1,039 research outputs found
Examining Nitroxyl in Biological Systems
No full text: Nitroxyl (HNO) has received significant recent attention due to its remarkable and novel biological activity and pharmacological potential. Unlike most other commonly studied nitrogen oxides, examination of HNO biology is not straightforward because of its unique chemical properties. Thus, the study of HNO in biological system requires researchers to be aware of this chemistry in order to properly design and interpret experiments. This chapter focuses on the experimental issues associated with the study of HNO and attempts to provide guidelines for working with this novel and fascinating nitrogen oxide
Mechanisms of cell death governed by the balance between nitrosative and oxidative stress
No full textMany cellular functions in physiology are regulated by the direct interaction of NO with target biomolecules. In many pathophysiologic and toxicologic mechanisms, NO first reacts with oxygen, superoxide or other nitrogen oxides to subsequently elicit indirect effects. The balance between nitrosative stress and oxidative stress within a specific biological compartment can determine whether the presence of NO will be ultimately deleterious or beneficial. Nitrosative stress can be defined primarily through reactions mediated by N2O3, a reactive nitrogen oxide species generated by high fluxes of NO in an aerobic environment. In contrast, oxidative stress is mediated primarily by superoxide and peroxides. In addition to reactive oxygen species, several reactive nitrogen oxide species such as peroxynitrite, nitroxyl, and nitrogen dioxide can also impose oxidative stress to a cell. We here describe how the mechanisms of cell death are interwoven in the balance between the different chemical intermediates involved in nitrosative and oxidative stress
Cysteine hydropersulfide reduces lipid peroxidation and protects against myocardial ischaemia-reperfusion injury - Are endogenous persulfides mediators of ischaemic preconditioning?
No full textEarlier studies revealed the presence of cysteine persulfide (CysSSH) and related polysulfide species in various mammalian tissues. CysSSH has both antioxidant and oxidant properties, modulates redox-dependent signal transduction and has been shown to mitigate oxidative stress. However, its functional relevance in the setting of myocardial ischaemia-reperfusion injury (IRI) remains unknown. The present study was undertaken to (1) study the dynamics of production and consumption of persulfides under normoxic and hypoxic conditions in the heart, and (2) determine whether exogenous administration of the CysSSH donor, cysteine trisulfide (Cys-SSS-Cys) at the onset of reperfusion rescues functional impairment and myocardial damage by interfering with lipid peroxidation. Utilising a well-established ex vivo Langendorff murine model, we here demonstrate that endogenous tissue concentrations of CysSSH are upregulated when oxygen supply is compromised (global myocardial ischaemia) and rapidly restored to baseline levels upon reperfusion, suggestive of active regulation. In a separate set of experiments, exogenous administration of Cys-SSS-Cys for 10 min at the onset of reperfusion was found to decrease malondialdehyde (MDA) concentrations, formation of 4-hydroxynonenal (4-HNE) protein adducts and rescue the heart from injury. Cys-SSS-Cys also restored post-ischaemic cardiac function, improving both coronary flow and left ventricular developed pressure (LVDP). Taken together, these results support the notion that endogenous CysSSH plays an important role as a “redox preconditioning” agent to combat the oxidative insult in myocardial IRI
Unique oxidative mechanisms for the reactive nitrogen oxide species, nitroxyl anion
No full textThe nitroxyl anion (NO-) is a highly reactive molecule that may be involved in pathophysiological actions associated with increased formation of reactive nitrogen oxide species. Angeli's salt (Na2N2O3; AS) is a NO- donor that has been shown to exert marked cytotoxicity. However, its decomposition intermediates have not been well characterized. In this study, the chemical reactivity of AS was examined and compared with that of peroxynitrite (ONOO-) and NO/N2O3. Under aerobic conditions, AS and ONOO- exhibited similar and considerably higher affinities for dihydrorhodamine (DHR) than NO/N2O3. Quenching of DHR oxidation by azide and nitrosation of diaminonaphthalene were exclusively observed with NO/N2O3. Additional comparison of ONOO- and AS chemistry demonstrated that ONOO- was a far more potent one-electron oxidant and nitrating agent of hydroxyphenylacetic acid than was AS. However, AS was more effective at hydroxylating benzoic acid than was ONOO-. Taken together, these data indicate that neither NO/N2O3 nor ONOO- is an intermediate of AS decomposition. Evaluation of the stoichiometry of AS decomposition and O2 consumption revealed a 1:1 molar ratio. Indeed, oxidation of DHR mediated by AS proved to be oxygen-dependent. Analysis of the end products of AS decomposition demonstrated formation of NO2- and NO3- in approximately stoichiometric ratios. Several mechanisms are proposed for O2 adduct formation followed by decomposition to NO3- or by oxidation of an HN2O3- molecule to form NO2-. Given that the cytotoxicity of AS is far greater than that of either NO/N2O3 or NO + O2, this study provides important new insights into the implications of the potential endogenous formation of NO- under inflammatory conditions in vivo
Comparison of the reactivity of nitric oxide and nitroxyl with heme proteins. A chemical discussion of the differential biological effects of these redox related products of NOS
