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Journal of Physiology and Pharmacology... Dec 2003Nitric oxide (NO) and reactive oxygen species exert multiple modulating effects on inflammation and play a key role in the regulation of immune responses. They affect... (Review)
Review
Nitric oxide (NO) and reactive oxygen species exert multiple modulating effects on inflammation and play a key role in the regulation of immune responses. They affect virtually every step of the development of inflammation. Low concentrations of nitric oxide produced by constitutive and neuronal nitric oxide synthases inhibit adhesion molecule expression, cytokine and chemokine synthesis and leukocyte adhesion and transmigration. Large amounts of NO, generated primarily by iNOS can be toxic and pro-inflammatory. Actions of nitric oxide are however not dependent primarily on the enzymatic source, but rather on the cellular context, NO concentration (dependent on the distance from NO source) and initial priming of immune cells. These observations may explain difficulties in determining the exact role of NO in Th1 and Th2 lymphocyte balance in normal immune responses and in allergic disease. Similarly superoxide anion produced by NAD(P)H oxidases present in all cell types participating in inflammation (leukocytes, endothelial and other vascular cells etc) may lead to toxic effects, when produced at high levels during oxidative burst, but may also modulate inflammation in a far more discrete way, when continuously produced at low levels by NOXs (non-phagocytic oxidases). The effects of both nitric oxide and superoxide in immune regulation are exerted through multiple mechanisms, which include interaction with cell signalling systems like cGMP, cAMP, G-protein, JAK/STAT or MAPK dependent signal transduction pathways. They may also lead to modification of transcription factors activity and in this way modulate the expression of multiple other mediators of inflammation. Moreover genetic polymorphisms exist within genes encoding enzymes producing both NO and superoxide. The potential role of these polymorphisms in inflammation and susceptibility to infection is discussed. Along with studies showing increasing role of NO and free radicals in mediating inflammatory responses drugs which interfere with these systems are being introduced in the treatment of inflammation. These include statins, angiotensin receptor blockers, NAD(P)H oxidase inhibitors, NO-aspirin and others. In conclusion in this mini-review we discuss the mechanisms of nitric oxide and superoxide dependent modulation of inflammatory reactions in experimental animals and humans. We also discuss potential roles of nitric oxide as a mediator of allergic inflammation.
Topics: Animals; Humans; Inflammation; Inflammation Mediators; Models, Biological; Nitric Oxide; Signal Transduction; Superoxides
PubMed: 14726604
DOI: No ID Found -
The New Phytologist Feb 2019Contents Summary 1197 I. Introduction 1198 II. Measurement and imaging of H O 1198 III. H O and O toxicity 1199 IV. Production of H O : enzymes and subcellular locations... (Review)
Review
Contents Summary 1197 I. Introduction 1198 II. Measurement and imaging of H O 1198 III. H O and O toxicity 1199 IV. Production of H O : enzymes and subcellular locations 1200 V. H O transport 1205 VI. Control of H O concentration: how and where? 1205 VII. Metabolic functions of H O 1207 VIII. H O signalling 1207 IX. Where next? 1209 Acknowledgements 1209 References 1209 SUMMARY: Hydrogen peroxide (H O ) is produced, via superoxide and superoxide dismutase, by electron transport in chloroplasts and mitochondria, plasma membrane NADPH oxidases, peroxisomal oxidases, type III peroxidases and other apoplastic oxidases. Intracellular transport is facilitated by aquaporins and H O is removed by catalase, peroxiredoxin, glutathione peroxidase-like enzymes and ascorbate peroxidase, all of which have cell compartment-specific isoforms. Apoplastic H O influences cell expansion, development and defence by its involvement in type III peroxidase-mediated polymer cross-linking, lignification and, possibly, cell expansion via H O -derived hydroxyl radicals. Excess H O triggers chloroplast and peroxisome autophagy and programmed cell death. The role of H O in signalling, for example during acclimation to stress and pathogen defence, has received much attention, but the signal transduction mechanisms are poorly defined. H O oxidizes specific cysteine residues of target proteins to the sulfenic acid form and, similar to other organisms, this modification could initiate thiol-based redox relays and modify target enzymes, receptor kinases and transcription factors. Quantification of the sources and sinks of H O is being improved by the spatial and temporal resolution of genetically encoded H O sensors, such as HyPer and roGFP2-Orp1. These H O sensors, combined with the detection of specific proteins modified by H O , will allow a deeper understanding of its signalling roles.
Topics: Biological Transport; Hydrogen Peroxide; Plants; Signal Transduction; Subcellular Fractions; Superoxides
PubMed: 30222198
DOI: 10.1111/nph.15488 -
Frontiers in Bioscience (Elite Edition) Jun 2009The radical anion of dioxygen superoxide (O2.-) is a physiological free radical formed in various enzymatic processes. On the one hand superoxide is a precursor of... (Review)
Review
The radical anion of dioxygen superoxide (O2.-) is a physiological free radical formed in various enzymatic processes. On the one hand superoxide is a precursor of reactive oxygen and nitrogen species (hydroxyl radicals, peroxy radicals, hydrogen peroxide, peroxynitrite, etc.), -the initiators of cellular damage; on the other hand it is a signaling molecule regulating numerous physiological processes including apoptosis, aging, and senescence. Therefore, the detection and measurement of superoxide in cells, tissues, and whole organisms is of a vital importance for in vitro and in vivo studies of many physiological and pathophysiological processes. At present different efficient methods were developed, which allow to identificate and measure superoxide in biological systems. In present review the credibility and efficiency of principal mostly applied methods of superoxide detection based on one-electron transfer and nucleophilic reactions are discussed, and spectrophotometrical, chemiluminescent, fluorescent, and ESR spin trapping methods are compared.
