-
Free Radical Biology & Medicine Aug 2021The heme peroxidase family generates a battery of oxidants both for synthetic purposes, and in the innate immune defence against pathogens. Myeloperoxidase (MPO) is the... (Review)
Review
The heme peroxidase family generates a battery of oxidants both for synthetic purposes, and in the innate immune defence against pathogens. Myeloperoxidase (MPO) is the most promiscuous family member, generating powerful oxidizing species including hypochlorous acid (HOCl). Whilst HOCl formation is important in pathogen removal, this species is also implicated in host tissue damage and multiple inflammatory diseases. Significant oxidant formation and damage occurs extracellularly as a result of MPO release via phagolysosomal leakage, cell lysis, extracellular trap formation, and inappropriate trafficking. MPO binds strongly to extracellular biomolecules including polyanionic glycosaminoglycans, proteoglycans, proteins, and DNA. This localizes MPO and subsequent damage, at least partly, to specific sites and species, including extracellular matrix (ECM) components and plasma proteins/lipoproteins. Biopolymer-bound MPO retains, or has enhanced, catalytic activity, though evidence is also available for non-catalytic effects. These interactions, particularly at cell surfaces and with the ECM/glycocalyx induce cellular dysfunction and altered gene expression. MPO binds with higher affinity to some damaged ECM components, rationalizing its accumulation at sites of inflammation. MPO-damaged biomolecules and fragments act as chemo-attractants and cell activators, and can modulate gene and protein expression in naïve cells, consistent with an increasing cycle of MPO adhesion, activity, damage, and altered cell function at sites of leukocyte infiltration and activation, with subsequent tissue damage and dysfunction. MPO levels are used clinically both diagnostically and prognostically, and there is increasing interest in strategies to prevent MPO-mediated damage; therapeutic aspects are not discussed as these have been reviewed elsewhere.
Topics: Humans; Hypochlorous Acid; Inflammation; Oxidants; Oxidation-Reduction; Peroxidase
PubMed: 34246778
DOI: 10.1016/j.freeradbiomed.2021.07.007 -
Redox Biology Jul 2023Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells... (Review)
Review
Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells generally represent a higher oxidant level, which suggests a dual therapeutic strategy by regulating redox status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, pro-oxidant therapy exhibits a great anti-cancer capability, attributing to a higher oxidant accumulation within cancer cells, whereas antioxidant therapy to restore redox homeostasis has been claimed to fail in several clinical practices. Targeting the redox vulnerability of cancer cells by pro-oxidants capable of generating excessive reactive oxygen species (ROS) has surfaced as an important anti-cancer strategy. However, multiple adverse effects caused by the indiscriminate attacks of uncontrolled drug-induced OS on normal tissues and the drug-tolerant capacity of some certain cancer cells greatly limit their further applications. Herein, we review several representative oxidative anti-cancer drugs and summarize their side effects on normal tissues and organs, emphasizing that seeking a balance between pro-oxidant therapy and oxidative damage is of great value in exploiting next-generation OS-based anti-cancer chemotherapeutics.
Topics: Humans; Antioxidants; Reactive Oxygen Species; Oxidative Stress; Oxidation-Reduction; Oxidants; Neoplasms
PubMed: 37224697
DOI: 10.1016/j.redox.2023.102754 -
Free Radical Research Apr 2012A broad scientific community is involved in investigations aimed at delineating the mechanisms of formation and cellular processing of oxidatively generated damage to... (Review)
Review
A broad scientific community is involved in investigations aimed at delineating the mechanisms of formation and cellular processing of oxidatively generated damage to nucleic acids. Perhaps as a consequence of this breadth of research expertise, there are nomenclature problems for several of the oxidized bases including 8-oxo-7,8-dihydroguanine (8-oxoGua), a ubiquitous marker of almost every type of oxidative stress in cells. Efforts to standardize the nomenclature and abbreviations of the main DNA degradation products that arise from oxidative pathways are reported. Information is also provided on the main oxidative radicals, non-radical oxygen species, one-electron agents and enzymes involved in DNA degradation pathways as well in their targets and reactivity. A brief classification of oxidatively generated damage to DNA that may involve single modifications, tandem base modifications, intrastrand and interstrand cross-links together with DNA-protein cross-links and base adducts arising from the addition of lipid peroxides breakdown products is also included.
Topics: Animals; DNA Adducts; DNA Damage; Deoxyribose; Guanine; Humans; Nucleic Acids; Oxidants; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species
PubMed: 22263561
DOI: 10.3109/10715762.2012.659248 -
Nature Communications Aug 2022Genomic reconstructions of the common ancestor to all life have identified genes involved in HO and O cycling. Commonly dismissed as an artefact of lateral gene transfer...
