Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8IXL6 (RNS)
 1,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Free radicals, such as superoxide, hydroxyl and nitric oxide, and other "reactive species", such as hydrogen peroxide, hypochlorous acid and peroxynitrite, are formed in vivo. Some of these molecules, e.g. superoxide and nitric oxide, can be physiologically useful, but they can also cause damage under certain circumstances. Excess production of reactive oxygen or nitrogen species (ROS, RNS), their production in inappropriate relative amounts (especially superoxide and NO) or deficiencies in antioxidant defences may result in pathological stress to cells and tissues. This oxidative stress can have multiple effects. It can induce defence systems, and render tissues more resistant to subsequent insult. If oxidative stress is excessive or if defence and repair responses are inadequate, cell injury can be caused by such mechanisms as oxidative damage to essential proteins, lipid peroxidation, DNA strand breakage and base modification, and rises in the concentration of intracellular "free" Ca(2+). Considerable evidence supports the view that oxidative damage involving both ROS and RNS is an important contributor to the development of atherosclerosis. Peroxynitrite (derived by reaction of superoxide with nitric oxide) and transition metal ions (perhaps released by injury to the vessel wall) may contribute to lipid peroxidation in atherosclerotic lesions.
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PMID:Blood radicals: reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system. 886 Apr 19

There is increasing evidence that endogenously generated reactive oxygen (ROS) and reactive nitrogen (RNS) species at sites of inflammation and in tumors may be genotoxic. We have developed a murine tumor model (MN-11) in which mutations at the hypoxanthine phosphoribosyltransferase (HPRT) locus, arising both in vitro and in vivo, can be detected. In the present report, we describe an in vitro study of the ability of ROS and RNS to induce mutations in our model system. 137Cs radiation and radiomimetic drugs caused a dose-dependent increase in mutant frequency. At D0, radiation induced about 170 mutants per 10(5) viable cells, compared to 50 and 95 for streptonigrin and bleomycin, respectively. H2O2 induced a lower frequency of mutants, 20-30 per 10(5), for enzymatically generated or bolus, respectively. For the following treatments, mutant frequency at 50% survival is shown. Incubation with human granulocytes induced a low frequency of mutants (about 15 per 10(5)). RNS was tested using a series of NO-donating drugs. Spermine/NO. induced cytotoxicity but no mutants while S-nitroso-N-acetylpenicillamine induced a low level, 10 per 10(5). Both release nitrogen monoxide spontaneously, with a t1/2 < 3 h. Glyceryl trinitrate and sodium nitroprusside are two drugs that were slowly metabolized by MN-11 cells (> 12 h). Glyceryl trinitrate induced about 20 per 10(5) while nitroprusside induced 50 per 10(5). Our results indicate that RNS can readily induce mutations detectable in MN-11 cells. At equicytotoxic doses, the induced mutant frequency varied considerably for different drugs, suggesting that different states of nitrogen monoxide (such as NO+ or NO.) may be generated and these may vary in their mutagenic/cytotoxic potential.
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PMID:Mutagenicity and cytotoxicity of reactive oxygen and nitrogen species in the MN-11 murine tumor cell line. 935 53

Reactive oxygen (ROS) or nitrogen (RNS) species can affect epithelial cells to cause acute damage and an array of pulmonary diseases. The goal of this study was to determine patterns of early response gene expression and functional end points of exposure to nitric oxide (NO.), H2O2, or peroxynitrite (ONOO-) in a line of rat lung epithelial (RLE) cells. Our focus was on c-fos and c-jun protooncogenes, as these genes play an important role in proliferation or apoptosis, possible end points of exposure to reactive metabolites in lung. Our data demonstrate that NO. generated by spermine 1,3-propanediamine N-14-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino]-butyl] or S-nitroso-N-acetylpenicillamine as well as H2O2 cause increased c-fos and c-jun mRNA levels, nuclear proteins, and complexes binding the activator protein-1 recognition sequence in RLE cells. These agents also lead to apoptosis and increased membrane permeability. In contrast, exogenously administered ONOO- or 3-morpholinosydnonimine do not induce protooncogenes or apoptosis in RLE cells despite nitration oftyrosines. We conclude that ROS and RNS can elicit distinct molecular and phenotypic responses in a target cell of pulmonary disease.
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PMID:Differential induction of c-fos, c-jun, and apoptosis in lung epithelial cells exposed to ROS or RNS. 935 54

