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)

Exposure to asbestos causes cellular damage, leading to asbestosis, bronchogenic carcinoma, and mesothelioma in humans. The pathogenesis of asbestos-related diseases is complicated and still poorly understood. Studies on animal models and cell cultures have indicated that asbestos fibers generate reactive oxygen and nitrogen species (ROS/RNS) and cause oxidation and/or nitrosylation of proteins and DNA. The ionic state of iron and its ability to be mobilized determine the oxidant-inducing potential of pathogenic iron-containing asbestos types. In addition to their capacity to damage macromolecules, oxidants play important roles in the initiation of numerous signal transduction pathways that are linked to apoptosis, inflammation, and proliferation. There is strong evidence supporting the premise that oxidants contribute to asbestos-induced lung injury; thus, strategies for reducing oxidant stress to pulmonary cells may attenuate the deleterious effects of asbestos.
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PMID:Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases. 1270 92

We have been investigating the potential utility of engineered cell lines as surrogates for primary islet cells in treatment of type 1 diabetes. To this end, two strategies that have emerged for procuring cell lines with resistance to immune-mediated damage are 1) selection of cytokine-resistant cell lines by growth of INS-1 insulinoma cells in iteratively increasing concentrations of interleukin (IL)-1beta + gamma-interferon (IFN-gamma), and 2) stable overexpression of the anti-apoptotic gene bcl-2 in INS-1 cells. Herein, we show that bcl-2-overexpressing cells are resistant to the cytotoxic effects of reactive oxygen and nitrogen species (ROS/RNS), but are only modestly protected against high concentrations of IL-1beta + INF-gamma, whereas the converse is true in cytokine selected cells. We also found that the combination of bcl-2 expression and cytokine selection confers a broader spectrum of resistance than either procedure alone, such that the resultant cells are highly resistant to cytokines and ROS/RNS, with no impairment in glucose-stimulated insulin secretion. INS-1-derived cells with combined bcl-2 expression and cytokine selection are also more resistant to damage induced by coculture with mitogen-activated peripheral blood mononuclear cells. Surprisingly, application of the cytokine selection procedure to bcl-2-overexpressing cells does not result in impairment of nuclear factor-kappaB translocation, iNOS expression, and NO production, as clearly occurs upon application of the selection procedure to cells without bcl-2 overexpression. Further investigation of the diverse pathways involved in the development of cytokine and ROS/RNS resistance may define simplified and specific strategies for preservation of beta-cell mass.
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PMID:Discrete and complementary mechanisms of protection of beta-cells against cytokine-induced and oxidative damage achieved by bcl-2 overexpression and a cytokine selection strategy. 1276 53

Increasing evidence suggests that oxidative and nitrosative stress play an important role in regulation of cardiac myocyte growth and survival. The cardiovascular system is continuously exposed to both reactive oxygen species (ROS) and nitrogen species (RNS), collectively termed reactive inflammatory species (RIS), and imbalances between the enzymes that regulate their bioavailability are associated with cardiac hypertrophy and the pathogenesis of cardiomyopathies, myocardial infarction and heart failure. It is now clear that RIS act as critical regulators of cardiac myocyte hypertrophy and apoptosis through control of redox-sensitive signaling cascades, such as tyrosine kinases and phosphatases, protein kinase C, and mitogen-activated protein kinases. This review will focus on the mechanisms by which ROS/RNS modulate cardiac myocyte growth and apoptosis induced by neurohormones and cytokines, and will discuss evidence for a role in the pathophysiology of heart failure.
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PMID:Regulation of hypertrophic and apoptotic signaling pathways by reactive oxygen species in cardiac myocytes. 1458 46

Hydroxystilbenes are naturally occurring polyphenols with protective effects against reactive oxygen and nitrogen species (ROS/RNS). Here, we investigated oxyresveratrol (OXY), which is contained in high amounts in mulberry wood, in comparison to the antioxidant resveratrol (RES). We found that OXY is a more effective scavenger for 2,2-diphenyl-1-picryl-hydrazyl (DPPH, 100 microM) used as a general free radical model, compared to RES or trans-4-hydroxystilbene (IC(50)=28.9, 38.5, and 39.6 microM, respectively). When primary glial cell cultures were loaded with the ROS/RNS-sensitive fluorochrome 2,7-dichlorodihydrofluorescein, the lowest rise in the fluorescence signal after H(2)O(2) exposure was seen when the cells were pretreated with OXY. Using 4,5-diaminofluorescein (DAF-2) to monitor free nitric oxide levels (7.7 microM NO) in a spectrofluorimetric cell-free assay, we found again that OXY (at 5 microM) is a more effective scavenger. Accordingly, cultures of the murine microglial cell line N9 and primary mixed glial cultures were used to test the drug effects of NO production upon expression of the inducible isoform of nitric oxide synthase (iNOS). We found that both compounds considerably diminished NO (nitrite) levels, RES more effectively than OXY (IC(50)=22.36 and 45.31 microM). RES but not OXY down-regulated the expression of iNOS protein, but both did not alter iNOS activity. Furthermore, OXY displayed a generally lower cytotoxicity than RES. The radical and ROS scavenging properties, as well as the lower cytotoxicity towards microglia and the known good water solubility suggest OXY as a potential protectant against ROS/RNS.
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PMID:Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: effect on nitrosative and oxidative stress derived from microglial cells. 1462 72

