Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.6.3.1 (NADPH oxidase)
11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystathionine beta synthase deficiency induces hyperhomocysteinemia which is considered as a risk factor for vascular diseases. Studies underlined the importance of altered cellular redox reactions in hyperhomocysteinemia-induced vascular pathologies. Nevertheless, hyperhomocysteinemia also induces hepatic dysfunction which may accelerate the development of vascular pathologies by modifying cholesterol homeostasis. The aim of the present study was to analyze the modifications of redox state in the liver of heterozygous cystathionine beta synthase-deficient mice, a murine model of hyperhomocysteinemia. In this purpose, we quantified levels of reactive oxygen and nitrogen species and we assayed activities of main antioxidant enzymes. We found that cystathionine beta synthase deficiency induced NADPH oxidase activation. However, there was no accumulation of reactive oxygen (superoxide anion, hydrogen peroxide) and nitrogen (nitrite, peroxynitrite) species. On the contrary, hepatic hydrogen peroxide level was decreased independently of an activation of glutathione-dependent mechanisms. In fact, cystathionine beta synthase deficiency had no effect on glutathione peroxidase, glutathione reductase and glutathione S-transferase activities. However, we found a 50% increase in hepatic catalase activity without any variation of expression. These findings demonstrate that cystathionine beta synthase deficiency initiates redox disequilibrium in the liver. However, the activation of catalase attenuates oxidative impairments.
...
PMID:Cystathionine beta synthase deficiency induces catalase-mediated hydrogen peroxide detoxification in mice liver. 1854 Nov 57

Hemodynamics, specifically, fluid shear stress, modulates the focal nature of atherosclerosis. Shear stress induces vascular oxidative stress via the activation of membrane-bound NADPH oxidases present in vascular smooth muscle cells, fibroblasts, and phagocytic mononuclear cells. Shear stress acting on the endothelial cells at arterial bifurcations or branching points regulates both NADPH oxidase and nitric oxide (NO) synthase activities. The former is considered a major source of oxygen-centered radicals (i.e., superoxide anion [O2(.-)]) that give rise to oxidative stress; the latter is a source of nitrogen-centered radicals (i.e., nitric oxide [NO]) that give rise to nitrative/nitrosative stress. In addition to conventional biochemical analyses, the emerging microelectromechanical systems (MEMS) provide spatial and temporal resolutions to investigate the mechanisms whereby the characteristics of shear stress regulate the biological activities of endothelial cells at the complicated arterial geometry. In parallel, the development of MEMS liquid chromatography (LC) provides a new venue to measure circulating oxidized low-density lipoprotein (ox-LDL) particles as a lab-on-a chip platform. Nanowire-based field effect transistors further pave the way for a high throughput approach to analyze the LDL redox state. Integration of MEMS with oxidative biology is synergistic in assessing vascular oxidative stress. The MEMS LC provides an emerging lab-on-a-chip platform for ox-LDL analysis. In this context, this chapter has integrated expertise from the fields of vascular biology and oxidative biology to address the dynamics of inflammatory responses.
...
PMID:Monitoring oxidative stress in vascular endothelial cells in response to fluid shear stress: from biochemical analyses to micro- and nanotechnologies. 1855 32

The cross talk between reactive oxygen species (ROS) and reactive nitrogen species (RNS) plays a pivotal role in the regulation of myocardial and vascular function. Both nitric oxide and redox-based signaling involve the posttranslational modification of proteins through S-nitrosylation and oxidation of specific cysteine residues. Disruption of this cross talk between ROS and RNS contributes to the pathogenesis of heart failure. Therefore, the elucidation of these complex chemical interactions may improve our understanding of cardiovascular pathophysiology. This chapter discusses the significant role of spatial confinement of nitric oxide synthases, NADPH oxidase, and xanthine oxidoreductase in the regulation of myocardial excitation-contraction coupling. This chapter describes techniques for assessing oxidative and nitrosative stress. A variety of assays have been developed that quantify S-nitrosylated proteins. Among them, the biotin-switch method directly evaluates endogenously nitrosylated proteins in a reproducible way. Identification of the biotinylated or S-nitrosylated proteins subjected to the biotin-switch assay are described and evaluated with a one-dimensional gel (Western blot) or with the newly developed two-dimensional fluorescence difference gel electrophoresis proteomic analysis. Quantifying the number of free thiols with the monobromobimane assay in a protein of interest allows estimation of cysteine oxidation and, in turn, the state of nitroso-redox balance of effector molecules. In summary, this chapter reviews the biochemical methods that assess the impact of nitroso/redox signaling in the cardiovascular system.
...
PMID:Nitric oxide and cardiobiology-methods for intact hearts and isolated myocytes. 1855 46