Topics: Acridines; Cytochromes c; Imidazoles; Luminescent Measurements; Luminol; Oxygen; Pyrazines; Spectrophotometry; Spin Trapping; Superoxides
PubMed: 19482633
DOI: 10.2741/E15 -
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 -
Trends in Cell Biology Oct 2012Mitochondrial free radicals and redox poise are central to metabolism and cell fate. Their measurement in living cells remains a major challenge and their in vivo... (Review)
Review
Mitochondrial free radicals and redox poise are central to metabolism and cell fate. Their measurement in living cells remains a major challenge and their in vivo dynamics are poorly understood. Reports of 'superoxide flashes' in single mitochondria have therefore been perceived as a major breakthrough: single mitochondria expressing the genetically encoded sensor circularly permuted yellow fluorescent protein (cpYFP) display spontaneous flashes of fluorescence that are responsive to metabolic changes and stressors. We critically review the evidence that underpins the interpretation of mitochondrial cpYFP flashes as bursts of superoxide production and conclude that flashes do not represent superoxide bursts but instead are caused by transient alkalinisation of the mitochondrial matrix. We provide a revised framework that will help to clarify the interpretation of mitochondrial flashes.
Topics: Animals; Cell Survival; Free Radicals; Humans; Hydrogen-Ion Concentration; Mitochondria; Superoxides
PubMed: 22917552
DOI: 10.1016/j.tcb.2012.07.007 -
Angewandte Chemie (International Ed. in... Apr 2021Cu/Zn superoxide dismutase (SOD1) is a frontline antioxidant enzyme catalysing superoxide breakdown and is important for most forms of eukaryotic life. The evolution of... (Review)
Review
Cu/Zn superoxide dismutase (SOD1) is a frontline antioxidant enzyme catalysing superoxide breakdown and is important for most forms of eukaryotic life. The evolution of aerobic respiration by mitochondria increased cellular production of superoxide, resulting in an increased reliance upon SOD1. Consistent with the importance of SOD1 for cellular health, many human diseases of the central nervous system involve perturbations in SOD1 biology. But far from providing a simple demonstration of how disease arises from SOD1 loss-of-function, attempts to elucidate pathways by which atypical SOD1 biology leads to neurodegeneration have revealed unexpectedly complex molecular characteristics delineating healthy, functional SOD1 protein from that which likely contributes to central nervous system disease. This review summarises current understanding of SOD1 biology from SOD1 genetics through to protein function and stability.
Topics: Antioxidants; Biocatalysis; Central Nervous System Diseases; Enzyme Stability; Humans; Superoxide Dismutase-1; Superoxides
PubMed: 32144830
DOI: 10.1002/anie.202000451 -
International Journal of Molecular... Jan 2023Classically, superoxide anion O and reactive oxygen species ROS play a dual role. At the physiological balance level, they are a by-product of O reduction, necessary for... (Review)
Review
Classically, superoxide anion O and reactive oxygen species ROS play a dual role. At the physiological balance level, they are a by-product of O reduction, necessary for cell signalling, and at the pathological level they are considered harmful, as they can induce disease and apoptosis, necrosis, ferroptosis, pyroptosis and autophagic cell death. This revision focuses on understanding the main characteristics of the superoxide O, its generation pathways, the biomolecules it oxidizes and how it may contribute to their modification and toxicity. The role of superoxide dismutase, the enzyme responsible for the removal of most of the superoxide produced in living organisms, is studied. At the same time, the toxicity induced by superoxide and derived radicals is beneficial in the oxidative death of microbial pathogens, which are subsequently engulfed by specialized immune cells, such as neutrophils or macrophages, during the activation of innate immunity. Ultimately, this review describes in some depth the chemistry related to O and how it is harnessed by the innate immune system to produce lysis of microbial agents.
Topics: Superoxides; Reactive Oxygen Species; Superoxide Dismutase; Apoptosis; Immunity, Innate
PubMed: 36768162
DOI: 10.3390/ijms24031841 -
Journal of Inorganic Biochemistry Apr 2022A conservative characteristic of manganese superoxide dismutase is the rapid formation of product inhibition at high temperatures. At lower temperatures, the enzyme is... (Review)
Review
A conservative characteristic of manganese superoxide dismutase is the rapid formation of product inhibition at high temperatures. At lower temperatures, the enzyme is less inhibited and undergoes more catalytic fast cycles before being product-inhibited. The temperature-dependent kinetics could be rationalized by the temperature-dependent coordination in the conserved center of manganese superoxide dismutase. As temperature decreases, a water molecule (WAT2) approaches or even coordinates Mn as the sixth ligand to interfere with O-Mn coordination and reduce product inhibition, so the dismutation should mainly proceed in the fast outer-sphere pathway at low temperatures. Cold-activation is an adaptive response to low temperature rather than a passive adaptation to excess superoxide levels since the cold-activated dismutase activity significantly exceeds the amount of superoxide in the cell or mitochondria. Physiologically speaking, cold activation of manganese superoxide dismutase mediates cold stress signaling and transduces temperature (physical signal) degree into HO fluxes (chemical signal), which in turn may act as a second messenger to induce a series of physiological responses such as cold shock.
