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

The ingredients of oxidative stress include a variety of reactive species such as reactive oxygen and reactive nitrogen species (ROS, RNS). While sulfur is usually considered as part of cellular antioxidant systems there is mounting evidence that reactive sulfur species (RSS) with stressor properties similar to the ones found in ROS are formed under conditions of oxidative stress. Thiols as well as disulfides are easily oxidised to sulfur species with sulfur in higher oxidation states. Such agents include thiyl radicals, disulfides, sulfenic acids and disulfide-S-oxides. They rapidly oxidise and subsequently inhibit thiol-proteins and enzymes and can be considered as a separate class of oxidative stressors providing new antioxidant drug targets.
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PMID:Reactive sulfur species: an emerging concept in oxidative stress. 1203 29

We postulated that anesthetic preconditioning (APC) is triggered by reactive oxygen/nitrogen species (ROS/RNS). We used the isolated guinea pig heart perfused with L-tyrosine, which reacts with ROS and RNS to form strong oxidants, principally peroxynitrite (ONOO(-)), and then forms fluorescent dityrosine. ROS scavengers superoxide dismutase, catalase, and glutathione (SCG) and NO. synthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) were given 5 min before and after sevoflurane preconditioning stimuli. Drugs were washed out before 30 min of ischemia and 120 min of reperfusion. Groups were control (nontreated ischemia control), APC (two, 2-min periods of perfusion with 0.32 +/- 0.02 mM of sevoflurane; separated by a 6-min period of perfusion without sevoflurane), SCG, APC + SCG, L-NAME, and APC + L-NAME. Effluent dityrosine at 1 min reperfusion was 56 +/- 6 (SE), 15 +/- 5, 40 +/- 5(++), 39 +/- 4(++), 35 +/- 4(++) , and 33 +/- 5(++) units ((++)P< 0.05 vs. APC), respectively; left ventricular pressure (%baseline) at 60 min of reperfusion was 30 +/- 5(++), 60 +/- 4, 35 +/- 5(++), 37 +/- 5(++), 44 +/- 4, and 47 +/- 4; and infarct size (%total heart weight) was 50 +/- 5(++), 19 +/- 2, 48 +/- 3(++), 46 +/- 4(++), 42 +/- 4(++), and 45 +/- 2(++). Thus APC is initiated by ROS as shown by improved function, reduced infarct size, and reduced dityrosine on reperfusion; protective and ROS/RNS-reducing effect of APC were attenuated when bracketed by ROS scavengers or NO* inhibition.
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PMID:Anesthetic preconditioning: triggering role of reactive oxygen and nitrogen species in isolated hearts. 1206 73

The effect of reactive oxygen/nitrogen species (ROS/RNS)(hydrogen peroxide -- H(2)O(2), superoxide anion radical O(2)*- and hydroxyl radical *OH -- the reaction products of hypoxanthine/xanthine oxidase system), nitric oxide (NO* from sodium nitroprusside -- SNP), and peroxynitrite (ONOO(-) from 3-morpholinosydnonimine -- SIN-1) on insulin mitogenic effect was studied in L6 muscle cells after one day pretreatment with/or without antioxidants. ROS/RNS inhibited insulin-induced mitogenicity (DNA synthesis). Insulin (0.1 microM), however, markedly improved mitogenicity in the muscle cells treated with increased concentrations (0.1, 0.5, 1 mM) of donors of H(2)O(2), O(2)*-, *OH, ONOO(-) and NO*. Cell viability assessed by morphological criteria was also monitored. Massive apoptosis was induced by 1 mM of donors of H(2)O(2) and ONOO(-), while NO* additionally induced necrotic cell death. Taken together, these results have shown that ROS/RNS provide a good explanation for the developing resistance to the growth promoting activity of insulin in myoblasts under conditions of oxidative or nitrosative stress. Cell viability showed that neither donor induced cell death when given below 0.5 mM. In order to confirm the deleterious effects of ROS/RNS prior to the subsequent treatment with ROS/RNS plus insulin one day pretreatment with selected antioxidants (sodium ascorbate - ASC (0.01, 0.1, 1 mM), or N-acetylcysteine - NAC (0.1, 1, 10 mM) was carried out. Surprisingly, at a low dose (micromolar) antioxidants did not abrogate and even worsened the concentration-dependent effects of ROS/RNS. In contrast, pretreatment with millimolar dose of ASC or NAC maintained an elevated mitogenicity in response to insulin irrespective of the ROS/RNS donor type used.
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PMID:Preconditioning with millimolar concentrations of vitamin C or N-acetylcysteine protects L6 muscle cells insulin-stimulated viability and DNA synthesis under oxidative stress. 1215 Oct 57

