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Bacterial Defense Systems against the Neutrophilic Oxidant Hypochlorous Acid.
Sultana, S, Foti, A, Dahl, JU
Infection and immunity. 2020;(7)
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Abstract
Neutrophils kill invading microbes and therefore represent the first line of defense of the innate immune response. Activated neutrophils assemble NADPH oxidase to convert substantial amounts of molecular oxygen into superoxide, which, after dismutation into peroxide, serves as the substrate for the generation of the potent antimicrobial hypochlorous acid (HOCl) in the phagosomal space. In this minireview, we explore the most recent insights into physiological consequences of HOCl stress. Not surprisingly, Gram-negative bacteria have evolved diverse posttranslational defense mechanisms to protect their proteins, the main targets of HOCl, from HOCl-mediated damage. We discuss the idea that oxidation of conserved cysteine residues and partial unfolding of its structure convert the heat shock protein Hsp33 into a highly active chaperone holdase that binds unfolded proteins and prevents their aggregation. We examine two novel members of the Escherichia coli chaperone holdase family, RidA and CnoX, whose thiol-independent activation mechanism differs from that of Hsp33 and requires N-chlorination of positively charged amino acids during HOCl exposure. Furthermore, we summarize the latest findings with respect to another bacterial defense strategy employed in response to HOCl stress, which involves the accumulation of the universally conserved biopolymer inorganic polyphosphate. We then discuss sophisticated adaptive strategies that bacteria have developed to enhance their survival during HOCl stress. Understanding bacterial defense and survival strategies against one of the most powerful neutrophilic oxidants may provide novel insights into treatment options that potentially compromise the ability of pathogens to resist HOCl stress and therefore may increase the efficacy of the innate immune response.
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Diminishing Inflammation by Reducing Oxidant Generation: Nitrated Fatty Acid-Mediated Inactivation of Xanthine Oxidoreductase.
Kelley, EE
Advances in experimental medicine and biology. 2019;:59-65
Abstract
Inhibition of xanthine oxidoreductase (XOR) has proven beneficial in a plethora of inflammatory disease processes due to a net reduction in pro-inflammatory oxidants and secondary nitrating species. Electrophilic nitrated fatty acid derivatives, such as nitro-oleic acid (OA-NO2) are also noted to display a broad spectrum of anti-inflammatory effects via interaction with critical signaling pathways. An alternative process in which nitrated fatty acids may extend anti-inflammatory actions is via inactivation of XOR, a process that is more effective than allo/oxypurinol-mediated inhibition. Herein, we describe the molecular aspects of nitrated fatty acid-associated inactivation of XOR, identify specificity via structure function relationships and discuss XOR as a crucial component of the anti-inflammatory portfolio of nitrated fatty acids.
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Impairment between Oxidant and Antioxidant Systems: Short- and Long-term Implications for Athletes' Health.
Nocella, C, Cammisotto, V, Pigozzi, F, Borrione, P, Fossati, C, D'Amico, A, Cangemi, R, Peruzzi, M, Gobbi, G, Ettorre, E, et al
Nutrients. 2019;(6)
Abstract
The role of oxidative stress, an imbalance between reactive oxygen species production (ROS) and antioxidants, has been described in several patho-physiological conditions, including cardiovascular, neurological diseases and cancer, thus impacting on individuals' lifelong health. Diet, environmental pollution, and physical activity can play a significant role in the oxidative balance of an organism. Even if physical training has proved to be able to counteract the negative effects caused by free radicals and to provide many health benefits, it is also known that intensive physical activity induces oxidative stress, inflammation, and free radical-mediated muscle damage. Indeed, variations in type, intensity, and duration of exercise training can activate different patterns of oxidant-antioxidant balance leading to different responses in terms of molecular and cellular damage. The aim of the present review is to discuss (1) the role of oxidative status in athletes in relation to exercise training practice, (2) the implications for muscle damage, (3) the long-term effect for neurodegenerative disease manifestations, (4) the role of antioxidant supplementations in preventing oxidative damages.
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Is maternal microbial metabolism an early-life determinant of health?
Romano, KA, Rey, FE
Lab animal. 2018;(9):239-243
Abstract
Mounting evidence suggests that environmental stress experienced in utero (for example, maternal nutritional deficits) establishes a predisposition in the newborn to the development of chronic diseases later in life. This concept is often referred to as the "fetal origins hypothesis" or "developmental origins of health and disease". Since its first proposal, epigenetics has emerged as an underlying mechanism explaining how environmental cues become gestationally "encoded". Many of the enzymes that impart and maintain epigenetic modifications are highly sensitive to nutrient availability, which can be influenced by the metabolic activities of the intestinal microbiota. Therefore, the maternal microbiome has the potential to influence epigenetics in utero and modulate offspring's long-term health trajectories. Here we summarize the current understanding of the interactions that occur between the maternal gut microbiome and the essential nutrient choline, that is not only required for fetal development and epigenetic regulation but is also a growth substrate for some microbes. Bacteria able to metabolize choline benefit from the presence of this nutrient and compete with the host for its access, which under extreme conditions may elicit signatures of choline deficiency. Another consequence of bacterial choline metabolism is the accumulation of the pro-inflammatory, pro-thrombotic metabolite trimethylamine-N-oxide (TMAO). Finally, we discuss how these different facets of microbial choline metabolism may influence infant development and health trajectories via epigenetic mechanisms and more broadly place a call to action to better understand how maternal microbial metabolism can shape their offspring's propensity to chronic disease development later in life.