Methylglyoxal is a normal metabolite and has the potential to affect a wide variety of cellular processes. In particular, it can act selectively against malignant cells. The study described herein was to investigate whether methylglyoxal can enhance the non-specific immunity of the host against tumor cells. Methylglyoxal increased the number of macrophages in the peritoneal cavity of both normal and tumor-bearing mice. It also elevated the phagocytic capacity of macrophages in both these groups of animals. This activation of macrophages was brought about by increased production of Reactive Oxygen Intermediates (ROIs) and Reactive Nitrogen Intermediates (RNIs). The possible mechanism for the production of ROIs and RNIs can be attributed to stimulation of the respiratory burst enzyme NADPH oxidase and iNOS, respectively. IFN-gamma, which is a regulatory molecule of iNOS pathway also showed an elevated level by methylglyoxal. TNF-alpha, which is an important cytokine for oxygen independent killing by macrophage also increased by methylglyoxal in both tumor-bearing and non tumor-bearing animals. Methylglyoxal also played a role in the proliferation and cytotoxicity of splenic lymphocytes. In short, it can be concluded that methylglyoxal profoundly stimulates the immune system against tumor cells.
...
PMID:Activation of macrophages and lymphocytes by methylglyoxal against tumor cells in the host. 1861 20

UVA should receive significant consideration as a human health risk as it is a large proportion of the solar spectrum that reaches the earth's surface and because of its ability to penetrate human skin. It is only relatively recently that this has been recognized and this previously under-researched part of the UV spectrum is becoming increasingly well characterized at doses that are quite low in relation to those experienced by humans. Absorption of UVA in a cell leads to the production of reactive oxygen and nitrogen species that can damage major biomolecules including DNA and membrane lipids. Various types of damage induced in these molecules lead to significant biological effects including cytotoxicity, mutations and alterations in cell signalling pathways. Longer-term effects such as persistent genomic instability and bystander effects have also been observed following UVA treatment of mammalian cells and, as with ionizing radiation, this changes some of the fundamental thinking around tissue effects of irradiation. Antioxidants have been assessed extensively for their ability to protect against the biological effects of UVA and a number have been shown to be successful at least in-vitro, for example vitamin E and epigallocatechin-3-gallate. Other potential targets for protection are suggested through the increased understanding of some of the signalling mechanisms activated following treatment, for example the inhibition of NADPH oxidase is seen to reduce a bystander effect. The search for appropriate and successful photoprotective agents remains an important area of research.
...
PMID:Cellular effects of long wavelength UV light (UVA) in mammalian cells. 1864 90

Oxidative stress is a "privilege" of aerobic organisms. It can be induced by endogenous and exogenous factors. Most often, it is characterized by the production of free radicals and nonradical oxygen and nitrogen products, referred to under a single term "reactive species" (RS). Oxidative stress is a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins and DNA. However, reactive oxygen (ROS) and nitrogen species (RNS) are "two-faced" products. Produced in low/moderate concentrations as molecular signals that regulate a series of physiological processes, such as a defence against infectious agents, the maintenance of vascular tone, the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. Many of ROS-mediated responses protect cells against oxidative stress and maintain "redox homeostasis". Then, both reactive species are produced by strictly regulated enzymes, such as nitric oxide synthase (NOS), and isoforms of NADPH oxidase, or as by-products from not so well regulated sources, such as the mitochondrial electron-transport chain. An excessive increase in ROS production has been implicated in the pathogenesis of atherosclerosis, cardiovascular diseases, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative and immuno-inflammatory diseases. Within the cells, ROS can act as secondary messengers in intracellular signalling cascades, which can induce the oncogenic phenotype of cancer cells, cellular senescence and apoptosis.
...
PMID:[Oxidative stress in human diseases]. 1892 87

At present, available treatments for Alzheimer's disease (AD) are largely unable to halt disease progression. Microglia, the resident macrophages in the brain, are strongly implicated in the pathology and progressively degenerative nature of AD. Specifically, microglia are activated in response to both beta amyloid (Abeta) and neuronal damage, and can become a chronic source of neurotoxic cytokines and reactive oxygen species (ROS). NADPH oxidase is a multi-subunit enzyme complex responsible for the production of both extracellular and intracellular ROS by microglia. Importantly, NADPH oxidase expression is upregulated in AD and is an essential component of microglia-mediated Abeta neurotoxicity. Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: 1) extracellular ROS produced by microglia are directly toxic to neurons; 2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several pro-inflammatory and neurotoxic cytokines (for example, tumor necrosis factor-alpha, prostaglandin E2, and interleukin-1beta). The following review describes how targeting NADPH oxidase can reduce a broad spectrum of toxic factors (for example, cytokines, ROS, and reactive nitrogen species) to result in inhibition of neuronal damage from two triggers of deleterious microglial activation (Abeta and neuron damage), offering hope in halting the progression of AD.
...
PMID:NADPH oxidase as a therapeutic target in Alzheimer's disease. 1909 Sep 96