No full textInvestigations on the biological effects of nitric oxide (NO) derived from nitric oxide synthase (NOS) have led to an explosion in biomedical research over the last decade. The chemistry of this diatomic radical is key to its biological effects. Recently, nitroxyl (HNO/NO(-)) has been proposed to be another important constituent of NO biology. However, these redox siblings often exhibit orthogonal behavior in physiological and cellular responses. We therefore explored the chemistry of NO and HNO with heme proteins in different redox states and observed that HNO favors reaction with ferric heme while NO favors ferrous, consistent with previous reports. Further results show that HNO and NO were equally effective in inhibiting cytochrome P450 activity, which involves ferric and ferrous complexes. The differential chemical behavior of NO and HNO toward heme proteins provides insight into mechanisms of activity that not only helps explain some of the opposing effects observed in NOS-mediated events, but offers a unique control mechanism for the biological action of NO
The pharmacology of nitroxyl (HNO) and its therapeutic potential: Not just the janus face of NO
No full textNitroxyl (HNO), the I-electron reduced and protonated congener of nitric oxide (NO), has received recent attention as a potential pharmacological agent for the treatment of heart failure and as a preconditioning agent for the mitigation of ischemia-reperfusion injury. Interest in the pharmacology and biology of HNO has prompted examination, or in some instances reexamination, of many of its chemical properties. Such studies have provided insight into the chemical basis for the biological effects of HNO, although the biochemical mechanisms for many of these effects remain to be established. In this review, a brief description of the biologically relevant chemistry of HNO is given, followed by a more detailed discussion of the pharmacology and potential toxicology of HNO. (c) 2006 Elsevier Inc. All rights reserved
The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen oxide species. Putting perspective on stressful biological situations
No full textThis review addresses many of the chemical aspects of nitrosative stress mediated by N2O3. From a cellular perspective, N2O3 and the resulting reactive nitrogen oxide species target specific motifs such as thiols, lysine active sites, and zinc fingers and is dependant upon both the rates of production as well as consumption of NO and must be taken into account in order to access the nitrosative environment. Since production and consumption are integral parts of N2O3 generation, we predict that nitrosative stress occurs under specific conditions, such as chronic inflammation. In contrast to conditions of stress, nitrosative chemistry may also provide cellular protection through the regulation of critical signaling pathways. Therefore, a careful evaluation of the chemistry of nitrosation based upon specific experimental conditions may provide a better understanding of how the subtle balance between oxidative and nitrosative stress may be involved in the etiology and control of various disease processes
Jon Frey, Michigan State University professor of Art and Art History talks about the reuse of building materials in late Roman and Byzantine buildings and into the Medieval period
No full textJon Frey, Michigan State University professor of Art and Art History and author of "Spolia in fortifications and the common builder in late antiquity", talks about the reuse of building materials in late Roman and Byzantine buildings and into the Medieval period, especially those elements with Latin or Greek inscriptions. Frey talks about literacy rates during those periods and asks if the elements were actually meant to be read or if it was sufficient to the builder that they be recognized simply as ancient writing. Frey is introduced by the Head of the Fine Arts Library, Terrie Wilson
Opposite effects of nitric oxide and nitroxyl on postischemic myocardial injury
No full textRecent experimental evidence suggests that reactive nitrogen oxide species can contribute significantly to postischemic myocardial injury. The aim of the present study was to evaluate the role of two reactive nitrogen oxide species, nitroxyl (NO(-)) and nitric oxide (NO(.)), in myocardial ischemia and reperfusion injury. Rabbits were subjected to 45 min of regional myocardial ischemia followed by 180 min of reperfusion. Vehicle (0.9% NaCl), 1 micromol/kg S-nitrosoglutathione (GSNO) (an NO(.) donor), or 3 micromol/kg Angeli's salt (AS) (a source of NO(-)) were given i.v. 5 min before reperfusion. Treatment with GSNO markedly attenuated reperfusion injury, as evidenced by improved cardiac function, decreased plasma creatine kinase activity, reduced necrotic size, and decreased myocardial myeloperoxidase activity. In contrast, the administration of AS at a hemodynamically equieffective dose not only failed to attenuate but, rather, aggravated reperfusion injury, indicated by an increased left ventricular end diastolic pressure, myocardial creatine kinase release and necrotic size. Decomposed AS was without effect. Co-administration of AS with ferricyanide, a one-electron oxidant that converts NO(-) to NO(.), completely blocked the injurious effects of AS and exerted significant cardioprotective effects similar to those of GSNO. These results demonstrate that, although NO(.) is protective, NO(-) increases the tissue damage that occurs during ischemia/reperfusion and suggest that formation of nitroxyl may contribute to postischemic myocardial injury
2021 Oregon seismic hazard database: purpose and methods
No full textReport. 2021 Oregon seismic hazard database : purpose and methods -- Plate 1. Perceived shaking and damage potential, probabilistic earthquake model -- Plate 2. Perceived shaking and damage potential, Cascadia subduction earthquake model -- Plate 3. Probability of damaging shaking.by Ian P. Madin, Jon J. Francyzk, John M. Bauer, and Carlie J.M. Azzopardi.Title from PDF cover (viewed on June 24, 2021).This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Includes bibliographical references (pages 44-47).Mode of access: Internet from the Oregon Government Publications Collection.Text in English
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