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The role of operating parameters and oxidative damage mechanisms of advanced chemical oxidation processes in the combat against antibiotic-resistant bacteria and resistance genes present in urban wastewater.
Michael-Kordatou, I, Karaolia, P, Fatta-Kassinos, D
Water research. 2018;:208-230
Abstract
An upsurge in the study of antibiotic resistance in the environment has been observed in the last decade. Nowadays, it is becoming increasingly clear that urban wastewater is a key source of antibiotic resistance determinants, i.e. antibiotic-resistant bacteria and antibiotic resistance genes (ARB&ARGs). Urban wastewater reuse has arisen as an important component of water resources management in the European Union and worldwide to address prolonged water scarcity issues. Especially, biological wastewater treatment processes (i.e. conventional activated sludge), which are widely applied in urban wastewater treatment plants, have been shown to provide an ideal environment for the evolution and spread of antibiotic resistance. The ability of advanced chemical oxidation processes (AOPs), e.g. light-driven oxidation in the presence of H2O2, ozonation, homogeneous and heterogeneous photocatalysis, to inactivate ARB and remove ARGs in wastewater effluents has not been yet evaluated through a systematic and integrated approach. Consequently, this review seeks to provide an extensive and critical appraisal on the assessment of the efficiency of these processes in inactivating ARB and removing ARGs in wastewater effluents, based on recent available scientific literature. It tries to elucidate how the key operating conditions may affect the process efficiency, while pinpointing potential areas for further research and major knowledge gaps which need to be addressed. Also, this review aims at shedding light on the main oxidative damage pathways involved in the inactivation of ARB and removal of ARGs by these processes. In general, the lack and/or heterogeneity of the available scientific data, as well as the different methodological approaches applied in the various studies, make difficult the accurate evaluation of the efficiency of the processes applied. Besides the operating conditions, the variable behavior observed by the various examined genetic constituents of the microbial community, may be directed by the process distinct oxidative damage mechanisms in place during the application of each treatment technology. For example, it was shown in various studies that the majority of cellular damage by advanced chemical oxidation may be on cell wall and membrane structures of the targeted bacteria, leaving the internal components of the cells relatively intact/able to repair damage. As a result, further in-depth mechanistic studies are required, to establish the optimum operating conditions under which oxidative mechanisms target internal cell components such as genetic material and ribosomal structures more intensively, thus conferring permanent damage and/or death and preventing potential post-treatment re-growth.
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Dioxygen activation by nonheme iron enzymes with the 2-His-1-carboxylate facial triad that generate high-valent oxoiron oxidants.
Kal, S, Que, L
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 2017;(2-3):339-365
Abstract
The 2-His-1-carboxylate facial triad is a widely used scaffold to bind the iron center in mononuclear nonheme iron enzymes for activating dioxygen in a variety of oxidative transformations of metabolic significance. Since the 1990s, over a hundred different iron enzymes have been identified to use this platform. This structural motif consists of two histidines and the side chain carboxylate of an aspartate or a glutamate arranged in a facial array that binds iron(II) at the active site. This triad occupies one face of an iron-centered octahedron and makes the opposite face available for the coordination of O2 and, in many cases, substrate, allowing the tailoring of the iron-dioxygen chemistry to carry out a plethora of diverse reactions. Activated dioxygen-derived species involved in the enzyme mechanisms include iron(III)-superoxo, iron(III)-peroxo, and high-valent iron(IV)-oxo intermediates. In this article, we highlight the major crystallographic, spectroscopic, and mechanistic advances of the past 20 years that have significantly enhanced our understanding of the mechanisms of O2 activation and the key roles played by iron-based oxidants.
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Antioxidant capacity of foods for scavenging reactive oxidants and inhibition of plasma lipid oxidation induced by multiple oxidants.
