Nanoparticle Inhalation Increases Microvascular Oxidative Stress and Compromises Nitric Oxide Bioavailability

EPA Science Inventory

We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs are unclear. The purpose of this study was to identify alterations in the production of oxidative stress an...

Respiratory symptoms, lung functions, and exhaled nitric oxide (FENO) in two types of fish processing workers: Russian trawler fishermen and Norwegian salmon industry workers.

PubMed

Shiryaeva, Olga; Aasmoe, Lisbeth; Straume, Bjørn; Bang, Berit Elisabeth

2015-01-01

Respiratory outcomes and work-related factors were studied in two seafood worker populations representing different occupational environments. Levels of fractional exhaled nitric oxide (FENO), spirometric values, prevalence of respiratory symptoms, and self-evaluated exposures were compared between 139 Norwegian salmon workers and 127 Russian trawler workers. Increased odds ratios (ORs) of shortness of breath with wheezing and prolonged cough as general respiratory symptoms were found in salmon workers, while increased ORs of work-related dry cough and running nose were found in trawler fishermen. Both worker groups ranked "cold work environment," "use of disinfectants," and "contaminated indoor air" as the first, second, and third most important causes of work-related respiratory symptoms, respectively. Fractional exhaled nitric oxide levels were higher in asthmatic trawler workers compared to asthmatic salmon workers. Respiratory symptoms commonly associated with obstructive airway diseases were more prevalent in salmon workers, while symptoms commonly associated with asthma and short-term effects of cold air exposure were more prevalent in trawler workers.

Nitric oxide leads to cytoskeletal reorganization in the retinal pigment epithelium under oxidative stress.

PubMed

Sripathi, Srinivas R; He, Weilue; Um, Ji-Yeon; Moser, Trevor; Dehnbostel, Stevie; Kindt, Kimberly; Goldman, Jeremy; Frost, Megan C; Jahng, Wan Jin

2012-01-01

Light is a risk factor for various eye diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). We aim to understand how cytoskeletal proteins in the retinal pigment epithetlium (RPE) respond to oxidative stress, including light and how these responses affect apoptotic signaling. Previously, proteomic analysis revealed that the expression levels of vimentin and serine/threonine protein phosphatase 2A (PP2A) are significantly increased when mice are exposed under continuous light for 7 days compared to a condition of 12 hrs light/dark cycling exposure using retina degeneration 1 (rd1) model. When melatonin is administered to animals while they are exposed to continuous light, the levels of vimentin and PP2A return to a normal level. Vimentin is a substrate of PP2A that directly binds to vimentin and dephosphorylates it. The current study shows that upregulation of PP2Ac (catalytic subunit) phosphorylation negatively correlates with vimentin phosphorylation under stress condition. Stabilization of vimentin appears to be achieved by decreased PP2Ac phosphorylation by nitric oxide induction. We tested our hypothesis that site-specific modifications of PP2Ac may drive cytoskeletal reorganization by vimentin dephosphorylation through nitric oxide signaling. We speculate that nitric oxide determines protein nitration under stress conditions. Our results demonstrate that PP2A and vimentin are modulated by nitric oxide as a key element involved in cytoskeletal signaling. The current study suggests that external stress enhances nitric oxide to regulate PP2Ac and vimentin phosphorylation, thereby stabilizing or destabilizing vimentin. Phosphorylation may result in depolymerization of vimentin, leading to nonfilamentous particle formation. We propose that a stabilized vimentin might act as an anti-apoptotic molecule when cells are under oxidative stress.

Nitric oxide leads to cytoskeletal reorganization in the retinal pigment epithelium under oxidative stress

PubMed Central

Um, Ji-Yeon; Moser, Trevor; Dehnbostel, Stevie; Kindt, Kimberly; Goldman, Jeremy; Frost, Megan C.; Jahng, Wan Jin

2016-01-01

Light is a risk factor for various eye diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). We aim to understand how cytoskeletal proteins in the retinal pigment epithetlium (RPE) respond to oxidative stress, including light and how these responses affect apoptotic signaling. Previously, proteomic analysis revealed that the expression levels of vimentin and serine/threonine protein phosphatase 2A (PP2A) are significantly increased when mice are exposed under continuous light for 7 days compared to a condition of 12 hrs light/dark cycling exposure using retina degeneration 1 (rd1) model. When melatonin is administered to animals while they are exposed to continuous light, the levels of vimentin and PP2A return to a normal level. Vimentin is a substrate of PP2A that directly binds to vimentin and dephosphorylates it. The current study shows that upregulation of PP2Ac (catalytic subunit) phosphorylation negatively correlates with vimentin phosphorylation under stress condition. Stabilization of vimentin appears to be achieved by decreased PP2Ac phosphorylation by nitric oxide induction. We tested our hypothesis that site-specific modifications of PP2Ac may drive cytoskeletal reorganization by vimentin dephosphorylation through nitric oxide signaling. We speculate that nitric oxide determines protein nitration under stress conditions. Our results demonstrate that PP2A and vimentin are modulated by nitric oxide as a key element involved in cytoskeletal signaling. The current study suggests that external stress enhances nitric oxide to regulate PP2Ac and vimentin phosphorylation, thereby stabilizing or destabilizing vimentin. Phosphorylation may result in depolymerization of vimentin, leading to nonfilamentous particle formation. We propose that a stabilized vimentin might act as an anti-apoptotic molecule when cells are under oxidative stress. PMID:27974994

In vitro time- and dose-effect response of JP-8 and S-8 jet fuel on alveolar type II epithelial cells of rats.

PubMed

Robb, Tiffany M; Rogers, Michael J; Woodward, Suann S; Wong, Simon S; Witten, Mark L

2010-07-01

This study was designed to characterize and compare the effects of jet propellant-8 (JP-8) fuel and synthetic-8 (S-8) on cell viability and nitric oxide synthesis in cultured alveolar type II epithelial cells of rats. Exposure times varied from 0.25, 0.5, 1, and 6 hours at the following concentrations of jet fuel: 0.0, 0.1, 0.4, and 2.0 microg/mL. Data indicate that JP-8 presents a gradual decline in cell viability and steady elevation in nitric oxide release as exposure concentrations increase. At a 2.0 microg/mL concentration of JP-8, nearly all of the cells are not viable. Moreover, S-8 exposure to rat type II lung cells demonstrated an abrupt fall in percentage cell viability and increases in nitric oxide measurement, particularly after the 2.0 microg/mL was reached at 1 and 6 hours. At 0.0, 0.2, and 0.4 microg/mL concentrations of S-8, percentage viability was sustained at steady concentrations. The results suggest different epithelial toxicity and mechanistic effects of S-8 and JP-8, providing further insight concerning the impairment imposed at specific levels of lung function and pathology induced by the different fuels.

HSP70 protects rats and hippocampal neurons from central nervous system oxygen toxicity by suppression of NO production and NF-κB activation.

PubMed

Yi, Hongjie; Huang, Guoyang; Zhang, Kun; Liu, Shulin; Xu, Weigang

2018-05-01

During diving, central nervous system oxygen toxicity may cause drowning or barotrauma, which has dramatically limited the working benefits of hyperbaric oxygen in underwater operations and clinical applications. The aim of this study is to understand the effects and the underlying mechanism of heat shock protein 70 on central nervous system oxygen toxicity and its mechanisms in vivo and in vitro. Rats were given geranylgeranylacetone (800 mg/kg) orally to induce hippocampal expression of heat shock protein 70 and then treated with hyperbaric oxygen. The time course of hippocampal heat shock protein 70 expression after geranylgeranylacetone administration was measured. Seizure latency and first electrical discharge were recorded to evaluate the effects of HSP70 on central nervous system oxygen toxicity. Effects of inhibitors of nitric oxide synthase and nuclear factor-κB on the seizure latencies and changes in nitric oxide, nitric oxide synthase, and nuclear factor-κB levels in the hippocampus tissues were examined. In cell experiments, hippocampal neurons were transfected with a virus vector carrying the heat shock protein 70 gene (H3445) before hyperbaric oxygen treatment. Cell viability, heat shock protein 70 expression, nitric oxide, nitric oxide synthase, and NF-κB levels in neurons were measured. The results showed that heat shock protein 70 expression significantly increased and peaked at 48 h after geranylgeranylacetone was given. Geranylgeranylacetone prolonged the first electrical discharge and seizure latencies, which was reversed by neuronal nitric oxide synthase, inducible nitric oxide synthase and NF-κB inhibitors. Nitric oxide, nitric oxide synthase, and inducible nitric oxide synthase levels in the hippocampus were significantly increased after hyperbaric oxygen exposure, but reversed by geranylgeranylacetone, while heat shock protein 70 inhibitor quercetin could inhibit this effect of geranylgeranylacetone. In the in vitro study, heat shock protein 70-overexpression decreased the nitric oxide, nitric oxide synthase, and inducible nitric oxide synthase levels as well as the cytoplasm/nucleus ratio of nuclear factor-κB and protected neurons from hyperbaric oxygen-induced cell injury. In conclusion, overexpression of heat shock protein 70 in hippocampal neurons may protect rats from central nervous system oxygen toxicity by suppression of neuronal nitric oxide synthase and inducible nitric oxide synthase-mediated nitric oxide production and translocation of nuclear factor-κB to nucleus. Impact statement Because the pathogenesis of central nervous system oxygen toxicity (CNS-OT) remains unclear, there are few interventions available. To develop an efficient strategy against CNS-OT, it is necessary to understand its pathogenesis and in particular, the relevant key factors involved. This study examined the protective effects of heat shock protein 70 (HSP70) on CNS-OT via in vivo and in vitro experiments. Our results indicated that overexpression of HSP70 in hippocampal neurons may protect rats from CNS-OT by suppression of nNOS and iNOS-mediated NO production and the activation of NF-κB. These findings contribute to clarification of the role of HSP70 in CNS-OT and provide us a potential novel target to prevent CNS-OT. Clarification of the involvement of NO, NOS and NF-κB provides new insights into the mechanism of CNS-OT and may help us to develop new approach against it by interfering these molecules.

Candida albicans Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions.

PubMed

Wagener, Jeanette; MacCallum, Donna M; Brown, Gordon D; Gow, Neil A R

2017-01-24

The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid l-arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host's arginase activity to prevent the conversion of l-arginine to nitric oxide. We report here that C. albicans blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the C. albicans-induced arginase activity with the arginase-specific substrate inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that C. albicans influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore, C. albicans modulates l-arginine metabolism in macrophages during an infection, potentiating its own survival. The availability and metabolism of amino acids are increasingly recognized as crucial regulators of immune functions. In acute infections, the conversion of the "conditionally essential" amino acid l-arginine by the inducible nitric oxide synthase to nitric oxide is a resistance factor that is produced by the host to fight pathogens. Manipulation of these host defense mechanisms by the pathogen can be key to successful host invasion. We show here that the human opportunistic fungal pathogen Candida albicans influences l-arginine availability for nitric oxide production by induction of the substrate-competing host enzyme arginase-1. This led to a reduced production of nitric oxide and, moreover, reduced eradication of the fungus by human macrophages. We demonstrate that blocking of host arginase-1 activity restored nitric oxide production and increased the killing potential of macrophages. These results highlight the therapeutic potential of l-arginine metabolism in fungal diseases. Copyright © 2017 Wagener et al.

Effect of exposure to an Asian dust storm on fractional exhaled nitric oxide in adult asthma patients in Western Japan.

PubMed

Watanabe, Masanari; Kurai, Jun; Sano, Hiroyuki; Shimizu, Eiji

2015-01-01

Epidemiological investigations indicate that an Asian dust storm (ADS) can aggravate respiratory disorders. However, the effects of ADS on airway inflammation remain unclear. The aim of this study was to investigate the association of exposure to ADS with airway inflammation. The subjects were 33 adult patients with asthma who measured daily peak flow expiratory (PEF) from March to May 2012. Fractional exhaled nitric oxide (FeNO) was measured before and after ADS. The FeNO values were 13.8±13.7 ppb before the ADS and 20.3±19.0 ppb after the ADS, with no significant difference. There was also no significant association of PEF with ADS exposure. However, the increase of FeNO after ADS exposure was proportional to the decrease of PEF (R=-0.78, P<0.0001). These results suggest that airway inflammation aggravated by ADS exposure may induce a decrease in pulmonary function in some adult patients with asthma.

Prenatal exposure to traffic-related air pollution and risk of early childhood cancers.

PubMed

Ghosh, Jo Kay C; Heck, Julia E; Cockburn, Myles; Su, Jason; Jerrett, Michael; Ritz, Beate

2013-10-15

Exposure to air pollution during pregnancy has been linked to the risk of childhood cancer, but the evidence remains inconclusive. In the present study, we used land use regression modeling to estimate prenatal exposures to traffic exhaust and evaluate the associations with cancer risk in very young children. Participants in the Air Pollution and Childhood Cancers Study who were 5 years of age or younger and diagnosed with cancer between 1988 and 2008 were had their records linked to California birth certificates, and controls were selected from birth certificates. Land use regression-based estimates of exposures to nitric oxide, nitrogen dioxide, and nitrogen oxides were assigned based on birthplace residence and temporally adjusted using routine monitoring station data to evaluate air pollution exposures during specific pregnancy periods. Logistic regression models were adjusted for maternal age, race/ethnicity, educational level, parity, insurance type, and Census-based socioeconomic status, as well as child's sex and birth year. The odds of acute lymphoblastic leukemia increased by 9%, 23%, and 8% for each 25-ppb increase in average nitric oxide, nitrogen dioxide, and nitrogen oxide levels, respectively, over the entire pregnancy. Second- and third-trimester exposures increased the odds of bilateral retinoblastoma. No associations were found for annual average exposures without temporal components or for any other cancer type. These results lend support to a link between prenatal exposure to traffic exhaust and the risk of acute lymphoblastic leukemia and bilateral retinoblastoma.

Pulmonary Nanoparticle Exposure Disrupts Systemic Microvascular Nitric Oxide Signaling

PubMed Central

Nurkiewicz, Timothy R.; Porter, Dale W.; Hubbs, Ann F.; Stone, Samuel; Chen, Bean T.; Frazer, David G.; Boegehold, Matthew A.; Castranova, Vincent

2009-01-01

We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs is/are unclear. The purpose of this study was to identify alterations in the production of reactive species and endogenous nitric oxide (NO) after nanoparticle exposure, and determine the relative contribution of hemoproteins and oxidative enzymes in this process. Sprague-Dawley rats were exposed to fine TiO2 (primary particle diameter ∼1 μm) and TiO2 nanoparticles (primary particle diameter ∼21 nm) via aerosol inhalation at depositions of 4–90 μg per rat. As in previous intravital experiments in the spinotrapezius muscle, dose-dependent arteriolar dilations were produced by intraluminal infusions of the calcium ionophore A23187. Nanoparticle exposure robustly attenuated these endothelium-dependent responses. However, this attenuation was not due to altered microvascular smooth muscle NO sensitivity because nanoparticle exposure did not alter arteriolar dilations in response to local sodium nitroprusside iontophoresis. Nanoparticle exposure significantly increased microvascular oxidative stress by ∼60%, and also elevated nitrosative stress fourfold. These reactive stresses coincided with a decreased NO production in a particle deposition dose-dependent manner. Radical scavenging, or inhibition of either myeloperoxidase or nicotinamide adenine dinucleotide phosphate oxidase (reduced) oxidase partially restored NO production as well as normal microvascular function. These results indicate that in conjunction with microvascular dysfunction, nanoparticle exposure also decreases NO bioavailability through at least two functionally distinct mechanisms that may mutually increase local reactive species. PMID:19270016

Ambient ultrafine particles reduce endothelial nitric oxide production via S-glutathionylation of eNOS.

PubMed

Du, Yunfeng; Navab, Mohamad; Shen, Melody; Hill, James; Pakbin, Payam; Sioutas, Constantinos; Hsiai, Tzung K; Li, Rongsong

2013-07-05

Exposure to airborne particulate pollutants is intimately linked to vascular oxidative stress and inflammatory responses with clinical relevance to atherosclerosis. Particulate matter (PM) has been reported to induce endothelial dysfunction and atherosclerosis. Here, we tested whether ambient ultrafine particles (UFP, diameter <200 nm) modulate eNOS activity in terms of nitric oxide (NO) production via protein S-glutathionylation. Treatment of human aortic endothelial cells (HAEC) with UFP significantly reduced NO production. UFP-mediated reduction in NO production was restored in the presence of JNK inhibitor (SP600125), NADPH oxidase inhibitor (Apocynin), anti-oxidant (N-acetyl cysteine), and superoxide dismutase mimetics (Tempol and MnTMPyP). UFP exposure increased the GSSG/GSH ratio and eNOS S-glutathionylation, whereas over-expression of Glutaredoxin-1 (to inhibit S-glutathionylation) restored UFP-mediated reduction in NO production by nearly 80%. Thus, our findings suggest that eNOS S-glutathionylation is a potential mechanism underlying ambient UFP-induced reduction of NO production. Copyright © 2013 Elsevier Inc. All rights reserved.

Ambient ultrafine particles reduce endothelial nitric oxide production via S-glutathionylation of eNOS

PubMed Central

Du, Yunfeng; Navab, Mohamad; Shen, Melody; Hill, James; Pakbin, Payam; Sioutas, Constantinos; Hsiai, Tzung; Li, Rongsong

2013-01-01

Exposure to airborne particulate pollutants is intimately linked to vascular oxidative stress and inflammatory responses with clinical relevance to atherosclerosis. Particulate matter (PM) has been reported to induce endothelial dysfunction and atherosclerosis. Here, we tested whether ambient ultrafine particles (UFP, diameter < 200 nm) modulate eNOS activity in terms of nitric oxide (NO) production via protein S-glutathionylation. Treatment of human aortic endothelial cells (HAEC) with UFP significantly reduced NO production. UFP-mediated reduction in NO production was restored in the presence of JNK inhibitor (SP600125), NADPH oxidase inhibitor (Apocynin), anti-oxidant (N-acetyl cysteine), and superoxide dismutase mimetics (Tempol and MnTMPyP). UFP exposure increased the GSSG/GSH ratio and eNOS S-glutathionylation, whereas over-expression of Glutaredoxin-1 (to inhibit S-glutathionylation) restored UFP-mediated reduction in NO production by nearly 80%. Thus, our findings suggest that eNOS S-glutathionylation is a potential mechanism underlying ambient UFP-induced reduction of NO production. PMID:23751346

A nitric oxide-releasing solution as a potential treatment for fungi associated with tinea pedis.

PubMed

Regev-Shoshani, G; Crowe, A; Miller, C C

2013-02-01

To test a nitric oxide-releasing solution (NORS) as a potential antifungal footbath therapy against Trichophyton mentagrophytes and Trichophyton rubrum during the mycelial and conidial phases. NORS (sodium nitrite citric acid) produces nitric oxide verified by gas chromatography and mass spectrometry (GC-MS). Antifungal activity of this solution was tested against mycelia and conidia of T. mentagrophytes and T. rubrum, using 1-20 mmol l(-1) nitrites and 10-30 min exposure times. The direct effect of the gas released from the solution on the viability of those fungi was tested. NORS demonstrated strong antifungal activity and was found to be dose and time dependent. NO and nitrogen dioxide (NO(2) ) were the only gases detected from this reaction and are likely responsible for the antifungal effect. This in vitro research suggests that a single 20-min exposure to NORS could potentially be used as an effective single-dose treatment against fungi that are associated with tinea pedis in both mycelia and spore phase. This study provides the background for developing a user-friendly footbath treatment for Athlete's Foot that will kill both vegetative fungi and its spores. © 2012 The Society for Applied Microbiology.

Phenotypic Consequences of a Genetic Predisposition to Enhanced Nitric Oxide Signaling.

PubMed

Emdin, Connor A; Khera, Amit V; Klarin, Derek; Natarajan, Pradeep; Zekavat, Seyedeh M; Nomura, Akihiro; Haas, Mary; Aragam, Krishna; Ardissino, Diego; Wilson, James G; Schunkert, Heribert; McPherson, Ruth; Watkins, Hugh; Elosua, Roberto; Bown, Matthew J; Samani, Nilesh J; Baber, Usman; Erdmann, Jeanette; Gormley, Padhraig; Palotie, Aarno; Stitziel, Nathan O; Gupta, Namrata; Danesh, John; Saleheen, Danish; Gabriel, Stacey; Kathiresan, Sekar

2018-01-16

Nitric oxide signaling plays a key role in the regulation of vascular tone and platelet activation. Here, we seek to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on risk for cardiovascular diseases, thus informing the potential utility of pharmacological stimulation of the nitric oxide pathway as a therapeutic strategy. We analyzed the association of common and rare genetic variants in 2 genes that mediate nitric oxide signaling (Nitric Oxide Synthase 3 [ NOS3 ] and Guanylate Cyclase 1, Soluble, Alpha 3 [ GUCY1A3 ]) with a range of human phenotypes. We selected 2 common variants (rs3918226 in NOS3 and rs7692387 in GUCY1A3 ) known to associate with increased NOS3 and GUCY1A3 expression and reduced mean arterial pressure, combined them into a genetic score, and standardized this exposure to a 5 mm Hg reduction in mean arterial pressure. Using individual-level data from 335 464 participants in the UK Biobank and summary association results from 7 large-scale genome-wide association studies, we examined the effect of this nitric oxide signaling score on cardiometabolic and other diseases. We also examined whether rare loss-of-function mutations in NOS3 and GUCY1A3 were associated with coronary heart disease using gene sequencing data from the Myocardial Infarction Genetics Consortium (n=27 815). A genetic predisposition to enhanced nitric oxide signaling was associated with reduced risks of coronary heart disease (odds ratio, 0.37; 95% confidence interval [CI], 0.31-0.45; P =5.5*10 -26 ], peripheral arterial disease (odds ratio 0.42; 95% CI, 0.26-0.68; P =0.0005), and stroke (odds ratio, 0.53; 95% CI, 0.37-0.76; P =0.0006). In a mediation analysis, the effect of the genetic score on decreased coronary heart disease risk extended beyond its effect on blood pressure. Conversely, rare variants that inactivate the NOS3 or GUCY1A3 genes were associated with a 23 mm Hg higher systolic blood pressure (95% CI, 12-34; P =5.6*10 -5 ) and a 3-fold higher risk of coronary heart disease (odds ratio, 3.03; 95% CI, 1.29-7.12; P =0.01). A genetic predisposition to enhanced nitric oxide signaling is associated with reduced risks of coronary heart disease, peripheral arterial disease, and stroke. Pharmacological stimulation of nitric oxide signaling may prove useful in the prevention or treatment of cardiovascular disease. © 2017 American Heart Association, Inc.

Mechanisms of lead-induced poisoning.

PubMed

Nemsadze, K; Sanikidze, T; Ratiani, L; Gabunia, L; Sharashenidze, T

2009-01-01

Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic circulatory, neurological, hematological, gastrointestinal, reproductive and immunological pathologies. The mechanism of lead induced toxicity is not fully understood. The prime targets to lead toxicity are the heme synthesis enzymes, thiol-containing antioxidants and enzymes (superoxide dismutase, catalase, glutathione peroxidase, glucose 6-phosphate dehydrogenase and antioxidant molecules like GSH). The low blood lead levels are sufficient to inhibit the activity of these enzymes and induce generation of reactive oxygen species and intensification oxidative stress. Oxidative stress plays important role in pathogenesis of lead-induced toxicity and pathogenesis of coupled disease. The primary target of lead toxicity is the central nervous system. There are different cellular, intracellular and molecular mechanisms of lead neurotoxicity: such as induction of oxidative stress, intensification of apoptosis of neurocites, interfering with Ca(2+) dependent enzyme like nitric oxide synthase. Population studies have demonstrated a link between lead exposure and subsequent development of hypertension and cardiovascular disease. The vascular endothelium is now regarded as the main target organ for the toxic effect of lead. Lead affects the vasoactive function of endothelium through the increased production of reactive oxygen species, inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species, leading to a limiting nitric oxide availability, impairing nitric oxide signaling. This review summarizes recent findings of the mechanism of the lead-induced toxicity and possibilities of its prevention.

Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages.

PubMed Central

Nunoshiba, T; deRojas-Walker, T; Wishnok, J S; Tannenbaum, S R; Demple, B

1993-01-01

Nitric oxide is a free radical (NO) formed biologically through the oxidation of L-arginine by nitric oxide synthases. NO is produced transiently in mammalian cells for intercellular signaling and in copious quantities to cause cytostasis and cytotoxicity. In the latter situation, NO is a deliberate cytotoxic product of activated macrophages, along with other reactive oxygen species such as hydrogen peroxide (H2O2) and superoxide (O2-). Escherichia coli has a complex set of responses to H2O2 and O2- that involves approximately 80 inducible proteins; we wondered whether these bacteria might induce analogous defenses against nitric oxide. We show here that a multigene system controlled by the redox-sensitive transcriptional regulator SoxR is activated by NO in vivo. This induction confers bacterial resistance to activated murine macrophages with kinetics that parallel the production of NO by these cells. Elimination of specific SoxR-regulated genes diminishes the resistance of these bacteria to the cytotoxic macrophages. The required functions include manganese-containing superoxide dismutase, endonuclease IV (a DNA-repair enzyme for oxidative damage), and micF, an antisense regulator of the outer membrane porin OmpF. These results demonstrate that SoxR is a sensor for cellular exposure to NO, and that the soxRS response system may contribute to bacterial virulence. PMID:8234347

Mid-Ir Cavity Ring-Down Spectrometer for Biological Trace Nitric Oxide Detection

NASA Astrophysics Data System (ADS)

Kan, Vincent; Ragab, Ahemd; Stsiapura, Vitali; Lehmann, Kevin K.; Gaston, Benjamin M.

2011-06-01

S-nitrosothiols have received much attention in biochemistry and medicine as donors of nitrosonium ion (NO^+) and nitric oxide (NO) - physiologically active molecules involved in vasodilation and signal transduction. Determination of S-nitrosothiols content in cells and tissues is of great importance for fundamental research and medical applications. We will report on our ongoing development of a instrument to measure trace levels of nitric oxide gas (NO), released from S-nitrosothiols after exposure to UV light (340 nm) or reaction with L-Cysteine+CuCl mixture. The instrument uses the method of cavity ring-down spectroscopy, probing rotationally resolved lines in the vibrational fundamental transition near 5.2 μm. The laser source is a continuous-wave, room temperature external cavity quantum cascade laser. An acousto-optic modulator is used to abruptly turn off the optical power incident on the cavity when the laser and cavity pass through resonance.

Participation of hippocampal nitric oxide synthase and soluble guanylate cyclase in the modulation of behavioral responses elicited by the rat forced swimming test.

PubMed

Sales, Amanda J; Hiroaki-Sato, Vinícius A; Joca, Sâmia R L

2017-02-01

Systemic or hippocampal administration of nitric oxide (NO) synthase inhibitors induces antidepressant-like effects in animals, implicating increased hippocampal levels of NO in the neurobiology of depression. However, the role played by different NO synthase in this process has not been clearly defined. As stress is able to induce neuroinflammatory mechanisms and trigger the expression of inducible nitric oxide synthase (iNOS) in the brain, as well as upregulate neuronal nitric oxide synthase (nNOS) activity, the aim of the present study was to investigate the possible differential contribution of hippocampal iNOS and nNOS in the modulation of the consequences of stress elicited by the forced swimming test. Male Wistar rats received intrahippocampal injections, immediately after the pretest or 1 h before the forced swimming test, of selective inhibitors of nNOS (N-propyl-L-arginine), iNOS (1400W), or sGC (ODQ), the main pharmacological target for NO. Stress exposure increased nNOS and phospho-nNOS levels at all time points, whereas iNOS expression was increased only 24 h after the pretest. All drugs induced an antidepressant-like effect. However, whereas the nNOS inhibitor was equally effective when injected at different times, the iNOS inhibitor was more effective 24 h after the pretest. These results suggest that hippocampal nNOS and iNOS contribute to increase in NO levels in response to stress, although with a differential time course after stress exposure.

Effect of Cadmium Stress on Non-enzymatic Antioxidant and Nitric Oxide Levels in Two Varieties of Maize (Zea mays).

PubMed

Akinyemi, Ayodele Jacob; Faboya, Oluwabamise Lekan; Olayide, Israel; Faboya, Opeyemi Ayodeji; Ijabadeniyi, Tosin

2017-06-01

Cadmium (Cd) is one of the most toxic heavy metals that inhibit physiological processes of plants. Hence, the present study sought to investigate the effect of cadmium-contaminated seeds from two varieties of maize (Zea mays) on non-enzymatic antioxidant and nitric oxide levels. Seeds of yellow and white maize were exposed to different concentrations of Cd (0, 1, 3 and 5 ppm) for two weeks. The results from this study revealed that both varieties of maize bio-accumulate Cd in leaves in a dose-dependent manner. In addition, Cd exposure caused a significant (p < 0.05) decrease in total phenolic, GSH and nitric oxide (NO) levels at the highest concentration tested when compared with control. Therefore, the observed decrease in NO and endogenous antioxidant status by Cd treatment in maize plants could suggest some possible mechanism of action for Cd-induced oxidative stress and counteracting effect of the plants against Cd toxicity.

Candida albicans Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions

PubMed Central

MacCallum, Donna M.; Brown, Gordon D.

2017-01-01

ABSTRACT   The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid l-arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host’s arginase activity to prevent the conversion of l-arginine to nitric oxide. We report here that C. albicans blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the C. albicans-induced arginase activity with the arginase-specific substrate inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that C. albicans influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore, C. albicans modulates l-arginine metabolism in macrophages during an infection, potentiating its own survival. PMID:28119468

Association of expired nitric oxide with occupational particulate exposure.

PubMed Central

Kim, Jee Young; Wand, Matthew P; Hauser, Russ; Mukherjee, Sutapa; Herrick, Robert F; Christiani, David C

2003-01-01

Particulate air pollution has been associated with adverse respiratory health effects. This study assessed the utility of expired nitric oxide to detect acute airway responses to metal-containing fine particulates. Using a repeated-measures study design, we investigated the association between the fractional concentration of expired nitric oxide (F(E)NO) and exposure to particulate matter with an aerodynamic mass median diameter of less than or equal to 2.5 micro m (PM(2.5)) in boilermakers exposed to residual oil fly ash and metal fumes. Subjects were monitored for 5 days during boiler repair overhauls in 1999 (n = 20) or 2000 (n = 14). The Wilcoxon median baseline F(E)NO was 10.6 ppb [95% confidence interval (CI): 9.1, 12.7] in 1999 and 7.4 ppb (95% CI: 6.7, 8.0) in 2000. The Wilcoxon median PM(2.5) 8-hr time-weighted average was 0.56 mg/m(3) (95% CI: 0.37, 0.93) in 1999 and 0.86 mg/m(3) (95% CI: 0.65, 1.07) in 2000. F(E)NO levels during the work week were significantly lower than baseline F(E)NO in 1999 (p < 0.001). A significant inverse exposure-response relationship between log-transformed F(E)NO and the previous workday's PM(2.5) concentration was found in 1999, after adjusting for smoking status, age, and sampling year. With each 1 mg/m(3) incremental increase in PM(2.5) exposure, log F(E)NO decreased by 0.24 (95% CI: -0.38, -0.10) in 1999. The lack of an exposure-response relationship between PM(2.5) exposure and F(E)NO in 2000 could be attributable to exposure misclassification resulting from the use of respirators. In conclusion, occupational exposure to metal-containing fine particulates was associated with significant decreases in F(E)NO in a survey of workers with limited respirator usage. PMID:12727593

Enhanced Nitric Oxide Production during Lead (Pb2+) Exposure Recovers Protein Expression but not Presynaptic Localization of Synaptic Proteins in Developing Hippocampal Neurons

PubMed Central

Neal, April P.; Stansfield, Kirstie H.; Guilarte, Tomás R.

2012-01-01

We have previously reported that lead (Pb2+) exposure results in both presynaptic and postsynaptic changes in developing neurons as a result of inhibition of the N-methyl-D-aspartate receptor (NMDAR). NMDAR inhibition by Pb2+ during synaptogenesis disrupts downstream trans-synaptic signaling of brain-derived neurotrophic factor (BDNF) and exogenous addition of BDNF can recover the effects of Pb2+ on both presynaptic protein expression and presynaptic vesicular release. NMDAR activity can modulate other trans-synaptic signaling pathways, such as nitric oxide (NO) signaling. Thus, it is possible that other trans-synaptic pathways in addition to BDNF signaling may be disrupted by Pb2+ exposure. The current study investigated whether exogenous addition of NO could recover the presynaptic vesicular proteins lost as a result of Pb2+ exposure during synaptogenesis, namely Synaptophysin (Syn) and Synaptobrevin (Syb). We observed that exogenous addition of NO during Pb2+ exposure results in complete recovery of whole-cell Syn levels and partial recovery of Syn and Syb synaptic targeting in Pb2+-exposed neurons. PMID:22265330

Neural mechanisms in nitric-oxide-deficient hypertension

NASA Technical Reports Server (NTRS)

Sander, M.; Victor, R. G.; Blomqvist, C. G. (Principal Investigator)

1999-01-01

Nitric oxide is hypothesized to be an inhibitory modulator of central sympathetic nervous outflow, and deficient neuronal nitric oxide production to cause sympathetic overactivity, which then contributes to nitric-oxide-deficient hypertension. The biochemical and neuroanatomical basis for this concept revolves around nitric oxide modulation of glutamatergic neurotransmission within brainstem vasomotor centers. The functional consequence of neuronal nitric oxide in blood pressure regulation is, however, marked by an apparent conflict in the literature. On one hand, conscious animal studies using sympathetic blockade suggest a significant role for neuronal nitric oxide deficiency in the development of nitric-oxide-deficient hypertension, and on the other hand, there is evidence against such a role derived from 'knock-out' mice lacking nitric-oxide synthase 1, the major source of neuronal nitric oxide.

A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats☆

PubMed Central

Jin, Minghua; Song, Peilin; Li, Na; Li, Xuejun; Chen, Jiajun

2012-01-01

Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and demonstrated that the poisoning was dose-dependent. PMID:25538742

Exogenous Nitric Oxide (NO) Interferes with Lead (Pb)-Induced Toxicity by Detoxifying Reactive Oxygen Species in Hydroponically Grown Wheat (Triticum aestivum) Roots

PubMed Central

Kaur, Gurpreet; Singh, Harminder Pal; Batish, Daizy R.; Mahajan, Priyanka; Kohli, Ravinder Kumar; Rishi, Valbha

2015-01-01

Nitric Oxide (NO) is a bioactive signaling molecule that mediates a variety of biotic and abiotic stresses. The present study investigated the role of NO (as SNP [sodium nitroprusside]) in ameliorating lead (Pb)-toxicity in Triticum aestivum (wheat) roots. Pb (50 and 250 μM) alone and in combination with SNP (100 μM) was given to hydroponically grown wheat roots for a period of 0–8 h. NO supplementation reduced the accumulation of oxidative stress markers (malondialdehyde, conjugated dienes, hydroxyl ions and superoxide anion) and decreased the antioxidant enzyme activity in wheat roots particularly up to 6 h, thereby suggesting its role as an antioxidant. NO ameliorated Pb-induced membrane damage in wheat roots as evidenced by decreased ion-leakage and in situ histochemical localization. Pb-exposure significantly decreased in vivo NO level. The study concludes that exogenous NO partially ameliorates Pb-toxicity, but could not restore the plant growth on prolonged Pb-exposure. PMID:26402793

Early life permethrin exposure leads to hypervitaminosis D, nitric oxide and catecholamines impairment.

PubMed

Fedeli, Donatella; Carloni, Manuel; Nasuti, Cinzia; Gambini, Anna; Scocco, Vitangelo; Gabbianelli, Rosita

2013-09-01

The aim of this study is to gain more knowledge on the impact of early life pesticide exposure on premature aging. The effect of a low dose of the insecticide permethrin administered to rats during early life (1/50 LD50, from 6th to 21st day of life) was analyzed by measuring some metabolites in plasma and urine of 500-day-old animals. Significant differences in early life treated rats compared to the control group were found in the plasma levels of Ca(++), Na(+), 25-hydroxy-vitamin D, adrenaline, noradrenaline, nitric oxide, cholesterol and urea while in urine only Na(+) content was different. These results add information on the impact of permethrin during the neonatal period, supporting the evidence that early life environmental exposure to xenobiotics has long-term effects, inducing modifications in adulthood that can be revealed by the analysis of some macroelements, metabolites and catecholamines in plasma, when rats are 500 days old. Copyright © 2013 Elsevier Inc. All rights reserved.

Nitric Oxide and Superoxide Mediate Diesel Particle Effects in Cytokine-Treated Mice and Murine Lung Epithelial Cells ─ Implications for Susceptibility to Traffic-Related Air Pollution

EPA Science Inventory

Abstract Background: Epidemiologic studies associate childhood exposure to traffic-related air pollution with increased respiratory infections and asthmatic and allergic symptoms. The strongest associations between traffic exposure and negative health impacts are observed in in...

THE ESTROGENS / CHROMIUM INTERACTION IN THE NITRIC OXIDE GENERATION.

PubMed

Sawicka, Ewa; Piwowar, Agnieszka; Musiala, Tomasz; Dlugosz, Anna

2017-05-01

The interaction of estrogens with environmental toxins in free radicals generation: reactive oxygen species (ROS) or reactive nitrogen species (RNS) which participates in cancerogenesis is not yet recognized. Chromium(VI) is widely present in environment. One of its toxicity pathway is free radicals generation. Estrogens have the ability to scavenge free radicals, but may also act as prooxidants. Both chromium(VI) and estrogens are classified by International Agency for Research on Cancer (IARC) as carcinogens, so synergistic effect seems very dangerous. The interaction of chromium and estrogens in ROS generation are partly described but there are no reports on estrogen/chromium interaction on nitric oxide (NO) generation. The aim of the study was to examine the interaction of chromium(VI) and 17-p-estradiol (E2) on NO level in human blood as well as the role of E2 metabolites: 4-hydroxyestradiol (4-OHE2) and 16a-hydroxyestrone (16α-OHE1) in these processes. The NO level was estimated with the diagnostic kit (Nitric Oxide Colorimetric Detection Kit from Arbor Assays) in human blood in vitm. The results showed that Cr(VI) in used concentration (0.5; 1.0 and 5.0 gg/mL) decreases significantly NO level in blood, acting antagonistically to E2 and 4-OHE2. Estrogens (E2, 4-OHE2 and 16α-OHEI) do not protect against inhibiting effect of Cr(VI) on nitric oxide generation in blood because after combined exposure the decreased production of NO in blood was noted. In conclusion, presented results provide the information about the character of estrogen/Cr(VI) interaction in NO level in human blood. It is important knowledge for cardio protected effect e.g., hormone replacement therapy in environmental or occupational exposure to Cr(VI), chromium supplementation, also important for cancer risk evaluation.