Epidemiologic and occupational studies indicate adverse health effects due to inhalation of particulate air pollutants, but precise biologic mechanisms responsible have yet to be fully established. The tracheobronchial epithelium forms the body's first physiologic barrier to such airborne pollutants, where ciliary movement functions to remove the offending substances caught in the overlying mucus layer. Resident and infiltrating phagocytic cells also function in this removal process. In this paper, we examine the role of reactive oxygen and nitrogen species (ROS/RNS) in the response of airway epithelium to particulates. Some particulates themselves can generate ROS, as can the epithelial cells, in response to appropriate stimulation. In addition, resident macrophages in the airways and the alveolar spaces can release ROS/RNS after phagocytosis of inhaled particles. These macrophages also release large amounts of tumor necrosis factor alpha (TNF-alpha), a cytokine that can generate responses within the airway epithelium dependent upon intracellular generation of ROS/RNS. As a result, signal transduction pathways are set in motion that may contribute to inflammation and other pathobiology in the airway. Such effects include increased expression of intercellular adhesion molecule 1, interleukin-6, cytosolic and inducible nitric oxide synthase, manganese superoxide dismutase, cytosolic phospholipase A2, and hypersecretion of mucus. Ultimately, ROS/RNS may play a role in the global response of the airway epithelium to particulate pollutants via activation of kinases and transcription factors common to many response genes. Thus, defense mechanisms involved in responding to offending particulates may result in a complex cascade of events that can contribute to airway pathology.
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PMID:The role of reactive oxygen and nitrogen species in the response of airway epithelium to particulates. 940 Jul 42

Intracellularly generated reactive species of both oxygen (ROS) and nitrogen (RNS) have been implicated in signaling responses in airway epithelial cells, but these radicals have not been measured directly in such cells. In this study, intracellular production of both ROS and RNS were measured in the same cell lysates of guinea pig tracheal epithelial (GPTE) cells maintained in primary culture. ROS and RNS were quantified under basal (constitutive) conditions and in response to different stimuli: LPS and TNFalpha [activators of inducible nitric oxide synthase (iNOS)]; several activators of calcium-dependent cNOS (ATP, bradykinin, ionophore A23187, and thapsigargin); and exogenous oxidant stress generated by addition of xanthine oxidase to purine (p + XO). Studies with LPS and TNFalpha also were performed using the murine macrophage cell line, RAW 264.7, as a positive control. Intracellular oxidant production was detected from oxidation of dihydrorhodamine to rhodamine. NOx was quantified by either chemiluminescent or fluorescent detection. NOS activity was measured as citrulline production from arginine. Basal production of oxidants by GPTE cells (0.08 + 0.00 nmol rhodamine) was less than 10% that of RAW.267 cells (0.91 + 0.03 nmol rhodamine). TNFalpha and LPS significantly increased intracellular oxidant production in GPTE cells, as did p + XO, but none of the cNOS activators affected production of oxidants in these cells. Concentrations of NO2 after 4 h in unstimulated RAW 264.7 and GPTE cells were similar and comprised 63% of total NOx in GPTE and 62% in RAW cells. TNFalpha and LPS both increased NO2 in GPTE cells, but none of the Ca++-mobilizing agents nor p + XO significantly affected intracellular RNS. The results suggest both ROS and RNS can be measured in the same lysates from airway epithelial cells, and that both ROS and RNS are produced in these cells in response to different stimuli.
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PMID:Concurrent production of reactive oxygen and nitrogen species by airway epithelial cells in vitro. 958 18

Peroxynitrite (ONOO-) is a strong oxidant derived from nitric oxide ('NO) and superoxide (O2.-), reactive nitrogen (RNS) and oxygen species (ROS) present in inflamed tissue. Other oxidant stresses, e.g., TNF-alpha and hyperoxia, induce mitochondrial, manganese-containing superoxide dismutase (MnSOD) gene expression. These experiments tested whether ONOO regulated MnSOD gene expression in human lung epithelial (A549) cells. 3-morpholinosydnonimine HCI (SIN-1) (10 or 1000 microM) increased MnSOD mRNA, but did not change hypoxanthine guanine phosphoribosyl transferase (HPRT) mRNA. Authentic peroxynitrite (ONOO ) (100-500 microM) also increased MnSOD mRNA but did not change constitutive HPRT mRNA expression. ONOO stimulated luciferase gene expression driven by a 2.5 kb fragment of the rat MnSOD gene 5' promoter region. MnSOD gene induction due to ONOO- was inhibited effectively by L-cysteine (10 mM) and partially inhibited by N-acetyl cysteine (50 mM) or pyrrole dithiocarbamate (10 mM). .NO from 1-propanamine, 3-(2-hydroxy-2-nitroso-1-propylhydrazine) (PAPA NONOate) (100 or 1000 microM) did not change MnSOD or HPRT mRNA. Neither H202 nor NO2-, breakdown products of SIN-1 and ONOO , had any effect on MnSOD mRNA expression; however, ONOO- and SIN-1 did not increase MnSOD protein content detectable by western blots, nor did they increase MnSOD enzymatic activity. Increased steady state [O2.-] in the presence of .NO yields ONOO , and ONOO has direct, stimulatory effects on MnSOD transcript expression.
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PMID:Peroxynitrite modulates MnSOD gene expression in lung epithelial cells. 974 82