Cell signaling pathways may be initiated by environmental particulates by indirect mechanisms such as elaboration of reactive oxygen or nitrogen species (ROS/RNS) or directly upon contact of particulates with the plasma membrane and uptake by epithelial or mesothelial cells. Research in the last few years has mainly addressed cell signaling cascades leading to activation of the redox-sensitive transcription factors, nuclear factor kappa-B (NF-kappaB), and activator protein-1 (AP-1). The activation of these transcription factors may be linked to increases in gene expression controlling cell injury or apoptosis, proliferation and/or cell survival, and inflammatory cytokines. Here, we provide an overview of the MAPK signaling pathways and their activation by asbestos, specifically the role of ROS, receptor-dependent and independent activation via the epidermal growth factor receptor (EGFR), and strategies for proving causal relationships between these pathways and changes in epithelial cell phenotype linked to disease causation.
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PMID:Role of mitogen-activated protein kinases (MAPK) in cell injury and proliferation by environmental particulates. 1216 23

A progressive rise of oxidative stress due to the altered reduction-oxidation (redox) homeostasis appears to be one of the hallmarks of the processes that regulate gene transcription in physiology and pathophysiology. Reactive oxygen (ROS) and nitrogen (RNS) species serve as signaling messengers for the evolution and perpetuation of the inflammatory process that is often associated with the condition of oxidative stress, which involves genetic regulation. Changes in the pattern of gene expression through ROS/RNS-sensitive regulatory transcription factors are crucial components of the machinery that determines cellular responses to oxidative/redox conditions. Transcription factors that are directly influenced by reactive species and pro-inflammatory signals include nuclear factor-kappaB (NF-kappaB) and hypoxia-inducible factor-1alpha (HIF-1alpha). Here, I describe the basic components of the intracellular oxidative/redox control machinery and its crucial regulation of oxygen- and redox-sensitive transcription factors such as NF-kappaB and HIF-1alpha.
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PMID:Antioxidant and prooxidant mechanisms in the regulation of redox(y)-sensitive transcription factors. 1222 Jun 15

The formation of intracellular reactive oxygen and nitrogen species (ROS and RNS) has been implicated in the pathogenesis of a variety of diseases. In excess, ROS and their byproducts may cause oxidative damage and be cytotoxic to cells. Recently, it has been established that these oxidants can also act as subcellular messengers in gene regulatory and signal transduction pathways. Estrogen, on the other hand, is known to offer protection from coronary artery diseases in post-menopausal women and to be involved in various ROS-related diseases, such as Alzheimer's and Parkinson's diseases, diabetes and aging. The existence of estrogen receptors in these tissues lead us to investigate whether ROS can regulate their expression. We demonstrated here, for the first time, that oxidative stress induced by hydrogen peroxide (H(2)O(2)), Fe(2+), 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) and activated macrophages, affect the expression of estrogen receptors alpha and beta (ERalpha and ERbeta) differently, demonstrating cell-specific response which can be blocked by antioxidants. This data suggest that oxidative stress and the production of ROS/RNS function as physiological regulators of ERalpha and ERbeta expression. This may provide a new insight into the ERbeta-dependent protective action of estrogen and phytoestrogens in inflammation involving diseases, and may contribute to the development of novel therapeutic treatment strategies.
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PMID:The effect of oxidative stress on ERalpha and ERbeta expression. 1236 22

Nitric oxide (NO) or its derivatives (reactive nitrogen species, RNS) inhibit mitochondrial respiration in two different ways: (i) an acute, potent, and reversible inhibition of cytochrome oxidase by NO in competition with oxygen; and, (ii) irreversible inhibition of multiple sites by RNS. NO inhibition of respiration may impinge on cell death in several ways. Inhibition of respiration can cause necrosis and inhibit apoptosis due to ATP depletion, if glycolysis is also inhibited or is insufficient to compensate. Inhibition of neuronal respiration can result in excitotoxic death of neurons due to induced release of glutamate and activation of NMDA-type glutamate receptors. Inhibition of respiration may cause apoptosis in some cells, while inhibiting apoptosis in other cells, by mechanisms that are not clear. However, NO can induce (and inhibit) cell death by a variety of mechanisms unrelated to respiratory inhibition.
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PMID:Nitric oxide inhibition of mitochondrial respiration and its role in cell death. 1244 1