Nitric oxide: a physiologic messenger.

PubMed

Lowenstein, C J; Dinerman, J L; Snyder, S H

1994-02-01

To review the physiologic role of nitric oxide, an unusual messenger molecule that mediates blood vessel relaxation, neurotransmission, and pathogen suppression. A MEDLINE search of articles published from 1987 to 1993 that addressed nitric oxide and the enzyme that synthesizes it, nitric oxide synthase. Animal and human studies were selected from 3044 articles to analyze the clinical importance of nitric oxide. Descriptions of the structure and function of nitric oxide synthase were selected to show how nitric oxide acts as a biological messenger molecule. Biochemical and physiologic studies were analyzed if the same results were found by three or more independent observers. Two major classes of nitric oxide synthase enzymes produce nitric oxide. The constitutive isoforms found in endothelial cells and neurons release small amounts of nitric oxide for brief periods to signal adjacent cells, whereas the inducible isoform found in macrophages releases large amounts of nitric oxide continuously to eliminate bacteria and parasites. By diffusing into adjacent cells and binding to enzymes that contain iron, nitric oxide plays many important physiologic roles. It regulates blood pressure, transmits signals between neurons, and suppresses pathogens. Excess amounts, however, can damage host cells, causing neurotoxicity during strokes and causing the hypotension associated with sepsis. Nitric oxide is a simple molecule with many physiologic roles in the cardiovascular, neurologic, and immune systems. Although the general principles of nitric oxide synthesis are known, further research is necessary to determine what role it plays in causing disease.

Role of the recombinant protein of the platelet receptor for type I collagen in the release of nitric oxide during platelet aggregation.

PubMed

Chiang, T M; Wang, Y B; Kang, E S

2000-12-01

Nitric oxide plays an important role in platelet function and platelets possess the endothelial isoform of nitric oxide synthase. Several reports have indicated that nitric oxide is released upon exposure of platelets to collagen. We have reported that a non-integrin platelet protein of 65 kDa is a receptor for type I collagen. By direct measurement of NO release from washed human platelets suspended in Tyrode buffer with a ISO-NO Mark II, World Precision Instruments, Sarasota, FL, USA, p30 sensor, type I collagen, but not ADP and epinephrine, induces the release of NO in a time-dependent manner. The production of NO is inhibited either by preincubation of type I collagen with the platelet type I collagen receptor recombinant protein or by preincubation of platelets with the antibody to the receptor protein, the anti-65 antibody. However, preincubation of platelets with anti-P-selectin and anti-glycoprotein IIb/IIIa did not affect the release of NO by platelets. These results suggest that the 65 kDa platelet receptor for type I collagen is specifically linked to the generation of NO, and that the 65 kDa platelet receptor for type I collagen plays an important new role in platelet function.

Synthesis of nitric oxide in human osteoblasts in response to physiologic stimulation of electrotherapy.

PubMed

Hamed, Ayman; Kim, Paul; Cho, Michael

2006-12-01

Electrotherapy for bone healing, remodeling and wound healing may be mediated by modulation of nitric oxide (NO). Using NO-specific fluorophore (DAF-2), we report here that application of non-invasive, physiologic electrical stimulation induces NO synthesis in human osteoblasts, and that such NO generation is comparable to that induced by estrogen treatment. For example, application of a sinusoidal 1 Hz, 2 V/cm (peak to peak) electrical stimulation (ES) increases NO-bound DAF-2 fluorescence intensity by a 2-fold within 60 min exposure by activating nitric oxide synthase (NOS). Increase in the NO level is found to depend critically on the frequency and strength of ES. While the frequency of 1 Hz ES seems optimal, the ES strength >0.5 V/cm is required to induce significant NO increase, however. Nitric oxide synthesis in response to ES is completely prevented by blocking estrogen receptors using a competitive inhibitor, suggesting that NO generation is likely initiated by activation of estrogen receptors at the cell surface. Based on these findings, physiologic stimulation of electrotherapy appears to represent a potential non-invasive, non-genomic, and novel physical technique that could be used to regulate NO-mediated bone density and facilitate bone remodeling without adverse effects associated with hormone therapy.

Enhanced nitric oxide production during lead (Pb²⁺) exposure recovers protein expression but not presynaptic localization of synaptic proteins in developing hippocampal neurons.

PubMed

Neal, April P; Stansfield, Kirstie H; Guilarte, Tomás R

2012-02-23

We have previously reported that lead (Pb(2+)) exposure results in both presynaptic and postsynaptic changes in developing neurons as a result of inhibition of the N-methyl-d-aspartate receptor (NMDAR). NMDAR inhibition by Pb(2+) during synaptogenesis disrupts downstream trans-synaptic signaling of brain-derived neurotrophic factor (BDNF) and exogenous addition of BDNF can recover the effects of Pb(2+) on both presynaptic protein expression and presynaptic vesicular release. NMDAR activity can modulate other trans-synaptic signaling pathways, such as nitric oxide (NO) signaling. Thus, it is possible that other trans-synaptic pathways in addition to BDNF signaling may be disrupted by Pb(2+) exposure. The current study investigated whether exogenous addition of NO could recover the presynaptic vesicular proteins lost as a result of Pb(2+) exposure during synaptogenesis, namely Synaptophysin (Syn) and Synaptobrevin (Syb). We observed that exogenous addition of NO during Pb(2+) exposure results in complete recovery of whole-cell Syn levels and partial recovery of Syn and Syb synaptic targeting in Pb(2+)-exposed neurons. Copyright © 2011 Elsevier B.V. All rights reserved.

Identification of inducible nitric oxide synthase in human macrophages surrounding loosened hip prostheses.

PubMed Central

Watkins, S. C.; Macaulay, W.; Turner, D.; Kang, R.; Rubash, H. E.; Evans, C. H.

1997-01-01

Exposure of rodent macrophages to certain cytokines and endotoxin results in the synthesis of inducible nitric oxide synthase (iNOS or NOS-II) leading to the production of large amounts of nitric oxide (NO). Cultures of human macrophages, in contrast, do not produce iNOS after cytokine stimulation, and their ability to act as a physiological source of NO remains questionable. Here we have used immunohistochemistry and in situ hybridization to demonstrate the presence of iNOS within human macrophages present in the interfacial membrane and pseudocapsule that surround failed prosthetic hip joints. Synovial tissue recovered from normal human joints did not express iNOS. Many of the iNOS-positive macrophages within the interfacial membrane had phagocytosed large amounts of polyethylene wear debris, suggesting a role for phagocytic stimuli in inducing iNOS in human macrophages. These findings additionally support a role for NO in modulating the localized bone resorption that accompanies the aseptic loosening of prosthetic joints. Images Figure 1 Figure 2 Figure 3 PMID:9094976

Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects

PubMed Central

Pall, Martin L

2013-01-01

The direct targets of extremely low and microwave frequency range electromagnetic fields (EMFs) in producing non-thermal effects have not been clearly established. However, studies in the literature, reviewed here, provide substantial support for such direct targets. Twenty-three studies have shown that voltage-gated calcium channels (VGCCs) produce these and other EMF effects, such that the L-type or other VGCC blockers block or greatly lower diverse EMF effects. Furthermore, the voltage-gated properties of these channels may provide biophysically plausible mechanisms for EMF biological effects. Downstream responses of such EMF exposures may be mediated through Ca2+/calmodulin stimulation of nitric oxide synthesis. Potentially, physiological/therapeutic responses may be largely as a result of nitric oxide-cGMP-protein kinase G pathway stimulation. A well-studied example of such an apparent therapeutic response, EMF stimulation of bone growth, appears to work along this pathway. However, pathophysiological responses to EMFs may be as a result of nitric oxide-peroxynitrite-oxidative stress pathway of action. A single such well-documented example, EMF induction of DNA single-strand breaks in cells, as measured by alkaline comet assays, is reviewed here. Such single-strand breaks are known to be produced through the action of this pathway. Data on the mechanism of EMF induction of such breaks are limited; what data are available support this proposed mechanism. Other Ca2+-mediated regulatory changes, independent of nitric oxide, may also have roles. This article reviews, then, a substantially supported set of targets, VGCCs, whose stimulation produces non-thermal EMF responses by humans/higher animals with downstream effects involving Ca2+/calmodulin-dependent nitric oxide increases, which may explain therapeutic and pathophysiological effects. PMID:23802593

Effect of a smoking ban on respiratory health in nonsmoking hospitality workers: a prospective cohort study.

PubMed

Rajkumar, Sarah; Stolz, Daiana; Hammer, Jürg; Moeller, Alexander; Bauer, Georg F; Huynh, Cong Khanh; Röösli, Martin

2014-10-01

The aim of this study was to examine the effect of a smoking ban on lung function, fractional exhaled nitric oxide, and respiratory symptoms in nonsmoking hospitality workers. Secondhand smoke exposure at the workplace, spirometry, and fractional exhaled nitric oxide were measured in 92 nonsmoking hospitality workers before as well as twice after a smoking ban. At baseline, secondhand smoke-exposed hospitality workers had lung function values significantly below the population average. After the smoking ban, the covariate-adjusted odds ratio for cough was 0.59 (95% confidence interval, 0.36 to 0.93) and for chronic bronchitis 0.75 (95% confidence interval, 0.55 to 1.02) compared with the preban period. The below-average lung function before the smoking ban indicates chronic damages from long-term exposure. Respiratory symptoms such as cough decreased within 12 months after the ban.

Interplay between high energy impulse noise (blast) and antioxidants in the lung.

PubMed

Elsayed, Nabil M; Gorbunov, Nikolai V

2003-07-15

High-energy impulse noise (BLAST) is a physical event characterized by an abrupt rise in atmospheric pressure above ambient lasting for a very short period, but potentially causing significant material and biological damage. Exposure to high-level BLAST can be destructive and lethal. Low-level BLAST similar to what is encountered repeatedly by military personnel during training and combat from detonation of munitions and firing of large caliber weapons, and during occupational use of explosives and some heavy machinery, can also cause significant injury. Globally, civilians are increasingly exposed to BLAST resulting from terrorist bombings or abandoned unmarked mines following numerous wars and conflicts. We have shown previously in several animal models that exposure to non-lethal BLAST results in pathological changes, mostly to the hollow organs characterized in the lungs, the most sensitive organ, by rupture of alveolar septa, and pulmonary hemorrhage and edema. These events potentially can cause alveolar flooding, respiratory insufficiency and adult respiratory distress syndrome (ARDS), leading to varying degrees of hypoxia, antioxidant depletion and oxidative damage. We have also observed progressive formation of nitric oxide in blood and other tissues. The totality of these observations supports our general hypothesis that exposure to BLAST can lead to antioxidant depletion and oxidative damage. Understanding the mechanism(s) of BLAST-induced oxidative stress may have important implications that include a potential beneficial role for antioxidants as a prophylaxis or as secondary treatment of injury after exposure alongside other protective and therapeutic modalities. In addition, it suggests a role for endogenous nitric oxide in the injury. This report reviews experimental evidence of BLAST-induced antioxidant depletion, and the potential benefit from antioxidant supplementation before exposure.

Expression and Activity of Nitric Oxide Synthase Isoforms in Methamphetamine-Induced Striatal Dopamine Toxicity

PubMed Central

Friend, Danielle M.; Son, Jong H.; Keefe, Kristen A.

2013-01-01

Nitric oxide is implicated in methamphetamine (METH)-induced neurotoxicity; however, the source of the nitric oxide has not been identified. Previous work has also revealed that animals with partial dopamine loss induced by a neurotoxic regimen of methamphetamine fail to exhibit further decreases in striatal dopamine when re-exposed to methamphetamine 7–30 days later. The current study examined nitric oxide synthase expression and activity and protein nitration in striata of animals administered saline or neurotoxic regimens of methamphetamine at postnatal days 60 and/or 90, resulting in four treatment groups: Saline:Saline, METH:Saline, Saline:METH, and METH:METH. Acute administration of methamphetamine on postnatal day 90 (Saline:METH and METH:METH) increased nitric oxide production, as evidenced by increased protein nitration. Methamphetamine did not, however, change the expression of endothelial or inducible isoforms of nitric oxide synthase, nor did it change the number of cells positive for neuronal nitric oxide synthase mRNA expression or the amount of neuronal nitric oxide synthase mRNA per cell. However, nitric oxide synthase activity in striatal interneurons was increased in the Saline:METH and METH:METH animals. These data suggest that increased nitric oxide production after a neurotoxic regimen of methamphetamine results from increased nitric oxide synthase activity, rather than an induction of mRNA, and that constitutively expressed neuronal nitric oxide synthase is the most likely source of nitric oxide after methamphetamine administration. Of interest, animals rendered resistant to further methamphetamine-induced dopamine depletions still show equivalent degrees of methamphetamine-induced nitric oxide production, suggesting that nitric oxide production alone in response to methamphetamine is not sufficient to induce acute neurotoxic injury. PMID:23230214

[Effect of inducible nitric oxide on intracellular homeostasis of hepatocytes].

PubMed

Tang, Xi-Feng; Zhou, Dong-Yao; Kang, Ge-Fei

2002-02-01

To investigate the effects of inducible nitric oxide (NO) and exogenous NO on the intracellular homeostasis of the hepatocytes. Endogenous NO was induced by combined action of lipopolysaccharide (LPS) and cytokines in cultured rat hepatocytes, and exogenous NO was supplied by sodium nitroprusside (SNP) to stimulate the hepatocytes. The changes in intracellular malondialdehyde (MDA), reduced glutathione(GSH) and free calcium ([Ca2+]i) were observed. substantial increase by 7.97 times in intracellular MDA level and a decrease by 57.9% in GSH occurred in the hepatocytes after the cells had been incubated with LPS and cytokines for 24 h, which were reversed by 43.5% and 98.4% respectively by treatment with N(G)-monomethyl-L-arginine (NMMA), a competitive nitric oxide synthase (NOS) inhibitor. Verapamil significantly reduced both endogenous NO production and oxidative stress, while the effect of A23187 was not conspicuous. Incubation with chlorpromazine and Vitamine E (VitE), however, did not result in decreased release of NO by LPS- and cytokines-induced hepatocytes. After SNP exposure of the hepatocytes, the oxidative status was reversibly enhanced in a time-dependent manner. Short exposure to SNP led to a concentration-dependent inhibition of the rapid and transient increase in free calcium induced by K(+) depolarization and hepatopoietin-coupled calcium mobilization. Inducible NO may initiate and play a key role in the latter stages of metabolic and functional stress responses of hepatocytes against endotoxin and cytokines, when the reduction occurs in the capacity of NO to independently mediate lipid peroxidation and counteract oxidation. The inhibitory effect of NO on [Ca2+]i mobilization may be an important autoregulatory mechanism by means of negative feedback on protein kinase C-associated NOS induction.

Unintended inhalation of nitric oxide by contamination of compressed air: physiologic effects and interference with intended nitric oxide inhalation in acute lung injury.

PubMed

Benzing, A; Loop, T; Mols, G; Geiger, K

1999-10-01

Compressed air from a hospital's central gas supply may contain nitric oxide as a result of air pollution. Inhaled nitric oxide may increase arterial oxygen tension and decrease pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. Therefore, the authors wanted to determine whether unintentional nitric oxide inhalation by contamination of compressed air influences arterial oxygen tension and pulmonary vascular resistance and interferes with the therapeutic use of nitric oxide. Nitric oxide concentrations in the compressed air of a university hospital were measured continuously by chemiluminescence during two periods (4 and 2 weeks). The effects of unintended nitric oxide inhalation on arterial oxygen tension (n = 15) and on pulmonary vascular resistance (n = 9) were measured in patients with acute lung injury and acute respiratory distress syndrome by changing the source of compressed air of the ventilator from the hospital's central gas supply to a nitric oxide-free gas tank containing compressed air. In five of these patients, the effects of an additional inhalation of 5 ppm nitric oxide were evaluated. During working days, compressed air of the hospital's central gas supply contained clinically effective nitric oxide concentrations (> 80 parts per billion) during 40% of the time. Change to gas tank-supplied nitric oxide-free compressed air decreased the arterial oxygen tension by 10% and increased pulmonary vascular resistance by 13%. The addition of 5 ppm nitric oxide had a minimal effect on arterial oxygen tension and pulmonary vascular resistance when added to hospital-supplied compressed air but improved both when added to tank-supplied compressed air. Unintended inhalation of nitric oxide increases arterial oxygen tension and decreases pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. The unintended nitric oxide inhalation interferes with the therapeutic use of nitric oxide.

Wavelength dependence of intracellular nitric oxide levels in hTERT-RPE cells in vitro

NASA Astrophysics Data System (ADS)

Pope, Nathaniel J.; Powell, Samantha M.; Wigle, Jeffrey C.

2018-02-01

Photobiomodulation (PBM) refers to the beneficial effects of low doses of light whether mediating therapeutic effects for pathophysiological processes, or stimulating resistance to physiological challenges. While much is known about beneficial outcomes, our understanding of the molecular mechanisms underlying these observed effects is still limited. It has been hypothesized that increases in ATP stimulate downstream signaling through transcription factors. However, it is also known that PBM can induce elevated levels of nitric oxide (NO) in cells, which is thought to occur by release of NO bound to cytochrome-c oxidase (COX). NO is a powerful signaling molecule involved in a host of biological responses; however, the mechanisms of NO production and the role of NO in the PBM response have received little attention. Utilizing human retinal pigmented epithelium cells (RPE) in vitro, coupled with a multi-laser exposure set-up, we have begun to systematically investigate the mechanism of NO production and function in the PBM response. Our data indicates that while NO levels are elevated following single exposures to 447, 532, 635 or 808 nm, the strength of the response is wavelength-dependent, and the response can be modulated by sequential exposures to two different wavelengths. Additionally, this wavelength-dependent rise in NO is independent of the function of nitric oxide synthase, and highly dependent on the source of electrons feeding the electron transport chain of the light-exposed cells. In sum, these results provide a roadmap for interrogating the molecular mechanisms of PBM, and provide novel tools and methods for dissecting NO signaling networks.

Nitric oxide ameliorates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

PubMed

Kaushik, Manish Singh; Srivastava, Meenakshi; Srivastava, Alka; Singh, Anumeha; Mishra, Arun Kumar

2016-11-01

In cyanobacterium Anabaena 7120, iron deficiency leads to oxidative stress with unavoidable consequences. Nitric oxide reduces pigment damage and supported the growth of Anabaena 7120 in iron-deficient conditions. Elevation in nitric oxide accumulation and reduced superoxide radical production justified the role of nitric oxide in alleviating oxidative stress in iron deficiency. Increased activities of antioxidative enzymes and higher levels of ROS scavengers (ascorbate, glutathione and thiol) in iron deficiency were also observed in the presence of nitric oxide. Nitric oxide also supported the membrane integrity of Anabaena cells and reduces protein and DNA damage caused by oxidative stress induced by iron deficiency. Results suggested that nitric oxide alleviates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

Analytical study of mechanisms for nitric oxide formation during combustion of methane in a jet-stirred combustor

NASA Technical Reports Server (NTRS)

Jachimowski, C. J.

1975-01-01

The role of chemical kinetics in the formation of nitric oxide during the combustion of methane was examined analytically by means of a detailed chemical mechanism for the oxidation of methane, for the reaction between hydrocarbon fragments, and for the formation of nitric oxide. By comparing predicted nitric oxide levels with values reported in the literature from jet-stirred combuster experiments, it was determined that the nitric oxide levels observed in fuel-rich flames cannot be described by a mechanism in which the rate of nitric oxide formation is controlled solely by the kinetics of oxygen atom formation. A proposed mechanism for the formation of nitric oxide in methane-rich flames reproduces the observed levels. The oxidation of hydrogen cyanide appears to be an important factor in nitric oxide formation.

Badger macrophages fail to produce nitric oxide, a key anti-mycobacterial effector molecule.

PubMed

Bilham, Kirstin; Boyd, Amy C; Preston, Stephen G; Buesching, Christina D; Newman, Chris; Macdonald, David W; Smith, Adrian L

2017-04-06

The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide. Exposure of bdMφ to TLR agonists and/or bdIFNγ resulted in upregulated cytokine (IL1β, IL6, IL12 and TNFα) mRNA levels indicating that these critical pathways were otherwise intact. Although stimulation with most TLR agonists resulted in strong cytokine mRNA responses, weaker responses were evident after exposure to TLR9 agonists, potentially due to very low expression of TLR9 in bdMφ. Both NO and TLR9 are important elements of innate immunity to mycobacteria, and these features of bdMφ biology would impair their capacity to resist bTB infection. These findings have significant implications for the development of bTB management strategies, and support the use of vaccination to reduce bTB infection in badgers.

Effects of 7-nitroindazole, a selective neural nitric oxide synthase inhibitor, on context-shock associative learning in a two-process contextual fear conditioning paradigm.

PubMed

Chen, Weihai; Yan, Minmin; Wang, Yan; Wang, Xiaqing; Yuan, Jiajin; Li, Ming

2016-10-01

Nitric oxide (NO) is an important retrograde neuronal intracellular messenger which plays an important role in synaptic plasticity and is involved in learning and memory. However, evidence that NO is particularly important for the acquisition of contextual fear conditioning is mixed. Also, little is known about at which stages of the contextual fear conditioning does NO make its contribution. In the present study, we used 7-nitroindazole to temporarily inhibit neural nitric oxide synthase at either the pre-exposure stage or conditioning stage in a two-process paradigm and examined the potential contribution that NO makes to the contextually conditioned fear. Results showed that the expression of contextual fear memory was significantly impaired in rats treated with 7-nitroindazole (30mg/kg, i.p.) prior to the pairing of context-shock (p=0.034, n=8), but not after the conditioning phase (p=0.846, n=8). In addition, the expression of contextual fear memory and reconsolidation was not significantly impaired by 7-nitroindazole administered prior to the context pre-exposure stage or prior to another context-shock learning. These findings suggest that NO is specifically involved in the acquisition but not the consolidation, retrieval or reconsolidation of contextual fear memory. Copyright © 2016 Elsevier Inc. All rights reserved.

L-citrulline immunostaining identifies nitric oxide production sites within neurons

NASA Technical Reports Server (NTRS)

Martinelli, G. P. T.; Friedrich, V. L. Jr; Holstein, G. R.

2002-01-01

The cellular and subcellular localization of L-citrulline was analyzed in the adult rat brain and compared with that of traditional markers for the presence of nitric oxide synthase. Light, transmission electron, and confocal laser scanning microscopy were used to study tissue sections processed for immunocytochemistry employing a monoclonal antibody against L-citrulline or polyclonal anti-neuronal nitric oxide synthase sera, and double immunofluorescence to detect neuronal nitric oxide synthase and L-citrulline co-localization. The results demonstrate that the same CNS regions and cell types are labeled by neuronal nitric oxide synthase polyclonal antisera and L-citrulline monoclonal antibodies, using both immunocytochemistry and immunofluorescence. Short-term pretreatment with a nitric oxide synthase inhibitor reduces L-citrulline immunostaining, but does not affect neuronal nitric oxide synthase immunoreactivity. In the vestibular brainstem, double immunofluorescence studies show that many, but not all, neuronal nitric oxide synthase-positive cells co-express L-citrulline, and that local intracellular patches of intense L-citrulline accumulation are present in some neurons. Conversely, all L-citrulline-labeled neurons co-express neuronal nitric oxide synthase. Cells expressing neuronal nitric oxide synthase alone are interpreted as neurons with the potential to produce nitric oxide under other stimulus conditions, and the subcellular foci of enhanced L-citrulline staining are viewed as intracellular sites of nitric oxide production. This interpretation is supported by ultrastructural observations of subcellular foci with enhanced L-citrulline and/or neuronal nitric oxide synthase staining that are located primarily at postsynaptic densities and portions of the endoplasmic reticulum. We conclude that nitric oxide is produced and released at focal sites within neurons that are identifiable using L-citrulline as a marker. Copyright 2002 IBRO.

Role of Nitric Oxide in MPTP-Induced Dopaminergic Neuron Degeneration

DTIC Science & Technology

2004-09-01

peroxynitrite exposure, that of dityrosine and nitrotyrosine by gas chromatography with mass spectrometry. 6 Quantification will be performed in...following MPTP administration by quantifying the two main products of peroxynitrite oxidation of tyrosine, dityrosine and nitrotyrosine using gas ...effectiveness as a neuroprotective agent was demonstrated against experimental brain ischaemia (21) and disease progression in the R6/2 mouse model of

21 CFR 868.5165 - Nitric oxide administration apparatus.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nitric oxide administration apparatus. 868.5165... apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to be...

21 CFR 868.5165 - Nitric oxide administration apparatus.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide administration apparatus. 868.5165... apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to be...

Exercise training increases basal tone in arterioles distal to chronic coronary occlusion

PubMed Central

Heaps, Cristine L.; Mattox, Mildred L.; Kelly, Katherine A.; Meininger, Cynthia J.; Parker, Janet L.

2014-01-01

Endurance exercise training increases basal active tone in coronary arteries and enhances myogenic tone in coronary arterioles of control animals. Paradoxically, exercise training has also been shown to augment nitric oxide production and nitric oxide-mediated relaxation in coronary arterioles. The purpose of the present study was to examine the effect of exercise training on basal active tone of arterioles (~150 µm ID) isolated from the collateral-dependent region of hearts exposed to chronic coronary occlusion. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of miniature swine. Arterioles were isolated from both the collateral-dependent and nonoccluded myocardial regions of sedentary (pen confined) and exercise-trained (treadmill run; 14 wk) pigs. Coronary tone was studied in isolated arterioles using microvessel myographs and standard isometric techniques. Exposure to nominally Ca2+-free external solution reduced resting tension in all arterioles; decreases were most profound (P < 0.05) in arterioles from the collateral-dependent region of exercise-trained animals. Furthermore, nitric oxide synthase (NOS) inhibition (Nω-nitro-l-arginine methylester; 100 µM) unmasked markedly increased nitric oxide-sensitive tone in arterioles from the collateral-dependent region of exercise-trained swine. Blockade of K+ channels revealed significantly enhanced K+ channel contribution to basal tone in collateral-dependent arterioles of exercise-trained pigs. Protein content of endothelial NOS (eNOS) and phosphorylated eNOS (pS1179), determined by immunoblot, was elevated in arterioles from exercise-trained animals with the greatest effect in collateral-dependent vasculature. Taken together, we demonstrate the interaction of opposing exercise training-enhanced arteriolar basal active tone, nitric oxide production, and K+ channel activity in chronic coronary occlusion, potentially enhancing the capacity to regulate blood flow to collateral-dependent myocardium. PMID:16243909

The role of nitric oxide radicals in removal of hyper-radiosensitivity by priming irradiation

PubMed Central

Edin, Nina Jeppesen; Sandvik, Joe Alexander; Vollan, Hilde Synnøve; Reger, Katharina; Görlach, Agnes; Pettersen, Erik Olai

2013-01-01

In this study, a mechanism in which low-dose hyper-radiosensitivity (HRS) is permanently removed, induced by low-dose-rate (LDR) (0.2–0.3 Gy/h for 1 h) but not by high-dose-rate priming (0.3 Gy at 40 Gy/h) was investigated. One HRS-negative cell line (NHIK 3025) and two HRS-positive cell lines (T-47D, T98G) were used. The effects of different pretreatments on HRS were investigated using the colony assay. Cell-based ELISA was used to measure nitric oxide synthase (NOS) levels, and microarray analysis to compare gene expression in primed and unprimed cells. The data show how permanent removal of HRS, previously found to be induced by LDR priming irradiation, can also be induced by addition of nitric oxide (NO)-donor DEANO combined with either high-dose-rate priming or exposure to prolonged cycling hypoxia followed by reoxygenation, a treatment not involving radiation. The removal of HRS appears not to involve DNA damage induced during priming irradiation as it was also induced by LDR irradiation of cell-conditioned medium without cells present. The permanent removal of HRS in LDR-primed cells was reversed by treatment with inducible nitric oxide synthase (iNOS) inhibitor 1400W. Furthermore, 1400W could also induce HRS in an HRS-negative cell line. The data suggest that LDR irradiation for 1 h, but not 15 min, activates iNOS, and also that sustained iNOS activation is necessary for the permanent removal of HRS by LDR priming. The data indicate that nitric oxide production is involved in the regulatory processes determining cellular responses to low-dose-rate irradiation. PMID:23685670

Production of nitric oxide using a microwave plasma torch and its application to fungal cell differentiation

NASA Astrophysics Data System (ADS)

Na, Young Ho; Kumar, Naresh; Kang, Min-Ho; Cho, Guang Sup; Choi, Eun Ha; Park, Gyungsoon; Uhm, Han Sup

2015-03-01

The generation of nitric oxide by a microwave plasma torch is proposed for its application to cell differentiation. A microwave plasma torch was developed based on basic kinetic theory. The analytical theory indicates that nitric oxide density is nearly proportional to oxygen molecular density and that the high-temperature flame is an effective means of generating nitric oxide. Experimental data pertaining to nitric oxide production are presented in terms of the oxygen input in units of cubic centimeters per minute. The apparent length of the torch flame increases as the oxygen input increases. The various levels of nitric oxide are observed depending on the flow rate of nitrogen gas, the mole fraction of oxygen gas, and the microwave power. In order to evaluate the potential of nitric oxide as an activator of cell differentiation, we applied nitric oxide generated from the microwave plasma torch to a model microbial cell (Neurospora crassa: non-pathogenic fungus). Germination and hyphal differentiation of fungal cells were not dramatically changed but there was a significant increase in spore formation after treatment with nitric oxide. In addition, the expression level of a sporulation related gene acon-3 was significantly elevated after 24 h upon nitric oxide treatment. Increase in the level of nitric oxide, nitrite and nitrate in water after nitric oxide treatment seems to be responsible for activation of fungal sporulation. Our results suggest that nitric oxide generated by plasma can be used as a possible activator of cell differentiation and development.

Expression of endothelin-1 and constitutional nitric oxide synthase messenger RNA in saphenous vein endothelial cells exposed to arterial flow shear stress.

PubMed

Zhu, Z G; Li, H H; Zhang, B R

1997-11-01

It has long been speculated that increased blood flow shear stress might be one of the major factors affecting the patency of grafted saphenous vein in coronary artery bypass operations. The underlying cellular and molecular mechanisms for so-called "shear stress damage" have not yet been well elucidated. Endothelial cells harvested from human saphenous vein were cultured in vitro and then exposed to a high arterial level flow shear stress in the parallel flow chamber. The expression levels of endothelin-1 and constitutional nitric oxide synthase by the endothelial cells were evaluated semiquantitatively at the gene transcription (messenger RNA) level using reverse transcription polymerase chain reaction. After 7 hours of exposure to arterial level shear stress, the expression of constitutional nitric oxide synthase messenger RNA by saphenous vein endothelial cells was significantly reduced, whereas the expression of endothelin-1 messenger RNA was substantially increased. These changes were more predominant at 24 hours. Arterial level flow shear stress could cause important changes in the gene transcription level in saphenous vein endothelial cells within a short period of time. The functional alterations of saphenous vein endothelial cells, as manifested by the increased expression of endothelin-1 and decreased expression of nitric oxide synthase messenger RNA, might play a crucial role in the vein graft remodeling process.

Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide

NASA Technical Reports Server (NTRS)

Nyhan, Daniel; Kim, Soonyul; Dunbar, Stacey; Li, Dechun; Shoukas, Artin; Berkowitz, Dan E.

2002-01-01

Vascular contractile hyporesponsiveness is an important mechanism underlying orthostatic intolerance after microgravity. Baroreceptor reflexes can modulate both pulmonary resistance and capacitance function and thus cardiac output. We hypothesized, therefore, that pulmonary vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model of microgravity. Pulmonary artery (PA) contractile responses to phenylephrine (PE) and U-46619 (U4) were significantly decreased in the PAs from HLU vs. control (C) animals. N(G)-nitro-L-arginine methyl ester (10(-5) M) enhanced the contractile responses in the PA rings from both C and HLU animals and completely abolished the differential responses to PE and U4 in HLU vs. C animals. Vasorelaxant responses to ACh were significantly enhanced in PA rings from HLU rats compared with C. Moreover, vasorelaxant responses to sodium nitroprusside were also significantly enhanced. Endothelial nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression were significantly enhanced in PA and lung tissue from HLU rats. In marked contrast, the expression of inducible nitric oxide synthase was unchanged in lung tissue. These data support the hypothesis that vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.

Dose- and time-dependent activation of rat alveolar macrophages by glucocorticoids

PubMed Central

BROUG-HOLUB, E; KRAAL, G

1996-01-01

Effects of glucocorticoids on immune functions are generally thought to be suppressive and anti-inflammatory. However, most reports dealing with this issue describe effects of long-term treatment with high doses of glucocorticoids on immune functions. In the present study we have investigated both dose and timing effects of exposure of alveolar macrophages with dexamethasone on lipopolysaccharide (LPS)-induced IL-1β and nitric oxide secretion. For this purpose, alveolar macrophages were preincubated with various doses of dexamethasone during varying intervals, followed by stimulation of the cells with endotoxin, either in the absence or presence of dexamethasone. Subsequently, the effects of this treatment on IL-1β and nitric oxide secretion were measured. It was shown that both short-term incubation of alveolar macrophages with high doses of dexamethasone and long-term incubation with low doses of dexamethasone lead to enhanced nitric oxide and enhanced IL-1β secretion upon subsequent stimulation of the cells with LPS. In contrast, long-term incubation of alveolar macrophages with high-dose dexamethasone leads to decreased IL-1β and nitric oxide secretion upon subsequent stimulation. Thus, it is concluded that the effects of dexamethasone on rat alveolar macrophages are both time- and dose-dependent. It is therefore argued that effects of glucocorticoids on immune functions are not a priori suppressive, but that both dose and timing effects should be taken into account. PMID:8625529

Nitric oxide regulation of calcitonin gene-related peptide gene expression in rat trigeminal ganglia neurons

PubMed Central

Bellamy, Jamie; Bowen, Elizabeth J.; Russo, Andrew F.; Durham, Paul L.

2006-01-01

Calcitonin gene-related peptide (CGRP) and nitric oxide are involved in the underlying pathophysiology of migraine and other diseases involving neurogenic inflammation. We have tested the hypothesis that nitric oxide might trigger signaling mechanisms within the trigeminal ganglia neurons that would coordinately stimulate CGRP synthesis and release. Treatment of primary trigeminal ganglia cultures with nitric oxide donors caused a greater than four-fold increase in CGRP release compared with unstimulated cultures. Similarly, CGRP promoter activity was also stimulated by nitric oxide donors and overexpression of inducible nitric oxide synthase (iNOS). Cotreatment with the antimigraine drug sumatriptan greatly repressed nitric oxide stimulation of CGRP promoter activity and secretion. Somewhat surprisingly, the mechanisms of nitric oxide stimulation of CGRP secretion did not require cGMP or PI3-kinase signaling pathways, but rather, nitric oxide action required extracellular calcium and likely involves T-type calcium channels. Furthermore, nitric oxide was shown to increase expression of the active forms of the mitogen-activated protein kinases Jun amino-terminal kinase and p38 but not extracellular signal-related kinase in trigeminal neurons. In summary, our results provide new insight into the cellular mechanisms by which nitric oxide induces CGRP synthesis and secretion from trigeminal neurons. PMID:16630053

Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

NASA Technical Reports Server (NTRS)

Reid, Ian A.

1994-01-01

Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric oxide donors in vitro and in vivo has variable effects on vasopressin secretion, but the most common one is inhibition. Blockade of nitric oxide synthesis has been reported to increase vasopressin secretion, but again variable results have been obtained. An attractive working hypothesis is that nitric oxide serves a neuromodulatory role as an inhibitor of vasopressin secretion.

Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism

PubMed Central

San Martín, Alejandro; Arce-Molina, Robinson; Galaz, Alex; Pérez-Guerra, Gustavo; Barros, L. Felipe

2017-01-01

Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic effects at physiological concentrations are incompletely characterized. To this end, we set out to investigate the metabolic effects of NO in cultured astrocytes from mice by taking advantage of the high spatiotemporal resolution afforded by genetically encoded Förster resonance energy transfer (FRET) nanosensors. NO exposure resulted in immediate and reversible intracellular glucose depletion and lactate accumulation. Consistent with cytochrome oxidase involvement, the glycolytic effect was enhanced at a low oxygen level and became irreversible at a high NO concentration or after prolonged exposure. Measurements of both glycolytic rate and mitochondrial pyruvate consumption revealed significant effects even at nanomolar NO concentrations. We conclude that NO can modulate astrocytic energy metabolism in the short term, reversibly, and at concentrations known to be released by endothelial cells under physiological conditions. These findings suggest that NO modulates the size of the astrocytic lactate reservoir involved in neuronal fueling and signaling. PMID:28341740

Nitrite therapy improves survival postexposure to chlorine gas

PubMed Central

Honavar, Jaideep; Doran, Stephen; Oh, Joo-Yeun; Steele, Chad; Matalon, Sadis

2014-01-01

Exposure to relatively high levels of chlorine (Cl2) gas can occur in mass-casualty scenarios associated with accidental or intentional release. Recent studies have shown a significant postexposure injury phase to the airways, pulmonary, and systemic vasculatures mediated in part by oxidative stress, inflammation, and dysfunction in endogenous nitric oxide homeostasis pathways. However, there is a need for therapeutics that are amenable to rapid and easy administration in the field and that display efficacy toward toxicity after chlorine exposure. In this study, we tested whether nitric oxide repletion using nitrite, by intramuscular injection after Cl2 exposure, could prevent Cl2 gas toxicity. C57bl/6 male mice were exposed to 600 parts per million Cl2 gas for 45 min, and 24-h survival was determined with or without postexposure intramuscular nitrite injection. A single injection of nitrite (10 mg/kg) administered either 30 or 60 min postexposure significantly improved 24-h survival (from ∼20% to 50%). Survival was associated with decreased neutrophil accumulation in the airways. Rendering mice neutropenic before Cl2 exposure improved survival and resulted in loss of nitrite-dependent survival protection. Interestingly, female mice were more sensitive to Cl2-induced toxicity compared with males and were also less responsive to postexposure nitrite therapy. These data provide evidence for efficacy and define therapeutic parameters for a single intramuscular injection of nitrite as a therapeutic after Cl2 gas exposure that is amenable to administration in mass-casualty scenarios. PMID:25326579

Nitrite therapy improves survival postexposure to chlorine gas.