To investigate the status of soluble adhesion molecules (sAMs) during aging, the present study determined protein levels of several major sAMs in serum samples obtained from rats at different ages. These sAMs include E-selectin, P-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1). Fischer 344 rats, ages 6, 12, 18, and 24 months, fed ad libitum (AL) and calorie restricted (CR) diets were used in this study. Analysis by Western blotting showed that the levels of all sAMs studied increased during aging in AL rats, but were effectively blunted in the CR rats. Total reactive oxygen species/reactive nitrogen species (ROS/RNS) levels were measured by fluorescent probe 2',7'-dichlorofluorescin diacetate. Increased ROS/RNS levels were found to coincide with increased levels of superoxide-generating xanthine oxidase in serum during aging, but were found suppressed by CR. Increases in sAMs levels were duplicated in another experiment in which young (13-month-old) and old (31-month-old) rats were injected with proinflammatory lipopolysaccharide. These findings suggest that the altered expressions of sAMs may be due to increased oxidative stress with advanced age and that these increases were prevented by CR through its antioxidative action.
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PMID:Alteration of soluble adhesion molecules during aging and their modulation by calorie restriction. 1468 95

Oxygen/nitrogen reactive species (ROS/RNS) are currently implicated in the pathogenesis of ulcerative colitis, drawing attention on the potential prophylactic and healing properties of antioxidants, scavengers, chelators. We evaluated the possible protective/curative effects of a natural antioxidant preparation based on Aloe vera and ubiquinol, against intestinal inflammation, lesions, and pathological alterations of the intestinal electrophysiological activity and motility, in a rat model of DSS-induced colitis. 5% dextrane sulfate (DDS) (3 days), followed by 1% DSS (4 days) was administered in drinking water. The antioxidant formulation (25 mg/kg) was delivered with a pre-treatment protocol, or simultaneously or post-colitis induction. Spontaneous and acetylcholine-stimulated electrical activity were impaired in the small intestine and in distal colon, upon exposure to DSS only. Severe inflammation occurred, with increased myeloperoxidase activity, and significant alterations of the oxidant/antioxidant status in colonic tissue and peritoneal cells. Lipoperoxidation, superoxide production, glutathione peroxidase and glutathione-S-transferase activities, and reduced glutathione content increased, whilst superoxide dismutase and catalase activities were sharply suppressed in colon tissue. ROS/RNS formation in peritoneal cells was strongly inhibited. Inflammation, electrical/mechanical impairment in the gut, and a great majority of oxidative stress parameters were improved substantially by pre-treatment with the antioxidant preparation, but not by simultaneous administration or post-treatment.
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PMID:The protective and healing effects of a natural antioxidant formulation based on ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in rats. 1469 41

Reactive oxygen and nitrogen species (ROS and RNS) have been extensively recognized as important signaling molecules implicated in physiological processes such as gene expression, cell differentiation and immune activation. Nevertheless, continuous production of these species may produce oxidative and/or nitrosative stress resulting in cell damage and ultimately leading to cell death. Due to the high oxygen consumption and relative poor antioxidant defense, the central nervous system is highly susceptible to ROS- and RNS-mediated toxicity. Actually, the oxidative and nitrosative stress have been implicated in the pathogenesis of neurodegeneration of a large variety of neurological disorders. This review will cover some aspects of the involvement of ROS- and RNS-mediated apoptotic processes occurring in cellular models of familial amyotrophic lateral sclerosis (FALS), in particular the cases associated with mutations in SOD1, the gene encoding Cu,Zn superoxide dismutase (Cu,Zn SOD). A possible role for proteasome in the inhibition of neurodegenerative process by balancing ROS and RNS species is envisaged on the basis of evidence provided by results obtained from studies on this experimental model.
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PMID:Interplay of Cu,Zn superoxide dismutase and nitric oxide synthase in neurodegenerative processes. 1471 Oct 10

