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)

Diabetes mellitus is one of the most common chronic diseases affecting millions of people worldwide. Cardiovascular complication including myocardial infarction is one of the major causes of death in diabetic patients. Diabetes mellitus induces abnormal pathological findings including cell hypertrophy, neuropathy, interstitial fibrosis, myocytolysis and apoptosis and lipid deposits in the heart. In addition, the cytoplasmic organelles of cardiomyocytes including the plasma membrane, mitochondrion and sarcoplasmic reticulum are also impaired in both type I and type II diabetes. Hyperglycaemia is a major aetiological factor in the development of diabetic cardiomyopathy in patients suffering from diabetes. Hyperglycaemia promotes the production of reactive oxygen (ROS) and nitrogen species (RNS). The release of ROS and RNS induces oxidative stress leading to abnormal gene expression, faulty signal transduction and apoptosis of cardiomyocytes. Hyperglycaemia also induces apoptosis by p53 and the activation of the cytochrome c-activated caspase-3 pathway. Stimulation of connective tissue growth factor and the formation of advanced glycation end products in extracellular matrix proteins induces collagen cross-linking and contribute to the fibrosis observed in the interstitium of the heart of diabetic subjects. In terms of signal transduction, defects in intracellular Ca2+ signalling due to alteration of expression and function of proteins that regulate intracellular Ca2+ also occur in diabetes. All of these abnormalities result in gross dysfunction of the heart. Beta-adrenoreceptor antagonists, ACE inhibitors, endothelin-receptor antagonist (Bonestan), adrenomedullin, hormones (insulin, IGF-1) and antioxidants (magniferin, metallothionein, vitamins C and E) reduce interstitial fibrosis and improve cardiac function in diabetic cardiomyopathy.
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PMID:Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: a short review. 1536 3

We determined whether isoflurane can confer delayed cardioprotection in the adult rat by triggering increased production of reactive oxygen (ROS) and nitrogen species (RNS). Our objectives were to determine 1) the concentration of isoflurane that confers delayed cardioprotection in the adult rat, 2) the role of ROS and RNS in the induction of delayed cardioprotection, and 3) the cellular sources of ROS and RNS responsible for induction of delayed cardioprotection by isoflurane. Male Sprague-Dawley rats at 8 wk of age (n = 8 rats/group) were exposed to 0.5%, 0.8%, 1%, and 2% (vol/vol) isoflurane-100% oxygen for 2 h. Isoflurane conferred delayed cardioprotection 24 h later at a concentration of 0.8% (vol/vol). Administration of manganese (III) tetrakis (4-benzoic acid)porphyrin chloride (MnTBAP), a superoxide scavenger (15 mg/kg ip), or N(G)-nitro-L-arginine methyl ester (L-NAME), a general nitric oxide synthase inhibitor (15 mg/kg ip), 15 min before isoflurane treatment abolished the delayed cardioprotective effects of isoflurane. MnTBAP and L-NAME had no effect on delayed cardioprotection in untreated hearts. Perfusion of isolated hearts with hydroethidine, a fluorescent probe for superoxide, after isoflurane treatment resulted in a twofold increase in ethidine staining of isoflurane-treated hearts compared with untreated controls, which was attenuated by myxothiazol, an inhibitor of the mitochondrial electron transport chain (0.2 mg/kg ip) and L-NAME (15 mg/kg ip). Nitrite and nitrate content in isoflurane-treated hearts was 1.5-fold higher than in untreated hearts, whereas myocardial reduced glutathione levels were decreased by 13% in 0.8% but not in 1.0% isoflurane-treated hearts. We conclude that isoflurane confers delayed cardioprotection in the adult rat, triggered by ROS and RNS.
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PMID:Delayed cardioprotection with isoflurane: role of reactive oxygen and nitrogen. 1538 8

The purpose of the present study was to determine if elevated reactive oxygen (ROS)/nitrogen species (RNS) reported to be present in adriamycin (ADR)-induced cardiotoxicity actually resulted in cardiomyocyte oxidative/nitrative damage, and to quantitatively determine the time course and subcellular localization of these postulated damage products using an in vivo approach. B6C3 mice were treated with a single dose of 20 mg/kg ADR. Ultrastructural damage and levels of 4-hydroxy-2-nonenal (4HNE)-protein adducts and 3-nitrotyrosine (3NT) were analyzed. Quantitative ultrastructural damage using computerized image techniques showed cardiomyocyte injury as early as 3 hours, with mitochondria being the most extensively and progressively injured subcellular organelle. Analysis of 4HNE protein adducts by immunogold electron microscopy showed appearance of 4HNE protein adducts in mitochondria as early as 3 hours, with a peak at 6 hours and subsequent decline at 24 hours. 3NT levels were significantly increased in all subcellular compartments at 6 hours and subsequently declined at 24 hours. Our data showed ADR induced 4HNE-protein adducts in mitochondria at the same time point as when mitochondrial injury initially appeared. These results document for the first time in vivo that mitochondrial oxidative damage precedes nitrative damage. The progressive nature of mitochondrial injury suggests that mitochondria, not other subcellular organelles, are the major site of intracellular injury.
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PMID:Oxidative damage precedes nitrative damage in adriamycin-induced cardiac mitochondrial injury. 1560 32