Mechanisms involved in hepatic encephalopathy (HE) still remain poorly understood. It is generally accepted that ammonia plays a major role in this disorder, and that astrocytes represent the principal target of ammonia neurotoxicity. In recent years, studies from several laboratories have uncovered a number of factors and pathways that appear to be critically involved in the pathogenesis of this disorder. Foremost is oxidative and nitrosative stress (ONS), which is largely initiated by an ammonia-induced increase in intracellular Ca(2+). Such increase in Ca(2+) activates a number of enzymes that promote the synthesis of reactive oxygen-nitrogen species, including constitutive nitric oxide synthase, NADPH oxidase and phospholipase A2. ONS subsequently induces the mitochondrial permeability transition, and activates mitogen-activated protein kinases and the transcription factor, nuclear factor-kappaB (NF-kappaB). These factors act to generate additional reactive oxygen-nitrogen species, to phosphorylate various proteins and transcription factors, and to cause mitochondrial dysfunction. This article reviews the role of these factors in the mechanism of HE and ammonia toxicity with a focus on astrocyte swelling and glutamate uptake, which are important consequences of ammonia neurotoxicity. These pathways and factors provide attractive targets for identifying agents potentially useful in the therapy of HE and other hyperammonemic disorders.
...
PMID:Signaling factors in the mechanism of ammonia neurotoxicity. 1910 23

Previous studies have shown a link between inhaled particulate matter (PM) exposure in urban areas and susceptibility to cardiovascular diseases. Although an oxidative stress pathway is strongly implicated, the locus of generation of reactive oxygen species (ROS) and the mechanisms by which these radicals exert their effects remain to be characterized. To test the hypothesis that exposure to environmentally relevant inhaled concentrated ambient PM (CAPs) enhances atherosclerosis through induction of vascular ROS and reactive nitrogen species. High-fat chow fed apolipoprotein E(-/-) mice were exposed to CAPs of less than 2.5 microm (PM(2.5)) or filtered air (FA), for 6 h/day, 5 days/week, for 4 months in Manhattan, NY. Atherosclerotic lesions were analyzed by histomorphometricly. Vascular reactivity, superoxide generation, mRNA expression of NADPH (nicotinamide adenine dinucleotide phosphate, reduced) oxidase subunits, inducible nitric oxide synthase, endothelial nitric oxide synthase, and GTP cyclohydrolase I were also assessed. Manhattan PM(2.5) CAPs were characterized by higher concentrations of organic and elemental carbon. Analysis of vascular responses revealed significantly decreased phenylephrine constriction in CAPs-exposed mice, which was restored by a soluble guanine cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. Vascular relaxation to A23187, but not to acetylcholine, was attenuated in CAPs mice. Aortic expression of NADPH oxidase subunits (p47(phox) and rac1) and iNOS were markedly increased, paralleled by increases in superoxide generation and extensive protein nitration in the aorta. The composite plaque area of thoracic aorta was significantly increased with pronounced macrophage infiltration and lipid deposition in the CAPs mice. CAPs exposure in Manhattan alters vasomotor tone and enhances atherosclerosis through NADPH oxidase dependent pathways.
...
PMID:Ambient particulates alter vascular function through induction of reactive oxygen and nitrogen species. 1918 7

One of the obstacles in irradiation therapy is cytoresistance, acquired by activation of self-defense systems, such as antioxidant or molecular chaperone systems, to cope with stress. We investigated whether irradiation preconditioning (IP) rendered resistance of the kidney against subsequent ischemia-reperfusion (I/R) and attempted to elucidate any such protective mechanisms. Mice were irradiated with a total of 4, 6, or 8 Gy using a cesium-137 source irradiator and then, 6 days later, were subjected to 28 min of bilateral renal ischemia followed by reperfusion. Eight Gy of IP significantly attenuated the increases in plasma creatinine (PCr) and blood urea nitrogen (BUN) concentration, structural damage, lipid peroxidation, superoxide formation, expression and activity of NADPH oxidase (NOX)-2, nitrotyrosine level, and hydrogen peroxide production after I/R in kidney tissues, indicating that IP protects the kidneys from I/R injury. IP markedly increased the activity of NOX, resulting in increased superoxide formation, manganese superoxide dismutase (MnSOD) activity and expression, and heat shock protein (HSP)-27 expression in kidneys. However, it did not change expressions of catalase, copper-zinc superoxide dismutase (CuZnSOD), and HSP-72. To investigate whether the protection afforded by IP was associated with increases in MnSOD and HSP-27 expression triggered by increased superoxide formation after IP, we administered manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin, a superoxide scavenger, to IP mice. This administration blocked superoxide formation and subsequent increases in MnSOD and HSP-27 expression and accelerated the post-I/R increases in PCr and BUN. In conclusion, IP renders kidney resistance to I/R injury, and this resistance is mediated by increased superoxide formation, which activates MnSOD activity and expression as well as HSP-27 expression.
...
PMID:Increased superoxide formation induced by irradiation preconditioning triggers kidney resistance to ischemia-reperfusion injury in mice. 2068 45


<< Previous 1 2 3 4 5 6 7 8 9 10

---