Genomic reconstructions of the common ancestor to all life have identified genes involved in HO and O cycling. Commonly dismissed as an artefact of lateral gene transfer after oxygenic photosynthesis evolved, an alternative is a geological source of HO and O on the early Earth. Here, we show that under oxygen-free conditions high concentrations of HO can be released from defects on crushed silicate rocks when water is added and heated to temperatures close to boiling point, but little is released at temperatures <80 °C. This temperature window overlaps the growth ranges of evolutionary ancient heat-loving and oxygen-respiring Bacteria and Archaea near the root of the Universal Tree of Life. We propose that the thermal activation of mineral surface defects during geological fault movements and associated stresses in the Earth's crust was a source of oxidants that helped drive the (bio)geochemistry of hot fractures where life first evolved.
Topics: Biological Evolution; Earth, Planet; Hydrogen Peroxide; Oxidants; Oxygen; Photosynthesis
PubMed: 35941147
DOI: 10.1038/s41467-022-32129-y -
Respiratory Medicine Sep 2009Oxidative stress is an imbalance between oxidants (reactive oxygen and nitrogen species) and antioxidants that may affect lipids, DNA, carbohydrates and proteins. The... (Review)
Review
Oxidative stress is an imbalance between oxidants (reactive oxygen and nitrogen species) and antioxidants that may affect lipids, DNA, carbohydrates and proteins. The lung is continuously exposed to endogenous and exogenous oxidants (cigarette smoke, mineral dust, ozone, radiation). Reactive oxygen and nitrogen species are mainly produced by phagocytes as well as by polymorphonuclear, alveolar, bronchial and endothelial cells. A potential role of oxidative stress in the pathogenesis of diffuse lung diseases (particularly idiopathic pulmonary fibrosis) has been demonstrated. Increased oxidant levels and decreased antioxidant defences can contribute to the progression of idiopathic pulmonary fibrosis and other diffuse lung diseases. The growing number of papers on the different aspects of oxidant/antioxidant imbalance in diffuse lung diseases in the last decade reflects increasing interest in this topic and suggests that specific DLDs may be characterized by specific patterns of oxidation and antioxidant responses. The study of oxidative stress can provide insights into etiopathogenesis and favour the discovery of new treatments. In this review of the literature on oxidants and antioxidants in diffuse lung diseases, the focus is on idiopathic pulmonary fibrosis, sarcoidosis, pneumoconiosis and pulmonary fibrosis associated with systemic sclerosis.
Topics: Antioxidants; Humans; Lung; Lung Diseases; Oxidants; Oxidative Stress
PubMed: 19464864
DOI: 10.1016/j.rmed.2009.04.014 -
The American Journal of Pathology Jul 2016The interplay that governs chronic diseases through pathways specifically associated with chronic inflammation remains undefined. Many metabolic events have been... (Review)
Review
The interplay that governs chronic diseases through pathways specifically associated with chronic inflammation remains undefined. Many metabolic events have been identified during the injury and repair process. Nonetheless, the cellular events that control the pathogenesis of inflammation-induced disease have not been fully characterized. We and others reason that chronic inflammatory diseases associated with a cascade of complex network mediators, such as nitric oxide, arachidonic acid metabolites, cytokines, and reactive oxygen species, play a significant role in the governance of alterations in homeostasis, oxidative stress, and thromboatherosclerosis. In this context, we discuss lipid mediators associated with the maintenance of health, including the specialized proresolving mediators that help drive cellular repair. Emphasis is placed on the pathophysiology of chronic metabolic insults involving both the airways and the cardiovascular system during oxidant-driven inflammatory disease. In this review, we highlight new pathways of inquiry that show promise for the identification of those metabolic targets that can improve therapy for chronic inflammation.
