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Journal of Nanobiotechnology Mar 2017Engineered nanomaterials (ENMs) are key drivers for the development of highly sophisticated new technologies. As all new attainments, the rapidly increasing used of ENMs... (Review)
Review
Engineered nanomaterials (ENMs) are key drivers for the development of highly sophisticated new technologies. As all new attainments, the rapidly increasing used of ENMs raise concerns about their safety for the environment and humans. There is growing evidence showing that if engineered nanomaterials are released into the environment, there is a possibility that they could cause harm to aquatic microorganisms. Among the divers effects triggering their toxicity the ability of ENMs to generate reactive oxygen species (ROS) capable of oxidizing biomolecules is currently considered a central mechanism of toxicity. Therefore, development of sensitive tools for quantification of the ROS generation and oxidative stress are highly sought. After briefly introducing ENMs-induced ROS generation and oxidative stress in the aquatic microorganisms (AMOs), this overview paper focuses on a new optical biosensor allowing sensitive and dynamic measurements of HO in real-time using multiscattering enhanced absorption spectroscopy. Its principle is based on sensitive absorption measurements of the heme protein cytochrome c whose absorption spectrum alters with the oxidation state of constituent ferrous Fe and ferric Fe. For biological applications cytochrome c was embedded in porous random media resulting in an extended optical path length through multiple scattering of light, which lowers the limit of detection to a few nM of HO. The sensor was also integrated in a microfluidic system containing micro-valves and sieves enabling more complex experimental conditions. To demonstrate its performance, abiotic absorption measurements of low concentrations of dye molecules and 10 nm gold particles were carried out achieving limits of detection in the low nM range. Other biologically relevant reactive oxygen species can be measured at sub-μM concentrations, which was shown for glucose and lactate through enzymatic reactions producing HO. In ecotoxicological investigations HO excreted by aquatic microorganisms exposed to various stressors were measured. Pro-oxidant effects of nano-TiO and nano-CuO towards green alga Chlamydomonas reinhardtii were explored in various exposure media and under different light illuminations. Dynamics of Cd induced effects on photosynthetic activity, sensitisation and recovery of cells of C. reinhardtii was also studied.
Topics: Biosensing Techniques; Chlamydomonas reinhardtii; Copper; Equipment Design; Hydrogen Peroxide; Lab-On-A-Chip Devices; Nanoparticles; Oxidants; Oxidative Stress; Titanium; Water Pollutants, Chemical
PubMed: 28270155
DOI: 10.1186/s12951-017-0253-x -
Free Radical Biology & Medicine Sep 2023Myeloperoxidase (MPO) is released by neutrophils in inflamed tissues. MPO oxidizes chloride, bromide, and thiocyanate to produce hypochlorous acid (HOCl), hypobromous...
Myeloperoxidase (MPO) is released by neutrophils in inflamed tissues. MPO oxidizes chloride, bromide, and thiocyanate to produce hypochlorous acid (HOCl), hypobromous acid (HOBr), and hypothiocyanous acid (HOSCN), respectively. These oxidants are toxic to pathogens, but may also react with host cells to elicit biological activity and potential toxicity. In cystic fibrosis (CF) and related diseases, increased neutrophil inflammation leads to increased airway MPO and airway epithelial cell (AEC) exposure to its oxidants. In this study, we investigated how equal dose-rate exposures of MPO-derived oxidants differentially impact the metabolome of human AECs (BEAS-2B cells). We utilized enzymatic oxidant production with rate-limiting glucose oxidase (GOX) coupled to MPO, and chloride, bromide (Br), or thiocyanate (SCN) as substrates. AECs exposed to GOX/MPO/SCN (favoring HOSCN) were viable after 24 h, while exposure to GOX/MPO (favoring HOCl) or GOX/MPO/Br (favoring HOBr) developed cytotoxicity after 6 h. Cell glutathione and peroxiredoxin-3 oxidation were insufficient to explain these differences. However, untargeted metabolomics revealed GOX/MPO and GOX/MPO/Br diverged significantly from GOX/MPO/SCN for dozens of metabolites. We noted methionine sulfoxide and dehydromethionine were significantly increased in GOX/MPO- or GOX/MPO/Br-treated cells, and analyzed them as potential biomarkers of lung damage in bronchoalveolar lavage fluid from 5-year-olds with CF (n = 27). Both metabolites were associated with increasing bronchiectasis, neutrophils, and MPO activity. This suggests MPO production of HOCl and/or HOBr may contribute to inflammatory lung damage in early CF. In summary, our in vitro model enabled unbiased identification of exposure-specific metabolite products which may serve as biomarkers of lung damage in vivo. Continued research with this exposure model may yield additional oxidant-specific biomarkers and reveal explicit mechanisms of oxidant byproduct formation and cellular redox signaling.
