free Radical Biology & Medicine Jul 2022Beta-2-microglobulin (B2M) is synthesized by all nucleated cells and forms part of the major histocompatibility complex (MHC) class-1 present on cell surfaces, which...
Beta-2-microglobulin (B2M) is synthesized by all nucleated cells and forms part of the major histocompatibility complex (MHC) class-1 present on cell surfaces, which presents peptide fragments to cytotoxic CD8 T-lymphocytes, or by association with CD1, antigenic lipids to natural killer T-cells. Knockout of B2M results in loss of these functions and severe combined immunodeficiency. Plasma levels of this protein are low in healthy serum, but are elevated up to 50-fold in some pathologies including chronic kidney disease and multiple myeloma, where it has both diagnostic and prognostic value. High levels of the protein are associated with amyloid formation, with such deposits containing significant levels of modified or truncated protein. In the current study we examine the chemical and structural changes induced of B2M generated by both inflammatory oxidants (HOCl and ONOOH), and photo-oxidation (O) which is linked with immunosuppression. Oxidation results in oligomer formation, with this occurring most readily with HOCl and O, and a loss of native protein conformation. LC-MS analysis provided evidence for nitrated (from ONOOH), chlorinated (from HOCl) and oxidized residues (all oxidants) with damage detected at Tyr, Trp, and Met residues, together with cleavage of the disulfide (cystine) bond. An intermolecular di-tyrosine crosslink is also formed between Tyr10 and Tyr63. The pattern of these modifications is oxidant specific, with ONOOH inducing a greater range of modifications than HOCl. Comparison of the sites of modification with regions identified as amyloidogenic indicate significant co-localization, consistent with the hypothesis that oxidation may contribute, and predispose B2M, to amyloid formation.
Topics: Chromatography, Liquid; Hypochlorous Acid; Oxidants; Oxidation-Reduction; Protein Conformation; Tyrosine
PubMed: 35609861
DOI: 10.1016/j.freeradbiomed.2022.05.012 -
Frontiers in Immunology 2021Redox medicine is a new therapeutic concept targeting reactive oxygen species (ROS) and secondary reaction products for health benefit. The concomitant function of ROS... (Review)
Review
Redox medicine is a new therapeutic concept targeting reactive oxygen species (ROS) and secondary reaction products for health benefit. The concomitant function of ROS as intracellular second messengers and extracellular mediators governing physiological redox signaling, and as damaging radicals instigating or perpetuating various pathophysiological conditions will require selective strategies for therapeutic intervention. In addition, the reactivity and quantity of the oxidant species generated, its source and cellular location in a defined disease context need to be considered to achieve the desired outcome. In inflammatory diseases associated with oxidative damage and tissue injury, ROS source specific inhibitors may provide more benefit than generalized removal of ROS. Contemporary approaches in immunity will also include the preservation or even elevation of certain oxygen metabolites to restore or improve ROS driven physiological functions including more effective redox signaling and cell-microenvironment communication, and to induce mucosal barrier integrity, eubiosis and repair processes. Increasing oxidants by host-directed immunomodulation or by exogenous supplementation seems especially promising for improving host defense. Here, we summarize examples of beneficial ROS in immune homeostasis, infection, and acute inflammatory disease, and address emerging therapeutic strategies for ROS augmentation to induce and strengthen protective host immunity.
Topics: Animals; Humans; Immune System Phenomena; Oxidants; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 34149739
DOI: 10.3389/fimmu.2021.698042 -
Annals of the American Thoracic Society Mar 2016Research over the past 30 years has identified mechanistic biochemical oxidation pathways that contribute to asthma pathophysiology. Redox imbalance is present in asthma... (Review)
Review
Research over the past 30 years has identified mechanistic biochemical oxidation pathways that contribute to asthma pathophysiology. Redox imbalance is present in asthma and strongly linked to the pathobiology of airflow obstruction, airway hyperreactivity, and remodeling. High levels of reactive oxygen species, reactive nitrogen species, and oxidatively modified proteins in the lung, blood, and urine provide conclusive evidence for pathologic oxidation in asthma. Concurrent loss of antioxidants, such as superoxide dismutases and catalase, is attributed to redox modifications of the enzymes, and further amplifies the oxidative injury in the airway. The presence of high levels of urine bromotyrosine, an oxidation product of eosinophil peroxidase, identifies activated eosinophils, and shows promise for use as a noninvasive biomarker of poor asthma control.