PubMed

Honavar, Jaideep; Doran, Stephen; Oh, Joo-Yeun; Steele, Chad; Matalon, Sadis; Patel, Rakesh P

2014-12-01

Exposure to relatively high levels of chlorine (Cl₂) gas can occur in mass-casualty scenarios associated with accidental or intentional release. Recent studies have shown a significant postexposure injury phase to the airways, pulmonary, and systemic vasculatures mediated in part by oxidative stress, inflammation, and dysfunction in endogenous nitric oxide homeostasis pathways. However, there is a need for therapeutics that are amenable to rapid and easy administration in the field and that display efficacy toward toxicity after chlorine exposure. In this study, we tested whether nitric oxide repletion using nitrite, by intramuscular injection after Cl₂ exposure, could prevent Cl₂ gas toxicity. C57bl/6 male mice were exposed to 600 parts per million Cl₂ gas for 45 min, and 24-h survival was determined with or without postexposure intramuscular nitrite injection. A single injection of nitrite (10 mg/kg) administered either 30 or 60 min postexposure significantly improved 24-h survival (from ∼20% to 50%). Survival was associated with decreased neutrophil accumulation in the airways. Rendering mice neutropenic before Cl₂ exposure improved survival and resulted in loss of nitrite-dependent survival protection. Interestingly, female mice were more sensitive to Cl₂-induced toxicity compared with males and were also less responsive to postexposure nitrite therapy. These data provide evidence for efficacy and define therapeutic parameters for a single intramuscular injection of nitrite as a therapeutic after Cl₂ gas exposure that is amenable to administration in mass-casualty scenarios. Copyright © 2014 the American Physiological Society.

Therapeutic strategies to address neuronal nitric oxide synthase deficiency and the loss of nitric oxide bioavailability in Duchenne Muscular Dystrophy.

PubMed

Timpani, Cara A; Hayes, Alan; Rybalka, Emma

2017-05-25

Duchenne Muscular Dystrophy is a rare and fatal neuromuscular disease in which the absence of dystrophin from the muscle membrane induces a secondary loss of neuronal nitric oxide synthase and the muscles capacity for endogenous nitric oxide synthesis. Since nitric oxide is a potent regulator of skeletal muscle metabolism, mass, function and regeneration, the loss of nitric oxide bioavailability is likely a key contributor to the chronic pathological wasting evident in Duchenne Muscular Dystrophy. As such, various therapeutic interventions to re-establish either the neuronal nitric oxide synthase protein deficit or the consequential loss of nitric oxide synthesis and bioavailability have been investigated in both animal models of Duchenne Muscular Dystrophy and in human clinical trials. Notably, the efficacy of these interventions are varied and not always translatable from animal model to human patients, highlighting a complex interplay of factors which determine the downstream modulatory effects of nitric oxide. We review these studies herein.

Nitric oxide alleviates aluminum-induced oxidative damage through regulating the ascorbate-glutathione cycle in roots of wheat.

PubMed

Sun, Chengliang; Liu, Lijuan; Yu, Yan; Liu, Wenjing; Lu, Lingli; Jin, Chongwei; Lin, Xianyong

2015-06-01

The possible association with nitric oxide (NO) and ascorbate-glutathione (AsA-GSH) cycle in regulating aluminum (Al) tolerance of wheat (Triticum aestivum L.) was investigated using two genotypes with different Al resistance. Exposure to Al inhibited root elongation, and triggered lipid peroxidation and oxidation of AsA to dehydroascorbate and GSH to glutathione disulfide in wheat roots. Exogenous NO significantly increased endogenous NO levels, and subsequently alleviated Al-induced inhibition of root elongation and oxidation of AsA and GSH to maintain the redox molecules in the reduced form in both wheat genotypes. Under Al stress, significantly increased activities and gene transcriptional levels of ascorbate peroxidase, glutathione reductase, and dehydroascorbate reductase, were observed in the root tips of the Al-tolerant genotype Jian-864. Nitric oxide application enhanced the activity and gene transcriptional level of these enzymes in both wheat genotypes. γ-Glutamylcysteine synthetase was not significantly affected by Al or NO, but NO treatments increased the activity of glutathione peroxidase and glutathione S-transferase to a greater extent than the Al-treated wheat seedlings. Proline was significantly decreased by Al, while it was not affected by NO. These results clearly suggest that NO protects wheat root against Al-induced oxidative stress, possibly through its regulation of the AsA-GSH cycle. © 2014 Institute of Botany, Chinese Academy of Sciences.

Study of the nitric oxide system in the rat cerebellum during aging.

PubMed

Blanco, Santos; Molina, Francisco J; Castro, Lourdes; Del Moral, Maria L; Hernandez, Raquel; Jimenez, Ana; Rus, Alma; Martinez-Lara, Esther; Siles, Eva; Peinado, Maria A

2010-06-24

The cerebellum is the neural structure with the highest levels of nitric oxide, a neurotransmitter that has been proposed to play a key role in the brain aging, although knowledge concerning its contribution to cerebellar senescence is still unclear, due mainly to absence of integrative studies that jointly evaluate the main factors involved in its cell production and function. Consequently, in the present study, we investigate the expression, location, and activity of nitric oxide synthase isoenzymes; the protein nitration; and the production of nitric oxide in the cerebellum of adult and old rats. Our results show no variation in the expression of nitric oxide synthase isoforms with aging, although, we have detected some changes in the cellular distribution pattern of the inducible isoform particularly in the cerebellar nuclei. There is also an increase in nitric oxide synthase activity, as well as greater protein-nitration levels, and maintenance of nitrogen oxides (NOx) levels in the senescent cerebellum. The nitric oxide/nitric oxide synthases system suffers from a number of changes, mainly in the inducible nitric oxide synthase distribution and in overall nitric oxide synthases activity in the senescent cerebellum, which result in an increase of the protein nitration. These changes might be related to the oxidative damage detected with aging in the cerebellum.

A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat. Prognostic value of malondialdehyde, N-acetyl-beta-D-glucosaminidase and nitric oxide determination.

PubMed

Ozguner, Fehmi; Oktem, Faruk; Ayata, Ali; Koyu, Ahmet; Yilmaz, H Ramazan

2005-09-01

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It has been used in folk medicine for many years in Middle East countries. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine long-term applied 900 MHz emitting mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and, was to investigate the role of CAPE on kidney tissue against the possible electromagnetic radiation (EMR)-induced renal impairment in rats. In particular, the ROS such as superoxide and nitric oxide (NO) may contribute to the pathophysiology of EMR-induced renal impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels, urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury) and nitric oxide (NO, an oxidant product) levels were used as markers of oxidative stress-induced renal impairment and the success of CAPE treatment. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissue were determined to evaluate the changes of antioxidant status. The rats used in the study were randomly grouped (10 each) as follows: i) Control group (without stress and EMR), ii) Sham-operated rats stayed without exposure to EMR (exposure device off), iii) Rats exposed to 900 MHz EMR (EMR group), and iv) A 900 MHz EMR exposed + CAPE treated group (EMR + CAPE group). In the EMR exposed group, while tissue MDA, NO levels and urinary NAG levels increased (p < 0.0001), the activities of SOD, CAT, and GSH-Px in renal tissue were reduced (p < 0.001). CAPE treatment reversed these effects as well (p < 0.0001, p < 0.001 respectively). In conclusion, the increase in NO and MDA levels of renal tissue, and in urinary NAG with the decrease in renal SOD, CAT, GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced renal tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative renal damage. These results strongly suggest that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative renal impairment in rats.

Stabilization of superoxide dismutase by acetyl-l-carnitine in human brain endothelium during alcohol exposure: novel protective approach.

PubMed

Haorah, James; Floreani, Nicholas A; Knipe, Bryan; Persidsky, Yuri

2011-10-15

Oxidative damage of the endothelium disrupts the integrity of the blood-brain barrier (BBB). We have shown before that alcohol exposure increases the levels of reactive oxygen species (ROS; superoxide and hydroxyl radical) and nitric oxide (NO) in brain endothelial cells by activating NADPH oxidase and inducible nitric oxide synthase. We hypothesize that impairment of antioxidant systems, such as a reduction in catalase and superoxide dismutase (SOD) activity, by ethanol exposure may elevate the levels of ROS/NO in endothelium, resulting in BBB damage. This study examines whether stabilization of antioxidant enzyme activity results in suppression of ROS levels by anti-inflammatory agents. To address this idea, we determined the effects of ethanol on the kinetic profile of SOD and catalase activity and ROS/NO generation in primary human brain endothelial cells (hBECs). We observed an enhanced production of ROS and NO levels due to the metabolism of ethanol in hBECs. Similar increases were found after exposure of hBECs to acetaldehyde, the major metabolite of ethanol. Ethanol simultaneously augmented ROS generation and the activity of antioxidative enzymes. SOD activity was increased for a much longer period of time than catalase activity. A decline in SOD activity and protein levels preceded elevation of oxidant levels. SOD stabilization by the antioxidant and mitochondria-protecting agent acetyl-L-carnitine (ALC) and the anti-inflammatory agent rosiglitazone suppressed ROS levels, with a marginal increase in NO levels. Mitochondrial membrane protein damage and decreased membrane potential after ethanol exposure indicated mitochondrial injury. These changes were prevented by ALC. Our findings suggest the counteracting mechanisms of oxidants and antioxidants during alcohol-induced oxidative stress at the BBB. The presence of enzymatic stabilizers favors the ROS-neutralizing antioxidant redox of the BBB, suggesting an underlying protective mechanism of NO for brain vascular tone and vasodilation. Published by Elsevier Inc.

Consequences of MnSOD interactions with nitric oxide: nitric oxide dismutation and the generation of peroxynitrite and hydrogen peroxide.

PubMed

Filipović, Milos R; Stanić, Dragana; Raicević, Smiljana; Spasić, Mihajlo; Niketić, Vesna

2007-01-01

The present study demonstrates that manganese superoxide dismutase (MnSOD) (Escherichia coli), binds nitric oxide (*NO) and stimulates its decay under both anaerobic and aerobic conditions. The results indicate that previously observed MnSOD-catalyzed *NO disproportionation (dismutation) into nitrosonium (NO+) and nitroxyl (NO-) species under anaerobic conditions is also operative in the presence of molecular oxygen. Upon sustained aerobic exposure to *NO, MnSOD-derived NO- species initiate the formation of peroxynitrite (ONOO-) leading to enzyme tyrosine nitration, oxidation and (partial) inactivation. The results suggest that both ONOO- decomposition and ONOO(-)-dependent tyrosine residue nitration and oxidation are enhanced by metal centre-mediated catalysis. We show that the generation of ONOO- is accompanied by the formation of substantial amounts of H2O2. MnSOD is a critical mitochondrial antioxidant enzyme, which has been found to undergo tyrosine nitration and inactivation in various pathologies associated with the overproduction of *NO. The results of the present study can account for the molecular specificity of MnSOD nitration in vivo. The interaction of *NO with MnSOD may represent a novel mechanism by which MnSOD protects the cell from deleterious effects associated with overproduction of *NO.

Chemical Excitation of Electrons: A Dark Path to Melanoma

PubMed Central

Premi, Sanjay; Brash, Douglas E.

2016-01-01

Sunlight’s ultraviolet wavelengths induce cyclobutane pyrimidine dimers (CPDs), which then cause mutations that lead to melanoma or to cancers of skin keratinocytes. In pigmented melanocytes, we found that CPDs arise both instantaneously and for hours after UV exposure ends. Remarkably, the CPDs arising in the dark originate by a novel pathway that resembles bioluminescence but does not end in light: First, UV activates the enzymes nitric oxide synthase (NOS) and NADPH oxidase (NOX), which generate the radicals nitric oxide (NO•) and superoxide (O2•−); these combine to form the powerful oxidant peroxynitrite (ONOO−). A fragment of the skin pigment melanin is then oxidized, exciting an electron to an energy level so high that it is rarely seen in biology. This process of chemically exciting electrons, termed “chemiexcitation”, is used by fireflies to generate light but it had never been seen in mammalian cells. In melanocytes, the energy transfers radiationlessly to DNA, inducing CPDs. Chemiexcitation is a new source of genome instability, and it calls attention to endogenous mechanisms of genome maintenance that prevent electronic excitation or dissipate the energy of excited states. Chemiexcitation may also trigger pathogenesis in internal tissues because the same chemistry should arise wherever superoxide and nitric oxide arise near cells that contain melanin. PMID:27262612

Chemical excitation of electrons: A dark path to melanoma.

PubMed

Premi, Sanjay; Brash, Douglas E

2016-08-01

Sunlight's ultraviolet wavelengths induce cyclobutane pyrimidine dimers (CPDs), which then cause mutations that lead to melanoma or to cancers of skin keratinocytes. In pigmented melanocytes, we found that CPDs arise both instantaneously and for hours after UV exposure ends. Remarkably, the CPDs arising in the dark originate by a novel pathway that resembles bioluminescence but does not end in light: First, UV activates the enzymes nitric oxide synthase (NOS) and NADPH oxidase (NOX), which generate the radicals nitric oxide (NO) and superoxide (O2(-)); these combine to form the powerful oxidant peroxynitrite (ONOO(-)). A fragment of the skin pigment melanin is then oxidized, exciting an electron to an energy level so high that it is rarely seen in biology. This process of chemically exciting electrons, termed "chemiexcitation", is used by fireflies to generate light but it had never been seen in mammalian cells. In melanocytes, the energy transfers radiationlessly to DNA, inducing CPDs. Chemiexcitation is a new source of genome instability, and it calls attention to endogenous mechanisms of genome maintenance that prevent electronic excitation or dissipate the energy of excited states. Chemiexcitation may also trigger pathogenesis in internal tissues because the same chemistry should arise wherever superoxide and nitric oxide arise near cells that contain melanin. Copyright © 2016 Elsevier B.V. All rights reserved.

Cu(1+) in HKUST-1: selective gas adsorption in the presence of water.

PubMed

Nijem, Nour; Bluhm, Hendrik; Ng, May L; Kunz, Martin; Leone, Stephen R; Gilles, Mary K

2014-09-11

Spectroscopic evidence for an enhanced binding of Nitric Oxide (NO) to metal centers with lower oxidation states (open Cu(1+) sites) in Cu3(btc)2 (HKUST-1) is presented. The Cu(1+) sites created by thermal treatment or X-ray exposure exhibit a preferential adsorption of NO compared to H2O. This phenomenon demonstrates the potential use of MOFs with lower oxidation state metal centers for selective gas separation.

Role of Nitric Oxide in MPTP-Induced Dopaminergic Neuron Degeneration

DTIC Science & Technology

2006-06-01

peroxynitrite exposure, that of dityrosine and nitrotyrosine by gas chromatography with mass spectrometry. 6 Quantification will be performed in different...MPTP administration by quantifying the two main products of peroxynitrite oxidation of tyrosine, dityrosine and nitrotyrosine using gas ...as a neuroprotective agent was demonstrated against experimental brain ischaemia (21) and disease progression in the R6/2 mouse model of Huntington’s

Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

NASA Astrophysics Data System (ADS)

Halasa, Salaheldin; Dickinson, Eva

2014-02-01

From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

Combined atmospheric oxidant capacity and increased levels of exhaled nitric oxide

NASA Astrophysics Data System (ADS)

Yang, Changyuan; Li, Huichu; Chen, Renjie; Xu, Wenxi; Wang, Cuicui; Tse, Lap Ah; Zhao, Zhuohui; Kan, Haidong

2016-07-01

Nitrogen dioxide and ozone are two interrelated oxidative pollutants in the atmosphere. Few studies have evaluated the health effects of combined oxidant capacity (O x ). We investigated the short-term effects of O x on fractional exhaled nitric oxide (FeNO), a well-established biomarker for airway inflammation, in a group of chronic obstructive pulmonary disease patients. Real-time concentrations of O x were obtained by calculating directly the sum of nitrogen dioxide and ozone. Linear mixed-effect models were applied to explore the acute effects of O x on FeNO levels. Short-term exposure to Ox was significantly associated with elevated FeNO. This effect was strongest in the first 24 h after exposure, and was robust to the adjustment of PM2.5. A 10 μg m-3 increase in 24 h average concentrations of O x was associated with 4.28% (95% confidence interval: 1.19%, 7.37%) increase in FeNO. The effect estimates were statistically significant only among males, elders, and those with body mass index ≥24 kg m-2, a comorbidity, higher educational attainment, or moderate airflow limitation. This analysis demonstrated an independent effect of O x on respiratory inflammation, and suggested that a single metric O x might serve as a preferable indicator of atmospheric oxidative capacity in further air pollution epidemiological studies.

Cd²⁺-induced alteration of the global proteome of human skin fibroblast cells.

PubMed

Prins, John M; Fu, Lijuan; Guo, Lei; Wang, Yinsheng

2014-03-07

Cadmium (Cd(2+)) is a toxic heavy metal and a well-known human carcinogen. The toxic effects of Cd(2+) on biological systems are diverse and thought to be exerted through a complex array of mechanisms. Despite the large number of studies aimed to elucidate the toxic mechanisms of action of Cd(2+), few have been targeted toward investigating the ability of Cd(2+) to disrupt multiple cellular pathways simultaneously and the overall cellular responses toward Cd(2+) exposure. In this study, we employed a quantitative proteomic method, relying on stable isotope labeling by amino acids in cell culture (SILAC) and LC-MS/MS, to assess the Cd(2+)-induced simultaneous alterations of multiple cellular pathways in cultured human skin fibroblast cells. By using this approach, we were able to quantify 2931 proteins, and 400 of them displayed significantly changed expression following Cd(2+) exposure. Our results unveiled that Cd(2+) treatment led to the marked upregulation of several antioxidant enzymes (e.g., metallothionein-1G, superoxide dismutase, pyridoxal kinase, etc.), enzymes associated with glutathione biosynthesis and homeostasis (e.g., glutathione S-transferases, glutathione synthetase, glutathione peroxidase, etc.), and proteins involved in cellular energy metabolism (e.g., glycolysis, pentose phosphate pathway, and the citric acid cycle). Additionally, we found that Cd(2+) treatment resulted in the elevated expression of two isoforms of dimethylarginine dimethylaminohydrolase (DDAH I and II), enzymes known to play a key role in regulating nitric oxide biosynthesis. Consistent with these findings, we observed elevated formation of nitric oxide in human skin (GM00637) and lung (IMR-90) fibroblast cells following Cd(2+) exposure. The upregulation of DDAH I and II suggests a role of nitric oxide synthesis in Cd(2+)-induced toxicity in human cells.

Association of recent exposure to ambient metals on fractional exhaled nitric oxide in 9-11 year old inner-city children.

PubMed

Rosa, Maria José; Perzanowski, Matthew S; Divjan, Adnan; Chillrud, Steven N; Hoepner, Lori; Zhang, Hanjie; Ridder, Robert; Perera, Frederica P; Miller, Rachel L

2014-08-31

Exposure to ambient metals in urban environments has been associated with wheeze, and emergency room visits and hospitalizations due to respiratory illness. However, the effect of ambient metals exposure on airway inflammation, and how these associations may be modified by seroatopy, has not been determined. Fractional exhaled nitric oxide (FENO) is a reliable proxy marker of airway inflammation. We hypothesized that recent ambient concentrations of Ni, V, Zn and Fe would be associated differentially with proximal and distal fractions of exhaled NO, and that these associations would be modified by seroatopy. As part of the Columbia Center for Children's Environmental Health (CCCEH) birth cohort study, 9-11 year old children (n=192) were evaluated. Ambient measures of Ni, V, Zn and Fe were obtained from a local central monitoring site and averaged over 9 days based on three 24h measures every third day. Fractional exhaled nitric oxide (FENO) samples were obtained at constant flows of 50 (FENO50), 83 and 100mL/s, and used to determine surrogate measures for proximal (JNO) and alveolar (Calv) inflammation. Seroatopy was determined by specific IgE at age 7. Data were analyzed using multivariable linear regression. Ambient V and Fe concentrations were associated positively with FENO50 (p=0.018, p=0.027). Ambient Fe was associated positively with JNO (p=0.017). Ambient Ni and V concentrations were associated positively with Calv (p=0.004, p=0.018, respectively). A stronger association of Ni concentrations with Calv was observed among the children with seroatopy. These results suggest that ambient metals are associated differentially with different fractions of FENO production, and this relationship may be modified by seroatopy. Copyright © 2014 Elsevier Inc. All rights reserved.

Proteomic analysis of human bladder epithelial cells by 2D blue native SDS-PAGE reveals TCDD-induced alterations of calcium and iron homeostasis possibly mediated by nitric oxide.

PubMed

Verma, Nisha; Pink, Mario; Petrat, Frank; Rettenmeier, Albert W; Schmitz-Spanke, Simone

2015-01-02

A proteomic analysis of the interaction among multiprotein complexes involved in 2,3,7,8-dibenzo-p-dioxin (TCDD)-mediated toxicity in urinary bladder epithelial RT4 cells was performed using two-dimensional blue native SDS-PAGE (2D BN/SDS-PAGE). To enrich the protein complexes, unexposed and TCDD-exposed cells were fractionated. BN/SDS-PAGE of the resulting fractions led to an effective separation of proteins and protein complexes of various origins, including cell membrane, mitochondria, and other intracellular compartments. Major differences between the proteome of control and exposed cells involved the alteration of many calcium-regulated proteins (calmodulin, protein S100-A2, annexin A5, annexin A10, gelsolin isoform b) and iron-regulated proteins (ferritin, heme-binding protein 2, transferrin). On the basis of these findings, the intracellular calcium concentration was determined, revealing a significant increase after 24 h of exposure to TCDD. Moreover, the concentration of the labile iron pool (LIP) was also significantly elevated in TCDD-exposed cells. This increase was strongly inhibited by the calmodulin (CaM) antagonist W-7, which pointed toward a possible interaction between iron and calcium signaling. Because nitric oxide (NO) production was significantly enhanced in TCDD-exposed cells and was also inhibited by W-7, we hypothesize that alterations in calcium and iron homeostasis upon exposure to TCDD may be linked through NO generated by CaM-activated nitric oxide synthase. In our model, we propose that NO produced upon TCDD exposure interacts with the iron centers of iron-regulatory proteins (IRPs) that modulate the alteration of ferritin and transferrin, resulting in an augmented cellular LIP and, hence, increased toxicity.

Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature

PubMed Central

Honavar, Jaideep; Bradley, Eddie; Bradley, Kelley; Oh, Joo Yeun; Vallejo, Matthew O.; Kelley, Eric E.; Cantu-Medellin, Nadiezhda; Doran, Stephen; Dell’italia, Louis J.; Matalon, Sadis; Patel, Rakesh P.

2014-01-01

Exposure to chlorine (Cl2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl2 gas exposure (400ppm, 30min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex-vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24–48 hours post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by ~2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E+) from PA isolated from Cl2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (~4mmHg) lower in rats that had been exposed to Cl2 gas 24 hours earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl2 gas exposure toxicity. PMID:24769334

Effects of endogenous nitric oxide and of DETA NONOate in arteriogenesis.

PubMed

Troidl, Kerstin; Tribulova, Silvia; Cai, Wei-Jun; Rüding, Inka; Apfelbeck, Hanna; Schierling, Wilma; Troidl, Christian; Schmitz-Rixen, Thomas; Schaper, Wolfgang

2010-02-01

Previous studies showed that targeted endothelial nitric oxide synthase (eNOS) disruption in mice with femoral artery occlusion does not impede and transgenic eNOS overexpression does not stimulate collateral artery growth after femoral artery occlusion, suggesting that nitric oxide from eNOS does not play a role in arteriogenesis. However, pharmacologic nitric oxide synthase inhibition with L-NAME markedly blocks arteriogenesis, suggestive of an important role of nitric oxide. To solve the paradox, we studied targeted deletion of eNOS and of inducible nitric oxide synthase (iNOS) in mice and found that only iNOS knockout could partially inhibit arteriogenesis. However, the combination of eNOS knockout and treatment with the iNOS inhibitor L-NIL completely abolished arteriogenesis. mRNA transcription studies (reverse transcriptase-polymerase chain reaction) performed on collateral arteries of rats showed that eNOS and especially iNOS (but not neural nitric oxide synthase) become upregulated in shear stress-stimulated collateral vessels, which supports the hypothesis that nitric oxide is necessary for arteriogenesis but that iNOS plays an important part. This was strengthened by the observation that the nitric oxide donor DETA NONOate strongly stimulated collateral artery growth, activated perivascular monocytes, and increased proliferation markers. Shear stress-induced nitric oxide may activate the innate immune system and activate iNOS. In conclusion, arteriogenesis is completely dependent on the presence of nitric oxide, a large part of it coming from mononuclear cells.

Multifaceted role of nitric oxide in an in vitro mouse neuronal injury model: transcriptomic profiling defines the temporal recruitment of death signalling cascades

PubMed Central

Peng, Zhao Feng; Chen, Minghui Jessica; Manikandan, Jayapal; Melendez, Alirio J; Shui, Guanghou; Russo-Marie, Françoise; Whiteman, Matthew; Beart, Philip M; Moore, Philip K; Cheung, Nam Sang

2012-01-01

Abstract Nitric oxide is implicated in the pathogenesis of various neuropathologies characterized by oxidative stress. Although nitric oxide has been reported to be involved in the exacerbation of oxidative stress observed in several neuropathologies, existent data fail to provide a holistic description of how nitrergic pathobiology elicits neuronal injury. Here we provide a comprehensive description of mechanisms contributing to nitric oxide induced neuronal injury by global transcriptomic profiling. Microarray analyses were undertaken on RNA from murine primary cortical neurons treated with the nitric oxide generator DETA-NONOate (NOC-18, 0.5 mM) for 8–24 hrs. Biological pathway analysis focused upon 3672 gene probes which demonstrated at least a ±1.5-fold expression in a minimum of one out of three time-points and passed statistical analysis (one-way anova, P < 0.05). Numerous enriched processes potentially determining nitric oxide mediated neuronal injury were identified from the transcriptomic profile: cell death, developmental growth and survival, cell cycle, calcium ion homeostasis, endoplasmic reticulum stress, oxidative stress, mitochondrial homeostasis, ubiquitin-mediated proteolysis, and GSH and nitric oxide metabolism. Our detailed time-course study of nitric oxide induced neuronal injury allowed us to provide the first time a holistic description of the temporal sequence of cellular events contributing to nitrergic injury. These data form a foundation for the development of screening platforms and define targets for intervention in nitric oxide neuropathologies where nitric oxide mediated injury is causative. PMID:21352476

Serine 1179 phosphorylation of endothelial nitric oxide synthase caused by 2,4,6-trinitrotoluene through PI3K/Akt signaling in endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun Yang; Sumi, Daigo; Kumagai, Yoshito

2006-07-01

Although 2,4,6-trinitrotoluene (TNT) has been found to uncouple nitric oxide synthase (NOS), thereby leading to reactive oxygen species (ROS), cellular response against TNT still remains unclear. Exposure of bovine aortic endothelial cells (BAECs) to TNT (100 {mu}M) resulted in serine 1179 phosphorylation of endothelial NOS (eNOS). With specific inhibitors (wortmannin and LY294002), we found that PI3K/Akt signaling participated in the eNOS phosphorylation caused by TNT, whereas the ERK pathway did not. ROS were generated following exposure of BAECs to TNT. However, TNT-mediated phosphorylation of either eNOS or Akt was drastically blocked by NAC and PEG-CAT. Interestingly, pretreatment with apocynin, amore » specific inhibitor for NADPH oxidase, diminished the phosphorylation of eNOS and Akt. These results suggest that TNT affects NADPH oxidase, thereby generating hydrogen peroxide, which is capable of activating PI3K/Akt signaling associated with eNOS Ser 1179 phosphorylation.« less

Glycoconjugates as Mediators of Nitric Oxide Production upon Exposure to Bacterial Spores by Macrophages

NASA Astrophysics Data System (ADS)

Lahiani, Mohamed; Soderberg, Lee; Tarasenko, Olga

2011-06-01

Phagocytes generate nitric oxide (NO) in large quantities to combat bacteria. The spore-producing Gram-positive organisms of Bacillus cereus family are causative agents from mild to a life threatening infection in humans and domestic animals. Our group have shown that glycoconjugates (GCs) activate macrophages and enhance killing of Bacillus spores. In this investigation, we will explore the effect of different GCs structures on NO production. The objective of this study is to study effects of GCs 2, 4, 6, 8, 10 on NO release upon exposure to B. cereus and Bacillus anthracis spores by macrophages. Our results demonstrated that GCs activated macrophages and increased NO production using studied GCs ligands compared to macrophage only (p<0.001). GC2 and GC8 were able to further increase NO production in macrophages compared to the B. anthracis spores treated macrophages (p<0.001). Our finding suggests that GCs could be used as potential mediators of NO production in macrophages to fight B. anthracis and other pathogens.

The Consistency of Isotopologues of Ambient Atmospheric Nitric Acid in Passively Collected Samples

NASA Astrophysics Data System (ADS)

Bell, M. D.; Sickman, J. O.; Bytnerowicz, A.; Padgett, P.; Allen, E. B.

2012-12-01

Anthropogenic sources of nitrogen oxides have previously been shown to have distinctive isotopic signatures of oxygen and nitrogen. Nylon filters are currently used in passive sampling arrays to measure ambient atmospheric nitric acid concentrations and estimate deposition rates. This experiment measured the ability of nylon filters to consistently collect isotopologues of atmospheric nitric acid in the same ratios as they are present in the atmosphere. Samplers were deployed in continuous stirred tank reactors (CSTR) and at field sites across a nitrogen deposition gradient in Southern California. Filters were exposed over a four week period with individual filters being subjected to 1-4 week exposure times. Extracted nitric acid were measured for δ18O and δ15N ratios and compared for consistency based on length of exposure and amount of HNO3 collected. Filters within the CSTRs collected HNO3 at a consistent rate in both high and low concentration chambers. After two weeks of exposure, the mean δ18O values were within 0.5‰ of the δ18O of the source HNO3 solution. The mean of all weekly exposures were within 0.5‰ of the δ15N of the source solution, but after three weeks, the mean δ15N of adsorbed HNO3 was within 0.2‰. As the length of the exposure increased, the variability of measured delta values decreased for both elements. The field samplers collected HNO3 consistent with previously measured values along a deposition gradient. The mean δ18O at high deposition sites was 52.2‰ compared to 35.7‰ at the low deposition sites. Mean δ15N values were similar at all sites across the deposition gradient. Due to precipitation events occurring during the exposure period, the δ15N and δ18O of nitric acid were highly variable at all field sites. At single sites, changes in δ15N and δ18O were negatively correlated, consistent with two-sourcing mixing dynamics, but the slope of the regressions differed between high and low deposition sites. Anthropogenic sources of atmospheric nitric acid accounted for 58% of the atmospheric nitric acid at the high deposition sites and 36.5% of the atmospheric nitric acid at the low deposition sites. The nylon filters proved to be an effective means of collecting isotopologues of HNO3 consistent with atmospheric concentrations. A length of the exposure of two weeks stabilizes isotopologue composition and minimizes the chance of variable weather events altering atmospheric values.

Endothelial nitric oxide synthase in hypoxic newborn porcine pulmonary vessels

PubMed Central

Hislop, A; Springall, D; Oliveira, H; Pollock, J; Polak, J; Haworth, S

1997-01-01

AIMS—To determine if the failure of neonatal pulmonary arteries to dilate is due to a lack of nitric oxide synthase (NOS).
METHODS—A monoclonal antibody to endothelial NOS was used to demonstrate the distribution and density of NOS in the developing porcine lung after a period in hypobaric hypoxia. Newborn piglets were made hypertensive by exposure to hypobaric hypoxia (50.8 kPa) from < 5 minutes of age to 2.5 days of age, 3-6 days of age or 14-17 days of age. A semiquantitative scoring system was used to assess the distribution of endothelial NOS by light microscopy.
RESULTS—NOS was present in the arteries in all hypoxic animals. However, hypoxia from birth caused a reduction in NOS compared with those lungs normal at birth and those normal at 3 days. Hypoxia from 3-6 days led to a high density of NOS compared with normal lungs at 6 days. Hypoxia from 14-17 days had little effect on the amount of NOS. On recovery in room air after exposure to hypoxia from birth there was a transient increase in endothelial NOS after three days of recovery, mirroring that seen at three days in normal animals.
CONCLUSIONS—Suppression of NOS production in the first few days of life may contribute to pulmonary hypertension in neonates.

 Keywords: pulmonary circulation; nitric oxide synthase; hypoxia; endothelium; piglets PMID:9279177

Nitric oxide reversibly impairs axonal conduction in Guinea pig spinal cord.

PubMed

Ashki, Negin; Hayes, Keith C; Shi, Riyi

2006-12-01

Increased expression of the inducible and neuronal isoforms of nitric oxide synthase (NOS), and elevated concentrations of nitric oxide (NO) metabolites, are present within the central nervous system (CNS) following neurotrauma and are implicated in the pathogenesis of the accompanying neurologic deficits. We tested the hypothesis that elevated extracellular concentrations of NO introduced by the donor Spermine NONOate, induce reversible axonal conduction deficits in neurons of the guinea pig spinal cord. The compound action potential (CAP) and compound membrane potential (CMP) of excised ventral cord white matter were recorded before, during, and after bathing the tissue (30 min) in varying concentrations (0.25-3.0 mM) of Spermine NONOate. The principal results were a rapid onset, dose-dependent, reduction in amplitude of the CAP (p < 0.05) accompanied by depolarization of the CMP during NO exposure. These effects were largely reversible on washout, at low concentration of the donor (0.5 mM), but were only partially reversed at higher concentrations. Changes in the electrophysiological properties were not evident when the donor had been a priori depleted of NO. The results extend previous reports that NO induces reversible axonal conduction deficits. They provide new evidence of dissociation of the effects of NO on CAP and CMP during washout, and after prolonged exposure to the donor. They add support to the emerging concept that immune-mediated axonal conduction failure contributes to reversible neurologic deficits following neurotrauma and aid in understanding clinical phenomena such as spinal shock and neurologic recovery.

The transport of nitric oxide in the upper atmosphere by planetary waves and the zonal mean circulation

NASA Technical Reports Server (NTRS)

Jones, G. A.; Avery, S. K.

1982-01-01

A time-dependent numerical model was developed and used to study the interaction between planetary waves, the zonal mean circulation, and the trace constituent nitric oxide in the region between 55 km and 120 km. The factors which contribute to the structure of the nitric oxide distribution were examined, and the sensitivity of the distribution to changes in planetary wave amplitude was investigated. Wave-induced changes in the mean nitric oxide concentration were examined as a possible mechanism for the observed winter anomaly. Results indicate that vertically-propagating planetary waves induce a wave-like structure in the nitric oxide distribution and that at certain levels, transports of nitric oxide by planetary waves could significantly affect the mean nitric oxide distribution. The magnitude and direction of these transports at a given level was found to depend not only on the amplitude of the planetary wave, but also on the loss rate of nitric oxide at that level.

Changes in oxidative potential of soil and fly ash after reaction with gaseous nitric acid

NASA Astrophysics Data System (ADS)

Zhan, Ying; Ginder-Vogel, Matthew; Shafer, Martin M.; Rudich, Yinon; Pardo, Michal; Katra, Itzhak; Katoshevski, David; Schauer, James J.

2018-01-01

The goal of this study was to examine the impact of simulated atmospheric aging on the oxidative potential of inorganic aerosols comprised primarily of crustal materials. Four soil samples and one coal fly ash sample were artificially aged in the laboratory through exposure to the vapor from 15.8 M nitric acid solution for 24 h at room temperature. Native and acid-aged samples were analyzed with a cellular macrophage and acellular dithionthreitol assays to determine oxidative potential. Additionally, the samples were analyzed to determine the concentration of 50 elements, both total and the water-soluble fraction of these elements by Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICMS) and crystalline mineral composition using X-ray Diffraction (XRD). The results show that reactions with gaseous nitric acid increase the water-soluble fraction of many elements, including calcium, iron, magnesium, zinc, and lead. The mineral composition analysis documented that calcium-rich minerals present in the soils (e.g., calcite) are converted into different chemical forms, such as calcium nitrate (Ca(NO3)2). The nitric acid aging process, which can occur in the atmosphere, leads to a 200-600% increase in oxidative potential, as measured by cellular and acellular assays. This laboratory study demonstrates that the toxic effects of aged versus freshly emitted atmospheric dust may be quite different. In addition, the results suggest that mineralogical analysis of atmospheric dust may be useful in understanding its degree of aging.

Reactive oxygen species are key mediators of the nitric oxide apoptotic pathway in anterior pituitary cells.

PubMed

Machiavelli, Leticia I; Poliandri, Ariel H; Quinteros, Fernanda A; Cabilla, Jimena P; Duvilanski, Beatriz H

2007-03-01

We previously showed that long-term exposure of anterior pituitary cells to nitric oxide (NO) induces apoptosis. The intracellular signals underlying this effect remained unclear. In this study, we searched for possible mechanisms involved in the early stages of the NO apoptotic cascade. Caspase 3 was activated by NO with no apparent disruption of mitochondrial membrane potential. NO caused a rapid increase of reactive oxygen species (ROS), and this increase seems to be dependent of mitochondrial electron transport chain. The antioxidant N-acetyl-cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and reduced the NO apoptotic effect. Catalase was inactivated by NO, while glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not modified at first, but increased at later times of NO exposure. The increase of GSH level is important for the scavenging of the NO-induced ROS overproduction. Our results indicate that ROS have an essential role as a trigger of the NO apoptotic cascade in anterior pituitary cells. The permanent inhibition of catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH level augment in response to the oxidative damage, though this increase seems not to be enough to rescue the cells from the NO effect.

Modulation of opioid actions by nitric oxide signaling.