Topics: Humans; Child, Preschool; Thiocyanates; Peroxidase; Cystic Fibrosis; Bromides; Chlorides; Oxidants; Antioxidants; Hypochlorous Acid; Epithelial Cells; Metabolomics
PubMed: 37356776
DOI: 10.1016/j.freeradbiomed.2023.06.021 -
Biochimica Et Biophysica Acta May 1995Reactive oxygen species (ROS: superoxide radical, O2.-; hydrogen peroxide, H2O2; hydroxyl radical, OH.), which arise from the univalent reduction of dioxygen are formed... (Review)
Review
Reactive oxygen species (ROS: superoxide radical, O2.-; hydrogen peroxide, H2O2; hydroxyl radical, OH.), which arise from the univalent reduction of dioxygen are formed in mitochondria. We summarize here results which indicate that ROS, and also the radical nitrogen monoxide ('nitric oxide', NO), act as physiological modulators of some mitochondrial functions, but may also damage mitochondria. Hydrogen peroxide, which originates in mitochondria predominantly from the dismutation of superoxide, causes oxidation of mitochondrial pyridine nucleotides and thereby stimulates a specific Ca2+ release from intact mitochondria. This release is prevented by cyclosporin A (CSA). Hydrogen peroxide thus contributes to the maintenance of cellular Ca2+ homeostasis. A stimulation of mitochondrial ROS production followed by an enhanced Ca2+ release and re uptake (Ca2+ 'cycling') by mitochondria causes apoptosis and necrosis, and contributes to hypoxia/reperfusion injury. These kinds of cell injury can be attenuated at the mitochondrial level by CSA. When ROS are produced in excessive amounts in mitochondria nucleic acids, proteins, and lipids are extensively modified by oxidation. Physiological (sub-micromolar) concentrations of NO potently and reversibly deenergize mitochondria at oxygen tensions that prevail in cells by transiently binding to cytochrome oxidase. This is paralleled by mitochondrial Ca2+ release and uptake. Higher NO concentrations or prolonged exposure of cells to NO causes their death. It is concluded that ROS and NO are important physiological reactants in mitochondria and become toxic only when present in excessive amounts.
Topics: Animals; Apoptosis; Calcium; Cell Survival; Disease; Glutathione; Humans; Liver; Mitochondria; Nitric Oxide; Nitroso Compounds; Oxidants; Oxidative Stress; Reactive Oxygen Species; Reference Values; S-Nitrosoglutathione
PubMed: 7599228
DOI: 10.1016/0925-4439(95)00012-s -
Brain Pathology (Zurich, Switzerland) Jan 1999This review summarises the role that reactive oxygen and nitrogen species play in demyelination, such as that occurring in the inflammatory demyelinating disorders... (Review)
Review
This review summarises the role that reactive oxygen and nitrogen species play in demyelination, such as that occurring in the inflammatory demyelinating disorders multiple sclerosis and Guillain-Barré syndrome. The concentrations of reactive oxygen and nitrogen species (e.g. superoxide, nitric oxide and peroxynitrite) can increase dramatically under conditions such as inflammation, and this can overwhelm the inherent antioxidant defences within lesions. Such oxidative and/or nitrative stress can damage the lipids, proteins and nucleic acids of cells and mitochondria, potentially causing cell death. Oligodendrocytes are more sensitive to oxidative and nitrative stress in vitro than are astrocytes and microglia, seemingly due to a diminished capacity for antioxidant defence, and the presence of raised risk factors, including a high iron content. Oxidative and nitrative stress might therefore result in vivo in selective oligodendrocyte death, and thereby demyelination. The reactive species may also damage the myelin sheath, promoting its attack by macrophages. Damage can occur directly by lipid peroxidation, and indirectly by the activation of proteases and phospholipase A2. Evidence for the existence of oxidative and nitrative stress within inflammatory demyelinating lesions includes the presence of both lipid and protein peroxides, and nitrotyrosine (a marker for peroxynitrite formation). The neurological deficit resulting from experimental autoimmune demyelinating disease has generally been reduced by trial therapies intended to diminish the concentration of reactive oxygen species. However, therapies aimed at diminishing reactive nitrogen species have had a more variable outcome, sometimes exacerbating disease.