Topics: Animals; Chronic Disease; Humans; Inflammation; Oxidants; Oxidative Stress
PubMed: 27171899
DOI: 10.1016/j.ajpath.2016.03.001 -
Circulation Journal : Official Journal... 2012Reactive oxygen species (ROS) have long been viewed as deleterious chemicals that lead to oxidative stress. More recently, ROS, especially the stable ROS hydrogen... (Review)
Review
Reactive oxygen species (ROS) have long been viewed as deleterious chemicals that lead to oxidative stress. More recently, ROS, especially the stable ROS hydrogen peroxide (H(2)O(2)), have been shown to have roles in normal physiological responses in vascular cells. Endothelial nitric oxide synthase (eNOS) is dynamically targeted to plasmalemmal caveolae, and represents the principal enzymatic source of nitric oxide (NO(•)) in the vascular wall. eNOS maintains normal vascular tone and inhibits the clinical expression of many cardiovascular diseases. Increases in oxidative stress are associated with eNOS dysfunction. In a paradigm shift in the conceptual framework linking redox biochemistry and vascular function, H(2)O(2) has been established as a physiological mediator in signaling pathways, yet the intracellular sources of H(2)O(2) and their regulation remain incompletely understood. The subcellular distributions of ROS and of ROS-modified proteins critically influence the redox-sensitive regulation of eNOS-dependent pathways. ROS localization in specific subcellular compartments can lead to selective oxidative modifications of eNOS and eNOS-associated proteins. Likewise, the dynamic targeting of eNOS and other signaling proteins influences their interactions with reactive nitrogen species and ROS that are also differentially distributed within the cell. Thus, the subcellular distribution both of eNOS and redox-active biomolecules serves as a critical basis for the control of the "redox switch" that influences NO(•)- and oxidant-regulated signaling pathways. Here we discuss the biochemical factors, cellular determinants, and molecular mechanisms that modulate redox-sensitive regulation of eNOS and NO(•) signaling under normal and pathological conditions.
Topics: Animals; Cardiovascular Diseases; Caveolae; Gene Expression Regulation, Enzymologic; Humans; Hydrogen Peroxide; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidants; Oxidation-Reduction; Signal Transduction
PubMed: 23075817
DOI: 10.1253/circj.cj-12-1207 -
Pathogens and Disease Aug 2016Staphylococcus aureus is a ubiquitous, versatile and dangerous pathogen. It colonizes over 30% of the human population, and is one of the leading causes of death by an... (Review)
Review
Staphylococcus aureus is a ubiquitous, versatile and dangerous pathogen. It colonizes over 30% of the human population, and is one of the leading causes of death by an infectious agent. During S. aureus colonization and invasion, leukocytes are recruited to the site of infection. To combat S. aureus, leukocytes generate an arsenal of reactive species including superoxide, hydrogen peroxide, nitric oxide and hypohalous acids that modify and inactivate cellular macromolecules, resulting in growth defects or death. When S. aureus colonization cannot be cleared by the immune system, antibiotic treatment is necessary and can be effective. Yet, this organism quickly gains resistance to each new antibiotic it encounters. Therefore, it is in the interest of human health to acquire a deeper understanding of how S. aureus evades killing by the immune system. Advances in this field will have implications for the design of future S. aureus treatments that complement and assist the host immune response. In that regard, this review focuses on how S. aureus avoids host-generated oxidative stress, and discusses the mechanisms used by S. aureus to survive oxidative damage including antioxidants, direct repair of damaged proteins, sensing oxidant stress and transcriptional changes. This review will elucidate areas for studies to identify and validate future antimicrobial targets.
Topics: Animals; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Microbial Viability; Neutrophils; Nitric Oxide; Oxidants; Oxidation-Reduction; Oxidative Stress; Respiratory Burst; Staphylococcal Infections; Staphylococcus aureus
PubMed: 27354296
DOI: 10.1093/femspd/ftw060 -
Nature Communications May 2022Removal of organic micropollutants from water through advanced oxidation processes (AOPs) is hampered by the excessive input of energy and/or chemicals as well as the...
Removal of organic micropollutants from water through advanced oxidation processes (AOPs) is hampered by the excessive input of energy and/or chemicals as well as the large amounts of residuals resulting from incomplete mineralization. Herein, we report a new water purification paradigm, the direct oxidative transfer process (DOTP), which enables complete, highly efficient decontamination at very low dosage of oxidants. DOTP differs fundamentally from AOPs and adsorption in its pollutant removal behavior and mechanisms. In DOTP, the nanocatalyst can interact with persulfate to activate the pollutants by lowering their reductive potential energy, which triggers a non-decomposing oxidative transfer of pollutants from the bulk solution to the nanocatalyst surface. By leveraging the activation, stabilization, and accumulation functions of the heterogeneous catalyst, the DOTP can occur spontaneously on the nanocatalyst surface to enable complete removal of pollutants. The process is found to occur for diverse pollutants, oxidants, and nanocatalysts, including various low-cost catalysts. Significantly, DOTP requires no external energy input, has low oxidant consumption, produces no residual byproducts, and performs robustly in real environmental matrices. These favorable features render DOTP an extremely promising nanotechnology platform for water purification.
Topics: Decontamination; Environmental Pollutants; Oxidants; Water; Water Pollutants, Chemical
PubMed: 35637224
DOI: 10.1038/s41467-022-30560-9 -
The Journal of Clinical Investigation Mar 2003
Review
Topics: Animals; DNA; DNA Damage; DNA Methylation; Humans; Nitric Oxide; Oxidants; Proteins; Reactive Oxygen Species
PubMed: 12618510
DOI: 10.1172/JCI18022