PubMed

Toda, Noboru; Kishioka, Shiroh; Hatano, Yoshio; Toda, Hiroshi

2009-01-01

Nitric oxide (NO) plays pivotal roles in controlling physiological functions, participates in pathophysiological intervention, and is involved in mechanisms underlying beneficial or untoward actions of therapeutic agents. Endogenous nitric oxide is formed by three isoforms of nitric oxide synthase: endothelial, neurogenic and inducible. The former two are constitutively present mainly in the endothelium and nervous system, respectively, and the latter one is induced by lipopolysaccharides or cytokines mainly in mitochondria and glial cells. Constitutively formed nitric oxide modulates the actions of morphine and related analgesics by either enhancing or reducing antinociception. Tolerance to and dependence on morphine or its withdrawal syndrome are likely prevented by nitric oxide synthase inhibition. Information concerning modulation of morphine actions by nitric oxide is undoubtedly useful in establishing new strategies for efficient antinociceptive treatment and for minimizing noxious and unintended reactions.

High temperature decomposition of hydrogen peroxide

NASA Technical Reports Server (NTRS)

Parrish, Clyde F. (Inventor)

2005-01-01

Nitric oxide (NO) is oxidized into nitrogen dioxide (NO2) by the high temperature decomposition of a hydrogen peroxide solution to produce the oxidative free radicals, hydroxyl and hydroperoxyl. The hydrogen peroxide solution is impinged upon a heated surface in a stream of nitric oxide where it decomposes to produce the oxidative free radicals. Because the decomposition of the hydrogen peroxide solution occurs within the stream of the nitric oxide, rapid gas-phase oxidation of nitric oxide into nitrogen dioxide occurs.

High Temperature Decomposition of Hydrogen Peroxide

NASA Technical Reports Server (NTRS)

Parrish, Clyde F. (Inventor)

2004-01-01

Nitric oxide (NO) is oxidized into nitrogen dioxide (NO2) by the high temperature decomposition of a hydrogen peroxide solution to produce the oxidative free radicals, hydroxyl and hydropemxyl. The hydrogen peroxide solution is impinged upon a heated surface in a stream of nitric oxide where it decomposes to produce the oxidative free radicals. Because the decomposition of the hydrogen peroxide solution occurs within the stream of the nitric oxide, rapid gas-phase oxidation of nitric oxide into nitrogen dioxide occurs.

Nitric oxide protects murine embryonic liver cells (BNL CL.2) from cytotoxicity induced by glucose deprivation.

PubMed

Pae, H O; Kim, H G; Paik, Y S; Paik, S G; Kim, Y M; Oh, G S; Chung, H T

2000-03-01

We investigated the protective effects of nitric oxide on cell death of murine embryonic liver cells (BNL CL.2) after glucose deprivation. Endogenous nitric oxide production by BNL CL.2 cells was induced by 6 hr pretreatment with interferon-gamma and lipopolysaccharide. We used sodium nitroprusside and S-nitroso-L-glutathione as exogenous nitric oxide-generating compounds. All agents were used at doses that did not show direct cytotoxicity as measured by crystal violet staining assay. In the BNL CL.2 cells, the viability dropped very steeply after 24 hr incubation with glucose-free media. Endogenous nitric oxide produced by treatment of the cells with interferon-gamma and lipopolysaccharide protected the cells from glucose deprivation-induced cytotoxicity, but did not protect them in the presence of the nitric oxide synthesis inhibitor, N(G)-monomethyl-L-arginine. Exogenous nitric oxide protected the cells from glucose deprivation-induced cytotoxicity in a concentration-dependent manner. Cytoprotection by nitric oxide donors was abolished by the use of nitric oxide scavenger, 2-phenyl-4,4,5,5,-tetramethylimidazole, but not by the soluble guanosine cyclase inhibitor, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. In addition, cytoprotective effects comparable to endogenous or exogenous nitric oxide were not observed when the cells were incubated with dibutyl guanosine 3',5'-cyclic monophosphate. Based upon these results, we suggest that nitric oxide may enhance the cell survival of BNL CL.2 cells after glucose deprivation via a guanosine 3',5'-cyclic monophosphate-independent pathway.

ASSOCIATION BETWEEN AIR POLLUTION EXPOSURE AND EXHALED NITRIC OXIDE IN AN ELDERLY PANEL. (R826780)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

The Involvement of Superoxide and Nitric Oxide in Inflammation-Enhanced Diesel Exhaust Particle Cytotoxicity

EPA Science Inventory

Thirty-four million Americans have asthma, a chronic inflammatory lung disease. Although the mechanisms are unclear, epidemiologic studies show that exposure of asthmatics to air pollutants, like diesel exhaust particles (DEP), is more likely to result in adverse health effects....

MINIMAL ROLE FOR REACTIVE OXYGEN SPECIES IN DICHLOROACETIC ACID-INDUCED DYSMORPHOLOGY IN MOUSE WHOLE EMBRYO CULTURE.

EPA Science Inventory

Administration of dichloroacetate (DCA) to pregnant rats produces craniofacial, heart and other defects in their offspring. Exposure of zebrafish to DCA induces malformations and increases superoxide and nitric oxide production suggesting that reactive oxygen species (ROS) are as...

Atmospheric pressure plasma accelerates tail regeneration in tadpoles Xenopus laevis

NASA Astrophysics Data System (ADS)

Rivie, A.; Martus, K.; Menon, J.

2017-08-01

Atmospheric pressure plasma is a partially ionized gas composed of neutral and charged particles, including electrons and ions, as well as reactive oxygen species (ROS). Recently, it is utilized as possible therapy in oncology, sterilization, skin diseases, wound healing and tissue regeneration. In this study we focused on effect of plasma exposure on tail regeneration of tadpoles, Xenopus leavis with special emphasis on role of ROS, antioxidant defenses and morphological features of the regenerate. When amputated region of the tail was exposed to the helium plasma it resulted in a faster rate of growth, elevated ROS and increase in antioxidant enzymes in the regenerate compared to that of untreated control. An increase in nitric oxide (free radical) as well as activity of nitric oxide synthase(s) were observed once the cells of the regeneration blastema - a mass of proliferating cells are ready for differentiation. Microscopically the cells of the regenerate of plasma treated tadpoles show altered morphology and characteristics of cellular hypoxia and oxidative stress. We summarize that plasma exposure accelerates the dynamics of wound healing and tail regeneration through its effects on cell proliferation and differentiation as well as angiogenesis mediated through ROS signaling.

Purafil-filtration prevents the development of ozone-induced frost injury: A potential role for nitric oxide

NASA Astrophysics Data System (ADS)

Neighbour, E. A.; Pearson, M.; Mehlhorn, H.

The relationship between exposure to ozone in the summer and the subsequent development of frost hardiness in the autumn was evaluated in recent experiments with red spruce ( Picea rubens Sarg. Syn. P. rubra). When O 3 was added to air filtered only through charcoal (contaminated with nitric oxide (NO)), frost sensitivity in late autumn was increased as measured by conductivity from electrocyte leakage. However, when O 3 was added to air filtered through charcoal and Purafil (no NO), no enhancement of frost sensitivity was found. A possible explanation of this difference, involving the chain-propagating property of NO in the O 3-initiated oxidation of unsaturated hydrocarbons (HCs), is proposed and discussed. N 2O 5, which was found to be generated at approximately 0.02 moles per mole of O 3 in the first year's experiment, only marginally modified O 3 toxicity.

High temperature decomposition of hydrogen peroxide

NASA Technical Reports Server (NTRS)

Parrish, Clyde F. (Inventor)

2004-01-01

Nitric oxide (NO) is oxidized into nitrogen dioxide (NO.sub.2) by the high temperature decomposition of a hydrogen peroxide solution to produce the oxidative free radicals, hydroxyl and hydroperoxyl. The hydrogen peroxide solution is impinged upon a heated surface in a stream of nitric oxide where it decomposes to produce the oxidative free radicals. Because the decomposition of the hydrogen peroxide solution occurs within the stream of the nitric oxide, rapid gas-phase oxidation of nitric oxide into nitrogen dioxide occurs.

High temperature decomposition of hydrogen peroxide

NASA Technical Reports Server (NTRS)

Parrish, Clyde F. (Inventor)

2011-01-01

Nitric oxide (NO) is oxidized into nitrogen dioxide (NO.sub.2) by the high temperature decomposition of a hydrogen peroxide solution to produce the oxidative free radicals, hydroxyl and hydroperoxyl. The hydrogen peroxide solution is impinged upon a heated surface in a stream of nitric oxide where it decomposes to produce the oxidative free radicals. Because the decomposition of the hydrogen peroxide solution occurs within the stream of the nitric oxide, rapid gas-phase oxidation of nitric oxide into nitrogen dioxide occurs.

Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism.

PubMed

San Martín, Alejandro; Arce-Molina, Robinson; Galaz, Alex; Pérez-Guerra, Gustavo; Barros, L Felipe

2017-06-02

Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic effects at physiological concentrations are incompletely characterized. To this end, we set out to investigate the metabolic effects of NO in cultured astrocytes from mice by taking advantage of the high spatiotemporal resolution afforded by genetically encoded Förster resonance energy transfer (FRET) nanosensors. NO exposure resulted in immediate and reversible intracellular glucose depletion and lactate accumulation. Consistent with cytochrome oxidase involvement, the glycolytic effect was enhanced at a low oxygen level and became irreversible at a high NO concentration or after prolonged exposure. Measurements of both glycolytic rate and mitochondrial pyruvate consumption revealed significant effects even at nanomolar NO concentrations. We conclude that NO can modulate astrocytic energy metabolism in the short term, reversibly, and at concentrations known to be released by endothelial cells under physiological conditions. These findings suggest that NO modulates the size of the astrocytic lactate reservoir involved in neuronal fueling and signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A Finite Rate Chemical Analysis of Nitric Oxide Flow Contamination Effects on Scramjet Performance

NASA Technical Reports Server (NTRS)

Cabell, Karen F.; Rock, Kenneth E.

2003-01-01

The level of nitric oxide contamination in the test gas of the Langley Research Center Arc-Heated Scramjet Test Facility and the effect of the contamination on scramjet test engine performance were investigated analytically. A finite rate chemical analysis was performed to determine the levels of nitric oxide produced in the facility at conditions corresponding to Mach 6 to 8 flight simulations. Results indicate that nitric oxide levels range from one to three mole percent, corroborating previously obtained measurements. A three-stream combustor code with finite rate chemistry was used to investigate the effects of nitric oxide on scramjet performance. Results indicate that nitric oxide in the test gas causes a small increase in heat release and thrust performance for the test conditions investigated. However, a rate constant uncertainty analysis suggests that the effect of nitric oxide ranges from no net effect, to an increase of about 10 percent in thrust performance.

Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome

PubMed Central

Yüksel, Meral; Okur, Hacer Kuzu; Pelin, Zerrin; Öğünç, Ayliz Velioğlu; Öztürk, Levent

2014-01-01

OBJECTIVE: Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide. METHODS: The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples. RESULTS: Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05). CONCLUSION: Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels. PMID:24714832

Nitric oxide signaling: systems integration of oxygen balance in defense of cell integrity.

PubMed

Gong, Li; Pitari, Giovanni M; Schulz, Stephanie; Waldman, Scott A

2004-01-01

Nitric oxide has emerged as a ubiquitous signaling molecule subserving diverse pathophysiologic processes, including cardiovascular homeostasis and its decompensation in atherogenesis. Recent insights into molecular mechanisms regulating nitric oxide generation and the rich diversity of mechanisms by which it propagates signals reveal the role of this simple gas as a principle mediator of systems integration of oxygen balance. The molecular lexicon by which nitric oxide propagates signals encompasses the elements of posttranslational modification of proteins by redox-based nitrosylation of transition metal centers and free thiols. Spatial and temporal precision and specificity of signal initiation, amplification, and propagation are orchestrated by dynamic assembly of supramolecular complexes coupling nitric oxide production to upstream and downstream components in specific subcellular compartments. The concept of local paracrine signaling by nitric oxide over subcellular distances for short durations has expanded to include endocrine-like effects over anatomic spatial and temporal scales. From these insights emerges a role for nitric oxide in integrating system responses controlling oxygen supply and demand to defend cell integrity in the face of ischemic challenge. In this context, nitric oxide coordinates the respiratory cycle to acquire and deliver oxygen to target tissues by regulating hemoglobin function and vascular smooth muscle contractility and matches energy supply and demand by down-regulating energy-requiring functions while shifting metabolism to optimize energy production. Insights into mechanisms regulating nitric oxide production and signaling and their integration into responses mediating homeostasis place into specific relief the role of those processes in pathophysiology. Indeed, endothelial dysfunction associated with altered production of nitric oxide regulating tissue integrity contributes to the pathogenesis underlying atherogenesis. Moreover, this central role in pathophysiology identifies nitric oxide signaling as a key target for novel therapeutic interventions to minimize irreversible tissue damage associated with ischemic cardiovascular disease.

*Differential injury in healthy and cytokine-treated epithelial cells exposed to diesel exhaust particles involves interaction of superoxide and nitric oxide

EPA Science Inventory

RATIONALE: Individuals with chronic pulmonary inflammation due to disease are more susceptible to the adverse health effects associated with exposure to particulate matter (PM) air pollutants, such as diesel exhaust particles (DEP). Increasing evidence suggests that these adverse...

Solubilization and Resolution of the Membrane-Bound Nitrite Reductase from Paracoccus Halodenitrificans into Nitrite and Nitric Oxide Reductases

NASA Technical Reports Server (NTRS)

Grant, Michael A.; Cronin, Sonja E.; Hochstein, Lawrence I.

1984-01-01

Membranes prepared from Paracoccus halodenitrificans reduced nitrite or nitric oxide to nitrous oxide. Extraction of these membranes with the detergent CHAPSO [3-(3-Chlolamidoporopyldimethylammonio)-1-(2- hydroxy-1-propanesulfonate)], followed by ammonium sulfate fractionation of the solubilized proteins, resulted in the separation of nitrite and nitric oxide reductase activities. The fraction containing nitrite reductase activity spectrally resembled a cd-type cytochrome. Several cytochromes were detected in the nitric oxide reductase fraction. Which, if any, of these cytochromes is associated with the reduction of nitric oxide is not clear at this time.

Carboxyhemoglobin formation secondary to nitric oxide therapy in the setting of interstitial lung disease and pulmonary hypertension.

PubMed

Ruisi, Phillip; Ruisi, Michael

2011-01-01

Carbon monoxide (CO) has been widely recognized as an exogenous poison, although endogenous mechanisms for its formation involve heme-oxygenase (HO) isoforms, more specifically HO-1, in the setting of oxidative stress such as acute respiratory distress syndrome, sepsis, trauma, and nitric oxide use have been studied. In patients with refractory hypoxemia, inhaled nitric oxide (iNO) therapy is used to selectively vasodilate the pulmonary vasculature and improve ventilation-perfusion match. Inhaled nitric oxide is rapidly inactivated on binding to hemoglobin in the formation of nitrosyl- and methemoglobin in the pulmonary vasculature. Hence, inhaled nitric oxide has minimal systemic dissemination. Several experimental design studies involving lab rats have demonstrated increased levels of carboxyhemoglobin and exhaled CO as a result of nitric oxide HO-1 induction.

Application of a Chemiluminescence Detector for the Measurement of Total Oxides of Nitrogen and Ammonia in the Atmosphere

NASA Technical Reports Server (NTRS)

Hodgeson, J. A.; Bell, J. P.; Rehme, K. A.; Krost, K. J.; Stevens, R. K.

1971-01-01

By means of the thermal conversion of nitrogen dioxide to the nitric oxide, the chemiluminescent nitric oxide monitor, based on the nitric oxide plus ozone reaction, may be used for monitoring nitrogen dioxide plus nitric oxide (NO(x)). Under conditions previously described, ammonia is also converted to nitric oxide and therefore interferes. A metal surface, gold wool or stainless steel, operated at two different temperatures has been used to convert only nitrogen dioxide or nitrogen dioxide plus ammonia. Quantitative conversion of nitrogen dioxide to nitric oxide has been obtained at temperatures as low as 200 C. Conversion of ammonia is effected at temperatures of 300 C or higher. By the addition of a converter the basic nitric oxide monitor may be used for measuring NO(x) or NO(x) plus ammonia. As an alternate mode, for a fixed high temperature, a specific scrubber is described for removing NH3 without affecting NO2 concentrations.

Serum metabolome biomarkers associate low-level environmental perfluorinated compound exposure with oxidative /nitrosative stress in humans.

PubMed

Wang, Xiaofei; Liu, Liangpo; Zhang, Weibing; Zhang, Jie; Du, Xiaoyan; Huang, Qingyu; Tian, Meiping; Shen, Heqing

2017-10-01

Previous in vivo and in vitro studies have linked perfluorinated compound (PFC) exposure with metabolic interruption, but the inter-species difference and high treatment doses usually make the results difficult to be extrapolated to humans directly. The best strategy for identifying the metabolic interruption may be to establish the direct correlations between monitored PFCs data and metabolic data on human samples. In this study, serum metabolome data and PFC concentrations were acquired for a Chinese adult male cohort. The most abundant PFCs are PFOA and PFOS with concentration medians 7.56 and 12.78 nM, respectively; in together they count around 81.6% of the total PFCs. PFC concentration-related serum metabolic profile changes and the related metabolic biomarkers were explored by using partial least squares-discriminant analysis (PLS-DA). Respectively taking PFOS, PFOA and total PFC as the classifiers, serum metabolome can be differentiated between the lowest dose group (1st quartile PFCs) and the highest PFC dose group (4th quartile PFCs). Ten potential PFC biomarkers were identified, mainly involving in pollutant detoxification, antioxidation and nitric oxide (NO) signal pathways. These suggested that low-level environmental PFC exposure has significantly adverse impacts on glutathione (GSH) cycle, Krebs cycle, nitric oxide (NO) generation and purine oxidation in humans. To the best of our knowledge, this is the first report investigating the association of environmental PFC exposure with human serum metabolome alteration. Given the important biological functions of the identified biomarkers, we suggest that PFC could increase the metabolism syndromes risk including diabetes and cardiovascular diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glutamate antagonism fails to reverse mitochondrial dysfunction in late phase of experimental neonatal asphyxia in rats.

PubMed

Reddy, Nagannathahalli Ranga; Krishnamurthy, Sairam; Chourasia, Tapan Kumar; Kumar, Ashok; Joy, Keerikkattil Paily

2011-04-01

Neonatal asphyxia is a primary contributor to neonatal mortality and neuro-developmental disorders. It progresses in two distinct phases, as initial primary process and latter as the secondary process. A dynamic relationship exists between excitotoxicity and mitochondrial dysfunction during the progression of asphyxic injury. Study of status of glutamate and mitochondrial function in tandem during primary and secondary processes may give new leads to the treatment of asphyxia. Neonatal asphyxia was induced in rat pups on the day of birth by subjecting them to two episodes (10min each) of anoxia, 24h apart by passing 100% N(2) into an enclosed chamber. The NMDA antagonist ketamine (20mg/kg/day) was administered either for 1 day or 7 days after anoxic exposure. Tissue glutamate and nitric oxide were estimated in the cerebral cortex, extra-cortex and cerebellum. The mitochondria from the above brain regions were used for the estimation of malondialdehyde, and activities of superoxide dismutase and succinate dehydrogenase. Mitochondrial membrane potential was evaluated by using Rhodamine dye. Anoxia during the primary process increased glutamate and nitric oxide levels; however the mitochondrial function was unaltered in terms of succinate dehydrogenase and membrane potential. Acute ketamine treatment reversed the increase in both glutamate and nitric oxide levels and partially attenuated mitochondrial function in terms of succinate dehydrogenase activity. The elevated glutamate and nitric oxide levels were maintained during the secondary process but however with concomitant loss of mitochondrial function. Repeated ketamine administration reversed glutamate levels only in the cerebral cortex, where as nitric oxide was decreased in all the brain regions. However, repeated ketamine administration was unable to reverse anoxia-induced mitochondrial dysfunction. The failure of glutamate antagonism in the treatment of asphyxia may be due to persistence of mitochondrial dysfunction. Therefore, additionally targeting mitochondrial function may prove to be therapeutically beneficial in the treatment of asphyxia. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enhancement of tolerance of Ganoderma lucidum to cadmium by nitric oxide.

PubMed

Guo, Shanshan; Yao, Yuan; Zuo, Lei; Shi, Wenjin; Gao, Ni; Xu, Heng

2016-01-01

Nitric oxide (NO) is considered as a signaling molecule involved in regulation of diverse physiological processes and stress responses in animals and plants. However, whether NO regulates fungal, particularly edible fungi, response to heavy metal stresses, is unknown. This study investigated the effect of nitric oxide on biological responses of mycelia of Ganoderma lucidum to cadmium (Cd) toxicity. Exposure of Ganoderma lucidum to Cd (400 µM) triggered production of H2O2 and O2(-) in the mycelia and further induced lipid peroxidation as well as sharply decrease of fresh biomass. However, such an effect can be reversed by exogenous supply of NO. Mycelia treated with 100 µM SNP accumulated less H2O2, O2(-), thiobarbituric acid reactive substances (TBARS), and fresh biomass of this treatment was improved. Treatment with SNP significantly increased activities of antioxidant enzyme (peroxidase and catalase) to resist Cd stress. Meanwhile, NO-mediated alleviation of Cd toxicity was closely related to the accumulated proline as well as reduced Cd accumulation. These results suggested that NO plays a crucial role in preventing the mycelia of Ganoderma lucidum from Cd toxicity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification and molecular characterization of nitric oxide synthase (NOS) gene in the intertidal copepod Tigriopus japonicus.

PubMed

Jeong, Chang-Bum; Kang, Hye-Min; Seo, Jung Soo; Park, Heum Gi; Rhee, Jae-Sung; Lee, Jae-Seong

2016-02-10

In copepods, no information has been reported on the structure or molecular characterization of the nitric oxide synthase (NOS) gene. In the intertidal copepod Tigriopus japonicus, we identified a NOS gene that is involved in immune responses of vertebrates and invertebrates. In silico analyses revealed that nitric oxide (NO) synthase domains, such as the oxygenase and reductase domains, are highly conserved in the T. japonicus NOS gene. The T. japonicus NOS gene was highly transcribed in the nauplii stages, implying that it plays a role in protecting the host during the early developmental stages. To examine the involvement of the T. japonicus NOS gene in the innate immune response, the copepods were exposed to lipopolysaccharide (LPS) and two Vibrio sp. After exposure to different concentrations of LPS and Vibrio sp., T. japonicus NOS transcription was significantly increased over time in a dose-dependent manner, and the NO/nitrite concentration increased as well. Taken together, our findings suggest that T. japonicus NOS transcription is induced in response to an immune challenge as part of the conserved innate immunity. Copyright © 2015 Elsevier B.V. All rights reserved.

Prolonged exposure of resveratrol induces reactive superoxide species-independent apoptosis in murine prostate cells.

PubMed

Kumar, Sanjay; Stokes, James; Singh, Udai P; Scissum-Gunn, Karyn; Singh, Rajesh; Manne, Upender; Mishra, Manoj K

2017-10-01

Nitric oxide, a signaling molecule, inhibits mitochondrial respiration by binding with cytochrome c oxidase, resulting in elevated production of reactive superoxide species (reactive oxygen and nitrogen) in the mitochondria and increased susceptibility to cell death. Generation of mitochondrial superoxide species can be suppressed by natural compounds such as resveratrol, a dietary polyphenol found in the skin of red fruits. In various cancer cells, resveratrol shows anti-oxidant and cancer preventive properties. Since, the effect of resveratrol on reactive superoxide species-independent apoptosis in prostate cancer cells is not well illustrated; therefore, we investigated this phenomenon in TRAMP murine prostate cancer cells. To accomplish this, TRAMP cells were incubated with resveratrol, resveratrol + DETA-NONOate, DETA-NONOate (nitric oxide donor), resveratrol + L-NMMA, or L-NMMA (nitric oxide inhibitor) for 48 h, and reactive superoxide species in the mitochondria and culture supernatant were measured. In addition, the mitochondrial membrane potential, cell viability, expression of apoptotic markers (Bax and Bcl2), γ-H2A.x, p53, and caspase-3 was determined. We found that resveratrol suppressed reactive superoxide species such as reactive oxygen species in the mitochondria and nitric oxide in culture supernatant when compared to the DETA-NONOate treatment and disrupted the mitochondrial membrane potential. Resveratrol also reduced cell viability, altered the expression of apoptotic markers (Bax and Bcl2), and increased expression of γ-H2A.x (indicative marker of DNA fragmentation) and p53 (a critical DNA damage response protein). However, there was no appreciable modulation of the caspase-3. Therefore, our data suggest that resveratrol induces superoxide species-independent apoptosis and may act as a therapeutic agent against prostate cancer.

Antioxidative role of nitric oxide on copper toxicity to a chlorophycean alga, Chlorella.

PubMed

Singh, Akhilesh kumar; Sharma, Laxuman; Mallick, Nirupama

2004-10-01

The response of Chlorella vulgaris to copper exposure was investigated under laboratory batch culture conditions. Increased toxicity of Cu with respect to photosynthetic carbon fixation, O(2) evolution, chlorophyll fluorescence, and oxidative burst was observed for N-NH(4)(+)-grown cultures. The addition of sodium nitroprusside, a nitric oxide (NO) donor, in combination with Cu to N-NH(4)(+)-grown Chlorella not only lowered the inhibition levels of carbon fixation, O(2) evolution, and maximum quantum yield of PS II, but also significantly reduced the oxidative burst. The protective action of sodium nitroprusside was, however, arrested in cultures in which sodium nitroprusside was supplemented in combination with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a specific scavenger of NO in the experimental system. The N-NO(3)(-)-grown Chlorella depicted less sensitivity to Cu compared to its N-NH(4)(+)-grown counterpart. The N-NO(3)(-)-, N-NH(4)(+)-, and N-NH(4)(+)+sodium nitroprusside-grown Chlorella did not show any significant differences with respect to their Cu uptake potential. The role of NO as an antioxidant is discussed.

Nitric Oxide Interacts with Caveolin-1 to Facilitate Autophagy-Lysosome-Mediated Claudin-5 Degradation in Oxygen-Glucose Deprivation-Treated Endothelial Cells

PubMed Central

Liu, Jie; Weaver, John; Jin, Xinchun; Zhang, Yuan; Xu, Ji; Liu, Ke J.; Li, Weiping; Liu, Wenlan

2017-01-01

Using in vitro oxygen-glucose deprivation (OGD) model, we have previously demonstrated that 2-h OGD induces rapid, caveolin-1-mediated dissociation of claudin-5 from the cellular cytoskeletal framework and quick endothelial barrier disruption. In this study, we further investigated the fate of translocated claudin-5 and the mechanisms by which OGD promotes caveolin-1 translocation. Exposure of bEND3 cells to 4-h OGD, but not 2-h OGD plus 2-h reoxygenation, resulted in claudin-5 degradation. Inhibition of autophagy or the fusion of autophagosome with lysosome, but not proteasome, blocked OGD-induced claudin-5 degradation. Moreover, knockdown of caveolin-1 with siRNA blocked OGD-induced claudin-5 degradation. Western blot analysis showed a transient colocalization of caveolin-1, claudin-5, and LC3B in autolysosome or lipid raft fractions at 2-h OGD. Of note, inhibiting autophagosome and lysosome fusion sustained the colocalization of caveolin-1, claudin-5, and LC3B throughout the 4-h OGD exposure. EPR spin trapping showed increased nitric oxide (NO) generation in 2-h OGD-treated cells, and inhibiting NO with its scavenger C-PTIO or inducible nitric oxide synthase (iNOS) inhibitor 1400W prevented OGD-induced caveolin-1 translocation and claudin-5 degradation. Taken together, our data provide a novel mechanism underlying endothelial barrier disruption under prolonged ischemic conditions, in which NO promotes caveolin-1-mediated delivery of claudin-5 to the autophagosome for autophagy-lysosome-dependent degradation. PMID:26515186

Nitric Oxide Interacts with Caveolin-1 to Facilitate Autophagy-Lysosome-Mediated Claudin-5 Degradation in Oxygen-Glucose Deprivation-Treated Endothelial Cells.

PubMed

Liu, Jie; Weaver, John; Jin, Xinchun; Zhang, Yuan; Xu, Ji; Liu, Ke J; Li, Weiping; Liu, Wenlan

2016-11-01

Using in vitro oxygen-glucose deprivation (OGD) model, we have previously demonstrated that 2-h OGD induces rapid, caveolin-1-mediated dissociation of claudin-5 from the cellular cytoskeletal framework and quick endothelial barrier disruption. In this study, we further investigated the fate of translocated claudin-5 and the mechanisms by which OGD promotes caveolin-1 translocation. Exposure of bEND3 cells to 4-h OGD, but not 2-h OGD plus 2-h reoxygenation, resulted in claudin-5 degradation. Inhibition of autophagy or the fusion of autophagosome with lysosome, but not proteasome, blocked OGD-induced claudin-5 degradation. Moreover, knockdown of caveolin-1 with siRNA blocked OGD-induced claudin-5 degradation. Western blot analysis showed a transient colocalization of caveolin-1, claudin-5, and LC3B in autolysosome or lipid raft fractions at 2-h OGD. Of note, inhibiting autophagosome and lysosome fusion sustained the colocalization of caveolin-1, claudin-5, and LC3B throughout the 4-h OGD exposure. EPR spin trapping showed increased nitric oxide (NO) generation in 2-h OGD-treated cells, and inhibiting NO with its scavenger C-PTIO or inducible nitric oxide synthase (iNOS) inhibitor 1400W prevented OGD-induced caveolin-1 translocation and claudin-5 degradation. Taken together, our data provide a novel mechanism underlying endothelial barrier disruption under prolonged ischemic conditions, in which NO promotes caveolin-1-mediated delivery of claudin-5 to the autophagosome for autophagy-lysosome-dependent degradation.

Real-time electrical detection of nitric oxide in biological systems with sub-nanomolar sensitivity

NASA Astrophysics Data System (ADS)

Jiang, Shan; Cheng, Rui; Wang, Xiang; Xue, Teng; Liu, Yuan; Nel, Andre; Huang, Yu; Duan, Xiangfeng

2013-07-01

Real-time monitoring of nitric oxide concentrations is of central importance for probing the diverse roles of nitric oxide in neurotransmission, cardiovascular systems and immune responses. Here we report a new design of nitric oxide sensors based on hemin-functionalized graphene field-effect transistors. With its single atom thickness and the highest carrier mobility among all materials, graphene holds the promise for unprecedented sensitivity for molecular sensing. The non-covalent functionalization through π-π stacking interaction allows reliable immobilization of hemin molecules on graphene without damaging the graphene lattice to ensure the highly sensitive and specific detection of nitric oxide. Our studies demonstrate that the graphene-hemin sensors can respond rapidly to nitric oxide in physiological environments with a sub-nanomolar sensitivity. Furthermore, in vitro studies show that the graphene-hemin sensors can be used for the detection of nitric oxide released from macrophage cells and endothelial cells, demonstrating their practical functionality in complex biological systems.

Nitric Oxide-Induced Apoptosis of Human Dental Pulp Cells Is Mediated by the Mitochondria-Dependent Pathway

PubMed Central

Park, Min Young; Jeong, Yeon Jin; Kang, Gi Chang; Kim, Mi-Hwa; Kim, Sun Hun; Chung, Hyun-Ju

2014-01-01

Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. NO is produced by nitric oxide synthase (NOS), and NOS is abundantly expressed in the human dental pulp cells (HDPCs). NO produced by NOS can be cytotoxic at higher concentrations to HDPCs. However, the mechanism by which this cytotoxic pathway is activated in cells exposed to NO is not known. The purpose of this study was to elucidate the NO-induced cytotoxic mechanism in HDPCs. Sodium nitroprusside (SNP), a NO donor, reduced the viability of HDPCs in a dose- and time-dependent manner. We investigated the in vitro effects of nitric oxide on apoptosis of cultured HDPCs. Cells showed typical apoptotic morphology after exposure to SNP. Besides, the number of Annexin V positive cells was increased among the SNP-treated HDPCs. SNP enhanced the production of reactive oxygen species (ROS), and N-acetylcysteine (NAC) ameliorated the decrement of cell viability induced by SNP. However, a soluble guanylate cyclase inhibitor (ODQ) did not inhibited the decrement of cell viability induced by SNP. SNP increased cytochrome c release from the mitochondria to the cytosol and the ratio of Bax/Bcl-2 expression levels. Moreover, SNP-treated HDPCs elevated activities of caspase-3 and caspase-9. While pretreatment with inhibitors of caspase (z-VAD-fmk, z-DEVD-fmk) reversed the NO-induced apoptosis of HDPCs. From these results, it can be suggested that NO induces apoptosis of HDPCs through the mitochondria-dependent pathway mediated by ROS and Bcl-2 family, but not by the cyclic GMP pathway. PMID:24634593

Flavorings in Tobacco Products Induce Endothelial Cell Dysfunction.

PubMed

Fetterman, Jessica L; Weisbrod, Robert M; Feng, Bihua; Bastin, Reena; Tuttle, Shawn T; Holbrook, Monica; Baker, Gregory; Robertson, Rose Marie; Conklin, Daniel J; Bhatnagar, Aruni; Hamburg, Naomi M

2018-06-14

Use of alternative tobacco products including electronic cigarettes is rapidly rising. The wide variety of flavored tobacco products available is of great appeal to smokers and youth. The flavorings added to tobacco products have been deemed safe for ingestion, but the cardiovascular health effects are unknown. The purpose of this study was to examine the effect of 9 flavors on vascular endothelial cell function. Freshly isolated endothelial cells from participants who use nonmenthol- or menthol-flavored tobacco cigarettes showed impaired A23187-stimulated nitric oxide production compared with endothelial cells from nonsmoking participants. Treatment of endothelial cells isolated from nonsmoking participants with either menthol (0.01 mmol/L) or eugenol (0.01 mmol/L) decreased A23187-stimulated nitric oxide production. To further evaluate the effects of flavoring compounds on endothelial cell phenotype, commercially available human aortic endothelial cells were incubated with vanillin, menthol, cinnamaldehyde, eugenol, dimethylpyrazine, diacetyl, isoamyl acetate, eucalyptol, and acetylpyrazine (0.1-100 mmol/L) for 90 minutes. Cell death, reactive oxygen species production, expression of the proinflammatory marker IL-6 (interleukin-6), and nitric oxide production were measured. Cell death and reactive oxygen species production were induced only at high concentrations unlikely to be achieved in vivo. Lower concentrations of selected flavors (vanillin, menthol, cinnamaldehyde, eugenol, and acetylpyridine) induced both inflammation and impaired A23187-stimulated nitric oxide production consistent with endothelial dysfunction. Our data suggest that short-term exposure of endothelial cells to flavoring compounds used in tobacco products have adverse effects on endothelial cell phenotype that may have relevance to cardiovascular toxicity. © 2018 American Heart Association, Inc.

Nitric Oxide Homeostasis in Neurodegenerative Diseases.

PubMed

Hannibal, Luciana

2016-01-01

The role of nitric oxide in the pathogenesis and progression of neurodegenerative illnesses such as Parkinson's and Alzheimer's diseases has become prominent over the years. Increased activity of the enzymes that produce reactive oxygen species, decreased activity of antioxidant enzymes and imbalances in glutathione pools mediate and mark the neurodegenerative process. Much of the oxidative damage of proteins is brought about by the overproduction of nitric oxide by nitric oxide synthases (NOS) and its subsequent reactivity with reactive oxygen species. Proteomic methods have advanced the field tremendously, by facilitating the quantitative assessment of differential expression patterns and oxidative modifications of proteins and alongside, mapping their non-canonical functions. As a signaling molecule involved in multiple biochemical pathways, the level of nitric oxide is subject to tight regulation. All three NOS isoforms display aberrant patterns of expression in Alzheimer's disease, altering intracellular signaling and routing oxidative stress in directions that are uncompounded. This review discusses the prime factors that control nitric oxide biosynthesis, reactivity footprints and ensuing effects in the development of neurodegenerative diseases.

Scavenging and antioxidant properties of different grape cultivars against ionizing radiation-induced liver damage ex vivo.

PubMed

Singha, Indrani; Das, Subir Kumar

2016-04-01

Ionizing radiation (IR) has become an integral part of the modern medicine--both for diagnosis as well as therapy. However, normal tissues or even distant cells also suffer IR-induced free radical insult. It may be more damaging in longer term than direct radiation exposure. Antioxidants provide protection against IR-induced damage. Grapes are the richest source of antioxidants. Here, we assessed the scavenging properties of four grape (Vitis vinifera) cultivars, namely Flame seedless (Black), Kishmish chorni (Black with reddish brown), Red globe (Red) and Thompson seedless mutant (Green), and also evaluated their protective action against γ-radiation-induced oxidative stress in liver tissue ex vivo. The scavenging abilities of grape seeds [2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC₅₀ = 0.008 ± 0.001 mg/mL), hydrogen peroxide (IC₅₀ = 0.49 to 0.8 mg/mL), hydroxyl radicals (IC₅₀ = 0.08 ± 0.008 mg/mL), and nitric oxide (IC₅₀ = 0.8 ± 0.08 mg/mL)] were higher than that of skin or pulp. Gamma (γ) radiation exposure to sliced liver tissues ex vivo from goat, @ 6 Gy significantly (P < 0.001) decreased reduced glutathione (GSH) content by 21.2% and also activities of catalase, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST) by 49.5, 66.0, 70.3, 73.6%, respectively. However, it increased thiobarbituric acid reactive substances (TBARS) by 2.04-fold and nitric oxide level by 48.6% compared to untreated group. Further increase in doses (10 or 16 Gy) of γ-radiation correspondingly decreased GSH content and enzyme activities, and increased TBARS and nitric oxide levels. Grape extract treatment prior to ionizing radiation exposure ameliorated theses effects at varying extent. The seed extracts exhibited strong antioxidant potential compared to skin or pulp extracts of different grape cultivars against oxidative damage by ionizing radiation (6 Gy, 10 Gy and 16 Gy) in sliced liver tissues ex vivo. Grape extracts at higher concentration (10 mg extract/g liver tissue) showed stronger antioxidant potential against lower dose (6 Gy) of ionizing radiation. Our results suggest that grape extracts could serve as a potential source of natural antioxidant against lower doses of IR-induced oxidative stress in liver extracts ex vivo.

Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Cheng; Nie, Xiaoke; Zhang, Yan

2015-10-15

Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NOmore » and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.« less

Novel neuroprotective and hepatoprotective effects of citric acid in acute malathion intoxication.