Calcium plays a key role in both apoptotic and necrotic cell death. Emptying of intracellular calcium stores and/or alteration in intracellular calcium levels can modulate cell death in almost all cell types. These calcium fluxes are determined by the activity of membrane channels normally under tight control. The channels may be ligand activated or voltage dependent as well as being under the control of affector molecules such as calmodulin. It has become increasingly apparent that many calcium channels are affected by reactive oxygen or reactive nitrogen species; ROS/RNS. This may be part of the normal signaling pathways in the cell or by the action of exogenously generated ROS or RNS often by toxins. This review covers the recent literature on the activity of these redox active channels as related to cell death.
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PMID:Redox active calcium ion channels and cell death. 1562 6

Nitric oxide is not only an obligatory intermediate in denitrification, but also a signalling and defence molecule of major importance. However, the basis of resistance to NO and RNS (reactive nitrogen species) is poorly understood in many microbes. The cellular targets of NO and RNS [e.g. metalloproteins, thiols in proteins, glutathione and Hcy (homocysteine)] may themselves serve as signal transducers, sensing NO and RNS, and resulting in altered gene expression and synthesis of protective enzymes. The properties of a number of such protective mechanisms are outlined here, including globins, flavorubredoxin, diverse enzymes with NO- or S-nitrosothiol-reducing properties and other redox proteins with poorly defined roles in protection from nitrosative stresses. However, the most fully understood mechanism for NO detoxification involves the enterobacterial flavohaemoglobin (Hmp). Aerobically, Hmp detoxifies NO by acting as an NO denitrosylase or 'oxygenase' and thus affords inducible protection of growth and respiration, and aids survival in macrophages. The flavohaemoglobin-encoding gene of Escherichia coli, hmp, responds to the presence of NO and RNS in an SoxRS-independent manner. Nitrosating agents, such as S-nitrosoglutathione, deplete cellular Hcy and consequently modulate activity of the MetR regulator that binds the hmp promoter. Regulation of Hmp synthesis under anoxic conditions involves nitrosylation of 4Fe-4S clusters in the global transcriptional regulator, FNR. The foodborne microaerophilic pathogen, Campylobacter jejuni, also expresses a haemoglobin, Cgb, but it does not possess the reductase domain of Hmp. A Cgb-deficient mutant of C. jejuni is hypersensitive to RNS, whereas cgb expression and holoprotein synthesis are specifically increased on exposure to RNS, resulting in NO-insensitive respiration. A 'systems biology' approach, integrating the methodologies of bacterial molecular genetics and physiology with post-genomic technologies, promises considerable advances in our understanding of bacterial NO tolerance mechanisms in pathogenesis.
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PMID:Nitric oxide and nitrosative stress tolerance in bacteria. 1566 99

Approximately 10% of newborns are born prematurely. Of these children, more than 10% will sustain neurological injuries leading to significant learning disabilities, cerebral palsy, or mental retardation, with very low birth weight infants having an even higher incidence of brain injury. Whereas intraventricular hemorrhage was the most common form of serious neurological injury a decade ago, periventricular white matter injury (PWMI) is now the most common cause of brain injury in preterm infants. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia; PVL) and diffuse myelination disturbances. Recent neuroimaging studies support that the incidence of PVL is declining, whereas diffuse cerebral white matter injury is emerging as the predominant lesion. Factors that predispose to PVL include prematurity, hypoxia, ischemia, and inflammation. It is believed that injury to oligodendrocyte (OL) progenitors contributes to the pathogenesis of myelination disturbances in PWMI by disrupting the maturation of myelin-myelin-forming oligodendrocytes. Other potential mechanisms of injury include activation of microglia and axonal damage. Chemical mediators that may contribute to white matter injury include reactive oxygen (ROS) and nitrogen species (RNS), glutamate, cytokines, and adenosine. As our understanding of the pathogenesis of PWMI improves, it is anticipated that new strategies for directly preventing brain injury in premature infants will evolve.
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PMID:Emerging concepts in periventricular white matter injury. 1569 97

