-
F1000Research 2019Hypochlorous acid (HOCl; bleach) is a powerful weapon used by our immune system to eliminate invading bacteria. Yet the way HOCl actually kills bacteria and how they... (Review)
Review
Hypochlorous acid (HOCl; bleach) is a powerful weapon used by our immune system to eliminate invading bacteria. Yet the way HOCl actually kills bacteria and how they defend themselves from its oxidative action have only started to be uncovered. As this molecule induces both protein oxidation and aggregation, bacteria need concerted efforts of chaperones and antioxidants to maintain proteostasis during stress. Recent advances in the field identified several stress-activated chaperones, like Hsp33, RidA, and CnoX, which display unique structural features and play a central role in protecting the bacterial proteome during HOCl stress.
Topics: Bacteria; Bacterial Infections; Bacterial Proteins; Humans; Hypochlorous Acid; Molecular Chaperones; Oxidants; Oxidation-Reduction; Proteolysis; Stress, Physiological
PubMed: 31583082
DOI: 10.12688/f1000research.19517.1 -
Free Radical Biology & Medicine Jul 2008Oxidants are produced as a by-product of aerobic metabolism, and organisms ranging from prokaryotes to mammals have evolved with an elaborate and redundant complement of... (Review)
Review
Oxidants are produced as a by-product of aerobic metabolism, and organisms ranging from prokaryotes to mammals have evolved with an elaborate and redundant complement of antioxidant defenses to confer protection against oxidative insults. Compelling data now exist demonstrating that oxidants are used in physiological settings as signaling molecules with important regulatory functions controlling cell division, migration, contraction, and mediator production. These physiological functions are carried out in an exquisitely regulated and compartmentalized manner by mild oxidants, through subtle oxidative events that involve targeted amino acids in proteins. The precise understanding of the physiological relevance of redox signal transduction has been hampered by the lack of specificity of reagents and the need for chemical derivatization to visualize reversible oxidations. In addition, it is difficult to measure these subtle oxidation events in vivo. This article reviews some of the recent findings that illuminate the significance of redox signaling and exciting future perspectives. We also attempt to highlight some of the current pitfalls and the approaches needed to advance this important area of biochemical and biomedical research.
Topics: Amino Acids; Animals; Gene Expression Regulation; Humans; Hydrogen Peroxide; Oxidants; Oxidation-Reduction; Signal Transduction
PubMed: 18423411
DOI: 10.1016/j.freeradbiomed.2008.03.011 -
Biomolecules Jun 2023Numerous chemical probes have been used to measure or image oxidative, nitrosative and related stress induced by free radicals in biology and biochemistry. In many... (Review)
Review
Numerous chemical probes have been used to measure or image oxidative, nitrosative and related stress induced by free radicals in biology and biochemistry. In many instances, the chemical pathways involved are reasonably well understood. However, the rate constants for key reactions involved are often not yet characterized, and thus it is difficult to ensure the measurements reflect the flux of oxidant/radical species and are not influenced by competing factors. Key questions frequently unanswered are whether the reagents are used under 'saturating' conditions, how specific probes are for particular radicals or oxidants and the extent of the involvement of competing reactions (e.g., with thiols, ascorbate and other antioxidants). The commonest-used probe for 'reactive oxygen species' in biology actually generates superoxide radicals in producing the measured product in aerobic systems. This review emphasizes the need to understand reaction pathways and in particular to quantify the kinetic parameters of key reactions, as well as measure the intracellular levels and localization of probes, if such reagents are to be used with confidence.
Topics: Reactive Oxygen Species; Oxidation-Reduction; Free Radicals; Superoxides; Oxidants; Antioxidants; Coloring Agents; Oxidative Stress
PubMed: 37509077
DOI: 10.3390/biom13071041 -
Cells Nov 2021Chronic airway inflammation and oxidative stress play crucial roles in the pathogenesis of chronic inflammatory lung diseases, with airway inflammation being a key...