Topics: Animals; Antioxidants; Demyelinating Diseases; Humans; Inflammation; Lipid Peroxidation; Nervous System; Nitrates; Nitric Oxide; Oxidants; Oxidative Stress; Reactive Oxygen Species
PubMed: 9989453
DOI: 10.1111/j.1750-3639.1999.tb00212.x -
Molecules (Basel, Switzerland) Feb 2020The development of sustainable processes and products through innovative catalytic materials and procedures that allow a better use of resources is undoubtedly one of... (Review)
Review
The development of sustainable processes and products through innovative catalytic materials and procedures that allow a better use of resources is undoubtedly one of the most significant issues facing researchers nowadays. Environmental and economically advanced catalytic processes for selective oxidation of alcohols are currently focused on designing new catalysts able to activate green oxidants (dioxygen or peroxides) and applying unconventional conditions of sustainable significance, like the use of microwave irradiation as an alternative energy source. This short review aims to provide an overview of the recently (2015-2020) discovered homogeneous aerobic and peroxidative oxidations of primary and secondary alcohols catalyzed by copper complexes, highlighting new catalysts with potential application in sustainable organic synthesis, with significance in academia and industry.
Topics: Alcohols; Catalysis; Copper; Green Chemistry Technology; Humans; Microwaves; Molecular Structure; Oxidants; Oxidation-Reduction; Oxygen; Peroxides
PubMed: 32050493
DOI: 10.3390/molecules25030748 -
Molecular Microbiology Oct 2022Repairing oxidative-targeted macromolecules is a central mechanism necessary for living organisms to adapt to oxidative stress. Reactive oxygen and chlorine species...
Repairing oxidative-targeted macromolecules is a central mechanism necessary for living organisms to adapt to oxidative stress. Reactive oxygen and chlorine species preferentially oxidize sulfur-containing amino acids in proteins. Among these amino acids, methionine can be converted into methionine sulfoxide. This post-translational oxidation can be reversed by methionine sulfoxide reductases, Msr enzymes. In Gram-negative bacteria, the antioxidant MsrPQ system is involved in the repair of periplasmic oxidized proteins. Surprisingly, in this study, we observed in Escherichia coli that msrPQ was highly expressed in the absence of oxygen. We have demonstrated that the anaerobic induction of msrPQ was due to chlorate (ClO ) contamination of the Casamino Acids. Molecular investigation led us to determine that the reduction of chlorate to the toxic oxidizing agent chlorite (ClO ) by the three nitrate reductases (NarA, NarZ, and Nap) led to methionine oxidation of periplasmic proteins. In response to this stress, the E. coli HprSR two-component system was activated, leading to the over-production of MsrPQ. This study, therefore, supports the idea that methionine oxidation in proteins is part of chlorate toxicity, and that MsrPQ can be considered as an anti-chlorate/chlorite defense system in bacteria. Finally, this study challenges the traditional view of the absence of Met-oxidation during anaerobiosis.
Topics: Escherichia coli; Methionine Sulfoxide Reductases; Periplasmic Proteins; Anaerobiosis; Chlorine; Antioxidants; Oxidation-Reduction; Methionine; Racemethionine; Oxygen; Oxidants; Sulfur
PubMed: 36271735
DOI: 10.1111/mmi.14971 -
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 -
Revista de NeurologiaAccording to the oxidative stress hypothesis, the pathogenesis of several diseases should be related with an excessive production of prooxidant substances (free... (Review)
Review
INTRODUCTION
According to the oxidative stress hypothesis, the pathogenesis of several diseases should be related with an excessive production of prooxidant substances (free radicals, transition metals), the deficiency of antioxidant defensive mechanisms, or both. Oxidative stress has been implicated in the pathogenesis of aging of the brain and several neurological diseases, including Alzheimer's disease (AD).
DEVELOPMENT
In recent years there are many data suggesting a possible role of oxidative stress in the pathogenesis of AD. These include the demonstration of increased oxidation of lipids, proteins and deoxyribonucleic acid, alterations in mitochondrial function and the possible role of amyloid beta and its precursor protein in the oxidative reactions in experimental models (cortical neuronal cultures and transgenic animals).
CONCLUSIONS
Many studies show increased oxidative stress in the brain of patients with AD, although its possible role con the pathogenesis of this disease are controversial.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Heme Oxygenase (Decyclizing); Humans; Lipid Peroxidation; Metals; Mitochondria; Nitric Oxide; Oxidants; Oxidation-Reduction; Oxidative Stress
PubMed: 16602059
DOI: No ID Found -
Nitric Oxide : Biology and Chemistry Aug 2011
Topics: Humans; Nitric Oxide; Oxidants; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Signal Transduction
PubMed: 21596152
DOI: 10.1016/j.niox.2011.05.002 -
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