Intra- and intercellular communication in or between cells allows adaptation to changes in the environment. Formation of reactive oxygen (ROS) and nitrogen (RNS) species in response to external insults gained considerable attention in provoking cell demise along an apoptotic subroute of cell death, thus attributing radical formation to pathologies. In close association, stabilization of the tumor suppressor p53 and activation of caspases convey proapoptotic signaling. Complexity was added with the notion that ROS and RNS signals overlap and/or produce synergistic as well as antagonistic effects. With respect to nitric oxide (NO) signaling, it became clear that the molecule is endowed with pro- or antiapoptotic signaling capabilities, depending to some extend on the concentration and cellular context, i.e., ROS generation. Here, some established concepts are summarized that allow an explanation of p53 accumulation under the impact of NO and an understanding of NO-evoked cell protection at the level of caspase inhibition, cyclic GMP formation, or expression of antiapoptotic proteins. In addition, the overlapping sphere of ROS and RNS signaling is recapitulated to appreciate cell physiology/pathology with the notion that marginal changes in the flux rates of either NO or superoxide may shift vital signals used for communication and cell survival into areas of pathology in close association with apoptosis/necrosis.
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PMID:The intimate relation between nitric oxide and superoxide in apoptosis and cell survival. 1570 97

Reactive oxygen and nitrogen species (ROS and RNS) have been proposed as mechanisms of cancer-induced cachexia. In this study, we assessed using Western blot analysis the levels of total protein carbonylation (2,4-dinitrophenylhydrazine assay), both malondialdehyde- (MDA-) and 2-hydroxy-4-nonenal- (HNE-) protein adducts, Mn-superoxide dismutase (Mn-SOD), catalase, heme oxygenase-1 (HO-1) and 3-nitrotyrosine formation in gastrocnemius muscles of rats bearing the Yoshida AH-130 hepatoma. In the muscles of the tumour-bearing animals, protein carbonylation as measured by total levels of carbonyl group formation and both HNE and MDA-protein adducts, and protein tyrosine nitration were significantly greater than in control muscles. Protein levels of the antioxidant enzymes Mn-SOD, catalase, and HO-1 were not significantly modified in the rat cachectic muscles compared to controls. The inefficiency of the antioxidant enzymes in neutralizing excessive ROS production may account for elevated markers of protein oxidation and be responsible for the development of both oxidative and nitrosative stress in cancer-induced cachexia.
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PMID:Both oxidative and nitrosative stress are associated with muscle wasting in tumour-bearing rats. 1575 55

Previously it was shown that thiol antioxidants are potent inhibitors of the NO-dependent induction of heme oxygenase 1 (HOX-1) gene. However, the mechanism of HOX-1 gene down-regulation by thiol antioxidants and underlying signaling pathway remain unclear. In this study we have examined, whether the scavenging of reactive oxygen and reactive nitrogen species (ROS and RNS) is the major cause for thiol-mediated suppression of the HOX-1 induction by NO. Further, to identify the ROS family members implicated in the HOX-1 induction, we also exposed cells to various non-thiol antioxidants: dimethyl sulfoxide, dimetylthiourea, sodium salicylate, sodium formate, uric acid, catalase, and superoxide dismutase. A partial inhibition of HOX-1 induction occurred in the presence of non-polar hydroxyl radical scavengers, dimethyl sulfoxide and dimetylthiourea. The other non-thiol antioxidants were ineffective towards HOX-1 expression. Then, in order to determine, whether RNS scavenging is implicated in the HOX-1 down-regulation by thiol antioxidants, we took advantage of the capacity of suboptimal concentrations of the NO scavenger PTIO (2-phenyl-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide) to oxidize NO to nitrosating species. We showed that simultaneous cell treatment with NO donor and PTIO significantly enhanced the rate of the HOX-1 gene NO-dependent induction indicating that RNS are mediators of HOX-1 gene transcriptional activation. Thiol antioxidants completely suppressed PTIO stimulatory action. These findings imply that inhibitory action of thiol antioxidants is mediated by RNS scavenging. The study provides an approach for pharmacologycal modulation of cell response to NO and its derivatives through the use of antioxidants.
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PMID:[Effect of the antioxidants on NO-dependent induction of heme oxigenase 1 gene in U937 monocytes]. 1577 52

Cellular redox signalling is mediated by the post-translational modification of proteins in signal-transduction pathways by ROS/RNS (reactive oxygen species/reactive nitrogen species) or the products derived from their reactions. NO is perhaps the best understood in this regard with two important modifications of proteins known to induce conformational changes leading to modulation of function. The first is the addition of NO to haem groups as shown for soluble guanylate cyclase and the newly discovered NO/cytochrome c oxidase signalling pathway in mitochondria. The second mechanism is through the modification of thiols by NO to form an S-nitrosated species. Other ROS/RNS can also modify signalling proteins although the mechanisms are not as clearly defined. For example, electrophilic lipids, formed as the reaction products of oxidation reactions, orchestrate adaptive responses in the vasculature by reacting with nucleophilic cysteine residues. In modifying signalling proteins ROS/RNS appear to change the overall activity of signalling pathways in a process that we have termed 'redox tone'. In this review, we discuss these different mechanisms of redox cell signalling, and give specific examples of ROS/RNS participation in signal transduction.
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PMID:Redox signalling: from nitric oxide to oxidized lipids. 1577 16


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