Chronic airway inflammation and oxidative stress play crucial roles in the pathogenesis of chronic inflammatory lung diseases, with airway inflammation being a key driving mechanism of oxidative stress in the lungs. Inflammatory responses in the lungs activate neutrophils and/or eosinophils, leading to the generation of hypohalous acids (HOX). These HOX oxidants can damage the extracellular matrix (ECM) structure and may influence cell-ECM interactions. The ECM of the lung provides structural, mechanical, and biochemical support for cells and determines the airway structure. One of the critical cells in chronic respiratory disease is the fibroblast. Thus, we hypothesised that primary human lung fibroblasts (PHLF) exposed to an oxidised cell-derived ECM will result in functional changes to the PHLF. Here, we show that PHLF adhesion, proliferation, and inflammatory cytokine secretion is affected by exposure to HOX-induced oxidisation of the cell-derived ECM. Furthermore, we investigated the impact on fibroblast function from the presence of haloamines in the ECM. Haloamines are chemical by-products of HOX and, like the HOX, haloamines can also modify the ECM. In conclusion, this study revealed that oxidising the cell-derived ECM might contribute to functional changes in PHLF, a key mechanism behind the pathogenesis of inflammatory lung diseases.
Topics: Bromates; Cell Adhesion; Cell Proliferation; Cell Shape; Collagen Type I; Cytokines; Extracellular Matrix; Fibroblasts; Granulocytes; Humans; Hypochlorous Acid; Inflammation Mediators; Lung; Middle Aged; Oxidants; Oxidation-Reduction
PubMed: 34943857
DOI: 10.3390/cells10123351 -
IUBMB Life 2007The decomposition of lipid hydroperoxides (LOOH) into peroxyl radicals is a potential source of singlet molecular oxygen ((1)O(2)) in biological systems. Recently, we... (Review)
Review
The decomposition of lipid hydroperoxides (LOOH) into peroxyl radicals is a potential source of singlet molecular oxygen ((1)O(2)) in biological systems. Recently, we have clearly demonstrated the generation of (1)O(2) in the reaction of lipid hydroperoxides with biologically important oxidants such as metal ions, peroxynitrite and hypochlorous acid. The approach used to unequivocally demonstrate the generation of (1)O(2) in these reactions was the use of an isotopic labeled hydroperoxide, the (18)O-labeled linoleic acid hydroperoxide, the detection of labeled compounds by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS) and the direct spectroscopic detection and characterization of (1)O(2) light emission. Using this approach we have observed the formation of (18)O-labeled (1)O(2) by chemical trapping of (1)O(2) with anthracene derivatives and detection of the corresponding labeled endoperoxide by HPLC-MS/MS. The generation of (1)O(2) was also demonstrated by direct spectral characterization of (1)O(2) monomol light emission in the near-infrared region (lambda = 1270 nm). In summary, our studies demonstrated that LOOH can originate (1)O(2). The experimental evidences indicate that (1)O(2) is generated at a yield close to 10% by the Russell mechanism, where a linear tetraoxide intermediate is formed in the combination of two peroxyl radicals. In addition to LOOH, other biological hydroperoxides, including hydroperoxides formed in proteins and nucleic acids, may also participate in reactions leading to the generation (1)O(2). This hypothesis is currently being investigated in our laboratory.
Topics: Cell Membrane; DNA; Hydrogen Peroxide; Lipid Peroxides; Molecular Structure; Oxidants; Proteins; Singlet Oxygen
PubMed: 17505972
DOI: 10.1080/15216540701242508 -
Inorganic Chemistry Jun 2022Hydrogen peroxide is produced upon radiolysis of water and has been shown to be the main oxidant driving oxidative dissolution of UO-based nuclear fuel under geological...
Hydrogen peroxide is produced upon radiolysis of water and has been shown to be the main oxidant driving oxidative dissolution of UO-based nuclear fuel under geological repository conditions. While the overall mechanism and speciation are well known for granitic groundwaters, considerably less is known for saline waters of relevance in rock salt or during emergency cooling of reactors using seawater. In this work, the ternary uranyl-peroxo-chloro and uranyl-peroxo-bromo complexes were identified using IR, Raman, and nuclear magnetic resonance (NMR) spectroscopy. Based on Raman spectra, the estimated stability constants for the identified uranyl-peroxo-chloro ((UO)(O)(Cl)(HO)) and uranyl-peroxo-bromo ((UO)(O)(Br)(HO)) complexes are 0.17 and 0.04, respectively, at ionic strength ≈5 mol/L. It was found that the uranyl-peroxo-chloro complex is more stable than the uranyl-peroxo-bromo complex, which transforms into studtite at high uranyl and HO concentrations. Studtite is also found to be dissolved at a high ionic strength, implying that this may not be a stable solid phase under very saline conditions. The uranyl-peroxo-bromo complex was shown to facilitate HO decomposition via a mechanism involving reactive intermediates.