Topics: Asthma; Humans; Lung; Oxidants; Oxidation-Reduction; Oxidative Stress; Reactive Nitrogen Species; Reactive Oxygen Species
PubMed: 27027950
DOI: 10.1513/AnnalsATS.201506-385MG -
The Journal of Biological Chemistry Dec 2019Exposure of biological molecules to oxidants is inevitable and therefore commonplace. Oxidative stress in cells arises from both external agents and endogenous processes... (Review)
Review
Exposure of biological molecules to oxidants is inevitable and therefore commonplace. Oxidative stress in cells arises from both external agents and endogenous processes that generate reactive species, either purposely ( during pathogen killing or enzymatic reactions) or accidentally ( exposure to radiation, pollutants, drugs, or chemicals). As proteins are highly abundant and react rapidly with many oxidants, they are highly susceptible to, and major targets of, oxidative damage. This can result in changes to protein structure, function, and turnover and to loss or (occasional) gain of activity. Accumulation of oxidatively-modified proteins, due to either increased generation or decreased removal, has been associated with both aging and multiple diseases. Different oxidants generate a broad, and sometimes characteristic, spectrum of post-translational modifications. The kinetics (rates) of damage formation also vary dramatically. There is a pressing need for reliable and robust methods that can detect, identify, and quantify the products formed on amino acids, peptides, and proteins, especially in complex systems. This review summarizes several advances in our understanding of this complex chemistry and highlights methods that are available to detect oxidative modifications-at the amino acid, peptide, or protein level-and their nature, quantity, and position within a peptide sequence. Although considerable progress has been made in the development and application of new techniques, it is clear that further development is required to fully assess the relative importance of protein oxidation and to determine whether an oxidation is a cause, or merely a consequence, of injurious processes.
Topics: Amino Acids; Animals; Anions; Antioxidants; Free Radicals; Humans; Kinetics; Nitric Oxide; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxygen; Peptides; Protein Processing, Post-Translational; Proteins; Reactive Oxygen Species; Ultraviolet Rays
PubMed: 31672919
DOI: 10.1074/jbc.REV119.006217 -
Journal of Hazardous Materials Jul 2023Ultraviolet (UV) irradiation is widely used for wastewater disinfection but suffers from low inactivation rates and can cause photoreactivation of microorganisms.... (Review)
Review
Ultraviolet (UV) irradiation is widely used for wastewater disinfection but suffers from low inactivation rates and can cause photoreactivation of microorganisms. Synergistic disinfection with UV and oxidants is promising for enhancing the inactivation performance. This review summarizes the inactivation effects on representative microorganisms by UV/hydrogen peroxide (HO), UV/ozone (O), UV/persulfate (PS), UV/chlorine, and UV/chlorine dioxide (ClO). UV synergistic processes perform better than UV or an oxidant alone. UV mainly attacks the DNA or RNA in microorganisms; the oxidants HO and O mainly attack the cell walls, cell membranes, and other external structures; and HOCl and ClO enter cells and oxidize proteins and enzymes. Free radicals can have strong oxidation effects on cell walls, cell membranes, proteins, enzymes, and even DNA. At similar UV doses, the inactivation rates of Escherichia coli with UV alone, UV/HO, UV/O, UV/PS (peroxydisulfate or peroxymonosulfate), and UV/chlorinated oxidant (chlorine, ClO, and NHCl) range from 2.03 to 3.84 log, 2.62-4.30 log, 4.02-6.08 log, 2.93-5.07 log, and 3.78-6.55 log, respectively. The E. coli inactivation rates are in the order of UV/O ≈ UV/Cl > UV/PS > UV/HO. This order is closely related to the redox potentials of the oxidants and quantum yields of the radicals. UV synergistic disinfection processes inhibit photoreactivation of E. coli in the order of UV/O > UV/PS > UV/HO. The activation mechanisms and formation pathways of free radicals with different UV-based synergistic processes are presented. In addition to generating HO·, O can reduce the turbidity and chroma of wastewater to increase UV penetration, which improves the disinfection performance of UV/O. This knowledge will be useful for further development of the UV-based synergistic disinfection processes.