Niki, E
Food & function. 2016;(5):2156-68
Abstract
Unregulated oxidation of biological molecules induced by multiple oxidants has been implicated in the pathogenesis of various diseases. Consequently, the effects of antioxidants contained in foods, beverages and supplements on the maintenance of health and prevention of diseases have attracted much attention of the public as well as scientists. However, recent human studies have shown inconsistent results and failed to demonstrate the beneficial effects of antioxidants. The mechanisms and dynamics of antioxidant action and assessment of antioxidant capacity have been the subject of extensive studies and arguments. In the present article, the antioxidant capacity has been reviewed focusing on two main issues: the capacity of antioxidants to scavenge multiple reactive oxidants and to inhibit plasma lipid oxidation induced by different biological oxidants. It is emphasized that the capacity of antioxidants to scavenge reactive oxidants does not always correlate linearly with the capacity to inhibit lipid oxidation and that it is necessary to specify the oxidant to assess the efficacy of antioxidants, since multiple oxidants contribute to oxidative damage in vivo and the effects of antioxidants depend on the nature of oxidants. A convenient and rapid method using a microplate reader is discussed for assessing the antioxidant capacity against plasma lipid oxidation induced by multiple oxidants including peroxyl radicals, peroxynitrite, hypochlorite, 15-lipoxygenase, and singlet oxygen.
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Antioxidants, oxidants, and redox impacts on cell function - A tribute to Helmut Sies.
Cadenas, E, Packer, L, Traber, MG
Archives of biochemistry and biophysics. 2016;:94-9
Abstract
This article is in tribute to Helmut Sies and is written by his friends from the Oxygen Club of California with personal recollections from each of us: Enrique Cadenas on "Oxidative Stress and Mentorship", Lester Packer on "The Antioxidant Network", and Maret G. Traber on "Nutrition and Chronic Disease". We conclude with a brief overview of the positive influence Helmut Sies has had on the Oxygen Club of California.
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Assessment of ethylene diurea-induced protection in plants against ozone phytotoxicity.
Singh, AA, Singh, S, Agrawal, M, Agrawal, SB
Reviews of environmental contamination and toxicology. 2015;:129-84
Abstract
Urbanization, industrialization and unsustainable utilization of natural resources have made tropospheric ozone (03) one of the world's most significant air pollutants. Past studies reveal that 0 3 is a phytotoxic air pollutant that causes or enhances food insecurity across the globe. Plant sensitivity, tolerance and resistance to 0 3 involve a wide array of responses that range from growth to the physiological, biochemical and molecular. Although plants have an array of defense systems to combat oxidative stress from 0 3 exposure, they still suffer sizable yield reductions. In recent years, the ground-level 0 3 concentrations to which crop plants have been exposed have caused yield loses that are economically damaging. Several types of chemicals have been applied or used to mitigate the effects produced by 0 3 on plants. These include agrochemicals (fungicides, insecticides, plant growth regulators), natural antioxidants, and others. Such treatments have been effective to one degree to another, in ameliorating Or generated stress in plants. Ethylene diurea (EDU) has been the most effective protectant used and has also served as a monitoring agent for assessing plant yield losses from 0 3 exposure. In this review, we summarize the data on how EDU has been used, the treatment methods tested, and application doses found to be both protective and toxic in plants. We have also summarized data that address the nature and modes of action (biophysical and biochemical) of EDU. In general, the literature discloses that EDU is effective in reducing ozone damage to plants, and indicates that EDU should be more widely used on 0 3 sensitive plants as a tool for biomonitoring of 0 3 concentrations. Biomonitoring studies that utilize EDU are very useful for rural and remote areas and in developing countries where 0 3 monitoring is constrained from unavailability of electricity. The mechanism(s) by which EDU prevents 0 3 toxicity in plants is still not completely known. EDU possesses great utility for screening plant sensitivity under field conditions in areas that experience high 0 3 concentrations, because EDU prevents 0 3 toxicity only in 0 3 sensitive plants. Ozone-resistant plants do not respond positively to EDU applications. However, EDU application dose and frequency must be standardized before it can be effectively and widely used for screening 0 3 sensitivity in plants. EDU acts primarily by enhancing biochemical plant defense and delaying Or induced senescence, thereby reducing chlorophyll loss, and maintaining physiological efficiency and primary metabolites; these actions enhance growth, biomass and yield of plants. We believe that future studies are needed to better address the EDU dose response relationship for many plant species, and to screen for new cultivars that can resist 0 3 stress. Although some research on the physiological and biochemical mechanisms of action of EDU have been performed, the new 'omics' tools have not been utilized to evaluate EDUs mechanism of action. Such data are needed, as is gene expression and proteome profiling studies on EDU-treated and -untreated plants.
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10.
Lidocaine-induced methemoglobinemia: a clinical reminder.
Barash, M, Reich, KA, Rademaker, D
The Journal of the American Osteopathic Association. 2015;(2):94-8
Abstract
Methemoglobinemia is a rare condition in which the iron in hemoglobin is stabilized in the ferric (Fe(3+)) form, making it unable to bind oxygen and leading to tissue hypoxia and possibly death. The condition may be hereditary or acquired, the latter resulting from ingestion or application of common oxidizing agents such as lidocaine. As management of methemoglobinemia depends on prompt recognition, clinicians who administer or prescribe oxidizing agents must be aware of the clinical symptoms of methemoglobinemia, including cyanosis, pulse oximetry values that do not respond to increased oxygen delivery, and altered mental status. Currently, methylene blue is the drug of choice for the management of methemoglobinemia.