Topics: Bacteria; Bacterial Proteins; Cold Temperature; Cold-Shock Response; Fungal Proteins; Fungi; Humans; Hydrogen Peroxide; Manganese; Oxidative Stress; Protein Conformation; Signal Transduction; Superoxide Dismutase; Superoxides; Thermoreceptors
PubMed: 35121188
DOI: 10.1016/j.jinorgbio.2022.111745 -
Antioxidants & Redox Signaling Oct 2023Mitochondrial (mt) reticulum network in the cell possesses amazing ultramorphology of parallel lamellar cristae, formed by the invaginated inner mitochondrial membrane.... (Review)
Review
Mitochondrial (mt) reticulum network in the cell possesses amazing ultramorphology of parallel lamellar cristae, formed by the invaginated inner mitochondrial membrane. Its non-invaginated part, the inner boundary membrane (IBM) forms a cylindrical sandwich with the outer mitochondrial membrane (OMM). Crista membranes (CMs) meet IBM at crista junctions (CJs) of mt cristae organizing system (MICOS) complexes connected to OMM sorting and assembly machinery (SAM). Cristae dimensions, shape, and CJs have characteristic patterns for different metabolic regimes, physiological and pathological situations. Cristae-shaping proteins were characterized, namely rows of ATP-synthase dimers forming the crista lamella edges, MICOS subunits, optic atrophy 1 (OPA1) isoforms and mitochondrial genome maintenance 1 (MGM1) filaments, prohibitins, and others. Detailed cristae ultramorphology changes were imaged by focused-ion beam/scanning electron microscopy. Dynamics of crista lamellae and mobile CJs were demonstrated by nanoscopy in living cells. With tBID-induced apoptosis a single entirely fused cristae reticulum was observed in a mitochondrial spheroid. The mobility and composition of MICOS, OPA1, and ATP-synthase dimeric rows regulated by post-translational modifications might be exclusively responsible for cristae morphology changes, but ion fluxes across CM and resulting osmotic forces might be also involved. Inevitably, cristae ultramorphology should reflect also mitochondrial redox homeostasis, but details are unknown. Disordered cristae typically reflect higher superoxide formation. To link redox homeostasis to cristae ultramorphology and define markers, recent progress will help in uncovering mechanisms involved in proton-coupled electron transfer the respiratory chain and in regulation of cristae architecture, leading to structural determination of superoxide formation sites and cristae ultramorphology changes in diseases. 39, 635-683.
Topics: Mitochondrial Membranes; Superoxides; Homeostasis; Oxidation-Reduction; Adenosine Triphosphate; Mitochondrial Proteins
PubMed: 36793196
DOI: 10.1089/ars.2022.0173 -
Biochimica Et Biophysica Acta Feb 2014The recent recognition that isoforms of the cellular NADPH-dependent oxidases, collectively known as the NOX protein family, participate in a wide range of physiologic... (Review)
Review
BACKGROUND
The recent recognition that isoforms of the cellular NADPH-dependent oxidases, collectively known as the NOX protein family, participate in a wide range of physiologic and pathophysiologic processes in both the animal and plant kingdoms has stimulated interest in the identification, localization, and quantitation of their products in biological settings. Although several tools for measuring oxidants released extracellularly are available, the specificity and selectivity of the methods for reliable analysis of intracellular oxidants have not matched the enthusiasm for studying NOX proteins.
SCOPE OF REVIEW
Focusing exclusively on superoxide anion and hydrogen peroxide produced by NOX proteins, this review describes the ideal probe for analysis of O2(-) and H2O2 generated extracellularly and intracellularly by NOX proteins. An overview of the components, organization, and topology of NOX proteins provides a rationale for applying specific probes for use and a context in which to interpret results and thereby construct plausible models linking NOX-derived oxidants to biological responses. The merits and shortcomings of methods currently in use to assess NOX activity are highlighted, and those assays that provide quantitation of superoxide or H2O2 are contrasted with those intended to examine spatial and temporal aspects of NOX activity.
MAJOR CONCLUSIONS
Although interest in measuring the extracellular and intracellular products of the NOX protein family is great, robust analytical probes are limited.
GENERAL SIGNIFICANCE
The widespread involvement of NOX proteins in many biological processes requires rigorous approaches to the detection, localization, and quantitation of the oxidants produced. 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.
Topics: Animals; Humans; Hydrogen Peroxide; NADPH Oxidases; Superoxides
PubMed: 23660153
DOI: 10.1016/j.bbagen.2013.04.040