Dysregulation of the myocardial extracellular matrix contributes to abnormal cardiac muscle function. Changes in the balance between matrix deposition and matrix degradation by matrix metalloproteinases (MMPs) can lead to cardiac fibrosis and dilation. In this review, we discuss the regulation of MMPs, their endogenous inhibitors (TIMPs) and collagen synthesis by inflammatory cytokines and reactive oxygen/nitrogen species (ROS/RNS). Inflammatory cytokines, such as interleukin-1beta and tumor necrosis factor-alpha, and ROS activate mitogen-activated protein kinases and stress-responsive protein kinases in cardiac cells. In non-cardiac tissues, inflammatory cytokine activation of these kinases is redox sensitive, suggesting ROS may also be involved in cytokine signaling in the heart. Subsequent activation of transcription factors including AP-1, Ets, and nuclear factor kappa-B leads to increased transcription of MMPs. ROS also directly activate MMPs post-translationally. In addition, inflammatory cytokines and ROS lead to decreased TIMP levels and collagen synthesis. Work in animal models suggests that inhibition of inflammatory cytokine or ROS signaling leads to less myocardial remodeling. Further study of the signaling of regulation of the cardiac extracellular matrix may lead to new approaches for the treatment of myocardial remodeling and failure.
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PMID:Regulation of matrix metalloproteinases by cytokines and reactive oxygen/nitrogen species in the myocardium. 1473 67

This study investigated the effects of the peripheral vasodilator hydralazine on in vitro generation of reactive species of oxygen (ROS), nitrogen (RNS) and prostaglandin (PG) biosynthesis in elicited murine peritoneal macrophages, and on the gene expression and protein synthesis of two key enzymes in the inflammatory process, inducible NO(*) synthase (NOS-2) and inducible cyclooxygenase 2 (COX-2). Hydralazine at 0.1-10 mM inhibited both extracellular and intracellular ROS production by inflammatory macrophages, by a ROS-scavenging mechanism probably affecting superoxide radical (O(2)(*-))-generation by xanthine oxidase (XO) and nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase. Hydralazine at 0.1-10 mM significantly reduced NO(*) generation, and this effect was attributable to an inhibition of NOS-2 gene expression and protein synthesis. At 1-10 mM, hydralazine also effectively blocked COX-2 gene expression which perfectly correlated with a reduction of protein levels and PGE(2) synthesis. These data suggest that hydralazine, at the concentrations tested, show antioxidant properties and strongly attenuates the macrophage activation.
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PMID:Antioxidant activity and inhibitory effects of hydralazine on inducible NOS/COX-2 gene and protein expression in rat peritoneal macrophages. 1499 8

As a powerful natural antioxidant, lipoic acid (LipSS) and its reduced form dihydrolipoic acid (DHLA) exert significant antioxidant activities in vivo and in vitro by deactivation of reactive oxygen and nitrogen species (ROS and RNS). In this study the riboflavin (RF, vitamin B2) sensitized UVA and visible-light irradiation of LipSS and DHLA was studied employing continuous irradiation, fluorescence spectroscopy, and laser flash photolysis (LFP). Our results indicate that LipSS and DHLA quench both the singlet state (1RF*) and the triplet state (3RF*) of RF by electron transfer to produce the riboflavin semiquinone radical (RFH.) and the radical cation of LipSS and DHLA, respectively. The radical cation of DHLA is rapidly deprotonated twice to yield a reducing species, the radical anion of LipSS (LipSS.-). When D2O was used as solvent, it was confirmed that the reaction of LipSS with 3RF* consists of a simple electron-transfer step, while loss of hydrogen occurs in the case of DHLA oxidation. Due to the strong absorption of RFH. and the riboflavin ground state, the absorption of the radical cation and the radical anion of LipSS can not be observed directly by LFP. N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) and N,N,N',N'-tetramethyl benzidine (TMB) were added as probes to the system. In the case of LipSS, the addition resulted in the formation of the radical cation of TMPD or TMB by quenching of the LipSS radical cation. If DHLA is the reducing substrate, no formation of probe radical cation is observed. This confirms that LipSS.- is produced by riboflavin photosensitization, and that there is no oxidizing species produced after DHLA oxidization.
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PMID:Photoinduced interactions between oxidized and reduced lipoic acid and riboflavin (vitamin B2). 1499 43


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