Topics: Disinfection; Hydrogen Peroxide; Wastewater; Chlorine; Escherichia coli; Oxidants; Oxidation-Reduction; Chlorides; Ultraviolet Rays; Water Purification
PubMed: 37062094
DOI: 10.1016/j.jhazmat.2023.131393 -
ACS Nano Jul 2022Whitening agents, such as hydrogen peroxide and carbamide peroxide, are currently used in clinical applications for dental esthetic and dental care. However, the free... (Review)
Review
Whitening agents, such as hydrogen peroxide and carbamide peroxide, are currently used in clinical applications for dental esthetic and dental care. However, the free radicals generated by whitening agents cause pathological damage; therefore, their safety issues remain controversial. Furthermore, whitening agents are known to be unstable and short-lived. Since 2001, nanoparticles (NPs) have been researched for use in tooth whitening. Importantly, nanoparticles not only function as abrasives but also release reactive oxygen species and help remineralization. This review outlines the historical development of several NPs based on their whitening effects and side effects. NPs can be categorized into metals or metal oxides, ceramic particles, graphene oxide, and piezoelectric particles. Moreover, the status quo and future prospects are discussed, and recent progress in the development of NPs and their applications in various fields requiring tooth whitening is examined. This review promotes the research and development of next-generation NPs for use in tooth whitening.
Topics: Tooth Bleaching Agents; Peroxides; Urea; Hydrogen Peroxide; Bleaching Agents; Nanoparticles
PubMed: 35704786
DOI: 10.1021/acsnano.2c01412 -
Journal of Environmental Sciences... Jun 2023Many studies have successfully built iron-mediated materials to activate or catalyze Fenton-like reactions, with applications in water and wastewater treatment being... (Review)
Review
Many studies have successfully built iron-mediated materials to activate or catalyze Fenton-like reactions, with applications in water and wastewater treatment being investigated. However, the developed materials are rarely compared with each other regarding their performance of organic contaminant removal. In this review, the recent advances of Fenton-like processes in homogeneous and heterogeneous ways are summarized, especially the performance and mechanism of activators including ferrous iron, zero valent iron, iron oxides, iron-loaded carbon, zeolite, and metal organic framework materials. Also, this work mainly compares three O-O bond containing oxidants including hydrogen dioxide, persulfate, and percarbonate, which are environmental-friendly oxidants and feasible for in-situ chemical oxidation. The influence of reaction conditions, catalyst properties and benefits are analyzed and compared. In addition, the challenges and strategies of these oxidants in applications and the major mechanisms of the oxidation process have been discussed. This work can help understand the mechanistic insights of variable Fenton-like reactions, the role of emerging iron-based materials, and provide guidance for choosing appropriate technologies when facing real-world water and wastewater applications.
Topics: Iron; Hydrogen Peroxide; Oxidation-Reduction; Oxidants; Water; Water Pollutants, Chemical
PubMed: 36801034
DOI: 10.1016/j.jes.2022.07.037 -
Environmental Microbiology Feb 2019Reactive oxygen species - superoxide, hydrogen peroxide and hydroxyl radicals - have long been suspected of constraining bacterial growth in important microbial habitats... (Review)
Review
Reactive oxygen species - superoxide, hydrogen peroxide and hydroxyl radicals - have long been suspected of constraining bacterial growth in important microbial habitats and indeed of shaping microbial communities. Over recent decades, studies of paradigmatic organisms such as Escherichia coli, Salmonella typhimurium, Bacillus subtilis and Saccharomyces cerevisiae have pinpointed the biomolecules that oxidants can damage and the strategies by which microbes minimize their injuries. What is lacking is a good sense of the circumstances under which oxidative stress actually occurs. In this MiniReview several potential natural sources of oxidative stress are considered: endogenous ROS formation, chemical oxidation of reduced species at oxic-anoxic interfaces, H O production by lactic acid bacteria, the oxidative burst of phagocytes and the redox-cycling of secreted small molecules. While all of these phenomena can be reproduced and verified in the lab, the actual quantification of stress in natural habitats remains lacking - and, therefore, we have a fundamental hole in our understanding of the role that oxidative stress actually plays in the biosphere.
Topics: Bacteria; Hydrogen Peroxide; Oxidants; Oxidation-Reduction; Oxidative Stress; Superoxides
PubMed: 30307099
DOI: 10.1111/1462-2920.14445