PubMed

Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Yassen, Noha N; Khadrawy, Yasser A; El-Toukhy, Safinaz Ebrahim; Sleem, Amany A

2016-12-01

To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Rats were received intraperitoneal (i.p.) injection of malathion 150 mg/kg along with citric acid (200 or 400 mg/kg, orally), atropine (1 mg/kg, i.p.) or citric acid 200 mg/kg + atropine 1 mg/kg and euthanized 4 h later. Malathion resulted in increased lipid peroxidation (malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase (GPx) activity, total antioxidant capacity (TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase (AChE) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase (iNOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain AChE increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and iNOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, AChE and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and iNOS expression in brain and liver. The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure. Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Experimental and analytical study of nitric oxide formation during combustion of propane in a jet-stirred combustor

NASA Technical Reports Server (NTRS)

Wakelyn, N. T.; Jachimowski, C. J.; Wilson, C. H.

1978-01-01

A jet-stirred combustor, constructed of castable zirconia and with an Inconel injector, was used to study nitric oxide formation in propane-air combustion with residence times in the range from 3.2 to 3.3 msec and equivalence ratios varying from 0.7 to 1.4. Measurements were made of combustor operating temperature and of nitric oxide concentration. Maximum nitric oxide concentrations of the order of 55 ppm were found in the range of equivalence ratio from 1.0 to 1.1. A finite-rate chemical kinetic mechanism for propane combustion and nitric oxide formation was assembled by coupling an existing propane oxidation mechanism with the Zeldovich reactions and reactions of molecular nitrogen with hydrocarbon fragments. Analytical studies using this mechanism in a computer simulation of the experimental conditions revealed that the hydrocarbon-fragment-nitrogen reactions play a significant role in nitric oxide formation during fuel-rich combustion.

An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

PubMed Central

Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

2016-01-01

Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

Effect of placental tissue on inhibition of uterine contraction by nitric oxide donors.

PubMed

Syal, A; Okawa, T; Vedernikov, Y; Chwalisz, K; Saade, G R; Garfield, R E

1999-08-01

Our purpose was to test the hypothesis that placental tissue modulates the effect of nitric oxide on spontaneous uterine contractility in pregnant rats. Rings (approximately 4 mm) of uterus taken from rats on day 14 (midpregnancy, n = 6), day 18 (late pregnancy, n = 4), and day 22 (term, n = 4) of gestation were placed in organ chambers filled with Krebs-bicarbonate buffer bubbled with 5% carbon dioxide in air (37 degrees C, pH approximately 7.4) for isometric tension recording. In some rings a piece of placenta was left attached to the uterine wall. In the other rings the fetuses, placentas, and membranes were removed completely. Change of spontaneous contractions of the rings (percentage change of basal integral activity for 10 minutes) in response to cumulative concentrations of the nitric oxide donors diethylamine-nitric oxide and nitroglycerin (10(-6) mol/L to 10(-4) mol/L) were compared between rings with and without placenta. Diethylamine-nitric oxide and nitroglycerin inhibited spontaneous uterine contractions in rings from midpregnancy, in both the absence and the presence of placenta. In rings from midpregnancy, the maximal inhibition of contractions by diethylamine-nitric oxide but not by nitroglycerin was significantly (P <.05) higher in the presence (26.7% +/- 3.5% of basal activity) than in the absence (39. 6% +/- 3.3%) of placenta. Inhibition of contraction by nitric oxide donors in rings from late and term pregnancy was less than in midpregnancy, and the presence of placental tissue did not influence the responses. The presence of placental tissue enhances inhibition of uterine contractility by agents that spontaneously release nitric oxide, such as diethylamine-nitric oxide, but not by nitroglycerin, which requires metabolic transformation for nitric oxide to be released. Refractoriness to nitric oxide near or at term does not depend on the presence or absence of placental tissue.

Acute trimethyltin exposure induces oxidative stress response and neuronal apoptosis in Sebastiscus marmoratus.

PubMed

Wang, Xinli; Cai, Jiali; Zhang, Jiliang; Wang, Chonggang; Yu, Ang; Chen, Yixin; Zuo, Zhenghong

2008-10-20

Trimethyltin (TMT) is a well-documented neurotoxicant that affects the function of central nervous system (CNS). In this study, we studied the neurotoxicity of TMT on the brain of marine fish Sebastiscus marmoratus. Our results showed that TMT acute exposure induced brain cell apoptosis in the telencephalon, optic tectum and cerebellum. In addition, we observed increased production of reactive oxygen species (ROS), nitric oxide (NO) and one asparate-specific cysteinyl protease named caspase-3 which are often associated with the processes of cell apoptosis, in the brain of S. marmoratus after acute treatment of TMT. Our results indicated that TMT induces neurotoxicity and oxidative stress in marine fish S. marmoratus. Our results suggested that TMT exposure in the environment may affect fish behaviors including schooling, sensory and motorial learnings, based on the observation of cell apoptosis in the cerebral regions.

Elevated nitric oxide in recurrent vulvovaginal candidiasis - association with clinical findings.

PubMed

Alvendal, Cathrin; Ehrström, Sophia; Brauner, Annelie; Lundberg, Jon O; Bohm-Starke, Nina

2017-03-01

Recurrent vulvovaginal candidiasis is defined as having three to four episodes per year and causes substantial suffering. Little is known about the mechanisms leading to relapses in otherwise healthy women. Nitric oxide is part of the nonspecific host defense and is increased during inflammation. Nitric oxide levels were measured and the expression of inducible nitric oxide synthase was analyzed in the vagina during an acute episode of recurrent vulvovaginal candidiasis and after treatment with fluconazole. Twenty-eight women with symptoms of recurrent vulvovaginal candidiasis were enrolled together with 31 healthy controls. Nitric oxide was measured with an air-filled 25-mL silicon catheter balloon incubated in the vagina for five minutes and then analyzed by chemiluminescence technique. Vaginal biopsies were analyzed for the expression of inducible nitric oxide synthase. Symptoms and clinical findings were surveyed using a scoring system. The measurements and biopsies were repeated in patients after six weeks of fluconazole treatment. Nitric oxide levels were increased during acute infection (median 352 ppb) compared with controls (median 6 ppb), p < 0.0001. The levels decreased after treatment (median 18 ppb) but were still higher than in controls. Increased expression of inducible nitric oxide synthase was observed in the epithelial basal layer in patients before and after treatment compared with controls. Before treatment, there were positive correlations between nitric oxide and symptom (r s  = 0.644) and examination scores (r s  = 0.677), p < 0.001. Nitric oxide is significantly elevated in patients with recurrent vulvovaginal candidiasis during acute episodes of infection and decreases after antifungal treatment. The results illustrate the pronounced inflammatory response in recurrent vulvovaginal candidiasis correlating to symptoms of pain and discomfort. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Impaired increase of retinal capillary blood flow to flicker light exposure in arterial hypertension.

PubMed

Ritt, Martin; Harazny, Joanna M; Ott, Christian; Raff, Ulrike; Bauernschubert, Philipp; Lehmann, Marina; Michelson, Georg; Schmieder, Roland E

2012-09-01

We hypothesized that the increase of retinal capillary blood flow (RCF) to flicker light exposure is impaired in subjects with arterial hypertension. In 146 nondiabetic untreated male subjects with (n=50) or without (n=96) arterial hypertension, RCF was measured before and after flicker light exposure noninvasively and in vivo using scanning laser Doppler flowmetry. In addition, in a subgroup of 28 subjects, the change of RCF to flicker light exposure was again assessed during parallel infusion of nitric oxide synthase inhibitor N-monomethyl-L-arginine (L-NMMA). The increase of RCF to flicker light exposure was lower in patients with untreated hypertension compared with normotensive subjects when expressed in absolute terms (7.69±54 versus 27.2±44 AU; P adjusted=0.013) or percent changes (2.95±14 versus 8.33±12%; P adjusted=0.023). Systolic (β=-0.216; P=0.023) but not diastolic blood pressure (β=-0.117; P=0.243) or mean arterial pressure (β=-0.178; P=0.073) was negatively related to the percent change of RCF to flicker light exposure, independently of other cardiovascular risk factors. In the subgroup of 28 subjects, the increase of RCF to flicker light exposure was similar at baseline and during parallel infusion of L-NMMA when expressed in absolute terms (20.0±51 versus 22.6±56 AU; P=0.731) or percent changes (7.12±16 versus 8.29±18%; P=0.607). The increase of RCF to flicker light exposure is impaired in arterial hypertension. In the subgroup of the total study cohort, nitric oxide was not a major determinant of the increase of RCF to flicker light exposure.

Nitric oxide induced by Indian ginseng root extract inhibits Infectious Bursal Disease virus in chicken embryo fibroblasts in vitro.

PubMed

Ganguly, Bhaskar; Umapathi, Vijaypillai; Rastogi, Sunil Kumar

2018-01-01

Infectious Bursal Disease is a severe viral disease of chicken responsible for serious economic losses to poultry farmers. The causative agent, Infectious Bursal Disease virus, is inhibited by nitric oxide. Root extract of the Indian ginseng, Withania somnifera , inhibits Infectious Bursal Disease virus in vitro. Also, Withania somnifera root extract is known to induce nitric oxide production in vitro. Therefore, the present study was undertaken to determine if the inhibitory activity of Withania somnifera against Infectious Bursal Disease virus was based on the production of nitric oxide. We show that besides other mechanisms, the inhibition of Infectious Bursal Disease virus by Withania somnifera involves the production of nitric oxide. Our results also highlight the paradoxical role of nitric oxide in the pathogenesis of Infectious Bursal Disease.

SOIL NITROUS OXIDE, NITRIC OXIDE, AND AMMONIA EMISSIONS FROM A RECOVERING RIPARIAN ECOSYSTEM IN SOUTHERN APPALACHIA

EPA Science Inventory

The paper presents two years of seasonal nitric oxide, ammonia, and nitrous oxide trace gas fluxes measured in a recovering riparian zone with cattle excluded and in an adjacent riparian zone grazed by cattle. In the recovering riparian zone, average nitric oxide, ammonia, and ni...

Mitochondrial dysfunction associated with nitric oxide pathways in glutamate neurotoxicity.

PubMed

Manucha, Walter

Multiple mechanisms underlying glutamate-induced neurotoxicity have recently been discussed. Likewise, a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with neurodegeneration, oxidative stress, and inflammation. This article highlights nitric oxide, an atypical neurotransmitter synthesized and released on demand by the post-synaptic neurons, and has many important implications for nerve cell survival and differentiation. Consequently, synaptogenesis, synapse elimination, and neurotransmitter release, are nitric oxide-modulated. Interesting, an emergent role of nitric oxide pathways has been discussed as regards neurotoxicity from glutamate-induced apoptosis. These findings suggest that nitric oxide pathways modulation could prevent oxidative damage to neurons through apoptosis inhibition. This review aims to highlight the emergent aspects of nitric oxide-mediated signaling in the brain, and how they can be related to neurotoxicity, as well as the development of neurodegenerative diseases development. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

A sub-nanomolar real-time nitric oxide probe: in vivo nitric oxide release in heart.

PubMed

Mantione, Kirk J; Stefano, George B

2004-04-01

Amperometric nitric oxide probes are critical in evaluating real-time nitric oxide levels. This valuable tool enables one to measure spontaneous baseline levels of nitric oxide as well as 'puffs' of the gaseous signal molecule that may last for only seconds to minutes. However, in the past, many probes suffered from a lack of sensitivity, durability and reliability, causing investigators to design numerous controls to support their data. Our laboratory evaluated the new ISO-NOPF100 NO probe manufactured by World Precision Instruments of Sarasota, Florida. An invertebrate in vivo heart preparation was used, which presents a high degree of difficuly in obtaining nitric oxide measurements due to space limitations, resulting in physical contact of the probe with tissues. Additionally, we used in vitro invertebrate ganglionic preparations as a comparison since this tissue releases spontaneous and low levels of NO. Calibration of the new probe demonstrated high linearity and sensitivity. The detection limit for this new probe was determined to be approximately two times lower than probes previously used in our laboratory. Basal nitric oxide fluctuations in Mytilus edulis heart and excised ganglia were able to be resolved in the sub-nanomolar range. The ISO-NOPF100 NO probe represents a significant advancement for measuring nitric oxide in real-time.

Nitric Oxide as a Mediator of Oxidant Lung Injury Due to Paraquat

NASA Astrophysics Data System (ADS)

Berisha, Hasan I.; Pakbaz, Hedayatollah; Absood, Afaf; Said, Sami I.

1994-08-01

At low concentrations, nitric oxide is a physiological transmitter, but in excessive concentrations it may cause cell and tissue injury. We report that in acute oxidant injury induced by the herbicide paraquat in isolated guinea pig lungs, nitric oxide synthesis was markedly stimulated, as evidenced by increased levels of cyclic GMP in lung perfusate and of nitrite and L-citrulline production in lung tissue. All signs of injury, including increased airway and perfusion pressures, pulmonary edema, and protein leakage into the airspaces, were dose-dependently attenuated or totally prevented by either N^G-nitro-L-arginine methyl ester or N^ω-nitro-L-arginine, selective and competitive inhibitors of nitric oxide synthase. Protection was reversed by excess L-arginine but not by its enantiomer D-arginine. When blood was added to the lung perfusate, the paraquat injury was moderated or delayed as it was when paraquat was given to anesthetized guinea pigs. The rapid onset of injury and its failure to occur in the absence of Ca2+ suggest that constitutive rather than inducible nitric oxide synthase was responsible for the stimulated nitric oxide synthesis. The findings indicate that nitric oxide plays a critical role in the production of lung tissue injury due to paraquat, and it may be a pathogenetic factor in other forms of oxidant tissue injury.

Triazine herbicides inhibit relaxin signaling and disrupt nitric oxide homeostasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Si Eun; Lim, Sa Rang; Choi, Hyung-kyoon

Triazines are herbicides that are widely used worldwide, and we previously observed that the maternal exposure of mice to simazine (50 or 500 μg/kg) resulted in smaller ovaries and uteri of their female offspring. Here, we investigated the underlying mechanism that may account for the reproductive dysfunction induced by simazine. We found that following maternal exposure, simazine is transmitted to the offspring, as evidenced by its presence in the offspring ovaries. Analyses of the simazine-exposed offspring revealed that the expression of the relaxin hormone receptor, relaxin-family peptide receptor 1 (RXFP1), prominently decreased in their ovaries and uteri. In addition, downstreammore » target genes of the relaxin pathway including nitric oxide (NO) synthase 2 (Nos2), Nos3, matrix metallopeptidase 9 (Mmp9), and vascular endothelial growth factor (Vegf) were downregulated in their ovaries. Moreover, AKT and extracellular signal-regulated kinases (ERK) levels and their phosphorylated active forms decreased in simazine-exposed ovaries. In vitro exposure of the human ovarian granulosa cells (KGN) and uterine endometrium cells (Hec-1A) to very low concentrations (0.001 to 1 nM) of triazines including atrazine, terbuthylazine, and propazine repressed NO production with a concurrent reduction in RXFP1, NOS2, and NOS3. The inhibitory action of triazines on NO release was dependent on RXFP1, phosphoinositol 3-kinase (PI3K)/AKT, and ERK. Radioligand-binding assay also confirmed that triazines competitively inhibited the binding of relaxin to its receptor. Therefore, the present study suggests that triazine herbicides act as endocrine disrupters by interfering with relaxin hormone signaling. Thus, further evaluation of their impact on human health is imperative. - Highlights: • Triazines downregulate critical molecules involved in the relaxin signaling pathway. • Triazines act as potent antagonists of binding of relaxin to its receptor. • Triazines disrupt nitric oxide homeostasis.« less

Exploring the Role of CYP3A4 Mediated Drug Metabolism in the Pharmacological Modulation of Nitric Oxide Production

PubMed Central

Pérez-del Palacio, José; Díaz, Caridad; Vergara, Noemí; Algieri, Francesca; Rodríguez-Nogales, Alba; de Pedro, Nuria; Rodríguez-Cabezas, M. Elena; Genilloud, Olga; Gálvez, Julio; Vicente, Francisca

2017-01-01

Nitric-oxide synthase, the enzyme responsible for mammalian nitric oxide generation, and cytochrome P450, the major enzymes involved in drug metabolism, share striking similarities. Therefore, it makes sense that cytochrome P450 drug mediated biotransformations might play an important role in the pharmacological modulation of nitric oxide synthase. In this work, we have undertaken an integrated in vitro assessment of the hepatic metabolism and nitric oxide modulation of previously described dual inhibitors (imidazoles and macrolides) of these enzymes in order assess the implication of CYP450 activities over production of nitric oxide. In vitro systems based in human liver microsomes and activated mouse macrophages were developed for these purposes. Additionally in vitro production the hepatic metabolites of dual inhibitor, roxithromycin, was investigated achieving the identification and isolation of main hepatic biotransformation products. Our results suggested that for some macrolide compounds, the cytochrome P450 3A4 derived drug metabolites have an important effect on nitric oxide production and might critically contribute to the pharmacological immunomodulatory activity observed. PMID:28446877

iNOS-derived nitric oxide promotes glycolysis by inducing pyruvate kinase M2 nuclear translocation in ovarian cancer.

PubMed

Li, Linlin; Zhu, Lingqun; Hao, Bingtao; Gao, Wenwen; Wang, Qianli; Li, Keyi; Wang, Meng; Huang, Mengqiu; Liu, Zhengjun; Yang, Qiaohong; Li, Xiqing; Zhong, Zhuo; Huang, Wenhua; Xiao, Guanghui; Xu, Yang; Yao, Kaitai; Liu, Qiuzhen

2017-05-16

Aerobic glycolysis is essential for tumor growth and survival. Activation of multiple carcinogenic signals contributes to metabolism reprogramming during malignant transformation of cancer. Recently nitric oxide has been noted to promote glycolysis but the mechanism remains elusive. We report here the dual role of nitric oxide in glycolysis: low/physiological nitric oxide (≤ 100 nM) promotes glycolysis for ATP production, oxidative defense and cell proliferation of ovary cancer cells, whereas excess nitric oxide (≥ 500 nM) inhibits it. Nitric oxide has a positive effect on glycolysis by inducing PKM2 nuclear translocation in an EGFR/ERK2 signaling-dependent manner. Moreover, iNOS induced by mild inflammatory stimulation increased glycolysis and cell proliferation by producing low doses of nitric oxide, while hyper inflammation induced iNOS inhibited it by producing excess nitric oxide. Finally, iNOS expression is abnormally increased in ovarian cancer tissues and is correlated with PKM2 expression. Overexpression of iNOS is associated with aggressive phenotype and poor survival outcome in ovarian cancer patients. Our study indicated that iNOS/NO play a dual role of in tumor glycolysis and progression, and established a bridge between iNOS/NO signaling pathway and EGFR/ERK2/PKM2 signaling pathway, suggesting that interfering glycolysis by targeting the iNOS/NO/PKM2 axis may be a valuable new therapeutic approach of treating ovarian cancer.

Attenuation of oxidative and nitrosative stress in cortical area associates with antidepressant-like effects of tropisetron in male mice following social isolation stress.

PubMed

Haj-Mirzaian, Arya; Amiri, Shayan; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Kordjazy, Nastaran; Olson, Carl O; Rastegar, Mojgan; Naserzadeh, Parvaneh; Marzban, Hassan; Dehpour, Ahmad Reza; Hosseini, Mir-Jamal; Samiei, Elika; Mehr, Shahram Ejtemaei

2016-06-01

Tropisetron, a 5-HT3 receptor antagonist widely used as an antiemetic, has been reported to have positive effects on mood disorders. Adolescence is a critical period during the development of brain, where exposure to chronic stress during this time is highly associated with the development of depression. In this study, we showed that 4 weeks of juvenile social isolation stress (SIS) provoked depressive-like behaviors in male mice, which was associated with disruption of mitochondrial function and nitric oxide overproduction in the cortical areas. In this study, tropisetron (5mg/kg) reversed the negative behavioral effects of SIS in male mice. We found that the effects of tropisetron were mediated through mitigating the negative activity of inducible nitric oxide synthase (iNOS) on mitochondrial activity. Administration of aminoguanidine (specific iNOS inhibitor, 20mg/kg) augmented the protective effects of tropisetron (1mg/kg) on SIS. Furthermore, l-arginine (nitric oxide precursor, 100mg/kg) abolished the positive effects of tropisetron. These results have increased our knowledge on the pivotal role of mitochondrial function in the pathophysiology of depression, and highlighted the role of 5-HT3 receptors in psychosocial stress response during adolescence. Finally, we observed that tropisetron alleviated the mitochondrial dysfunction through decreased nitrergic system activity in the cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

Nitric oxide synthase-I containing cortical interneurons co-express antioxidative enzymes and anti-apoptotic Bcl-2 following focal ischemia: evidence for direct and indirect mechanisms towards their resistance to neuropathology.

PubMed

Bidmon, H J; Emde, B; Kowalski, T; Schmitt, M; Mayer, B; Kato, K; Asayama, K; Witte, O W; Zilles, K

2001-09-01

Neuronal nitric oxide-I is constitutively expressed in approximately 2% of cortical interneurons and is co-localized with gamma-amino butric acid, somatostatin or neuropeptide Y. These interneurons additionally express high amounts of glutamate receptors which mediate the glutamate-induced hyperexcitation following cerebral injury, under these conditions nitric oxide production increases contributing to a potentiation of oxidative stress. However, perilesional nitric oxide synthase-I containing neurons are known to be resistant to ischemic and excitotoxic injury. In vitro studies show that nitrosonium and nitroxyl ions inactivate N-methyl-D-aspartate receptors, resulting in neuroprotection. The question remains of how these cells are protected against their own high intracellular nitric oxide production after activation. In this study, we investigated immunocytochemically nitric oxide synthase-I containing cortical neurons in rats after unilateral, cortical photothrombosis. In this model of focal ischemia, perilesional, constitutively nitric oxide synthase-I containing neurons survived and co-expressed antioxidative enzymes, such as manganese- and copper-zinc-dependent superoxide dismutases, heme oxygenase-2 and cytosolic glutathione peroxidase. This enhanced antioxidant expression was accompanied by a strong perinuclear presence of the antiapoptotic Bcl-2 protein. No colocalization was detectable with upregulated heme oxygenase-1 in glia and the superoxide and prostaglandin G(2)-producing cyclooxygenase-2 in neurons. These results suggest that nitric oxide synthase-I containing interneurons are protected against intracellular oxidative damage and apoptosis by Bcl-2 and several potent antioxidative enzymes. Since nitric oxide synthase-I positive neurons do not express superoxide-producing enzymes such as cyclooxygenase-1, xanthine oxidase and cyclooxygenase-2 in response to injury, this may additionally contribute to their resistance by reducing their internal peroxynitrite, H(2)O(2)-formation and caspase activation.

Ischemic and oxidative damage to the hypothalamus may be responsible for heat stroke.

PubMed

Chen, Sheng-Hsien; Lin, Mao-Tsun; Chang, Ching-Ping

2013-03-01

The hypothalamus may be involved in regulating homeostasis, motivation, and emotional behavior by controlling autonomic and endocrine activity. The hypothalamus communicates input from the thalamus to the pituitary gland, reticular activating substance, limbic system, and neocortex. This allows the output of pituitary hormones to respond to changes in autonomic nervous system activity. Environmental heat stress increases cutaneous blood flow and metabolism, and progressively decreases splanchnic blood flow. Severe heat exposure also decreases mean arterial pressure (MAP), increases intracranial pressure (ICP), and decreases cerebral perfusion pressure (CPP = MAP - ICP), all of which lead to cerebral ischemia and hypoxia. Compared with normothermic controls, rodents with heatstroke have higher hypothalamic values of cellular ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and damage (e.g., glycerol) markers, pro-oxidant enzymes (e.g., lipid peroxidation and glutathione oxidation), proinflammatory cytokines (e.g., interleukin-1β and tumor necrosis factor-α), inducible nitric oxide synthase-dependent nitric oxide, and an indicator for the accumulation of polymorphonuclear leukocytes (e.g., myeloperoxidase activity), as well as neuronal damage (e.g., apoptosis, necrosis, and autophagy) after heatstroke. Hypothalamic values of antioxidant defenses (e.g., glutathione peroxidase and glutathione reductase), however, are lower. The ischemic, hypoxic, and oxidative damage to the hypothalamus during heatstroke may cause multiple organ dysfunction or failure through hypothalamic-pituitary-adrenal axis mechanisms. Finding the link between the signaling and heatstroke-induced hypothalamic oxidative and ischemic damage might allow us to clinically attenuate heatstroke. In particular, free radical scavengers, heat shock protein-70 inducers, hypervolemic hemodilution, inducible nitric oxide synthase inhibitors, progenitor stem cells, flutamide, estrogen, interleukin-1 receptor antagonists, glucocorticoid, activated protein C, and baicalin mitigate preclinical heatstroke levels.

Impact of exposure to low concentrations of nitric oxide on protein profile in murine and human pancreatic islet cells

PubMed Central

Tapia-Limonchi, Rafael; Díaz, Irene; Cahuana, Gladys M; Bautista, Mario; Martín, Franz; Soria, Bernat; Tejedo, Juan R; Bedoya, Francisco J

2014-01-01

Homeostatic levels of nitric oxide (NO) protect efficiently against apoptotic death in both human and rodent pancreatic β cells, but the protein profile of this action remains to be determined. We have applied a 2 dimensional LC-MS-MALDI-TOF/TOF-based analysis to study the impact of protective NO in rat insulin-producing RINm5F cell line and in mouse and human pancreatic islets (HPI) exposed to serum deprivation condition. 24 proteins in RINm5F and 22 in HPI were identified to undergo changes in at least one experimental condition. These include stress response mitochondrial proteins (UQCRC2, VDAC1, ATP5C1, ATP5A1) in RINm5F cells and stress response endoplasmic reticulum proteins (HSPA5, PDIA6, VCP, GANAB) in HPI. In addition, metabolic and structural proteins, oxidoreductases and chaperones related with protein metabolism are also regulated by NO treatment. Network analysis of differentially expressed proteins shows their interaction in glucocorticoid receptor and NRF2-mediated oxidative stress response pathways and eNOS signaling. The results indicate that exposure to exogenous NO counteracts the impact of serum deprivation on pancreatic β cell proteome. Species differences in the proteins involved are apparent. PMID:25658244

Two Dimensional Polymer That Generates Nitric Oxide.

DOEpatents

McDonald, William F.; Koren, Amy B.

2005-10-04

A polymeric composition that generates nitric oxide and a process for rendering the surface of a substrate nonthrombogenic by applying a coating of the polymeric composition to the substrate are disclosed. The composition comprises: (1) a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, and (ii) a crosslinking agent containing functional groups capable of reacting with the amino groups; and (2) a plurality of nitric oxide generating functional groups associated with the crosslinked chemical combination. Once exposed to a physiological environment, the coating generates nitric oxide thereby inhibiting platelet aggregation. In one embodiment, the nitric oxide generating functional groups are provided by a nitrated compound (e.g., nitrocellulose) imbedded in the polymeric composition. In another embodiment, the nitric oxide generating functional groups comprise N2O2- groups covalently bonded to amino groups on the polymer.

Nitric oxide synthesis in patients with advanced HIV infection.

PubMed Central

Evans, T G; Rasmussen, K; Wiebke, G; Hibbs, J B

1994-01-01

The discovery that humans produce nitric oxide and that this molecule plays an important role in cell communication, host resistance to infection, and perhaps in host defence to neoplastic disease, has created much interest in further research on its function in the body. A cytokine-inducible high output L-arginine/nitric oxide pathway was recently detected in patients with advanced malignancy treated with IL-2. The production of nitric oxide was thus examined in patients with advanced HIV infection and in intensive care unit control patients. Extrinsic nitrate and nitrite consumption were carefully controlled in the diet or through the use of total parenteral nutrition. Seven of eight HIV+ patients were placed into positive nitrogen balance. Nitric oxide synthesis was found to be within the normal human range. In contrast, nitric oxide synthesis in extremely ill intensive care unit patients was low normal to depressed. PMID:8033424

Chronic exposure to nitric oxide alters the free iron pool in endothelial cells: Role of mitochondrial respiratory complexes and heat shock proteins

PubMed Central

Ramachandran, Anup; Ceaser, Erin; Darley-Usmar, Victor M.

2004-01-01

The mechanisms of nitric oxide (NO) signaling include binding to the iron centers in soluble guanylate cyclase and cytochrome c oxidase and posttranslational modification of proteins by S-nitrosation. Low levels of NO control mitochondrial number in cells, but little is known of the impact of chronic exposure to high levels of NO on mitochondrial function in endothelial cells. The focus of this study is the interaction of NO with mitochondrial respiratory complexes in cell culture and the effect this has on iron homeostasis. We demonstrate that chronic exposure of endothelial cells to NO decreased activity and protein levels of complexes I, II, and IV, whereas citrate synthase and ATP synthase were unaffected. Inhibition of these respiratory complexes was accompanied by an increase in cellular S-nitrosothiol levels, modification of cysteines residues, and an increase in the labile iron pool. The NO-dependent increase in the free iron pool and inhibition of complex II was prevented by inhibition of mitochondrial protein synthesis, consistent with a major contribution of the organelle to iron homeostasis. In addition, inhibition of mitochondrial protein synthesis was associated with an increase in heat shock protein 60 levels, which may be an additional mechanism leading to preservation of complex II activity. PMID:14691259

Acrolein Can Cause Cardiovascular Disease: A Review.

PubMed

Henning, Robert J; Johnson, Giffe T; Coyle, Jayme P; Harbison, Raymond D

2017-07-01

Acrolein is a highly reactive unsaturated aldehyde that is formed during the burning of gasoline and diesel fuels, cigarettes, woods and plastics. In addition, acrolein is generated during the cooking or frying of food with fats or oils. Acrolein is also used in the synthesis of many organic chemicals and as a biocide in agricultural and industrial water supply systems. The total emissions of acrolein in the United States from all sources are estimated to be 62,660 tons/year. Acrolein is classified by the Environmental Protection Agency as a high-priority air and water toxicant. Acrolein can exert toxic effects following inhalation, ingestion, and dermal exposures that are dose dependent. Cardiovascular tissues are particularly sensitive to the toxic effects of acrolein based primarily on in vitro and in vivo studies. Acrolein can generate free oxygen radical stress in the heart, decrease endothelial nitric oxide synthase phosphorylation and nitric oxide formation, form cytoplasmic and nuclear protein adducts with myocyte and vascular endothelial cell proteins and cause vasospasm. In this manner, chronic exposure to acrolein can cause myocyte dysfunction, myocyte necrosis and apoptosis and ultimately lead to cardiomyopathy and cardiac failure. Epidemiological studies of acrolein exposure and toxicity should be developed and treatment strategies devised that prevent or significantly limit acrolein cardiovascular toxicity.

Cloning and Characterization of Inducible Nitric Oxide Synthase from Mouse Macrophages

NASA Astrophysics Data System (ADS)

Xie, Qiao-Wen; Cho, Hearn J.; Calaycay, Jimmy; Mumford, Richard A.; Swiderek, Kristine M.; Lee, Terry D.; Ding, Aihao; Troso, Tiffany; Nathan, Carl

1992-04-01

Nitric oxide (NO) conveys a variety of messages between cells, including signals for vasorelaxation, neurotransmission, and cytotoxicity. In some endothelial cells and neurons, a constitutive NO synthase is activated transiently by agonists that elevate intracellular calcium concentrations and promote the binding of calmodulin. In contrast, in macrophages, NO synthase activity appears slowly after exposure of the cells to cytokines and bacterial products, is sustained, and functions independently of calcium and calmodulin. A monospecific antibody was used to clone complementary DNA that encoded two isoforms of NO synthase from immunologically activated mouse macrophages. Liquid chromatography-mass spectrometry was used to confirm most of the amino acid sequence. Macrophage NO synthase differs extensively from cerebellar NO synthase. The macrophage enzyme is immunologically induced at the transcriptional level and closely resembles the enzyme in cytokine-treated tumor cells and inflammatory neutrophils.

Dietary nitrates, nitrites, and cardiovascular disease.

PubMed

Hord, Norman G

2011-12-01

Dietary nitrate (NO(3)), nitrite (NO(2)), and arginine can serve as sources for production of NO(x) (a diverse group of metabolites including nitric oxide, nitrosothiols, and nitroalkenes) via ultraviolet light exposure to skin, mammalian nitrate/nitrite reductases in tissues, and nitric oxide synthase enzymes, respectively. NO(x) are responsible for the hypotensive, antiplatelet, and cytoprotective effects of dietary nitrates and nitrites. Current regulatory limits on nitrate intakes, based on concerns regarding potential risk of carcinogenicity and methemoglobinemia, are exceeded by normal daily intakes of single foods, such as soya milk and spinach, as well as by some recommended dietary patterns such as the Dietary Approaches to Stop Hypertension diet. This review includes a call for regulatory bodies to consider all available data on the beneficial physiologic roles of nitrate and nitrite in order to derive rational bases for dietary recommendations.

Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

PubMed

Curran, Jerry; Tang, Lifei; Roof, Steve R; Velmurugan, Sathya; Millard, Ashley; Shonts, Stephen; Wang, Honglan; Santiago, Demetrio; Ahmad, Usama; Perryman, Matthew; Bers, Donald M; Mohler, Peter J; Ziolo, Mark T; Shannon, Thomas R

2014-01-01

Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+) leak) through ryanodine receptors. Beta-adrenergic (β-AR) tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII) and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+) waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+) leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+) leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+) leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis that CaMKII is regulated by nitric oxide as part of the adrenergic cascade leading to arrhythmogenesis.

Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain TrichCH4B.

PubMed

Rao, Minxi; Smith, Brian C; Marletta, Michael A

2015-05-05

Nitric oxide (NO) plays an important signaling role in all domains of life. Many bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that selectively binds NO. These H-NOX proteins often act as sensors that regulate histidine kinase (HK) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. In several organisms, NO binding to the H-NOX protein governs bacterial biofilm formation; however, the source of NO exposure for these bacteria is unknown. In mammals, NO is generated by the enzyme nitric oxide synthase (NOS) and signals through binding the H-NOX domain of soluble guanylate cyclase. Recently, several bacterial NOS proteins have also been reported, but the corresponding bacteria do not also encode an H-NOX protein. Here, we report the first characterization of a bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system capable of both synthesizing and sensing NO. We characterized the NO signaling pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B, determining that the NOS is activated by an algal symbiont, Trichodesmium erythraeum. NO signaling through a histidine kinase-response regulator two-component signaling pathway results in increased concentrations of cyclic diguanosine monophosphate, a key bacterial second messenger molecule that controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B biofilm formation, activated by T. erythraeum, may be an important mechanism for symbiosis between the two organisms, revealing that NO plays a previously unknown key role in bacterial communication and symbiosis. Bacterial nitric oxide (NO) signaling via heme-nitric oxide/oxygen binding (H-NOX) proteins regulates biofilm formation, playing an important role in protecting bacteria from oxidative stress and other environmental stresses. Biofilms are also an important part of symbiosis, allowing the organism to remain in a nutrient-rich environment. In this study, we show that in Silicibacter sp. strain TrichCH4B, NO mediates symbiosis with the alga Trichodesmium erythraeum, a major marine diazotroph. In addition, Silicibacter sp. TrichCH4B is the first characterized bacteria to harbor both the NOS and H-NOX proteins, making it uniquely capable of both synthesizing and sensing NO, analogous to mammalian NO signaling. Our study expands current understanding of the role of NO in bacterial signaling, providing a novel role for NO in bacterial communication and symbiosis. Copyright © 2015 Rao et al.

Differential Pro-Inflammatory Responses of Astrocytes and Microglia Involve STAT3 Activation in Response to 1800 MHz Radiofrequency Fields

PubMed Central

Lu, Yonghui; He, Mindi; Zhang, Yang; Xu, Shangcheng; Zhang, Lei; He, Yue; Chen, Chunhai; Liu, Chuan; Pi, Huifeng; Yu, Zhengping; Zhou, Zhou

2014-01-01

Microglia and astrocytes play important role in maintaining the homeostasis of central nervous system (CNS). Several CNS impacts have been postulated to be associated with radiofrequency (RF) electromagnetic fields exposure. Given the important role of inflammation in neural physiopathologic processes, we investigated the pro-inflammatory responses of microglia and astrocytes and the involved mechanism in response to RF fields. Microglial N9 and astroglial C8-D1A cells were exposed to 1800 MHz RF for different time with or without pretreatment with STAT3 inhibitor. Microglia and astrocytes were activated by RF exposure indicated by up-regulated CD11b and glial fibrillary acidic protein (GFAP). However, RF exposure induced differential pro-inflammatory responses in astrocytes and microglia, characterized by different expression and release profiles of IL-1β, TNF-α, IL-6, PGE2, nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Moreover, the RF exposure activated STAT3 in microglia but not in astrocytes. Furthermore, the STAT3 inhibitor Stattic ameliorated the RF-induced release of pro-inflammatory cytokines in microglia but not in astrocytes. Our results demonstrated that RF exposure differentially induced pro-inflammatory responses in microglia and astrocytes, which involved differential activation of STAT3 in microglia and astrocytes. Our data provide novel insights into the potential mechanisms of the reported CNS impacts associated with mobile phone use and present STAT3 as a promising target to protect humans against increasing RF exposure. PMID:25275372

Differential pro-inflammatory responses of astrocytes and microglia involve STAT3 activation in response to 1800 MHz radiofrequency fields.

PubMed

Lu, Yonghui; He, Mindi; Zhang, Yang; Xu, Shangcheng; Zhang, Lei; He, Yue; Chen, Chunhai; Liu, Chuan; Pi, Huifeng; Yu, Zhengping; Zhou, Zhou

2014-01-01

Microglia and astrocytes play important role in maintaining the homeostasis of central nervous system (CNS). Several CNS impacts have been postulated to be associated with radiofrequency (RF) electromagnetic fields exposure. Given the important role of inflammation in neural physiopathologic processes, we investigated the pro-inflammatory responses of microglia and astrocytes and the involved mechanism in response to RF fields. Microglial N9 and astroglial C8-D1A cells were exposed to 1800 MHz RF for different time with or without pretreatment with STAT3 inhibitor. Microglia and astrocytes were activated by RF exposure indicated by up-regulated CD11b and glial fibrillary acidic protein (GFAP). However, RF exposure induced differential pro-inflammatory responses in astrocytes and microglia, characterized by different expression and release profiles of IL-1β, TNF-α, IL-6, PGE2, nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Moreover, the RF exposure activated STAT3 in microglia but not in astrocytes. Furthermore, the STAT3 inhibitor Stattic ameliorated the RF-induced release of pro-inflammatory cytokines in microglia but not in astrocytes. Our results demonstrated that RF exposure differentially induced pro-inflammatory responses in microglia and astrocytes, which involved differential activation of STAT3 in microglia and astrocytes. Our data provide novel insights into the potential mechanisms of the reported CNS impacts associated with mobile phone use and present STAT3 as a promising target to protect humans against increasing RF exposure.