Topics: Hydrogen Peroxide; Magnetic Resonance Spectroscopy; Oxidants; Oxidation-Reduction; Uranium Compounds
PubMed: 35608075
DOI: 10.1021/acs.inorgchem.2c00233 -
Environmental Health Perspectives Dec 1994The ability of a cell, tissue, or organism to better resist stress damage by prior exposure to a lesser amount of stress is known as adaptive response. It is observed in... (Review)
Review
The ability of a cell, tissue, or organism to better resist stress damage by prior exposure to a lesser amount of stress is known as adaptive response. It is observed in all organisms in response to a number of different cytotoxic agents. One of these agents, oxidative stress, is known to induce an adaptive response in bacteria that is accompanied by the induction of many proteins. De novo protein synthesis is required for adaptive response to oxidative and other types of stress, indicating that newly synthesized protective proteins are necessary for adaptation. Adaptive response to oxidative stress also has been observed in mammalian cells. Several studies suggest it is necessary to first preexpose mammalian cells to a somewhat toxic oxidative stress in order to observe significant resistance to a subsequent highly lethal dose of oxidant. Cross-resistance of oxidatively stressed cells to other toxic agents including gamma- and X-irradiation, heat shock, aldehydes, heavy metals, MNNG, N-ethylmaleimide, and heme also has been reported. Understanding oxidant adaptive response in more detail and identifying the protective proteins involved may prove to be of clinical benefit.
Topics: Adaptation, Physiological; Animals; Escherichia coli; Eukaryotic Cells; Humans; Oxidants; Oxidative Stress
PubMed: 7705299
DOI: 10.1289/ehp.94102s1025 -
Proceedings of the National Academy of... Mar 2004The occurrence of protein tyrosine nitration under disease conditions is now firmly established and represents a shift from the signal transducing physiological actions...
The occurrence of protein tyrosine nitration under disease conditions is now firmly established and represents a shift from the signal transducing physiological actions of (.)NO to oxidative and potentially pathogenic pathways. Tyrosine nitration is mediated by reactive nitrogen species such as peroxynitrite anion (ONOO(-)) and nitrogen dioxide ((.)NO2), formed as secondary products of (.)NO metabolism in the presence of oxidants including superoxide radicals (O2(.-)), hydrogen peroxide (H2O2), and transition metal centers. The precise interplay between (.)NO and oxidants and the identification of the proximal intermediate(s) responsible for nitration in vivo have been under controversy. Despite the capacity of peroxynitrite to mediate tyrosine nitration in vitro, its role on nitration in vivo has been questioned, and alternative pathways, including the nitrite/H2O2/hemeperoxidase and transition metal-dependent mechanisms, have been proposed. A balanced analysis of existing evidence indicates that (i) different nitration pathways can contribute to tyrosine nitration in vivo, and (ii) most, if not all, nitration pathways involve free radical biochemistry with carbonate radicals (CO3(.-)) and/or oxo-metal complexes oxidizing tyrosine to tyrosyl radical followed by the diffusion-controlled reaction with (.)NO2 to yield 3-nitrotyrosine. Although protein tyrosine nitration is a low-yield process in vivo, 3-nitrotyrosine has been revealed as a relevant biomarker of (.)NO-dependent oxidative stress; additionally, site-specific nitration focused on particular protein tyrosines may result in modification of function and promote a biological effect. Tissue distribution and quantitation of protein 3-nitrotyrosine, recognition of the predominant nitration pathways and individual identification of nitrated proteins in disease states open new avenues for the understanding and treatment of human pathologies.
Topics: Animals; Erythrocytes; Hemoglobins; Humans; Mitochondria; Nitrates; Nitric Oxide; Oxidants; Peroxynitrous Acid; Superoxides; Tyrosine
PubMed: 15020765
DOI: 10.1073/pnas.0307446101 -
Water Research Jan 2019The combination of biological growth and particle loading can adversely affect hydraulic performance in drinking water biofilters. In this study, upstream oxidant...
