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)

Oxidative injury has been implicated in the pathogenesis of numerous neurodegenerative diseases. Recently, it has been found that with the existence of hydrogen peroxide and nitrite, hemin catalyzes protein nitration. We hypothesize under certain pathological conditions, hemin catalyzed protein nitration may happen in the brain. In this paper, the effects of three flavonoids, i.e. quercetin, catachin and baicalein on hemin/nitrite/H2O2 induced brain homogenate oxidation and nitration were studied. The results showed that hemin/nitrite/H2O2 system could effectively induce brain homogenate protein oxidation and nitration. Quercetin, catachin and baicalein dose-dependently inhibited hemin/nitrite/H2O2 system-induced protein nitration in a dose-dependent manner, the inhibition of protein nitration was in the order of quercetin>catachin>baicalein. These compounds also inhibited hemin/H2O2 system-induced lipid peroxidation, the inhibition order was baicalein >quercetin>catachin. However, these flavonoids showed marginal effect on hemin/nitrite/H2O2 system caused protein oxidation and thiol oxidation. The inhibition activities of flavonoids on hemin/nitrite/H2O2 system-induced protein nitration may closely relate to their radical scavenging activities, since the inhibition order of protein nitration is the same as the radical scavenging order. These results indicate hemin/nitrite/H2O2 system induces different types of oxidative assault on bio-molecules. Flavonoids could act as antioxidants inhibiting ROS and RNS caused brain damage.
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PMID:Hemin/nitrite/H2O2 induces brain homogenate oxidation and nitration: effects of some flavonoids. 1553 73

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

Methylglyoxal (MG) is a metabolite of glucose. Our previous study demonstrated an elevated MG level with an increased oxidative stress in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats. Whether MG causes the generation of nitric oxide (NO) and superoxide anion (O2*-), leading to peroxynitrite (ONOO-) formation in VSMCs, was investigated in the present study. Cultured rat thoracic aortic SMCs (A-10) were treated with MG or other different agents. Oxidized DCF, reflecting H2O2 and ONOO- production, was significantly increased in a concentration- and time-dependent manner after the treatment of SMCs with MG (3-300 microM) for 45 min-18 h (n = 12). MG-increased oxidized DCF was effectively blocked by reduced glutathione or N-acetyl-l-cysteine, as well as L-NAME (p < 0.05, n = 12). Both O2*- scavenger SOD and NAD(P)H oxidase inhibitor DPI significantly decreased MG-induced oxidized DCF formation. MG significantly and concentration-dependently increased NO and O2*- generation in A-10 cells, which was significantly inhibited by L-NAME and SOD or DPI, respectively. In conclusion, MG induces significant generation of NO and O2*- in rat VSMCs, which in turn causes ONOO- formation. An elevated MG level and the consequential ROS/RNS generation would alter cellular signaling pathways, contributing to the development of different insulin resistance states such as diabetes or hypertension.
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PMID:Methylglyoxal-induced nitric oxide and peroxynitrite production in vascular smooth muscle cells. 1560 12

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

ROS, RNS, BRIs and ROS-RNS hybrids are produced during drug or chemical metabolism in vivo. These reactive species are instrumental to the culmination of cellular oxidative stress (OS). OS, once turned on, does not spare any vital intracellular macromolecule, such as glutathione, DNA, RNA, proteins, enzymes, lipids and ATP. Since concentration gradients of such components are very delicately balanced for normal cellular functioning, a gross perturbation leads to cell injury and cell death. Abundant evidence now suggests that intracellular antioxidants keep OS in check and maintain homeostasis. Our laboratory has focused on the role of OS in orchestrating various forms of cell death during drug and chemically-induced target organ toxicity and their counteraction by various natural or synthetic antioxidants in in vivo models. Despite complexity of the in vivo models, results show that metabolism of xenobiotics are invariably associated with different degrees of OS and natural antioxidants such as grape seed extract, bitter melon extract (Momordica charantia) and N-acetylcysteine (NAC) which were very effective in counteracting organ toxicities by minimizing events linked to OS (lipid peroxidation and total glutathione), and CAD-mediated DNA fragmentation. Phytoextract exposure rescued cells from toxic assaults, protected genomic integrity, and minimized apoptotic, necrotic and apocrotic (oncotic necrosis) cell deaths. Pre-exposure mode was more effective than post-exposure route. Overall scenario suggests that OS may have been the prime modulator of death and/or survival programs, whereas, antioxidants may have imparted a dual role in either erasing death signals or reviving survival signals, and a combination of antioxidants may be more beneficial than a single entity to influence a number of intracellular events operating simultaneously to neutralize chaotic toxicological consequences.
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PMID:Oxidative stress is the master operator of drug and chemically-induced programmed and unprogrammed cell death: Implications of natural antioxidants in vivo. 1563 Feb 1

Autoxidation pathways and redox reactions of dihydroxytryptamines (5,6- and 5,7-DHT) and of 6-hydroxydopamine (6-OH-DA) are illustrated, and their potential role in aminergic neurotoxicity is discussed. It is proposed that certain aspects of the cytotoxicity of 6-OH-DA and of the DHTs, namely redox cycling of their quinone- and quinoneimine-intermediates as a source of free radicals, may also apply to quinoidal reactive intermediates and to glutathionyl- or cysteinyl conjugates ("thioether adducts") of o-dihydroxylated (catechol-like) metabolites of certain substituted amphetamines (of methylenedioxymethamphetamine (MDMA) and of methylenedioxyamphetamine (MDA)). Despite similarities in their primary interaction with the plasmalemmal (serotonergic transporter/dopamine transporter, SERT/DAT) and vesicular monoamine transporters (VMAT2), MDMA and fenfluramine (N-ethyl-meta-trifluoromethamphetamine, Fen) differ substantially in many aspects of their metabolism, pharmacokinetics, pharmacology, and neurotoxicology profile; the consequences of these differences for neuronal response patterns and long-term survival prospects are not yet fully understood. However, sustained hyperthermia appears to be a critical factor in these differences. Methodological requirements for adequate detection and description of pre- and postsynaptic forms of drug-induced neurotoxicity are exemplified using recently published accounts. The inclusion of microglial markers into research strategies has widened contemporary pathogenetic concepts on methamphetamine (MA)-induced neurotoxicity as an example of inflammatory neurodegeneration, thus complementing the traditional ROS and RNS-dependent stress models. Amphetamine-type neurotoxicity studies may assist in elaborating of preventive strategies for human neurodegenerative disorders.
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PMID:Serotonin neurotoxins--past and present. 1563 91

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


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