[Ultrasound induced the formation of nitric oxide and nitrosonium ions in water and aqueous solutions].

PubMed

Stepuro, I I; Adamchuk, R I; Stepuro, V I

2004-01-01

Nitric oxide, nitrosonium ions, nitrites, and nitrates are formed in water saturated with air under the action of ultrasound. Nitrosonium ions react with water and hydrogen peroxide to form nitrites and nitrates in sonicated solution, correspondingly. Nitric oxide is practically completely released from sonicated water into the atmosphere and reacts with air oxygen, forming NOx compounds. The oxidation of nitric oxide in aqueous medium by hydroxyl radicals and dissolved oxygen is a minor route of the formation of nitrites and nitrates in ultrasonic field.

Arginine supplementation induces myoblast fusion via augmentation of nitric oxide production.

PubMed

Long, Jodi H D; Lira, Vitor A; Soltow, Quinlyn A; Betters, Jenna L; Sellman, Jeff E; Criswell, David S

2006-01-01

The semi-essential amino acid, L-arginine (L-Arg), is the substrate for endogenous synthesis of nitric oxide, a molecule that is involved in myoblast proliferation and fusion. Since L-Arg supply may limit nitric oxide synthase (NOS) activity in endothelial cells, we examined L-Arg supplementation in differentiating mouse myoblasts and tested the hypothesis that L-Arg exerts direct effects on myoblast fusion via augmentation of endogenous nitric oxide production. C(2)C(12) myoblasts in differentiation media received one of the following treatments for 120 h: 1 mM L-Arg, 0.1 mM N-nitro-L-arginine methyl ester (L-NAME), L-Arg + L-NAME, 10 mM L-Lysine, or no supplement (Control). Cultures were fixed and stained with hematoxylin and eosin for microphotometric image analysis of myotube density, nuclear density, and fusion index (% of total nuclei in myotubes). Endogenous production of nitric oxide during the treatment period peaked between 24 and 48 h. L-Arg amplified nitric oxide production between 0 and 24 h and increased myotube density, total nuclei number, and nuclear fusion index. These L-Arg effects were prevented by the NOS inhibitor, L-NAME. Further, L-Lysine, a competitive inhibitor of L-Arg uptake, repressed nitric oxide production and reduced myotube density and fusion index. In summary, L-Arg augments myotube formation and increases nitric oxide production in a process limited by cellular L-Arg uptake.

Stimulation of nitric oxide synthesis by the aqueous extract of Panax ginseng root in RAW 264.7 cells

PubMed Central

Friedl, Roswitha; Moeslinger, Thomas; Kopp, Brigitte; Spieckermann, Paul Gerhard

2001-01-01

In this study, we investigated the effect of Panax ginseng root aqueous extracts upon inducible nitric oxide synthesis in RAW 264.7 cells. Panax ginseng root extract has been used in the Asian world for centuries as a traditional herb to enhance physical strength and resistance and is becoming more and more popular in Europe and North America. Incubation of murine macrophages (RAW 264.7 cells) with increasing amounts of aqueous extracts of Panax ginseng (0.05 – 0.8 μg μl−1) showed a dose dependent stimulation of inducible nitric oxide synthesis. Polysaccharides isolated from Panax ginseng showed strong stimulation of inducible nitric oxide synthesis, whereas a triterpene-enriched fraction from an aqueous extract of Panax ginseng did not show any stimulation. Inducible nitric oxide synthase protein expression was enhanced in a dose dependent manner as revealed by immunoblotting when cells were incubated with increasing amounts of Panax ginseng extract. This was associated with an incline in inducible nitric oxide synthase mRNA-levels as determined by semiquantitative polymerase chain reaction and electromobility shift assay studies indicated enhanced nuclear factor-κB DNA binding activity. As nitric oxide plays an important role in immune function, Panax ginseng treatment could modulate several aspects of host defense mechanisms due to stimulation of the inducible nitric oxide synthase. PMID:11739242

A protective role for nitric oxide and salicylic acid for arsenite phytotoxicity in rice (Oryza sativa L.).

PubMed

Singh, Amit Pal; Dixit, Garima; Kumar, Amit; Mishra, Seema; Kumar, Navin; Dixit, Sameer; Singh, Pradyumna Kumar; Dwivedi, Sanjay; Trivedi, Prabodh Kumar; Pandey, Vivek; Dhankher, Om Prakash; Norton, Gareth J; Chakrabarty, Debasis; Tripathi, Rudra Deo

2017-06-01

Nitric oxide (NO) and salicylic acid (SA) are important signaling molecules in plant system. In the present study both NO and SA showed a protective role against arsenite (As III ) stress in rice plants when supplied exogenously. The application of NO and SA alleviated the negative impact of As III on plant growth. Nitric oxide supplementation to As III treated plants greatly decreased arsenic (As) accumulation in the roots as well as shoots/roots translocation factor. Arsenite exposure in plants decreased the endogenous levels of NO and SA. Exogenous supplementation of SA not only enhanced endogenous level of SA but also the level of NO through enhanced nitrate reductase (NR) activity, whether As III was present or not. Exogenously supplied NO decreased the NR activity and level of endogenous NO. Arsenic accumulation was positively correlated with the expression level of OsLsi1, a transporter responsible for As III uptake. The endogenous level of NO and SA were positively correlated to each other either when As III was present or not. This close relationship indicates that NO and SA work in harmony to modulate the signaling response in As III stressed plants. Copyright © 2017. Published by Elsevier Masson SAS.

Ultraviolet A irradiation of the eye activates a nitric oxide-dependent hypothalamo-pituitary pro-opiomelanocortin pathway and modulates the functions of Langerhans cells.

PubMed

Hiramoto, Keiichi

2009-06-01

Ultraviolet A (UV-A) radiation decreases Langerhans cells (LC) in the skin specifically at the site of exposure. Unexpectedly, UV-A irradiation of the eye has been found systemically downregulating epidermal LC in mice. Male C57BL/6j mice and an inducible type of nitric oxide synthase knockout mice (iNOS(-/-)) were used in this study. The eye or ear was locally exposed to UV-A after covering the remaining body surface with aluminum foil at a dose of 110 kJ/m(2) using a sunlamp. Localized UV-A irradiation of the eye downregulated epidermal LC. The hypophysectomy strongly inhibited the UV-A-induced downregulation of LC. To elucidate the pathway by UV-A irradiation of the eye, the effect of a bilateral ciliary ganglionectomy and denervation of the optic nerves was examined. Optic nerve denervation strongly inhibited LC downregulation in response to localized irradiation of the eye. Furthermore, no LC downregulation in response to localized UV-A irradiation of the eye was observed in iNOS(-/-) mice. These results clearly indicate that a signal evoked by UV-A irradiation of the eye is transmitted in a nitric oxide-dependent manner through the optic nerves to the hypothalamo-pituitary pro-opiomelanocortin system.

Molecular analysis of erection regulatory factors in sickle cell disease associated priapism in the human penis.

PubMed

Lagoda, Gwen; Sezen, Sena F; Cabrini, Marcelo R; Musicki, Biljana; Burnett, Arthur L

2013-02-01

Priapism is a vasculopathy that occurs in approximately 40% of patients with sickle cell disease. Mouse models suggest that dysregulated nitric oxide synthase and RhoA/ROCK signaling as well as increased oxidative stress may contribute to the mechanisms of sickle cell disease associated priapism. We examined changes in the protein expression of nitric oxide synthase and ROCK signaling pathways, and a source of oxidative stress, NADPH oxidase, in penile erectile tissue from patients with a priapism history etiologically related and unrelated to sickle cell disease. Human penile erectile tissue was obtained from 5 patients with sickle cell disease associated priapism and from 6 with priapism of other etiologies during nonemergent penile prosthesis surgery for erectile dysfunction or priapism management and urethroplasty. Tissue was also obtained from 5 control patients without a priapism history during penectomy for penile cancer. Samples were collected, immediately placed in cold buffer and then frozen in liquid nitrogen. The expression of phosphodiesterase 5, endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase, RhoA, ROCK1, ROCK2, p47(phox), p67(phox), gp91(phox) and β-actin were determined by Western blot analysis. Nitric oxide was measured using the Griess reaction. In the sickle cell disease group phosphodiesterase 5 (p <0.05), endothelial nitric oxide synthase (p <0.01) and RhoA (p <0.01) expression was significantly decreased, while gp91(phox) expression (p <0.05) was significantly increased compared to control values. In the nonsickle cell disease group endothelial nitric oxide synthase, ROCK1 and p47(phox) expression (each p <0.05) was significantly decreased compared to control values. Total nitric oxide levels were not significantly different between the study groups. Mechanisms of sickle cell disease associated priapism in the human penis may involve dysfunctional nitric oxide synthase and ROCK signaling, and increased oxidative stress associated with NADPH oxidase mediated signaling. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Separate Nitrite, Nitric Oxide, and Nitrous Oxide Reducing Fractions from Pseudomonas perfectomarinus

PubMed Central

Payne, W. J.; Riley, P. S.; Cox, C. D.

1971-01-01

Pseudomonas perfectomarinus was found to grow anaerobically at the expense of nitrate, nitrite, or nitrous oxide but not chlorate or nitric oxide. In several repetitive experiments, anaerobic incubation in culture media containing nitrate revealed that an average of 82% of the cells in aerobically grown populations were converted to the capacity for respiration of nitrate. Although they did not form colonies under these conditions, the bacteria synthesized the denitrifying enzymes within 3 hr in the absence of oxygen or another acceptable inorganic oxidant. This was demonstrated by the ability, after anaerobic incubation, of cells and of extracts to reduce nitrite, nitric oxide, and nitrous oxide to nitrogen. From crude extracts of cells grown on nitrate, nitrite, or nitrous oxide, separate complex fractions were obtained that utilized reduced nicotinamide adenine dinucleotide as the source of electrons for the reduction of (i) nitrite to nitric oxide, (ii) nitric oxide to nitrous oxide, and (iii) nitrous oxide to nitrogen. Gas chromatographic analyses revealed that each of these fractions reduced only one of the nitrogenous oxides. PMID:4324803

Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

PubMed

Erdmann, Jeanette; Stark, Klaus; Esslinger, Ulrike B; Rumpf, Philipp Moritz; Koesling, Doris; de Wit, Cor; Kaiser, Frank J; Braunholz, Diana; Medack, Anja; Fischer, Marcus; Zimmermann, Martina E; Tennstedt, Stephanie; Graf, Elisabeth; Eck, Sebastian; Aherrahrou, Zouhair; Nahrstaedt, Janja; Willenborg, Christina; Bruse, Petra; Brænne, Ingrid; Nöthen, Markus M; Hofmann, Per; Braund, Peter S; Mergia, Evanthia; Reinhard, Wibke; Burgdorf, Christof; Schreiber, Stefan; Balmforth, Anthony J; Hall, Alistair S; Bertram, Lars; Steinhagen-Thiessen, Elisabeth; Li, Shu-Chen; März, Winfried; Reilly, Muredach; Kathiresan, Sekar; McPherson, Ruth; Walter, Ulrich; Ott, Jurg; Samani, Nilesh J; Strom, Tim M; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert

2013-12-19

Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce α1-sGC as well as β1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in α1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.

Effect of fatty acids on endothelium-dependent relaxation in the rabbit aorta.

PubMed

Edirisinghe, Indika; McCormick Hallam, Kellie; Kappagoda, C Tissa

2006-08-01

The metabolic syndrome, Type II (non-insulin-dependent) diabetes and obesity are associated with endothelial dysfunction and increased plasma concentrations of NEFAs (non-esterified fatty acids; free fatty acids). The present study was undertaken to define the inhibitory effects of saturated NEFAs on EDR (endothelium-dependent relaxation). Experiments were performed in rings of rabbit aorta to establish (i) dose-response relationships, (ii) the effect of chain length, (iii) the effect of the presence of double bonds, (iv) reversibility and time course of inhibition, and (v) the effect on nitric oxide production. Aortic rings were incubated (1 h) with NEFA-albumin complexes derived from lauric (C(12:0)), myristic (C(14:0)), palmitic (C(16:0)), stearic (C(18:0)) and linolenic (C(18:3)) acids. EDR induced by acetylcholine (0.1-10 mumol/l) was measured after pre-contraction with noradrenaline. Inhibition of EDR was dose-dependent (0.5-2 mmol/l NEFA), and the greatest inhibition (51%) was observed with stearic acid (2 mmol/l). Lauric acid had the smallest inhibitory effect. The inhibitory effects were always reversible and were evident after 15 min of incubation. Linolenic acid caused a significantly lower inhibition of EDR than stearic acid. SOD (superoxide dismutase) restored the inhibitory effect caused by NEFAs, suggesting the involvement of ROS (reactive oxygen species) in removing nitric oxide. The nitric oxide concentration measured after exposure of the rings to acetylcholine was lower after incubation with NEFAs than with Krebs buffer alone. This finding is consistent with removal of nitric oxide by ROS. This claim was supported by the demonstration of increased concentrations of nitrated tyrosine in the rings incubated with NEFAs.

Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation.

PubMed

Belcik, J Todd; Mott, Brian H; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J; Ammi, Azzdine; Linden, Joel M; Lindner, Jonathan R

2015-04-01

Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators. Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.6 or 1.3) or ultrasound with lipid microbubbles (2×10(8) IV). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (P<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3- and 10-fold higher than control for mechanical index 0.6 and 1.3, respectively; P<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase attenuated flow augmentation produced by ultrasound and microbubbles by 70% (P<0.01), whereas inhibition of adenosine-A2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide production and muscle phospho-endothelial nitric oxide synthase increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40%-50% reduction in flow), ultrasound (mechanical index, 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control nonischemic limb. Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of endothelial nitric oxide synthase. © 2015 American Heart Association, Inc.

iNOS-derived nitric oxide promotes glycolysis by inducing pyruvate kinase M2 nuclear translocation in ovarian cancer

PubMed Central

Hao, Bingtao; Gao, Wenwen; Wang, Qianli; Li, Keyi; Wang, Meng; Huang, Mengqiu; Liu, Zhengjun; Yang, Qiaohong; Li, Xiqing; Zhong, Zhuo; Huang, Wenhua; Xiao, Guanghui; Xu, Yang; Yao, Kaitai; Liu, Qiuzhen

2017-01-01

Aerobic glycolysis is essential for tumor growth and survival. Activation of multiple carcinogenic signals contributes to metabolism reprogramming during malignant transformation of cancer. Recently nitric oxide has been noted to promote glycolysis but the mechanism remains elusive. We report here the dual role of nitric oxide in glycolysis: low/physiological nitric oxide (≤ 100 nM) promotes glycolysis for ATP production, oxidative defense and cell proliferation of ovary cancer cells, whereas excess nitric oxide (≥ 500 nM) inhibits it. Nitric oxide has a positive effect on glycolysis by inducing PKM2 nuclear translocation in an EGFR/ERK2 signaling-dependent manner. Moreover, iNOS induced by mild inflammatory stimulation increased glycolysis and cell proliferation by producing low doses of nitric oxide, while hyper inflammation induced iNOS inhibited it by producing excess nitric oxide. Finally, iNOS expression is abnormally increased in ovarian cancer tissues and is correlated with PKM2 expression. Overexpression of iNOS is associated with aggressive phenotype and poor survival outcome in ovarian cancer patients. Our study indicated that iNOS/NO play a dual role of in tumor glycolysis and progression, and established a bridge between iNOS/NO signaling pathway and EGFR/ERK2/PKM2 signaling pathway, suggesting that interfering glycolysis by targeting the iNOS/NO/PKM2 axis may be a valuable new therapeutic approach of treating ovarian cancer. PMID:28380434

Oxidation of nitroxyl anion to nitric oxide by copper ions

PubMed Central

Nelli, Silvia; Hillen, Mark; Buyukafsar, Kansu; Martin, William

2000-01-01

This study made use of a nitric oxide-sensitive electrode to examine possible means of generating nitric oxide from nitroxyl anion (NO−) released upon the decomposition of Angeli's salt. Our results show that copper ions (from CuSO4) catalyze the rapid and efficient oxidation of nitroxyl to nitric oxide. Indeed, the concentrations of copper required to do so (0.1–100 μM) are roughly 100-times lower than those required to generate equivalent amounts of nitric oxide from S-nitroso-N-acetyl-D,L-penicillamine (SNAP). Experiments with ascorbate (1 mM), which reduces Cu2+ ions to Cu+, and with the Cu2+ chelators, EDTA and cuprizone, and the Cu+ chelator, neocuproine, each at 1 mM, suggest that the oxidation is catalyzed by copper ions in both valency states. Some compounds containing other transition metals, i.e. methaemoglobin, ferricytochrome c and Mn(III)TMPyP, were much less efficient than CuSO4 in catalyzing the formation of nitric oxide from nitroxyl, while FeSO4, FeCl3, MnCl2, and ZnSO4 were inactive. Of the copper containing enzymes examined, Cu-Zn superoxide dismutase and ceruloplasmin were weak generators of nitric oxide from nitroxyl, even at concentrations (2500 and 30 u ml−1, respectively) vastly greater than are present endogenously. Two others, ascorbate oxidase (10 u ml−1) and tyrosinase (250 u ml−1) were inactive. Our findings suggest that a copper-containing enzyme may be responsible for the rapid oxidation of nitroxyl to nitric oxide by cells, but the identity of such an enzyme remains elusive. PMID:10991931

Prolonged exposure of chromaffin cells to nitric oxide down-regulates the activity of soluble guanylyl cyclase and corresponding mRNA and protein levels

PubMed Central

Ferrero, Rut; Torres, Magdalena

2002-01-01

Background Soluble guanylyl cyclase (sGC) is the main receptor for nitric oxide (NO) when the latter is produced at low concentrations. This enzyme exists mainly as a heterodimer consisting of one α and one β subunit and converts GTP to the second intracellular messenger cGMP. In turn, cGMP plays a key role in regulating several physiological processes in the nervous system. The aim of the present study was to explore the effects of a NO donor on sGC activity and its protein and subunit mRNA levels in a neural cell model. Results Continuous exposure of bovine adrenal chromaffin cells in culture to the nitric oxide donor, diethylenetriamine NONOate (DETA/NO), resulted in a lower capacity of the cells to synthesize cGMP in response to a subsequent NO stimulus. This effect was not prevented by an increase of intracellular reduced glutathione level. DETA/NO treatment decreased sGC subunit mRNA and β1 subunit protein levels. Both sGC activity and β1 subunit levels decreased more rapidly in chromaffin cells exposed to NO than in cells exposed to the protein synthesis inhibitor, cycloheximide, suggesting that NO decreases β1 subunit stability. The presence of cGMP-dependent protein kinase (PKG) inhibitors effectively prevented the DETA/NO-induced down regulation of sGC subunit mRNA and partially inhibited the reduction in β1 subunits. Conclusions These results suggest that activation of PKG mediates the drop in sGC subunit mRNA levels, and that NO down-regulates sGC activity by decreasing subunit mRNA levels through a cGMP-dependent mechanism, and by reducing β1 subunit stability. PMID:12350235

Role of Nitric Oxide in Stress-Induced Anxiety: From Pathophysiology to Therapeutic Target.

PubMed

Kumar, A; Chanana, P

2017-01-01

Stress is often marked by a state of hyperarousal to aid the initiation of necessary stress response for the successful management of stressful stimuli. It can be manifested as a challenge (stimulus) that requires behavioral, psychological, and physiological adaptations for the maintenance of a state of homeostasis in response to stressful stimuli. In an organism, miscellaneous stressors trigger a wide spectrum of alterations in hormonal and neuronal physiologies, resulting in behavioral (anxiety and depression disorders, diminished food intake and gastrointestinal dysfunctions, decline in sexual behavior, diabetes, and loss of cognitive function) and other physiological responses. Stress serves as a potent etiological link to development of several neuropsychiatric diseases such as depression, anxiety, and cognitive impairments. Exposure to stressful stimuli has been found to be associated with activation of nitric oxide synthase and generation of NO which reacts with spontaneous oxygen species to aid formation of active nitrogen radicals. High concentrations of reactive nitrogen radicals may cause damage to intracellular proteins, in addition to causing impairment to components of the mitochondrial transport chain, leading to cellular energy deficiency. This may further serve as an etiological link to the development of secondary neurological diseases associated with chronic stress. Also, during stress exposure, pharmacological inhibition of nitric oxide production displays reduction in indicators of anxiety- and depressive-like behavior in animal models. Therefore, the purpose of this chapter is to present an overview on the role of NO in stress-evoked emergence of secondary neurological disorders like anxiety as well as citing examples where NO has been used as a therapeutic target for the management of stress-induced anxiety-like behavior. © 2017 Elsevier Inc. All rights reserved.

Label-free proteomic analysis to confirm the predicted proteome of Corynebacterium pseudotuberculosis under nitrosative stress mediated by nitric oxide.

PubMed

Silva, Wanderson M; Carvalho, Rodrigo D; Soares, Siomar C; Bastos, Isabela Fs; Folador, Edson L; Souza, Gustavo Hmf; Le Loir, Yves; Miyoshi, Anderson; Silva, Artur; Azevedo, Vasco

2014-12-04

Corynebacterium pseudotuberculosis biovar ovis is a facultative intracellular pathogen, and the etiological agent of caseous lymphadenitis in small ruminants. During the infection process, the bacterium is subjected to several stress conditions, including nitrosative stress, which is caused by nitric oxide (NO). In silico analysis of the genome of C. pseudotuberculosis ovis 1002 predicted several genes that could influence the resistance of this pathogen to nitrosative stress. Here, we applied high-throughput proteomics using high definition mass spectrometry to characterize the functional genome of C. pseudotuberculosis ovis 1002 in the presence of NO-donor Diethylenetriamine/nitric oxide adduct (DETA/NO), with the aim of identifying proteins involved in nitrosative stress resistance. We characterized 835 proteins, representing approximately 41% of the predicted proteome of C. pseudotuberculosis ovis 1002, following exposure to nitrosative stress. In total, 102 proteins were exclusive to the proteome of DETA/NO-induced cells, and a further 58 proteins were differentially regulated between the DETA/NO and control conditions. An interactomic analysis of the differential proteome of C. pseudotuberculosis in response to nitrosative stress was also performed. Our proteomic data set suggested the activation of both a general stress response and a specific nitrosative stress response, as well as changes in proteins involved in cellular metabolism, detoxification, transcriptional regulation, and DNA synthesis and repair. Our proteomic analysis validated previously-determined in silico data for C. pseudotuberculosis ovis 1002. In addition, proteomic screening performed in the presence of NO enabled the identification of a set of factors that can influence the resistance and survival of C. pseudotuberculosis during exposure to nitrosative stress.

Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

PubMed

Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

2012-08-01

Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

Increased Contextual Fear Conditioning in iNOS Knockout Mice: Additional Evidence for the Involvement of Nitric Oxide in Stress-Related Disorders and Contribution of the Endocannabinoid System

PubMed Central

Gomes, Felipe V.; Silva, Andréia L.; Uliana, Daniela L.; Camargo, Laura H. A.; Guimarães, Francisco S.; Cunha, Fernando Q.; Joca, Sâmia R. L.; Resstel, Leonardo B. M.

2015-01-01

Background: Inducible or neuronal nitric oxide synthase gene deletion increases or decreases anxiety-like behavior in mice, respectively. Since nitric oxide and endocannabinoids interact to modulate defensive behavior, the former effect could involve a compensatory increase in basal brain nitric oxide synthase activity and/or changes in the endocannabinoid system. Thus, we investigated the expression and extinction of contextual fear conditioning of inducible nitric oxide knockout mice and possible involvement of endocannabinoids in these responses. Methods: We evaluated the effects of a preferential neuronal nitric oxide synthase inhibitor, 7-nitroindazol, nitric oxide synthase activity, and mRNA changes of nitrergic and endocannabinoid systems components in the medial prefrontal cortex and hippocampus of wild-type and knockout mice. The effects of URB597, an inhibitor of the fatty acid amide hydrolase enzyme, which metabolizes the endocannabinoid anandamide, WIN55,212-2, a nonselective cannabinoid agonist, and AM281, a selective CB1 antagonist, on contextual fear conditioning were also evaluated. Results: Contextual fear conditioning expression was similar in wild-type and knockout mice, but the latter presented extinction deficits and increased basal nitric oxide synthase activity in the medial prefrontal cortex. 7-Nitroindazol decreased fear expression and facilitated extinction in wild-type and knockout mice. URB597 decreased fear expression in wild-type and facilitated extinction in knockout mice, whereas WIN55,212-2 and AM281 increased it in wild-type mice. Nonconditioned knockout mice showed changes in the mRNA expression of nitrergic and endocannabinoid system components in the medial prefrontal cortex and hippocampus that were modified by fear conditioning. Conclusion: These data reinforce the involvement of the nitric oxide and endocannabinoids (anandamide) in stress-related disorders and point to a deregulation of the endocannabinoid system in situations where nitric oxide signaling is increased. PMID:25618404

Agmatine enhances the anticonvulsant effect of lithium chloride on pentylenetetrazole-induced seizures in mice: Involvement of L-arginine/nitric oxide pathway.

PubMed

Bahremand, Arash; Ziai, Pouya; Khodadad, Tina Kabiri; Payandemehr, Borna; Rahimian, Reza; Ghasemi, Abbas; Ghasemi, Mehdi; Hedayat, Tina; Dehpour, Ahmad Reza

2010-07-01

After nearly 60years, lithium is still the mainstay in the treatment of mood disorders. In addition to its antimanic and antidepressant effects, lithium also has anticonvulsant properties. Similar to lithium, agmatine plays a protective role in the central nervous system against seizures and has been reported to enhance the effect of different antiepileptic agents. Moreover, both agmatine and lithium have modulatory effects on the L-arginine/nitric oxide pathway. This study was designed to investigate: (1) whether agmatine and lithium exert a synergistic effect against clonic seizures induced by pentylenetetrazole and (2) whether or not this synergistic effect is mediated through inhibition of the L-arginine/nitric oxide pathway. In our study, acute administration of a single potent dose of lithium chloride (30mg/kg ip) increased seizure threshold, whereas pretreatment with a low and independently noneffective dose of agmatine (3mg/kg) potentiated a subeffective dose of lithium (10mg/kg). N(G)-L-arginine methyl ester (L-NAME, nonspecific nitric oxide synthase inhibitor) at 1 and 5mg/kg and 7-nitroindazole (7-NI, preferential neuronal nitric oxide synthase inhibitor) at 15 and 30mg/kg augmented the anticonvulsant effect of the noneffective combination of lithium (10mg/kg ip) and agmatine (1mg/kg), whereas several doses (20 and 40mg/kg) of aminoguanidine (inducible nitric oxide synthase inhibitor) failed to alter the seizure threshold of the same combination. Furthermore, pretreatment with independently noneffective doses (30 and 60mg/kg) of L-arginine (substrate for nitric oxide synthase) inhibited the potentiating effect of agmatine (3mg/kg) on lithium (10mg/kg). Our findings demonstrate that agmatine and lithium chloride have synergistic anticonvulsant properties that may be mediated through the L-arginine/nitric oxide pathway. In addition, the role of constitutive nitric oxide synthase versus inducible nitric oxide synthase is prominent in this phenomenon. Copyright 2010 Elsevier Inc. All rights reserved.

Increased Contextual Fear Conditioning in iNOS Knockout Mice: Additional Evidence for the Involvement of Nitric Oxide in Stress-Related Disorders and Contribution of the Endocannabinoid System.

PubMed

Lisboa, Sabrina F; Gomes, Felipe V; Silva, Andréia L; Uliana, Daniela L; Camargo, Laura H A; Guimarães, Francisco S; Cunha, Fernando Q; Joca, Sâmia R L; Resstel, Leonardo B M

2015-01-24

Inducible or neuronal nitric oxide synthase gene deletion increases or decreases anxiety-like behavior in mice, respectively. Since nitric oxide and endocannabinoids interact to modulate defensive behavior, the former effect could involve a compensatory increase in basal brain nitric oxide synthase activity and/or changes in the endocannabinoid system. Thus, we investigated the expression and extinction of contextual fear conditioning of inducible nitric oxide knockout mice and possible involvement of endocannabinoids in these responses. We evaluated the effects of a preferential neuronal nitric oxide synthase inhibitor, 7-nitroindazol, nitric oxide synthase activity, and mRNA changes of nitrergic and endocannabinoid systems components in the medial prefrontal cortex and hippocampus of wild-type and knockout mice. The effects of URB597, an inhibitor of the fatty acid amide hydrolase enzyme, which metabolizes the endocannabinoid anandamide, WIN55,212-2, a nonselective cannabinoid agonist, and AM281, a selective CB1 antagonist, on contextual fear conditioning were also evaluated. Contextual fear conditioning expression was similar in wild-type and knockout mice, but the latter presented extinction deficits and increased basal nitric oxide synthase activity in the medial prefrontal cortex. 7-Nitroindazol decreased fear expression and facilitated extinction in wild-type and knockout mice. URB597 decreased fear expression in wild-type and facilitated extinction in knockout mice, whereas WIN55,212-2 and AM281 increased it in wild-type mice. Nonconditioned knockout mice showed changes in the mRNA expression of nitrergic and endocannabinoid system components in the medial prefrontal cortex and hippocampus that were modified by fear conditioning. These data reinforce the involvement of the nitric oxide and endocannabinoids (anandamide) in stress-related disorders and point to a deregulation of the endocannabinoid system in situations where nitric oxide signaling is increased. © The Author 2015. Published by Oxford University Press on behalf of CINP.

A potential mechanism for the impairment of nitric oxide formation caused by prolonged oral exposure to arsenate in rabbits.

PubMed

Pi, Jingbo; Horiguchi, Satomi; Sun, Yang; Nikaido, Masatoshi; Shimojo, Nobuhiro; Hayashi, Toshio; Yamauchi, Hiroshi; Itoh, Ken; Yamamoto, Masayuki; Sun, Guifan; Waalkes, Michael P; Kumagai, Yoshito

2003-07-01

We have recently found evidence for impairment of nitric oxide (NO) formation and induction of oxidative stress in residents of an endemic area of chronic arsenic poisoning in Inner Mongolia, China. To investigate the underlying mechanisms responsible for these phenomena, a subchronic animal experiment was conducted using male New Zealand White rabbits. After 18 weeks of continuous exposure of rabbits to 5 mg/l of arsenate in drinking water, a significant decrease in systemic NO production occurred, as shown by significantly reduced plasma NO metabolites levels (76% of control) and a tendency towards decreased serum cGMP levels (81.4% of control). On the other hand, increased oxidative stress, as shown by significantly increased urinary hydrogen peroxide (H(2)O(2)) (120% of control), was observed in arsenate-exposed rabbits. In additional experiments measuring aortic tension, the addition of either the calcium ionophore A23187 or acethylcholine (ACh) induced a transient vasoconstriction of aortic rings prepared from arsenate-exposed rabbits, but not in those prepared from control animals. This calcium-dependent contractility action observed in aorta rings from arsenate-exposed rabbits was markedly attenuated by the superoxide (O2(.-)) scavenging enzyme Cu, Zn-SOD, as well as diphenyleneiodonium (DPI) or N(G)-nitro-L-arginine methyl ester (L-NAME), which are inhibitors for nitric oxide synthase (NOS). However, the cyclooxygenase inhibitor indomethacin or the xanthine oxidase blocker allopurinol had no effect on this vasoconstriction. These results suggest that arsenate-mediated reduction of systemic NO may be associated with the enzymatic uncoupling reaction of NOS with a subsequent enhancement of reactive oxygen species such as O2(.-), an endothelium-derived vasoconstricting factor. Furthermore, hepatic levels of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH(4)), a cofactor for NOS, were markedly reduced in arsenate-exposed rabbits to 62% of control, while no significant change occurred in cardiac L-arginine levels. These results suggest that prolonged exposure of rabbits to oral arsenate may impair the bioavailability of BH(4) in endothelial cells and, as a consequence, disrupt the balance between NO and O2(.-) produced from endothelial NOS, such that enhanced free radicals are produced at the expense of NO.

Inhibitory effects of indole α-lipoic acid derivatives on nitric oxide production in LPS/IFNγ activated RAW 264.7 macrophages.

PubMed

Karabay, Arzu Zeynep; Koc, Aslı; Gurkan-Alp, A Selen; Buyukbingol, Zeliha; Buyukbingol, Erdem

2015-04-01

Alpha-lipoic acid (α-lipoic acid) is a potent antioxidant compound that has been shown to possess anti-inflammatory effects. RAW 264.7 macrophages produce various inflammatory mediators such as nitric oxide, IL-1β, IL-6 and TNF-alpha upon activation with LPS (Lipopolysaccharide) and IFNγ (interferon gamma). In this study, the effect of 12 synthetic indole α-lipoic acid derivatives on nitric oxide production and iNOS (inducible nitric oxide synthase) protein expression in LPS/IFNγ activated RAW 264.7 macrophages was determined. Cell proliferation, nitric oxide levels and iNOS protein expression were examined with thiazolyl blue tetrazolium blue test, griess assay and western blot, respectively. Our results showed that all of the indole α-lipoic acid derivatives showed significant inhibitory effects on nitric oxide production and iNOS protein levels (p < 0.05). The most active compounds were identified as compound I-4b, I-4e and II-3b. In conclusion, these indole α-lipoic acid derivatives may have the potential for treatment of inflammatory conditions related with high nitric oxide production. Copyright © 2015 John Wiley & Sons, Ltd.

The Expression of Type-1 and Type-2 Nitric Oxide Synthase in Selected Tissues of the Gastrointestinal Tract during Mixed Mycotoxicosis

PubMed Central

Gajęcka, Magdalena; Stopa, Ewa; Tarasiuk, Michał; Zielonka, Łukasz; Gajęcki, Maciej

2013-01-01

The aim of the study was to verify the hypothesis that intoxication with low doses of mycotoxins leads to changes in the mRNA expression levels of nitric oxide synthase-1 and nitric oxide synthase-2 genes in tissues of the gastrointestinal tract and the liver. The experiment involved four groups of immature gilts (with body weight of up to 25 kg) which were orally administered zearalenone in a daily dose of 40 μg/kg BW (group Z, n = 18), deoxynivalenol at 12 μg/kg BW (group D, n = 18), zearalenone and deoxynivalenol (group M, n = 18) or placebo (group C, n = 21) over a period of 42 days. The lowest mRNA expression levels of nitric oxide synthase-1 and nitric oxide synthase-2 genes were noted in the sixth week of the study, in particular in group M. Our results suggest that the presence of low mycotoxin doses in feed slows down the mRNA expression of both nitric oxide synthase isomers, which probably lowers the concentrations of nitric oxide, a common precursor of inflammation. PMID:24284830

Laser absorption of nitric oxide for thermometry in high-enthalpy air

NASA Astrophysics Data System (ADS)

Spearrin, R. M.; Schultz, I. A.; Jeffries, J. B.; Hanson, R. K.

2014-12-01

The design and demonstration of a laser absorption sensor for thermometry in high-enthalpy air is presented. The sensor exploits the highly temperature-sensitive and largely pressure-independent concentration of nitric oxide in air at chemical equilibrium. Temperature is thus inferred from an in situ measurement of nascent nitric oxide. The strategy is developed by utilizing a quantum cascade laser source for access to the strong fundamental absorption band in the mid-infrared spectrum of nitric oxide. Room temperature measurements in a high-pressure static cell validate the suitability of the Voigt lineshape model to the nitric oxide spectra at high gas densities. Shock-tube experiments enable calibration of a collision-broadening model for temperatures between 1200-3000 K. Finally, sensor performance is demonstrated in a high-pressure shock tube by measuring temperature behind reflected shock waves for both fixed-chemistry experiments where nitric oxide is seeded, and for experiments involving nitric oxide formation in shock-heated mixtures of N2 and O2. Results show excellent performance of the sensor across a wide range of operating conditions from 1100-2950 K and at pressures up to 140 atm.

Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells.

PubMed

Ugusman, Azizah; Zakaria, Zaiton; Hui, Chua Kien; Nordin, Nor Anita Megat Mohd

2010-07-01

Nitric oxide produced by endothelial nitric oxide synthase (eNOS) possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs). HUVECS WERE DIVIDED INTO FOUR GROUPS: control, treatment with 180 microM hydrogen peroxide (H(2)O(2)), treatment with 150 microg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H(2)O(2) for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

Interference of oxygen, carbon dioxide, and water vapor on the analysis for oxides of nitrogen by chemiluminescence

NASA Technical Reports Server (NTRS)

Maahs, H. G.

1975-01-01

The interference of small concentrations (less than 4 percent by volume) of oxygen, carbon dioxide, and water vapor on the analysis for oxides of nitrogen by chemiluminescence was measured. The sample gas consisted primarily of nitrogen, with less than 100 parts per million concentration of nitric oxide, and with small concentrations of oxygen, carbon dioxide, and water vapor added. Results obtained under these conditions indicate that although oxygen does not measurably affect the analysis for nitric oxide, the presence of carbon dioxide and water vapor causes the indicated nitric oxide concentration to be too low. An interference factor - defined as the percentage change in indicated nitric oxide concentration (relative to the true nitric oxide concentration) divided by the percent interfering gas present - was determined for carbon dioxide to be -0.60 + or - 0.04 and for water vapor to be -2.1 + or - 0.3.

Nitric oxide scavengers differentially inhibit ammonia oxidation in ammonia-oxidizing archaea and bacteria.

PubMed

Sauder, Laura A; Ross, Ashley A; Neufeld, Josh D

2016-04-01

Differential inhibitors are important for measuring the relative contributions of microbial groups, such as ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA), to biogeochemical processes in environmental samples. In particular, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) represents a nitric oxide scavenger used for the specific inhibition of AOA, implicating nitric oxide as an intermediate of thaumarchaeotal ammonia oxidation. This study investigated four alternative nitric oxide scavengers for their ability to differentially inhibit AOA and AOB in comparison to PTIO. Caffeic acid, curcumin, methylene blue hydrate and trolox were tested onNitrosopumilus maritimus, two unpublished AOA representatives (AOA-6f and AOA-G6) as well as the AOB representative Nitrosomonas europaea All four scavengers inhibited ammonia oxidation by AOA at lower concentrations than for AOB. In particular, differential inhibition of AOA and AOB by caffeic acid (100 μM) and methylene blue hydrate (3 μM) was comparable to carboxy-PTIO (100 μM) in pure and enrichment culture incubations. However, when added to aquarium sponge biofilm microcosms, both scavengers were unable to inhibit ammonia oxidation consistently, likely due to degradation of the inhibitors themselves. This study provides evidence that a variety of nitric oxide scavengers result in differential inhibition of ammonia oxidation in AOA and AOB, and provides support to the proposed role of nitric oxide as a key intermediate in the thaumarchaeotal ammonia oxidation pathway. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Microbial removal of no.sub.x from gases

DOEpatents

Sublette, Kerry L.