The body first encounters deleterious inhaled substances, such as allergens, industrial particles, pollutants, and infectious agents, at the airway epithelium. When this occurs, the epithelium and its resident inflammatory cells respond defensively by increasing production of cytokines, mucus, and reactive oxygen and nitrogen species (ROS/RNS). As inflammation in the airway increases, additional infiltrating cells increase the level of these products. Recent interest has focused on ROS/RNS as potential modulators of the expression of inflammation-associated genes important to the pathogenesis of various respiratory diseases. ROS/RNS appear to play a variety of roles that lead to changes in expression of genes such as interleukin-6 and intercellular adhesion molecule 1. By controlling this regulation, the reactive species can serve as exogenous stimuli, as intercellular signaling molecules, and as modulators of the redox state in epithelial cells. Unraveling the molecular mechanisms affected by ROS/RNS acting in these capacities should aid in the understanding of how stimulated defense mechanisms within the airway can lead to disease.
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PMID:The role of reactive oxygen and nitrogen species in airway epithelial gene expression. 978 98

Atmospheric pollutants represent an important source of oxidative and nitrosative stress to both terrestrial plants and to animals. The exposed biosurfaces of plants and animals are directly exposed to these pollutant stresses. Not surprisingly, living organisms have developed complex integrated extracellular and intracellular defense systems against stresses related to reactive oxygen and nitrogen species (ROS, RNS), including O3 and NO2. Plant and animal epithelial surfaces and respiratory tract surfaces contain antioxidants that would be expected to provide defense against environmental stress caused by ambient ROS and RNS, thus ameliorating their injurious effects on more delicate underlying cellular constituents. Parallelisms among these surfaces with regard to their antioxidant constituents and environmental oxidants are presented. The reactive substances at these biosurfaces not only represent an important protective system against oxidizing environments, but products of their reactions with ROS/RNS may also serve as biomarkers of environmental oxidative stress. Moreover, the reaction products may also induce injury to underlying cells or cause cell activation, resulting in production of proinflammatory substances including cytokines. In this review we discuss antioxidant defense systems against environmental toxins in plant cell wall/apoplastic fluids, dead keratinized cells/interstitial fluids of stratum corneum (the outermost skin layer), and mucus/respiratory tract lining fluids.
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PMID:Oxidative stress and antioxidants at biosurfaces: plants, skin, and respiratory tract surfaces. 978 5

Iron regulatory proteins 1 and 2 (IRP1 and IRP2) are RNA binding proteins that posttranscriptionally regulate the expression of mRNAs coding for proteins involved in the maintenance of iron and energy homeostasis. The RNA binding activities of the IRPs are regulated by changes in cellular iron. Thus, the IRPs are considered iron sensors and the principle regulators of cellular iron homeostasis. The mechanisms governing iron regulation of the IRPs are well described. Recently, however, much attention has focused on the regulation of IRPs by reactive nitrogen and oxygen species (RNS, ROS). Here we focus on summarizing the iron-regulated RNA binding activities of the IRPs, as well as the recent findings of IRP regulation by RNS and ROS. The recent observations that changes in oxygen tension regulate both IRP1 and IRP2 RNA binding activities will be addressed in light of ROS regulation of the IRPs.
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PMID:Regulation of the iron regulatory proteins by reactive nitrogen and oxygen species. 1044 Feb 37

The ISIAH rat strain with stress-sensitive arterial hypertension was intentionally selected to study the role of stress as a factor in the development of arterial hypertension. This study aimed to determine the role of reactive oxygen and nitrogen species (ROS and RNS) in the pathogenesis of hypertension in ISIAH rats. The nitric oxide concentrations measured by EPR were found to be significantly higher for hypertensive ISIAH rats compared with that for normotensive Wistar rats in both the aortic wall (2 times) and cerebellum (1.5 times). The activity of superoxide dismutase measured in the blood of ISIAH rats was found to be about 1.5 times lower compared with that of Wistar rats. These data support the suggestion that ROS and RNS, including superoxide radicals and nitric oxide, may play an important role in development of stress-induced hypertension in ISIAH rats. The tissue content of reduced thiols has been considered as a marker of oxidative damage. To study the tissue oxidative status we used an EPR method for quantitative determination of SH groups. The concentration of reduced thiols in the blood of ISIAH rats was much lower than that in Wistar rats (0.6 +/- 0.05 and 1.57 +/- 0.1 mM, respectively).
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PMID:Manifestation of oxidative stress in the pathogenesis of arterial hypertension in ISIAH rats. 1049 14


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