The combination of biological growth and particle loading can adversely affect hydraulic performance in drinking water biofilters. In this study, upstream oxidant addition was used to distribute biologically-derived filter clogging in granular activated carbon (GAC) biofilters. Oxidant penetration was assessed during pilot-scale operation and backwashing of dual media (GAC/sand) and multimedia (GAC/anthracite/sand) biofilters. Influent chlorine (HOCl), monochloramine (NHCl), and hydrogen peroxide (HO) residuals were optimized to react with the GAC surface in the upper portion of the filter media bed (depth < 0.5 m) to attenuate biomass development. As the oxidant residual was quenched by surface-mediated reaction with the filter media, biomass growth was promoted deeper in the filter bed (depth > 0.5 m). The oxidant-induced effects on biomass and hydraulic performance were monitored through measurements of adenosine triphosphate (ATP) and head loss accumulation at different media depths. Addition of oxidants (e.g., 0.6 mg Cl/L HOCl) could decrease terminal head loss by 20% in dual media filters and 40% in multimedia filters. These hydraulic benefits were achieved without significantly affecting removal of assimilable organic carbon (AOC), total organic carbon (TOC), turbidity, and particle counts. Oxidant type, residual concentration, media type, media age, and media depth influenced the passage of oxidant residuals and distribution of filter biomass. When oxidants were added during backwashing, oxidant residual was quenched through the bed depth from a combination of reactions with GAC media and biofilm degradation. This attenuation of residual oxidant may prevent the oxidant residual from penetrating the entire bed depth, potentially compromising backwashing objectives.
Topics: Biofouling; Charcoal; Filtration; Hydrogen Peroxide; Oxidants; Water Purification
PubMed: 30414536
DOI: 10.1016/j.watres.2018.10.085 -
The Journal of Physiology Jun 2021LRRC8A-containing anion channels associate with NADPH oxidase 1 (Nox1) and regulate superoxide production and tumour necrosis factor-α (TNFα) signalling. Here we show...
KEY POINTS
LRRC8A-containing anion channels associate with NADPH oxidase 1 (Nox1) and regulate superoxide production and tumour necrosis factor-α (TNFα) signalling. Here we show that LRRC8C and 8D also co-immunoprecipitate with Nox1 in vascular smooth muscle cells. LRRC8C knockdown inhibited TNFα-induced O production, receptor endocytosis, nuclear factor-κB (NF-κB) activation and proliferation while LRRC8D knockdown enhanced NF-κB activation. Significant changes in LRRC8 isoform expression in human atherosclerosis and psoriasis suggest compensation for increased inflammation. The oxidant chloramine-T (ChlorT, 1 mM) weakly (∼25%) inhibited LRRC8C currents but potently (∼80%) inhibited LRRC8D currents. Substitution of the extracellular loop (EL1, EL2) domains of 8D into 8C conferred significantly stronger (69%) ChlorT-dependent inhibition. ChlorT exposure impaired subsequent current block by DCPIB, which occurs through interaction with EL1, further implicating external oxidation sites. LRRC8A/C channels most effectively sustain Nox1 activity at the plasma membrane. This may result from their ability to remain active in an oxidized microenvironment.
ABSTRACT
Tumour necrosis factor-α (TNFα) activates NADPH oxidase 1 (Nox1) in vascular smooth muscle cells (VSMCs), producing superoxide (O ) required for subsequent signalling. LRRC8 family proteins A-E comprise volume-regulated anion channels (VRACs). The required subunit LRRC8A physically associates with Nox1, and VRAC activity is required for Nox activity and the inflammatory response to TNFα. VRAC currents are modulated by oxidants, suggesting that channel oxidant sensitivity and proximity to Nox1 may play a physiologically relevant role. In VSMCs, LRRC8C knockdown (siRNA) recapitulated the effects of siLRRC8A, inhibiting TNFα-induced extracellular and endosomal O production, receptor endocytosis, nuclear factor-κB (NF-κB) activation and proliferation. In contrast, siLRRC8D potentiated NF-κB activation. Nox1 co-immunoprecipitated with 8C and 8D, and colocalized with 8D at the plasma membrane and in vesicles. We compared VRAC currents mediated by homomeric and heteromeric LRRC8C and LRRC8D channels expressed in HEK293 cells. The oxidant chloramine T (ChlorT, 1 mM) weakly inhibited 8C, but potently inhibited 8D currents. ChlorT exposure also impaired subsequent current block by the VRAC blocker DCPIB, implicating external sites of oxidation. Substitution of the 8D extracellular loop domains (EL1, EL2) into 8C conferred significantly stronger ChlorT-mediated inhibition of 8C currents. Our results suggest that LRRC8A/C channel activity can be effectively maintained in the oxidized microenvironment expected to result from Nox1 activation at the plasma membrane. Increased ratios of 8D:8C expression may potentially depress inflammatory responses to TNFα. LRRC8A/C channel downregulation represents a novel strategy to reduce TNFα-induced inflammation.
Topics: Anions; HEK293 Cells; Humans; Membrane Proteins; NADPH Oxidase 1; Oxidants; Superoxides
PubMed: 33932953
DOI: 10.1113/JP281577