1991-01-01

Disclosed is a process by which a gas containing nitric oxide is contacted with an anaerobic microbial culture of denitrifying bacteria to effect the chemical reduction of the nitric oxide to elemental nitrogen. The process is particularly suited to the removal of nitric oxide from flue gas streams and gas streams from nitric acid plants. Thiobacillus dentrificians as well as other bacteria are disclosed for use in the process.

21 CFR 868.5165 - Nitric oxide administration apparatus.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nitric oxide administration apparatus. 868.5165 Section 868.5165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration...

21 CFR 868.5165 - Nitric oxide administration apparatus.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nitric oxide administration apparatus. 868.5165 Section 868.5165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration...

The ADMA/DDAH/NO pathway in human vein endothelial cells exposed to arsenite.

PubMed

Osorio-Yáñez, Citlalli; Chin-Chan, Miguel; Sánchez-Peña, Luz C; Atzatzi-Aguilar, Octavio G; Olivares-Reyes, Jesus A; Segovia, José; Del Razo, Luz M

2017-08-01

Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is characterized by endothelial dysfunction and nitric oxide (NO) depletion. The mechanisms underlying NO depletion as related to iAs exposure are not fully understood. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), might be a molecular target of iAs. ADMA concentrations are regulated by proteins involved in its synthesis (arginine methyl transferase 1 [PRMT-1]) and degradation (dimethylarginine dimethylaminohydrolase [DDAH]). Both, ADMA and NO are susceptible to oxidative stress. We aimed to determine the ADMA/DDAH/NO pathway in human vein endothelial cells (HUVEC-CS) exposed to arsenite. We exposed HUVEC-CS cells to 1, 2.5 and 5μM of arsenite for 24h. We proved that arsenite at 5μM was able to decrease NO levels with an associated increase in ADMA and depletion of l-arginine in HUVEC-CS cells. We also found a decrease in DDAH-1 protein expression with 5μM of arsenite compared to the control group. However, we did not observe significant differences in PRMT-1 protein expression at any of the concentrations of arsenite employed. Finally, arsenite (2.5 and 5μM) increased NADPH oxidase 4 protein levels compared with the control group. We conclude that ADMA, l-arginine and DDAH are involved in NO depletion produced by arsenite, and that the mechanism is related to oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nitric oxide-mediated pathogenesis during nicotine and alcohol consumption.

PubMed

Cooper, R G; Magwere, T

2008-01-01

Nitric oxide (NO) is formed by different cell types in response to a variety of physiological and patho-physiological stimuli. The intake of nicotine and/or alcohol has patho-physiological effects on organ function, and the progression of alcohol-/tobacco-related diseases seem to be directly influenced by NO-mediated mechanisms. Nicotine has an adverse influence on blood vessel functionality, repair and maintenance. Chronic nicotine exposure augments atherosclerosis by enhancing the production of proinflammatory cytokines by macrophages which then activate atherogenic NF-kB target genes in aortic lesions. Alcohol produces NO which speeds up the apoptosis of neutrophils. Alcohol sensitizes the liver to endotoxemic shock. Nitrosative stress and increased basal levels of NO contribute to tumour growth. The progression of disease seems to be directed via a definite NO-mediated mechanism. This review gives an insight into how intake of tobacco and alcohol may affect quality of life.

Estimation of the nitric oxide formed from hydroxylamine by Nitrosomonas

PubMed Central

Anderson, J. H.

1965-01-01

1. Nitric oxide that was produced by reducing nitrite with an excess of acidified potassium iodide under nitrogen in Warburg respirometer flasks was rapidly absorbed by a solution of permanganate in sodium hydroxide held in the side arm. A small amount of nitrous oxide (or nitrogen) that was also produced was not absorbed. 2. By using a quantitative method for the recovery of nitrite from samples of the alkaline permanganate, it was found that the sum of the nitrite N formed and the residual nitrous oxide N was equivalent to the nitrite N used to generate the gases. These results showed that alkaline permanganate completely oxidized nitric oxide to nitrite. The method was suitable for determining 0·4–20 μmoles of nitric oxide. 3. The technique was used to determine the nitric oxide content of the nitrogenous gas that was produced anaerobically from hydroxylamine by an extract of the autotrophic nitrifying micro-organism Nitrosomonas in the presence of methylene blue as electron acceptor. PMID:14342235

Gestational diabetes mellitus was related to ambient air pollutant nitric oxide during early gestation.

PubMed

Pan, Shih-Chun; Huang, Ching-Chun; Lin, Shio-Jean; Chen, Bing-Yu; Chang, Chang-Chuan; Leon Guo, Yue-Liang

2017-10-01

Ambient air pollution has been linked to the risk of gestational diabetes mellitus (GDM). However, evidence of this association is limited, and no study has examined the effects of nitric oxide (NO). This study investigated the association between air pollution exposure during gestation and GDM. The Taiwan Birth Cohort Study database was used to examine the association between the risk of GDM and all routinely monitored air pollutants among 21,248 women who were pregnant during 2004-2005. We further employed a two-pollutant model for confirming the effect of each pollutant on GDM. After the exclusion criteria were applied, 19,606 women were included in the final analysis. Among them, 378 (1.9%) had been diagnosed as having GDM. These women were older and had higher BMIs than the women without GDM. The risks of GDM onset were significantly associated with NO exposure during the first [adjusted OR (aOR): 1.05, 95% confidence interval (CI): 1.02-1.08] and second (aOR: 1.05, 95%CI: 1.02-1.08) trimesters. Under the two-pollutant model, the effect of NO exposure was also significant during the first (aOR: 1.05, 95%CI: 1.02-1.08) and second (aOR: 1.05, 95%CI: 1.02-1.09) trimesters. The results indicated that exposure to higher NO levels during pregnancy increases the risk of GDM. Copyright © 2017. Published by Elsevier Inc.

Association of expired nitric oxide with urinary metal concentrations in boilermakers exposed to residual oil fly ash.

PubMed

Kim, Jee Young; Hauser, Russ; Wand, Matthew P; Herrick, Robert F; Houk, R S; Aeschliman, David B; Woodin, Mark A; Christiani, David C

2003-11-01

Exposure to metal-containing particulate matter has been associated with adverse pulmonary responses. Metals in particulate matter are soluble, hence are readily recovered in urine of exposed individuals. This study investigated the association between urinary metal concentrations and the fractional concentration of expired nitric oxide (F(E)NO) in boilermakers (N = 32) exposed to residual oil fly ash (ROFA). Subjects were monitored at a boiler overhaul site located in the New England area, USA. F(E)NO and urine samples were collected pre- and post-workshift for 5 consecutive workdays. Metals investigated included vanadium (V), chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), and lead (Pb). The median F(E)NO was 7.5 ppb (95% CI: 7.4-8.0), and the median creatinine-adjusted urinary metal concentrations (mug/g creatinine) were: vanadium, 1.37; chromium, 0.48; manganese, 0.30; nickel, 1.52; copper, 3.70; and lead, 2.32. Linear mixed-effects models indicated significant inverse exposure-response relationships between log F(E)NO and the log-transformed urinary concentrations of vanadium, manganese, nickel, copper, and lead at several lag times, after adjusting for smoking status. Urine samples may be utilized as a biomarker of occupational metal exposure. The inverse association between F(E)NO and urinary metal concentrations suggests that exposure to metals in particulate matter may have an adverse effect on respiratory health. Copyright 2003 Wiley-Liss, Inc.

Nitric oxide fumigation for postharvest pest control

USDA-ARS?s Scientific Manuscript database

Nitric oxide fumigation is effective against all arthropod pests at various life stages tested. Nine insect pests at various life stages and bulb mites were subjected to nitric oxide fumigation treatments under ultralow oxygen conditions of =50 ppm O2 in 1.9L glass jars as fumigation chambers. The ...

Effect of soy isoflavone supplementation on nitric oxide metabolism and blood pressure in menopausal women

USDA-ARS?s Scientific Manuscript database

Isoflavones, having chemical structures similar to estrogens, are believed to stimulate nitric oxide production and thus lower blood pressure. The efficacy of soy isoflavone supplementation to stimulate nitric oxide production and lower blood pressure in menopausal women with high normal blood press...

Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria

USDA-ARS?s Scientific Manuscript database

Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea cycle disorder, and leads to deficiency of both urea...

Modification of Traffic-related Respiratory Response by Asthma Control in a Population of Car Commuters.

PubMed

Mirabelli, Maria C; Golan, Rachel; Greenwald, Roby; Raysoni, Amit U; Holguin, Fernando; Kewada, Priya; Winquist, Andrea; Flanders, W Dana; Sarnat, Jeremy A

2015-07-01

Effects of traffic-related exposures on respiratory health are well documented, but little information is available about whether asthma control influences individual susceptibility. We analyzed data from the Atlanta Commuter Exposure study to evaluate modification of associations between rush-hour commuting, in- vehicle air pollution, and selected respiratory health outcomes by asthma control status. Between 2009 and 2011, 39 adults participated in Atlanta Commuter Exposure, and each conducted two scripted rush-hour highway commutes. In-vehicle particulate components were measured during all commutes. Among adults with asthma, we evaluated asthma control by questionnaire and spirometry. Exhaled nitric oxide, forced expiratory volume in 1 second (FEV1), and other metrics of respiratory health were measured precommute and 0, 1, 2, and 3 hours postcommute. We used mixed effects linear regression to evaluate associations between commute-related exposures and postcommute changes in metrics of respiratory health by level of asthma control. We observed increased exhaled nitric oxide across all levels of asthma control compared with precommute measurements, with largest postcommute increases observed among participants with below-median asthma control (2 hours postcommute: 14.6% [95% confidence interval {CI} = 5.7, 24.2]; 3 hours postcommute: 19.5% [95% CI = 7.8, 32.5]). No associations between in-vehicle pollutants and percent of predicted FEV1 were observed, although higher PM2.5 was associated with lower FEV1 % predicted among participants with below-median asthma control (3 hours postcommute: -7.2 [95% CI = -11.8, -2.7]). Level of asthma control may influence respiratory response to in-vehicle exposures experienced during rush-hour commuting.

Formation of vascular S-nitrosothiols and plasma nitrates/nitrites following inhalation of diesel emissions.

PubMed

Knuckles, Travis L; Buntz, Jennifer G; Paffett, Michael; Channell, Meghan; Harmon, Molly; Cherng, Tom; Lucas, Selita N; McDonald, Jacob D; Kanagy, Nancy L; Campen, Matthew J

2011-01-01

Epidemiological studies have associated traffic-related airborne pollution with adverse cardiovascular outcomes. Nitric oxide (NO) is a common component of fresh diesel and gasoline engine emissions that rapidly transforms both in the atmosphere and once inhaled. Because of this rapid transformation, limited information is available in terms of potential human exposures and adverse health effects. Young rats were exposed to whole diesel emissions (DE) adjusted to 300 μg/m(3) of particulate matter (containing 3.5 ppm NO) or 0, 3, or 10 ppm NO as a positive control. Animals were also pre-injected (ip) with either saline or N-acetylcysteine (NAC), a precursor of glutathione. Predictably, pure NO exposures led to a concentration-dependent increase in plasma nitrates compared to controls, which lasted for roughly 4 h postexposure. Whole DE exposure for 1 h also led to a doubling of plasma NOx. NAC injection increased the levels of plasma nitrates and nitrites (NOx) in the DE exposure group. Inhibition of nitric oxide symthase (NOS) by N(G)-nitro-L-arginine (L-NNA) did not block the rise in plasma NOx, demonstrating that the increase was entirely due to exogenous sources. Both DE and pure NO exposures paradoxically led to elevated eNOS expression in aortic tissue. Furthermore, coronary arterioles from NO-exposed animals exhibited greater constriction to endothelin-1 compared to controls, consistent with a derangement of the NOS system. Thus, NO may be an important contributor to traffic-related cardiovascular morbidity, although further research is necessary for proper hazard identification.

Peroxynitrite induces destruction of the tetrahydrobiopterin and heme in endothelial nitric oxide synthase: transition from reversible to irreversible enzyme inhibition†

PubMed Central

Chen, Weiguo; Druhan, Lawrence J.; Chen, Chun-An; Hemann, Craig; Chen, Yeong-Renn; Berka, Vladimir; Tsai, Ah-Lim; Zweier, Jay L.

2010-01-01

Endothelial nitric oxide synthase (eNOS) is an important regulator of vascular and cardiac function. Peroxynitrite (ONOO−) inactivates eNOS, but questions remain regarding the mechanisms of this process. It has been reported that inactivation is due to oxidation of the eNOS zinc-thiolate cluster, rather than the cofactor tetrahydrobiopterin (BH4); however, this remains highly controversial. Therefore, we investigated the mechanisms of ONOO−-induced eNOS dysfunction and their dose-dependence. Exposure of human eNOS to ONOO− resulted in a dose-dependent loss of activity with a marked destabilization of the eNOS dimer. HPLC analysis indicated that both free and eNOS-bound BH4 were oxidized during exposure to ONOO−; however, full oxidation of protein bound biopterin required higher ONOO− levels. Additionally, ONOO− triggered changes in UV/Visible spectrum and heme content of the enzyme. Pre-incubation of eNOS with BH4 decreased dimer destabilization and heme alteration. Addition of BH4 to the ONOO−-destabilized eNOS dimer only partially rescued enzyme function. In contrast to ONOO− treatment, incubation with the zinc chelator TPEN with removal of enzyme-bound zinc did not change the eNOS activity or stability of the SDS-resistant eNOS dimer, demonstrating that the dimer stabilization induced by BH4 does not require zinc occupancy of the zinc-thiolate cluster. While ONOO− treatment was observed to induce loss of Zn-binding this can not account for the loss of enzyme activity. Therefore, ONOO−-induced eNOS inactivation is primarily due to oxidation of BH4 and irreversible destruction of the heme/heme-center. PMID:20184376

Mild zinc deficiency in male and female rats: early postnatal alterations in renal nitric oxide system and morphology.

PubMed

Tomat, Analia Lorena; Veiras, Luciana Cecilia; Aguirre, Sofía; Fasoli, Héctor; Elesgaray, Rosana; Caniffi, Carolina; Costa, María Ángeles; Arranz, Cristina Teresa

2013-03-01

Fetal and postnatal zinc deficiencies induce an increase in arterial blood pressure and impair renal function in male adult rats. We therefore hypothesized that these renal alterations are present in early stages of life and that there are sexual differences in the adaptations to this nutritional injury. The aim was to study the effects of moderate zinc deficiency during fetal life and lactation on renal morphology, oxidative stress, apoptosis, and the nitric oxide system in male and female rats at 21 d of life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy to weaning. Glomerulus number, morphology, oxidative stress, apoptotic cells, nitric oxide synthase activity, and protein expression were evaluated in the kidneys of offspring at 21 d. Zinc deficiency decreased the nephron number, induced glomerular hypertrophy, increased oxidative damage, and decreased nitric oxide synthase activity in the male and female rat kidneys. Nitric oxide synthase activity was not affected by inhibitors of the neuronal or inducible isoforms, so nitric oxide was mainly generated by the endothelial isoenzyme. Gender differences were observed in glomerular areas and antioxidant enzyme activities. Zinc deficiency during fetal life and lactation induces an early decrease in renal functional units, associated with a decrease in nitric oxide activity and an increase in oxidative stress, which would contribute to increased arterial blood pressure and renal dysfunction in adulthood. The sexual differences observed in this model may explain the dissimilar development of hypertension and renal diseases in adult life. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of a pyrrole-based, microtubule-depolymerizing compound on RAW 264.7 macrophages.

PubMed

Ciemniecki, John A; Lewis, Clarke P; Gupton, John T; Fischer-Stenger, Krista

2016-02-25

RAW 264.7 murine macrophages were exposed to the pyrrole-based compound 3,5-Dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester (JG-03-14), which is a known microtubule depolymerizing agent with antitumor activity [1,2,3]. In this study exposure to JG-03-14 reduced the production of pro-inflammatory molecules by macrophages activated with lipopolysaccharide (LPS). Treatment with the pyrrole-based compound decreased the concentration of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) released from the macrophages. Exposure to JG-03-14 also decreased TNF-α mRNA expression levels and the protein expression levels of inducible nitric oxide synthase (iNOS), the enzyme responsible for NO production in the activated macrophages. Furthermore, JG-03-14 treatment significantly changed the degradation profile of IκB-β, an inhibitor of the NF-κB transcription factor, which suggests that JG-03-14 may attenuate the activation of the LPS-induced NF-κB signaling pathway needed to produce the pro-inflammatory mediators. We conclude that JG-03-14 possesses anti-inflammatory properties. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dose Dependent Effects of Reactive Oxygen and Nitrogen Species on the Function of Neuronal Nitric Oxide Synthase

PubMed Central

Sun, Jian; Druhan, Lawrence J.; Zweier, Jay L.

2014-01-01

Reactive nitrogen species (RNS) and oxygen species (ROS) have been reported to modulate the function of nitric oxide synthase (NOS); however, the precise dosedependent effects of specific RNS and ROS on NOS function are unknown. Questions remain unanswered regarding whether pathophysiological levels of RNS and ROS alter NOS function, and if this alteration is reversible. We measured the effects of peroxynitrite (ONOO-), superoxide (O2.-), hydroxyl radical (.OH), and H2O2 on nNOS activity. The results showed that NO production was inhibited in a dose-dependent manner by all four oxidants, but only O2.- and ONOO- were inhibitory at pathophysiological concentrations (≤ 50 μM). Subsequent addition of tetrahydrobiopterin (BH4) fully restored activity after O2.- exposure, while BH4 partially rescued the activity decrease induced by the other three oxidants. Furthermore, treatment with either ONOO- or O2.- stimulated nNOS uncoupling with decreased NO and enhanced O2.- generation. Thus, nNOS is reversibly uncoupled by O2.- (≤ 50 μM), but irreversibly uncoupled and inactivated by ONOO-. Additionally, we observed that the mechanism by which oxidative stress alters nNOS activity involves not only BH4 oxidation, but also nNOS monomerization as well as possible degradation of the heme. PMID:18201545

[Oxidative Stress Level of Vanadium-exposed Workers].

PubMed

Wei, Teng-da; Li, Shun-pin; Liu, Yun-xing; Tan, Chun-ping; Li, Juan; Zhang, Zu-hui; Lan, Ya-jia; Zhang, Qin

2015-11-01

To determine the oxidative stress level in peripheral blood of vanadium-exposed workers, as an indication of population health effect of vanadium on human neurobehavioral system. 86 vanadium-exposed workers and 65 non-exposed workers were recruited by cluster sampling. A questionnaire was administered to collect demographic and occupational exposure information. Serum activity of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS) and malonaldehyde (MDA) contents were detected by kit assay. The differences in oxidative stress level between vanadium-exposed and non-exposed workers were compared. Vanadium-exposed workers had higher levels of MDA contents than the controls. The total superoxide dismutase(T-SOD) activity in vanadium-exposed workers was significantly lower than that in the controls, which was associated with lowered levels of manganese superoxide dismutase (Mn-SOD) activity. No changes in serum levels of cupro-zinc superoxide dismutase (CuZn-SOD) was found in vanadium-exposed workers. No difference in iNOS activity was found between vanadium-exposed workers and controls. Vanadium exposure increases free radical production in serum and reduces antioxidant capacity. But the relationship between vanadium exposure and iNOS damage remains uncertain.

Evaluation of lipid peroxidation and antioxidant status on fenvalerate, nitrate and their co-exposure in Bubalus bubalis.

PubMed

Gill, Kamalpreet Kaur; Sandhu, Harpal Singh; Kaur, Rajdeep

2015-09-01

The toxic effects of pesticides and minerals have been explored in different species, but still there is paucity of information regarding their combined toxicological effects. The present investigation reports oxidative stress induced by oral subacute exposure to fenvalerate (1 mg/kg) and sodium nitrate (20 mg/kg) alone, as well as in combination daily for 21 days in buffalo calves. Fenvalerate exposure produced significant elevation in lipid peroxidation (LPO), glutathione peroxidase (GPx), while it produced significant decline in blood glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT). No significant alteration was evidenced in nitric oxide (NOx) levels. Oral exposure to sodium nitrate produced significant inclination in LPO and NOx, while on the other hand significant depreciation in SOD and CAT with no significant change in GPx activity. Combined exposure to fenvalerate and sodium nitrate produced severe effects with an appreciably more prominent elevation in extent of LPO and decline in blood GSH levels. Copyright © 2015 Elsevier Inc. All rights reserved.

Exhaled nitric oxide levels in exacerbations of asthma, chronic obstructive pulmonary disease and pneumonia.

PubMed

Al-Ali, M K; Howarth, P H

2001-03-01

Nitric oxide is known to be present in the exhaled air of normal subjects and at higher concentrations in asthmatics. The aim of this study was to measure exhaled nitric oxide levels in patients admitted to hospital with acute exacerbations of asthma, or chronic obstructive pulmonary disease, or with pneumonia. Within 24 hours of admission exhaled nitric oxide levels were measured by a chemiluminescent analyzer in 11 patients with acute sever asthma, 19 patients with acute exacerbation of chronic obstructive pulmonary disease, and in 12 patients with pneumonia. In asthmatics measurements were made on 3 occasions, at day 1, 4, and 28 and were related to changes in peak expiratory flow rate. On admission median exhaled nitric oxide levels (range) were significantly higher in asthmatics 22 (9.3-74) parts per billion in comparison to patients with chronic obstructive pulmonary disease 10.3 (2.7-34) parts per billion; p < 0.01, pneumonia 7 (4-17) parts per billion; p<0.001, and normal subjects 8.7 (5-13.3) parts per billion; p < 0.001. Following treatment the asthmatics had a significant reduction in their exhaled nitric oxide levels from 22 (9.3-74) parts per billion on day 1 to 9.7 (5.7-18.3) parts per billion on day 28; p = 0.005. Peak expiratory flow rate measurements increased from 200 (120-280) l/min on day 1 to 280 (150-475) l/min on day 4; p < 0.05 and to 390 (150-530) l/min on day 28; p < 0.01. A strong negative correlation existed between peak expiratory flow rate measurements and exhaled nitric oxide levels in asthmatics on day 28 (r = -0.70; p = 0.017). Acute exacerbations of asthma are associated with increased levels of exhaled nitric oxide in contrast to exacerbations of chronic obstructive pulmonary disease and acute pneumonia. Exhaled nitric oxide may be a useful indirect marker of asthmatic airway inflammation. The differing time course of response of nitric oxide to peak flow measures suggests that these two measures are reflecting differing airway events.

Inhibition of neuronal nitric oxide synthase in ovine model of acute lung injury*

PubMed Central

Enkhbaatar, Perenlei; Connelly, Rhykka; Wang, Jianpu; Nakano, Yoshimitsu; Lange, Matthias; Hamahata, Atsumori; Horvath, Eszter; Szabo, Csaba; Jaroch, Stefan; Hölscher, Peter; Hillmann, Margrit; Traber, Lillian D.; Schmalstieg, Frank C.; Herndon, David N.; Traber, Daniel L.

2013-01-01

Objective Acute respiratory distress syndrome/acute lung injury is a serious complication of burn patients with concomitant smoke inhalation injury. Nitric oxide has been shown to play a major role in pulmonary dysfunction from thermal damage. In this study, we have tested the hypothesis that inhibition of neuronal nitric oxide synthase could ameliorate the severity of acute lung injury using our well-established ovine model of cutaneous burn and smoke inhalation. Design Prospective, randomized, controlled, experimental animals study. Setting Investigational intensive care unit at university hospital. Subjects Adult female sheep Interventions Female sheep (n = 16) were surgically prepared for the study. Seven days after surgery, all sheep were randomly allocated into three study groups: sham (noninjured, nontreated, n = 6); control (injured, treated with saline, n = 6); and neuronal nitric oxide synthase (injured, treated with specific neuronal nitric oxide synthase inhibitor, ZK 234238 (n = 4). Control and neuronal nitric oxide synthase groups were given a cutaneous burn (40% of total body surface, third degree) and insufflated with cotton smoke (48 breaths, <40°C) under halothane anesthesia. Animals in sham group received fake injury also under halothane anesthesia. After injury or fake injury procedure, all sheep were placed on ventilators and resuscitated with lactated Ringer's solution. Neuronal nitric oxide synthase group was administered with continuous infusion of ZK 234238 started 1 hr postinjury with a dose of 100 μg/kg/hr. Sham and control groups received same amount of saline. Measurements and Main Results Cardiopulmonary hemodynamics monitored during the 24-hr experimental time period was stable in the sham group. Control sheep developed multiple signs of acute lung injury. This pathophysiology included decreased pulmonary gas exchange and lung compliance, increased pulmonary edema, and inflammatory indices, such as interleukin-8. Treatment of injured sheep with neuronal nitric oxide synthase inhibitor attenuated all the observed pulmonary pathophysiology. Conclusions The results provide definitive evidence that inhibition of neuronal nitric oxide synthase-derived excessive nitric oxide may be a novel and beneficial treatment strategy for pulmonary pathology in burn victims with smoke inhalation injury. PMID:19050603

Remote sensing of nitric oxide emissions from planes, trains and automobiles

NASA Astrophysics Data System (ADS)

Popp, Peter John

Remote sensing has been proven as an effective method for measuring in-use mobile source emissions. This document describes the development of a remote sensor for mobile source nitric oxide, based on an instrument previously developed at the University of Denver for measuring carbon monoxide and hydrocarbon emissions. The new remote sensor makes use of a high-speed ultraviolet spectrometer to quantify nitric oxide by absorption spectroscopy at 226 nm in the ultraviolet region. The high-speed spectrometer is coupled to an existing FEAT remote sensor, for the simultaneous measurement of CO, CO2 and hydrocarbons by non-dispersive infrared absorption spectroscopy. The utility of the instrument was demonstrated in the measurement of nitric oxide emissions from automobiles, commercial aircraft, and railroad locomotives. The remote sensor was used to measure nitric oxide emissions from motor vehicles in Chicago in 1997 and 1998, as part of a five-year study to characterize motor vehicle emissions and deterioration in that city. Emissions data were collected for over 19,000 vehicles in 1997 and almost 23,000 vehicles in 1998. All of these records contained valid measurements for carbon monoxide and hydrocarbons, in addition to nitric oxide. In September of 1997, a study was conducted with the cooperation of British Airways and the British Airports Authority to demonstrate the capability of the remote sensor in measuring nitric oxide emissions from in-use commercial aircraft. In two days of sampling at London Heathrow Airport, a total of 122 measurements were made of 90 different aircraft, ranging in size from Gulfstream executive jets to Boeing 747-400s. The measured nitric oxide emission indices were not inconsistent with commercial aircraft emission indices published by the International Civil Aviation Organization. The utility of the remote sensor in measuring nitric oxide emissions from railroad locomotives was demonstrated in January of 1999, in a study conducted with the cooperation of the Burlington Northern Santa Fe Railway. Nitric oxide emissions measured from freight locomotives in a controlled test at a switchyard agreed with previously published values. Measurements of in-use locomotives hauling coal trains revealed higher NO emissions than those measured from similar locomotives in the controlled test.

Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens

PubMed Central

Vázquez-Torres, Andrés; Bäumler, Andreas

2016-01-01

The electrochemical gradient that ensues from the enzymatic activity of cytochromes such as nitrate reductase, nitric oxide reductase, and quinol oxidase contributes to the bioenergetics of the bacterial cell. Reduction of nitrogen oxides by bacterial pathogens can, however, be uncoupled from proton translocation and biosynthesis of ATP or NH4+, but still linked to quinol and NADH oxidation. Ancestral nitric oxide reductases, as well as cytochrome coxidases and quinol bo oxidases evolved from the former, are capable of binding and detoxifying nitric oxide to nitrous oxide. The NO-metabolizing activity associated with these cytochromes can be a sizable source of antinitrosative defense in bacteria during their associations with host cells. Nitrosylation of terminal cytochromes arrests respiration, reprograms bacterial metabolism, stimulates antioxidant defenses and alters antibiotic cytotoxicity. Collectively, the bioenergetics and regulation of redox homeostasis that accompanies the utilization of nitrogen oxides and detoxification of nitric oxide by cytochromes of the electron transport chain increases fitness of many Gram-positive and –negative pathogens during their associations with invertebrate and vertebrate hosts. PMID:26426528

Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, In-Sik; Lee, Mee-Young; Cho, Eun-Sang

Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant micemore » that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue.« less

Effects of tributyltin and benzo[a]pyrene on the immune-associated activities of hemocytes and recovery responses in the gastropod abalone, Haliotis diversicolor.

PubMed

Gopalakrishnan, Singaram; Huang, Wei-Bin; Wang, Qiang-Wei; Wu, Man-Li; Liu, Jie; Wang, Ke-Jian

2011-08-01

Our previous study reports that short-term exposure to sublethal concentrations of benzo[a]pyrene (BaP) induces immunomodulation in the gastropod abalone, Haliotis diversicolor. In the present study, it was further observed that long-term chronic exposure to sublethal concentrations of BaP modulated the immunocompetence of abalones in terms of the change in activity of the antioxidant and immune associated parameters tested. In addition, the effect of tributyltin (TBT), another important genotoxicant in the aquatic environment, was investigated. Exposure of abalones to sublethal concentrations of TBT and BaP for 21 days resulted in significant decrease of total hemocyte count, phagocytosis, membrane stability and lysozyme activity. Conversely induction of extra and intra cellular superoxide generation, nitric oxide, nitric oxide synthase and myeloperoxidase activity was present when the abalones were exposed to TBT and BaP. Most of the immune associated parameters tested showed clear time dependent response to both toxicants. Within 14 days after the 21 day exposure to BaP, recovery was observed as evidenced by most of the parameters returning to their normal level. However, no recovery was observed within 14 days after the 21 day exposure to TBT as evidenced by continued elevation of intra cellular superoxide and nitrite production and decrease in THC, membrane stability and lysozyme activity. This suggested a prolonged TBT-induced impact on the immune reaction and possibly more damage than that caused by BaP. Overall the results suggest that chronic exposure to sublethal concentrations of TBT or BaP causes modulations in the immunocompetence of abalones with most of the immune associated parameters tested being stimulated, and this might be harmful to the host. Copyright © 2011 Elsevier Inc. All rights reserved.

Prevention of the pulmonary vasoconstrictor effects of HBOC-201 in awake lambs by continuously breathing nitric oxide.

PubMed

Yu, Binglan; Volpato, Gian Paolo; Chang, Keqin; Bloch, Kenneth D; Zapol, Warren M

2009-01-01

Hemoglobin-based oxygen-carrying solutions (HBOC) provide emergency alternatives to blood transfusion to carry oxygen to tissues without the risks of disease transmission or transfusion reaction. Two primary concerns hampering the clinical acceptance of acellular HBOC are the occurrence of systemic and pulmonary vasoconstriction and the maintenance of the heme-iron in the reduced state (Fe2+). We recently demonstrated that pretreatment with inhaled nitric oxide prevents the systemic hypertension induced by HBOC-201 (polymerized bovine hemoglobin) infusion in awake mice and sheep without causing methemoglobinemia. However, the impact of HBOC-201 infusion with or without inhaled nitric oxide on pulmonary vascular tone has not yet been examined. The pulmonary and systemic hemodynamic effects of breathing nitric oxide both before and after the administration of HBOC-201 were determined in healthy, awake lambs. Intravenous administration of HBOC-201 (12 ml/kg) induced prolonged systemic and pulmonary vasoconstriction. Pretreatment with inhaled nitric oxide (80 parts per million [ppm] for 1 h) prevented the HBOC-201--induced increase in mean arterial pressure but not the increase of pulmonary arterial pressure, systemic vascular resistance, or pulmonary vascular resistance. Pretreatment with inhaled nitric oxide (80 ppm for 1 h) followed by breathing a lower concentration of nitric oxide (5 ppm) during and after HBOC-201 infusion prevented systemic and pulmonary vasoconstriction without increasing methemoglobin levels. These findings demonstrate that pretreatment with inhaled nitric oxide followed by breathing a lower concentration of the gas during and after administration of HBOC-201 may enable administration of an acellular hemoglobin substitute without vasoconstriction while preserving its oxygen-carrying capacity.

Nitric oxide-mediated blood flow regulation as affected by smoking and nicotine.

PubMed

Toda, Noboru; Toda, Hiroshi

2010-12-15

Cigarette smoking is a major risk factor for atherosclerosis, cerebral and coronary vascular diseases, hypertension, and diabetes mellitus. Chronic smoking impairs endothelial function by decreasing the formation of nitric oxide and increasing the degradation of nitric oxide via generation of oxygen free radicals. Nitric oxide liberated from efferent nitrergic nerves is also involved in vasodilatation, increased regional blood flow, and hypotension that are impaired through nitric oxide sequestering by smoking-induced factors. Influence of smoking on nitric oxide-induced blood flow regulation is not necessarily the same in all organs and tissues. However, human studies are limited mainly to the forearm blood flow measurement that assesses endothelial function under basal and stimulated conditions and also determination of penile tumescence and erection in response to endothelial and neuronal nitric oxide. Therefore, information about blood flow regulation in other organs, such as the brain and placenta, has been provided mainly from studies on experimental animals. Nicotine, a major constituent of cigarette smoke, acutely dilates cerebral arteries and arterioles through nitric oxide liberated from nitrergic neurons, but chronically interferes with endothelial function in various vasculatures, both being noted in studies on experimental animals. Cigarette smoke constituents other than nicotine also have some vascular actions. Not only active but also passive smoking is undoubtedly harmful for both the smokers themselves and their neighbors, who should bear in mind that they can face serious diseases in the future, which may result in lengthy hospitalization, and a shortened lifespan. Copyright © 2010 Elsevier B.V. All rights reserved.

Distinct role of nitric oxide and peroxynitrite in mediating oligodendrocyte toxicity in culture and in experimental autoimmune encephalomyelitis.

PubMed

Li, S; Vana, A C; Ribeiro, R; Zhang, Y

2011-06-16

Nitric oxide has been implicated in the pathogenesis of multiple sclerosis. However, it is still unclear whether nitric oxide plays a protective role or is deleterious. We have previously shown that peroxynitrite, a reaction product of nitric oxide and superoxide, is toxic to mature oligodendrocytes (OLs). The toxicity is mediated by intracellular zinc release, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), activation of 12-lipoxygenase (12-LOX) and the formation of reactive oxygen species (ROS). In this study, we found that the donors of nitric oxide, dipropylenetriamine NONOate (DPT NONOate) and diethylenetriamine NONOate (DETA NONOate), protected OLs from peroxynitrite or zinc-induced toxicity. The protective mechanisms appear to be attributable to their inhibition of peroxynitrite- or zinc-induced ERK1/2 phosphorylation and 12-LOX activation. In cultures of mature OLs exposed to lipopolysaccharide (LPS), induction of inducible nitric oxide synthase (iNOS) generated nitric oxide and rendered OLs resistant to peroxynitrite-induced toxicity. The protection was eliminated when 1400W, a specific inhibitor of iNOS, was co-applied with LPS. Using MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, we found that nitrotyrosine immunoreactivity, an indicator of peroxynitrite formation, was increased in the spinal cord white matter, which correlated with the loss of mature OLs. Targeted gene deletion of the NADPH oxidase component gp91phox reduced clinical scores, the formation of nitrotyrosine and the loss of mature OLs. These results suggest that blocking the formation specifically of peroxynitrite, rather than nitric oxide, may be a protective strategy against oxidative stress induced toxicity to OLs. Published by Elsevier Ltd.

Nitric oxide fumigation for control of bulb mites on flower bulbs and tubers

USDA-ARS?s Scientific Manuscript database

Nitric oxide fumigation was studied for efficacy to control bulb mites in the genus Rhizoglyphus and effects on germination and growth of flower bulbs and tubers. Bulb mites on infested peanuts were fumigated with nitric oxide at different concentrations under ultralow oxygen conditions in 1.9L jar...

The light-induced reduction of horizontal cell receptive field size in the goldfish retina involves nitric oxide.

PubMed

Daniels, Bryan A; Baldridge, William H

2011-03-01

Horizontal cells of the vertebrate retina have large receptive fields as a result of extensive gap junction coupling. Increased ambient illumination reduces horizontal cell receptive field size. Using the isolated goldfish retina, we have assessed the contribution of nitric oxide to the light-dependent reduction of horizontal cell receptive field size. Horizontal cell receptive field size was assessed by comparing the responses to centered spot and annulus stimuli and from the responses to translated slit stimuli. A period of steady illumination decreased the receptive field size of horizontal cells, as did treatment with the nitric oxide donor (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (100 μM). Blocking the endogenous production of nitric oxide with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (1 mM), decreased the light-induced reduction of horizontal cell receptive field size. These findings suggest that nitric oxide is involved in light-induced reduction of horizontal cell receptive field size. Copyright © Cambridge University Press, 2011

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malaviya, Rama; Venosa, Alessandro; Hall, LeRoy

Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d–28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition,more » bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 ×/day, 1 d–3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ► Nitrogen mustard (NM) induces acute lung injury and fibrosis. ► Pulmonary toxicity is associated with increased expression of iNOS. ► Transient inhibition of iNOS attenuates acute lung injury induced by NM.« less

Nitric Oxide Mediates Glutamate-Linked Enhancement of cGMP Levels in the Cerebellum

NASA Astrophysics Data System (ADS)

Bredt, David S.; Snyder, Solomon H.

1989-11-01

Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. We show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. Nω-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of Nω-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

Coupling Between the Thermosphere and the Stratosphere: the Role of Nitric Oxide

NASA Technical Reports Server (NTRS)

Brasseur, G.