Liver damage ranges from acute hepatitis to hepatocellular carcinoma, through apoptosis, necrosis, inflammation, immune response, fibrosis, ischemia, altered gene expression and regeneration, all processes that involve hepatocyte, Kupffer, stellate, and endothelial cells. Reactive oxygen and nitrogen species (ROS, RNS) play a crucial role in the induction and in the progression of liver disease, independently from its etiology. They are involved in the transcription and activation of a large series of cytokines and growth factors that, in turn, can contribute to further production of ROS and RNS. The main sources of free radicals are represented by hepatocyte mitochondria and cytochrome p450 enzymes, by endotoxin-activated macrophages (Kupffer cells), and by neutrophils. The consequent alteration of cellular redox state is potentiated by the correlated decrease of antioxidant and energetic reserves. Indices of free radical-mediated damage, such as the increase of malondialdehyde, 4-hydroxynonenal, protein-adducts, peroxynitrite, nitrotyrosine, etc., and/or decrease of glutathione, vitamin E, vitamin C, selenium, etc., have been documented in patients with viral or alcoholic liver disease. These markers may contribute to the monitoring the degree of liver damage, the response to antiviral therapies and to the design of new therapeutic strategies. In fact, increasing attention is now paid to a possible "redox gene therapy." By enhancing the antioxidant ability of hepatocytes, through transgene vectors, one could counteract oxidative/nitrosative stress and, in this way, contribute to blocking the progression of liver disease.
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PMID:Oxidative stress in viral and alcoholic hepatitis. 1249 74

The mechanisms by which Leishmania parasites survive exposure to highly reactive oxygen (ROS) and nitrogen (RNS) species within phagosomes of macrophages are not well known. Recently it has been shown that RNS alone is sufficient and necessary to control Leishmania donovani infection in mice (Murray, H. W., and Nathan, C. F. (1999) J. Exp. Med. 189, 741-746). No enzymatic defense against RNS has been discovered in Leishmania to date. We have previously isolated two peroxidoxins (LcPxn1 and LcPxn2) from Leishmania chagasi and showed that recombinant LcPxn1 protein was capable of detoxifying hydrogen peroxide, hydroperoxide, and hydroxyl radicals (Barr, S. D., and Gedamu, L. (2001) J. Biol. Chem. 276, 34279-34287). In further characterizing the physiological role of peroxidoxins in Leishmania survival, we show here that recombinant LcPxn1 protein can detoxify RNS in addition to ROS, whereas recombinant LcPxn2 protein can only detoxify hydrogen peroxide. LcPxn1 and LcPxn2 are localized to the cytoplasm, and overexpression of LcPxn1 in L. chagasi parasites enhanced survival when exposed to exogenous ROS and RNS and enhanced survival within U937 macrophage cells. Site-directed mutagenesis studies revealed that the conserved Cys-52 residue is essential for detoxifying hydrogen peroxide, t-butyl hydroperoxide, and hydroxyl radicals, whereas the conserved Cys-173 residue is essential for detoxifying t-butyl hydroperoxide and peroxynitrite. This is the first report of an enzymatic defense against RNS in Leishmania.
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PMID:Role of peroxidoxins in Leishmania chagasi survival. Evidence of an enzymatic defense against nitrosative stress. 1252 67

Life demands intra- and intercellular communication in and between cells to respond and adapt to changes in the environment. Among signaling molecules, reactive oxygen (ROS) and nitrogen (RNS) species gained attention in facilitating intracellular communication and causing cell demise during pathology. Complexity was added with the notion that ROS and RNS signals overlap and/or produce synergistic, as well as antagonistic, effects. This is exemplified by using oxidized lipoproteins (oxLDL), or NO donors, in provoking the stabilization of two well recognized transcription factors, such as tumor suppressor p53 and hypoxia-inducible factor-1 alpha (HIF-1 alpha). Radical (i.e., superoxide) (O2-) formation in response to oxLDL is associated with p53, as well as HIF-1 alpha accumulation in human macrophages, a process that is antagonized by NO. On the other side, NO-elicited HIF-1 alpha stabilization is modulated by O2-. Thus, ROS- and RNS-signaling is important in understanding cell physiology and pathology, with the notion that marginal changes in the flux rates of either NO or O2- may shift vital signals used for communication into areas of pathology in close association with human diseases.
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PMID:Nitric oxide, oxidative stress, and apoptosis. 1269 1


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