1984-01-01

In order to understand the lower ionosphere and its probable control by dynamical processes, the behavior of nitric oxide below 100 km was investigated. A two dimensional model with coupled chemical and dynamical processes was constructed. Calculations based on the model reveal that the chemical conditions at the stratopause are related to the state of the thermosphere. This coupling mechanism can be partly explained by the downward transport of nitric oxide during the winter season, and consequently depends on the dynamical conditions in the mesosphere and in the lower thermosphere (mean circulation and waves). In summer, the photodissociation of nitric oxide plays an important role and the thermospheric NO abundance modulates the radiation field reaching the upper stratosphere. Perturbations in the nitric oxide concentration above the mesopause could therefore have an impact in the vicinity of the stratopause.

The Protective Effect of Selenium on Oxidative Stress Induced by Waterpipe (Narghile) Smoke in Lungs and Liver of Mice.

PubMed

Charab, Mohamad A; Abouzeinab, Noura S; Moustafa, Mohamed E

2016-12-01

Waterpipe smoking is common in the Middle East populations and results in health problems. In this study, we investigated the effects of exposure of mice to waterpipe smoke on oxidative stress in lungs and liver and the effects of selenium administration before smoke exposure on the oxidative stress. Twenty-four mice were divided equally into four groups: (i) the control mice received no exposure or treatment; (ii) mice exposed to waterpipe smoke; (iii) mice received intraperitoneal injection of 0.59 μg selenium/kg body weight as sodium selenite 15 min before the exposure to waterpipe smoke; and (iv) mice received intraperitoneal injection of 1.78 μg selenium/kg body weight as sodium selenite 15 min before the exposure to waterpipe smoke. Mice were exposed to waterpipe smoke every other day for four times within 8 successive days. Malondialdehyde and nitric oxide levels were significantly higher in the lungs and liver, while the activities of superoxide dismutase, glutathione peroxidase-1, and catalase were significantly lower in the waterpipe smoke group when compared to control mice. Treating mice with 1.78 μg selenium/kg body weight significantly restored the normal levels of these parameters. Histological examinations of lungs and liver confirmed the protective actions of selenium against the effects of exposure to waterpipe smoke. In conclusion, exposure of mice to waterpipe smoke-induced oxidative stress in lungs and liver. Administration of low level of selenium, 1.78 μg selenium/kg body weight as sodium selenite, exerted protective effects against oxidative stress induced by exposure to waterpipe smoke.

Inducible nitric oxide synthase gene methylation and parkinsonism in manganese-exposed welders

PubMed Central

Nielsen, Susan Searles; Checkoway, Harvey; Criswell, Susan R.; Farin, Federico M.; Stapleton, Patricia L.; Sheppard, Lianne; Racette, Brad A.

2015-01-01

Introduction Neurologist-assessed parkinsonism signs are prevalent among workers exposed to manganese (Mn)-containing welding fume. Neuroinflammation may possibly play a role. Inducible nitric oxide synthase, coded by NOS2, is involved in inflammation, and particulate exposure increases the gene’s expression through methylation of CpG sites in the 5′ region. Methods We assessed DNA methylation at three CpG sites in the NOS2 exon 1 from blood from 201 welders. All were non-Hispanic Caucasian men 25–65 years old who were examined by a neurologist specializing in movement disorders. We categorized the workers according to their Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3) scores as parkinsonism cases (UPDRS3 ≥ 15; n = 49), controls (UPDRS3 < 6; n = 103), or intermediate (UPDRS3 ≥6 to <15; n = 49). Results While accounting for age, examiner and experimental plate, parkinsonism cases had lower mean NOS2 methylation than controls (p-value for trend = 0.04), specifically at CpG site 8329 located in an exonic splicing enhancer of NOS2 (p-value for trend = 0.07). These associations were not observed for the intermediate UPDRS3 group (both p-value for trend ≥ 0.59). Conclusions Inflammation mediated by inducible nitric oxide synthase may possibly contribute to the association between welding fume and parkinsonism, but requires verification in a longitudinal study. PMID:25634431

Neuronal nitric oxide synthase (NOS1) polymorphisms interact with financial hardship to affect depression risk.

PubMed

Sarginson, Jane E; Deakin, J F William; Anderson, Ian M; Downey, Darragh; Thomas, Emma; Elliott, Rebecca; Juhasz, Gabriella

2014-11-01

There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression.

Neuronal Nitric Oxide Synthase (NOS1) Polymorphisms Interact with Financial Hardship to Affect Depression Risk

PubMed Central

Sarginson, Jane E; Deakin, JF William; Anderson, Ian M; Downey, Darragh; Thomas, Emma; Elliott, Rebecca; Juhasz, Gabriella

2014-01-01

There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression. PMID:24917196

The reduction of nitric oxide by ammonia over polycrystalline platinum model catalysts in the presence of oxygen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katona, T.; Guczi, L.; Somorjai, G.A.

1992-06-01

The reaction system of nitric oxide, ammonia, and oxygen was studied using batch-mode measurements in partial pressure ranges of 65-1000 Pa (0.5-7.6 Torr) on polycrystalline Pt foils over the temperature range 423-598 K. Under these conditions the oxidation of nitric oxide was not detectable. The ammonia oxidation reaction, using dioxygen, occurred in the temperature range 423-493 K, producing nitrogen and water as the only products. The activation energy of the nitrogen formation was found to be 86 kJ/mol. Above this temperature range, flow-mode measurements showed the formation of both nitrous oxide and nitric oxide. The reaction rate between ammonia andmore » oxygen was greatly decreased (about a factor of 10) by nitric oxide, while the reaction rate between nitric oxide and ammonia was accelerated (about 10-fold) due to the presence of oxygen. Nitric oxide reduction by ammonia in the presence of oxygen occurred in the temperature range 423-598 K. The products of the reaction were nitrogen, oxygen nitrous oxide, and water. The Arrhenius plot of the reaction showed a break near 523 K. Below this temperature the activation energy of the reaction was 13 kJ/mol, and in the higher-temperature range it was 62 kJ/mol. At 473 K, the N[sub 2]/N[sub 2]O ratio was about 0.6 and O[sub 2] formation was also monitored. At 573 K, the N[sub 2]N[sub 2]O ratio was approximately 2 and oxygen was consumed in the course of the reaction as well.« less

Intracellular redox state determines whether nitric oxide is toxic or protective to rat oligodendrocytes in culture.

PubMed

Rosenberg, P A; Li, Y; Ali, S; Altiok, N; Back, S A; Volpe, J J

1999-08-01

We found that several nitric oxide donors had similar potency in killing mature and immature forms of oligodendrocytes (OLs). Because of the possibility of interaction of nitric oxide with intracellular thiols, we tested the effect of the nitrosonium ion donor S-nitrosylglutathione (SNOG) in OL cultures in the setting of cystine deprivation, which has been shown to cause intracellular glutathione depletion. Surprisingly, the presence of 200 microM SNOG completely protected OLs against the toxicity of cystine depletion. This protection appeared to be due to nitric oxide, because it could be blocked by hemoglobin and potentiated by inclusion of superoxide dismutase. We tested the effect of three additional NO* donors and found that protection was not seen with diethylamine NONOate, a donor with a half-life measured in minutes, but was seen with dipropylenetriamine NONOate and diethylaminetriamine NONOate, donors with half-lives measured in hours. This need for donors with longer half-lives for the protective effect suggested that NO* was required when intracellular thiol concentrations were falling, a process evolving over hours in medium depleted of cystine. These studies suggest a novel protective role for nitric oxide in oxidative stress injury and raise the possibility that intracerebral nitric oxide production might be a mechanism of defense against oxidative stress injury in OLs.

Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats.

PubMed

Flora, Swaran J S; Bhatt, Kapil; Mehta, Ashish

2009-10-15

Gallium arsenide (GaAs), an intermetallic semiconductor finds widespread applications in high frequency microwave and millimeter wave, and ultra fast supercomputers. Extensive use of GaAs has led to increased exposure to humans working in semiconductor industry. GaAs has the ability to dissociate into its constitutive moieties at physiological pH and might be responsible for the oxidative stress. The present study was aimed at evaluating, the principle moiety (Ga or As) in GaAs to cause neurological dysfunction based on its ability to cause apoptosis, in vivo and in vitro and if this neuronal dysfunction translated to neurobehavioral changes in chronically exposed rats. Result indicated that arsenic moiety in GaAs was mainly responsible for causing oxidative stress via increased reactive oxygen species (ROS) and nitric oxide (NO) generation, both in vitro and in vivo. Increased ROS further caused apoptosis via mitochondrial driven pathway. Effects of oxidative stress were also confirmed based on alterations in antioxidant enzymes, GPx, GST and SOD in rat brain. We noted that ROS induced oxidative stress caused changes in the brain neurotransmitter levels, Acetylcholinesterase and nitric oxide synthase, leading to loss of memory and learning in rats. The study demonstrates for the first time that the slow release of arsenic moiety from GaAs is mainly responsible for oxidative stress induced apoptosis in neuronal cells causing behavioral changes.

l-Arginine is a Radioprotector for Hematopoietic Progenitor Cells

PubMed Central

Pearce, Linda L.; Zheng, Xichen; Martinez-Bosch, Sandra; Kerr, Patrick P.; Khlangwiset, Pornsri; Epperly, Michael W.; Fink, Mitchell P.; Greenberger, Joel S.; Peterson, Jim

2012-01-01

l-Arginine is shown to protect hematopoietic progenitor (32D cl 3) cells from death due to exposure to γ radiation (137Cs). Some of the other intermediates in the urea cycle, namely ornithine and citrulline, plus urea itself, were not found to have any significant impact on cell survival after irradiation. Intriguingly, supplementation of irradiated cells with l-arginine results in decreased production of peroxynitrite, suggesting that suppression of superoxide generation by nitric oxide synthase in one or more microenvironments is an important factor in the observed radioprotection. The absence of any radioprotective effect of l-arginine in cells at 3% oxygen also confirms the involvement of one or more oxygen-derived species. Knockdown experiments with nitric oxide synthase (NOS) siRNAs in cells and NOS knockout animals confirm that the observed radioprotection is associated with nNOS (NOS-1). l-Arginine also ameliorates the transient inhibition of the electron-transport chain complex I that occurs within 30 min of completing the dose (10 Gy) and that appears to be a functional marker for postirradiation mitochondrial oxidant production. PMID:22175298

Differential induction of apoptosis in Swiss 3T3 cells by nitric oxide and the nitrosonium cation.

PubMed

Khan, S; Kayahara, M; Joashi, U; Mazarakis, N D; Sarraf, C; Edwards, A D; Hughes, M N; Mehmet, H

1997-09-01

We have investigated the effect of nitric oxide (NO) on apoptosis in Swiss 3T3 fibroblasts and compared it to the effect of the nitrosonium cation (NO+). Both species induced apoptosis, confirmed by electron microscopy, propidium iodide staining, DNA laddering and activation of caspases. The kinetics of triggering apoptosis were different for the two redox species: NO+ required only a 2 hour exposure, whereas NO required 24 hours. Three sources of NO were used: aqueous solutions of NO and two NO donors, S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine. The time course of apoptosis induced by these two S-nitrosothiols correlated with their rate of decomposition to NO. The apoptotic effect of NO was reduced in the presence of the NO scavenger oxyhaemoglobin, or the antioxidants N-acetylcysteine and ascorbic acid, whereas in the case of NO+ these antioxidants potentiated apoptosis. Glutathione also had a potentiating effect on the cytotoxicity of NO+. This suggests that cellular antioxidants may play a role in protecting the cell from NO-induced apoptosis while NO+ may trigger apoptosis independently of oxidative stress mechanisms.

Smoking, COPD and 3-Nitrotyrosine Levels of Plasma Proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Hongjun; Webb-Robertson, Bobbie-Jo M.; Peterson, Elena S.

BACKGROUND: Nitric oxide is a physiologically regulator of endothelial function and hemodynamics. Oxidized products of nitric oxide can form nitrotyrosine, which is a marker of nitrative stress. Cigarette smoking decreases exhaled nitric oxide, and the underlying mechanism may be important in the cardiovascular toxicity of cigarette smoke, although it is not clear if this effect results from decreased nitric oxide production or oxidation of nitric oxide to reactive, nitrating, species. These processes would be expected to have opposite effects on nitrotyrosine levels, a marker of nitrative stress. OBJECTIVE: In this study, we determine the effects of smoking and chronic obstructivemore » pulmonary disease (COPD) on circulating levels of nitrotyrosine, and thereby gain insight into the processes regulating nitrotyrosine formation. METHODS: A custom antibody microarray platform was used to analyze the levels of 3-nitrotyrosine modifications on 24 proteins in plasma. Plasma samples from 458 individuals were analyzed. RESULTS: Nitrotyrosine levels in circulating proteins were uniformly reduced in smokers but increased in COPD patients. We also observed a persistent suppression of nitrotyrosine in former smokers. CONCLUSIONS: Smoking broadly suppresses the levels of 3-nitrotyrosine in plasma proteins, suggesting that cigarette smoke suppresses endothelial nitric oxide production. In contrast, the increase in nitrotyrosine levels in COPD patients most likely results from inflammatory processes. This study provides the first evidence that smoking has irreversible effects on endothelial production of nitric oxide, and provides insight into how smoking could induce a loss of elasticity in the vasculature and a long-term increase in the risk of cardiovascular disease.« less

Involvement of nitric oxide in anticompulsive-like effect of agmatine on marble-burying behaviour in mice.

PubMed

Gawali, Nitin B; Chowdhury, Amrita A; Kothavade, Pankaj S; Bulani, Vipin D; Nagmoti, Dnyaneshwar M; Juvekar, Archana R

2016-01-05

In view of the reports that nitric oxide modulates the neurotransmitters implicated in obsessive-compulsive disorder (OCD), patients with OCD exhibit higher plasma nitrate levels, and drugs useful in OCD influence nitric oxide. Agmatine is a polyamine and widely distributed in mammalian brain which interacts with nitrergic systems. Hence, the present study was carried out to understand the involvement of nitrergic systems in the anticompulsive-like effect of agmatine. We used marble-burying behaviour (MBB) of mice as the animal model of OCD, and nitric oxide levels in hippocampus (HC) and cortex homogenate were measured. Results revealed that, agmatine (20 and 40mg/kg, i.p) significantly inhibited the MBB. Intraperitoneal administration of nitric oxide enhancers viz. nitric oxide precursor - l-arginine (l-ARG) (400mg/kg and 800mg/kg) increased MBB as well as brain nitrites levels, whereas treatment with N(G)-nitro-l-arginine methyl ester (l-NAME) neuronal nitric oxide synthase inhibitor (30mg/kg and 50mg/kg, i.p.) and 7-nitroindazole (7-NI) (20mg/kg and 40mg/kg) attenuated MBB and nitrites levels in brain. Further, in combination studies, the anticompulsive-like effect of agmatine (20mg/kg, ip) was exacerbated by prior administration of l-ARG (400mg/kg) and conversely l-NAME (15mg/kg) or 7-NI (10.0mg/kg) attenuated OCD-like behaviour with HC and cortex changes in the levels of NO. None of the above treatment had any significant influence on locomotor activity. In conclusion, Agmatine is effective in ameliorating the compulsive-like behaviour in mice which appears to be related to nitric oxide in brain. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of Heat Shock Protein 90 and Endothelial Nitric Oxide Synthase during Early Anesthetic and Ischemic Preconditioning

PubMed Central

Amour, Julien; Brzezinska, Anna K.; Weihrauch, Dorothee; Billstrom, Amie R.; Zielonka, Jacek; Krolikowski, John G.; Bienengraeber, Martin W.; Warltier, David C.; Pratt, Philip F.; Kersten, Judy R.

2009-01-01

Background Nitric oxide is known to be essential for early anesthetic (APC) and ischemic (IPC) preconditioning of myocardium. Heat shock protein 90 (Hsp90) regulates endothelial nitric oxide synthase (eNOS) activity. In this study, we tested the hypothesis that Hsp90-eNOS interactions modulate APC and IPC. Methods Myocardial infarct size was measured in rabbits after coronary occlusion and reperfusion in the absence or presence of preconditioning with 30 min of isoflurane (APC) or 5 min of coronary artery occlusion (IPC), and with or without pre-treatment with geldanamycin or radicicol, two chemically distinct Hsp90 inhibitors, or NG-nitro-L-arginine methylester, a non-specific NOS inhibitor. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells or mouse cardiomyocytes, in the absence or presence of Hsp90 inhibitors or NG-nitro-L-arginine methylester. Interactions between Hsp90 and eNOS, and eNOS activation were assessed with immunoprecipitation, immunoblotting, and confocal microscopy. Results APC and IPC decreased infarct size (50% and 59%, respectively) and this action was abolished by Hsp90 inhibitors. NG-nitro-L-arginine methylester blocked APC but not IPC. Isoflurane increased nitric oxide production in human coronary artery endothelial cells, concomitantly with an increase in Hsp90-eNOS interaction (immunoprecipitation, immunoblotting, and immunohistochemistry). Pretreatment with Hsp90 inhibitors abolished isoflurane-dependent nitric oxide production and decreased Hsp90-eNOS interactions. Isoflurane did not increase nitric oxide production in mouse cardiomyocytes and eNOS was below the level of detection. Conclusion The results indicate that Hsp90 plays a critical role in mediating APC and IPC through protein-protein interactions, and suggest that endothelial cells are important contributors to nitric oxide-mediated signalling during APC. PMID:19194158

Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs

PubMed Central

Keeble, J E; Moore, P K

2002-01-01

This review examines the biological significance, therapeutic potential and mechanism(s) of action of a range of nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAID) and related nitric oxide-releasing donating drugs (NODD). The slow release of nitric oxide (NO) from these compounds leads to subtle changes in the profile of pharmacological activity of the parent, non-steroidal anti-inflammatory drugs (NSAID). For example, compared with NSAID, NO-NSAID cause markedly diminished gastrointestinal toxicity and improved anti-inflammatory and anti-nociceptive efficacy. In addition, nitroparacetamol exhibits hepatoprotection as opposed to the hepatotoxic activity of paracetamol. The possibility that NO-NSAID or NODD may be of therapeutic benefit in a wide variety of disease states including pain and inflammation, thrombosis and restenosis, neurodegenerative diseases of the central nervous system, colitis, cancer, urinary incontinence, liver disease, impotence, bronchial asthma and osteoporosis is discussed. PMID:12237248

NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity

PubMed Central

2012-01-01

A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the μ-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the μ-opioid GPCR was predicated on the modulatory role of nitric oxide on μ-opioid receptor function. Structure–activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 μM), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent μ-opioid binding affinity, Ki = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 μM). This work represents a novel approach in the development of new analgesics for the treatment of pain. PMID:24900459

NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity.

PubMed

Renton, Paul; Green, Brenda; Maddaford, Shawn; Rakhit, Suman; Andrews, John S

2012-03-08

A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the μ-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the μ-opioid GPCR was predicated on the modulatory role of nitric oxide on μ-opioid receptor function. Structure-activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 μM), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent μ-opioid binding affinity, K i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 μM). This work represents a novel approach in the development of new analgesics for the treatment of pain.

Inhaled Nitric Oxide Therapy for Pulmonary Disorders of the Term and Preterm Infant

PubMed Central

Sokol, Gregory M.; Konduri, G. Ganesh; Van Meurs, Krisa P.

2016-01-01

The 21st century began with the FDA approval of inhaled nitric oxide therapy for the treatment of neonatal hypoxic respiratory failure associated with pulmonary hypertension in recognition of the two randomized clinical trials demostrating a significant reduction in the need for extracorporeal support in the term and near-term infant. Inhaled nitric oxide is one of only a few therapeutic agents approved for use through clinical investigations primarily in the neonate. This article provides an overview of the pertinent biology and chemistry of nitric oxide, discusses potential toxicities, and reviews the results of pertinent clinical investigations and large randomized clinical trials including neurodevelopmental follow-up in term and preterm neonates. The clinical investigations conducted by the Eunice Kennedy Shriver NICHD Neonatal Research Network will be discussed and placed in context with other pertinent clinical investigations exploring the efficacy of inhaled nitric oxide therapy in neonatal hypoxic respiratory failure. PMID:27480246

The Moraxella catarrhalis nitric oxide reductase is essential for nitric oxide detoxification.

PubMed

Wang, Wei; Kinkel, Traci; Martens-Habbena, Willm; Stahl, David A; Fang, Ferric C; Hansen, Eric J

2011-06-01

Moraxella catarrhalis is a Gram-negative obligate aerobe that is an important cause of human respiratory tract infections. The M. catarrhalis genome encodes a predicted truncated denitrification pathway that reduces nitrate to nitrous oxide. We have previously shown that expression of both the M. catarrhalis aniA (encoding a nitrite reductase) and norB (encoding a putative nitric oxide reductase) genes is repressed by the transcriptional regulator NsrR under aerobic conditions and that M. catarrhalis O35E nsrR mutants are unable to grow in the presence of low concentrations of nitrite (W. Wang, et al., J. Bacteriol. 190:7762-7772, 2008). In this study, we constructed an M. catarrhalis norB mutant and showed that planktonic growth of this mutant is inhibited by low levels of nitrite, whether or not an nsrR mutation is present. To determine the importance of NorB in this truncated denitrification pathway, we analyzed the metabolism of nitrogen oxides by norB, aniA norB, and nsrR norB mutants. We found that norB mutants are unable to reduce nitric oxide and produce little or no nitrous oxide from nitrite. Furthermore, nitric oxide produced from nitrite by the AniA protein is bactericidal for a Moraxella catarrhalis O35E norB mutant but not for wild-type O35E bacteria under aerobic growth conditions in vitro, suggesting that nitric oxide catabolism in M. catarrhalis is accomplished primarily by the norB gene product. Measurement of bacterial protein S-nitrosylation directly implicates nitrosative stress resulting from AniA-dependent nitric oxide formation as a cause of the growth inhibition of norB and nsrR mutants by nitrite.

Intercellular communications-redox interactions in radiation toxicity; potential targets for radiation mitigation.

PubMed

Farhood, Bagher; Goradel, Nasser Hashemi; Mortezaee, Keywan; Khanlarkhani, Neda; Salehi, Ensieh; Nashtaei, Maryam Shabani; Shabeeb, Dheyauldeen; Musa, Ahmed Eleojo; Fallah, Hengameh; Najafi, Masoud

2018-06-17

Nowadays, using ionizing radiation (IR) is necessary for clinical, agricultural, nuclear energy or industrial applications. Accidental exposure to IR after a radiation terror or disaster poses a threat to human. In contrast to the old dogma of radiation toxicity, several experiments during the last two recent decades have revealed that intercellular signaling and communications play a key role in this procedure. Elevated level of cytokines and other intercellular signals increase oxidative damage and inflammatory responses via reduction/oxidation interactions (redox system). Intercellular signals induce production of free radicals and inflammatory mediators by some intermediate enzymes such as cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), NADPH oxidase, and also via triggering mitochondrial ROS. Furthermore, these signals facilitate cell to cell contact and increasing cell toxicity via cohort effect. Nitric oxide is a free radical with ability to act as an intercellular signal that induce DNA damage and changes in some signaling pathways in irradiated as well as non-irradiated adjacent cells. Targeting of these mediators by some anti-inflammatory agents or via antioxidants such as mitochondrial ROS scavengers opens a window to mitigate radiation toxicity after an accidental exposure. Experiments which have been done so far suggests that some cytokines such as IL-1β, TNF-α, TGF-β, IL-4 and IL-13 are some interesting targets that depend on irradiated organs and may help mitigate radiation toxicity. Moreover, animal experiments in recent years indicated that targeting of toll like receptors (TLRs) may be more useful for radioprotection and mitigation. In this review, we aimed to describe the role of intercellular interactions in oxidative injury, inflammation, cell death and killing effects of IR. Moreover, we described evidence on potential mitigation of radiation injury via targeting of these mediators.

D-Methionine attenuated cisplatin-induced vestibulotoxicity through altering ATPase activities and oxidative stress in guinea pigs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, P.-W.; Department of Otolaryngology, Far Eastern Memorial Hospital, Taipei, Taiwan; Liu, S.-H.

2006-09-01

Cisplatin has been used as a chemotherapeutic agent to treat many kinds of malignancies. Its damage to the vestibulo-ocular reflex (VOR) system has been reported. However, the underlying biochemical change in the inner ear or central vestibular nervous system is not fully understood. In this study, we attempted to examine whether cisplatin-induced vestibulotoxicity and D-methionine protection were correlated with the changes of ATPase activities and oxidative stress of ampullary tissue of vestibules as well as cerebellar cortex (the inhibitory center of VOR system) of guinea pigs. By means of a caloric test coupled with electronystagmographic recordings, we found that cisplatinmore » exposure caused a dose-dependent (1, 3, or 5 mg/kg) vestibular dysfunction as revealed by a decrease of slow phase velocity (SPV). In addition, cisplatin significantly inhibited the Na{sup +}, K{sup +}-ATPase and Ca{sup 2+}-ATPase activities in the ampullary tissue with a good dose-response relationship but not those of cerebellar cortex. Regression analysis indicated that a decrease of SPV was well correlated with the reduction of Na{sup +}, K{sup +}-ATPase and Ca{sup 2+}-ATPase activities of the ampullary tissue. D-Methionine (300 mg/kg) reduced both abnormalities of SPV and ATPase activities in a correlated manner. Moreover, cisplatin exposure led to a significant dose-dependent increase of lipid peroxidation and nitric oxide concentrations of the vestibules, which could be significantly suppressed by D-methionine. However, cisplatin did not alter the levels of lipid peroxidation and nitric oxide of the cerebellum. In conclusion, cisplatin inhibited ATPase activities and increased oxidative stress in guinea pig vestibular labyrinths. D-Methionine attenuated cisplatin-induced vestibulotoxicity associated with ionic disturbance through its antioxidative property.« less

Prospect of nitric oxide as a new fumigant for postharvest pest control

USDA-ARS?s Scientific Manuscript database

Nitric oxide (NO) is a newly discovered fumigant for postharvest pest control. In laboratory tests, complete control was achieved against all insect and mite species tested to date with 0.2% to 5% NO fumigations in 2 h to 48 h at 2 to 25°C depending on species and life stages. Nitric oxide reacts ...

Oleic acid-dependent modulation of Nitric oxide associated 1 protein levels regulates nitric oxide-mediated defense signaling in Arabidopsis

USDA-ARS?s Scientific Manuscript database

The conserved cellular metabolites nitric oxide (NO) and oleic acid (18:1) are well-known regulators of disease physiologies in diverse organism. We show that NO production in plants is regulated via 18:1. Reduction in 18:1 levels, via a genetic mutation in the 18:1-synthesizing gene SUPPRESSOR OF S...

Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice.

PubMed

Reece, Stephen T; Vogelzang, Alexis; Tornack, Julia; Bauer, Wolfgang; Zedler, Ulrike; Schommer-Leitner, Sandra; Stingl, Georg; Melchers, Fritz; Kaufmann, Stefan H E

2018-04-23

Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M. tuberculosis propagate hallmarks of disease if nitric oxide-mediated killing of bacteria is defective.

Effects of plasma nitric oxide levels on platelet activation in single donor apheresis and random donor concentrates.

PubMed

Büyükkağnici, Demet Iren; Ilhan, Osman; Kavas, Güzin Ozelçi; Arslan, Onder; Arat, Mutlu; Dalva, Klara; Ayyildiz, Erol

2007-02-01

P-selectin is an useful marker to determine platelet activation and nitric oxide inhibits platelet activation, secretion, adhesion and aggregation. The aim of this study was to investigate the relationship between nitric oxide and P-selectin values in both single donor apheresis and random donor platelet concentrates. According to the results of this study, we found that the best platelet concentrate is freshly prepared single donor apheresis concentrate and it is important to prevent activation at the beginning of the donation. Nitric oxide, which is synthesized from platelets during the storage period, is not sufficient to prevent platelet activation.

Effect of caffeine coadministration and of nitric oxide synthesis inhibition on the antinociceptive action of ketorolac.

PubMed

López-Muñoz, F J; Castañeda-Hernández, G; Flores-Murrieta, F J; Granados-Soto, V

1996-07-25

The effects of caffeine and nitric oxide synthesis inhibition on the antinociceptive action of ketorolac were assessed using the pain-induced functional impairment model in the rat. Nociception was induced by the intra-articular injection of uric acid. Ketorolac, but not caffeine, produced an antinociceptive effect which was reduced by NG nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis. Caffeine coadministration potentiated the ketorolac effect. L-NAME induced a dose-dependent reduction of this potentiation. The results suggest the participation of the L-arginine-nitric oxide-cyclic GMP pathway in the caffeine potentiation of ketorolac-induced antinociception.

Rocuronium Bromide Inhibits Inflammation and Pain by Suppressing Nitric Oxide Production and Enhancing Prostaglandin E2 Synthesis in Endothelial Cells.

PubMed

Baek, Sang Bin; Shin, Mal Soon; Han, Jin Hee; Moon, Sang Woong; Chang, Boksoon; Jeon, Jung Won; Yi, Jae Woo; Chung, Jun Young

2016-12-01

Rocuronium bromide is a nondepolarizing neuromuscular blocking drug and has been used as an adjunct for relaxation or paralysis of the skeletal muscles, facilitation of endotracheal intubation, and improving surgical conditions during general anesthesia. However, intravenous injection of rocuronium bromide induces injection pain or withdrawal movement. The exact mechanism of rocuronium bromide-induced injection pain or withdrawal movement is not yet understood. We investigated whether rocuronium bromide treatment is involved in the induction of inflammation and pain in vascular endothelial cells. For this study, calf pulmonary artery endothelial (CPAE) cells were used, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Western blot, nitric oxide detection, and prostaglandin E 2 immunoassay were conducted. Rocuronium bromide treatment inhibited endothelial nitric oxide synthase and suppressed nitric oxide production in CPAE cells. Rocuronium bromide activated cyclooxygenase-2, inducible nitric oxide synthase and increased prostaglandin E 2 synthesis in CPAE cells. Rocuronium bromide induced inflammation and pain in CPAE cells. Suppressing nitric oxide production and enhancing prostaglandin E 2 synthesis might be associated with rocuronium bromide-induced injection pain or withdrawal movement.

Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle cells

NASA Technical Reports Server (NTRS)

Koh, T. J.; Tidball, J. G.

2000-01-01

We tested the hypothesis that nitric oxide can inhibit cytoskeletal breakdown in skeletal muscle cells by inhibiting calpain cleavage of talin. The nitric oxide donor sodium nitroprusside prevented many of the effects of calcium ionophore on C(2)C(12) muscle cells, including preventing talin proteolysis and release into the cytosol and reducing loss of vinculin, cell detachment, and loss of cellular protein. These results indicate that nitric oxide inhibition of calpain protected the cells from ionophore-induced proteolysis. Calpain inhibitor I and a cell-permeable calpastatin peptide also protected the cells from proteolysis, confirming that ionophore-induced proteolysis was primarily calpain mediated. The activity of m-calpain in a casein zymogram was inhibited by sodium nitroprusside, and this inhibition was reversed by dithiothreitol. Previous incubation with the active site-targeted calpain inhibitor I prevented most of the sodium nitroprusside-induced inhibition of m-calpain activity. These data suggest that nitric oxide inhibited m-calpain activity via S-nitrosylation of the active site cysteine. The results of this study indicate that nitric oxide produced endogenously by skeletal muscle and other cell types has the potential to inhibit m-calpain activity and cytoskeletal proteolysis.

[Effects of soy bean isoflavone on inhibition of benign prostatic hyperplasia and the expressions of NO and NOS of rats].

PubMed

Yang, Aiqing; Ren, Guofeng; Tang, Ling; Jiang, Weiwei

2009-03-01

To explore the inhibitive effect of soybean isoflavone on the prostatic hyperplasia on the expressions of nitric oxid and nitric oxide synthase in the prostatic hyperplasia rats. Subcutaneously injected testosterone propionate were to induce prostate hyperplasia in rats. The changes of prostate wet weight, prostatic index, liver index, the changes of some biochemical indexes in rat prostate tissue in the control and the treatment, the low, moderate, high dose groups of soybean isoflavone groups were observed. The prostate wet weight and prostatic index in all dose groups were merely lower than those in the treatment and the moderate groups were lowest in all dose group. There were no significant differences in liver index, urea nitrogen, glutamic-pyruvic transaminase of each group. Acid phosphatase, prostatic acid phosphatase and lactate dehydrogenase in all dose groups were merely lower than those in the treatment group. Nitric oxide and nitric oxide synthase in all dose groups were merely higher than those in the treatment group. Soybean isoflavone could inhibit prostate hyperplasia and increase the expressions of nitric oxide and nitric oxide synthase in rats.

Cytosolic NADP(+)-dependent isocitrate dehydrogenase protects macrophages from LPS-induced nitric oxide and reactive oxygen species.

PubMed

Maeng, Oky; Kim, Yong Chan; Shin, Han-Jae; Lee, Jie-Oh; Huh, Tae-Lin; Kang, Kwang-il; Kim, Young Sang; Paik, Sang-Gi; Lee, Hayyoung

2004-04-30

Macrophages activated by microbial lipopolysaccharides (LPS) produce bursts of nitric oxide and reactive oxygen species (ROS). Redox protection systems are essential for the survival of the macrophages since the nitric oxide and ROS can be toxic to them as well as to pathogens. Using suppression subtractive hybridization (SSH) we found that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is strongly upregulated by nitric oxide in macrophages. The levels of IDPc mRNA and of the corresponding enzymatic activity were markedly increased by treatment of RAW264.7 cells or peritoneal macrophages with LPS or SNAP (a nitric oxide donor). Over-expression of IDPc reduced intracellular peroxide levels and enhanced the survival of H2O2- and SNAP-treated RAW264.7 macrophages. IDPc is known to generate NADPH, a cellular reducing agent, via oxidative decarboxylation of isocitrate. The expression of enzymes implicated in redox protection, superoxide dismutase (SOD) and catalase, was relatively unaffected by LPS and SNAP. We propose that the induction of IDPc is one of the main self-protection mechanisms of macrophages against LPS-induced oxidative stress.

Modification of Traffic-related Respiratory Response by Asthma Control in a Population of Car Commuters

PubMed Central

Mirabelli, Maria C.; Golan, Rachel; Greenwald, Roby; Raysoni, Amit U.; Holguin, Fernando; Kewada, Priya; Winquist, Andrea; Flanders, W. Dana; Sarnat, Jeremy A.

2015-01-01

Background Effects of traffic-related exposures on respiratory health are well documented, but little information is available about whether asthma control influences individual susceptibility. We analyzed data from the Atlanta Commuter Exposure study to evaluate modification of associations between rush-hour commuting, in-vehicle air pollution, and selected respiratory health outcomes by asthma control status. Methods Between 2009 and 2011, 39 adults participated in Atlanta Commuter Exposure, and each conducted two scripted rush-hour highway commutes. In-vehicle particulate components were measured during all commutes. Among adults with asthma, we evaluated asthma control by questionnaire and spirometry. Exhaled nitric oxide, forced expiratory volume in 1 second (FEV1), and other metrics of respiratory health were measured precommute and 0, 1, 2, and 3 hours postcommute. We used mixed effects linear regression to evaluate associations between commute-related exposures and postcommute changes in metrics of respiratory health by level of asthma control. Results We observed increased exhaled nitric oxide across all levels of asthma control compared with precommute measurements, with largest postcommute increases observed among participants with below-median asthma control (2 hours postcommute: 14.6% [95% confidence interval {CI} = 5.7, 24.2]; 3 hours postcommute: 19.5% [95% CI = 7.8, 32.5]). No associations between in-vehicle pollutants and percent of predicted FEV1 were observed, although higher PM2.5 was associated with lower FEV1 % predicted among participants with below-median asthma control (3 hours postcommute: −7.2 [95% CI = −11.8, −2.7]). Conclusions Level of asthma control may influence respiratory response to in-vehicle exposures experienced during rush-hour commuting. PMID:25901844

Clomiphene citrate increases nitric oxide, interleukin-10 and reduces matrix metalloproteinase-9 in women with polycystic ovary syndrome.

PubMed

Sylus, Angel Mercy; Nandeesha, Hanumanthappa; Sridhar, Magadi Gopalakrishna; Chitra, Thyagaraju; Sreenivasulu, Karli

2018-06-08

Matrix metalloproteinase-9, Nitric oxide and inflammation plays a role in the pathogenesis of poly cystic ovary syndrome (PCOS). Even though these parameters are altered in PCOS, the effect of clomiphene citrate on them has not been studied till date. The present study was done to assess the effect of clomiphene citrate on matrix metalloproteinase-9, nitric oxide and interleukin-10 levels in women with PCOS. 72 women diagnosed with PCOS were enrolled in the study. Matrix metalloproteinase-9, nitric oxide and interleukin-10 levels were compared at baseline and after three weeks following Clomiphene citrate treatment. Clomiphene citrate increases both nitric oxide (p = 0.03) and interleukin-10 (p < 0.001) levels and reduces matrix metalloproteinase-9 levels (p < 0.001) in women with PCOS. It also improves the ovulation rate (52.8%) and clinical pregnancy rate (19.4%) in PCOS. Also there was a significant reduction in matrix metalloproteinase-9 levels in both the ovulatory (p < 0.001) and conceived groups (p = 0.024) compared to non ovulatory and non conceived group. There was no difference in nitric oxide and interleukin-10 levels in ovulatory and conceived groups compared to non ovulatory and non conceived group. We conclude that clomiphene citrate increases the levels of nitric oxide and interleukin-10 and decreases the matrix metalloproteinase - 9 levels and improves the ovulation rate and clinical pregnancy rate in PCOS. Copyright © 2018 Elsevier B.V. All rights reserved.

(-)-Epicatechin-induced recovery of mitochondria from simulated diabetes: Potential role of endothelial nitric oxide synthase.

PubMed

Ramírez-Sánchez, Israel; Rodríguez, Alonso; Moreno-Ulloa, Aldo; Ceballos, Guillermo; Villarreal, Francisco

2016-05-01

(-)-Epicatechin increases indicators associated with mitochondrial biogenesis in endothelial cells and myocardium. We investigated endothelial nitric oxide synthase involvement on (-)-epicatechin-induced increases in indicators associated with mitochondrial biogenesis in human coronary artery endothelial cells cultured in normal-glucose and high-glucose media, as well as to restore indicators of cardiac mitochondria from the effects of simulated diabetes. Here, we demonstrate the role of endothelial nitric oxide synthase on (-)-epicatechin-induced increases in mitochondrial proteins, transcription factors and sirtuin 1 under normal-glucose conditions. In simulated diabetes endothelial nitric oxide synthase function, mitochondrial function-associated and biogenesis-associated indicators were adversely impacted by high glucose, effects that were reverted by (-)-epicatechin. As an animal model of type 2 diabetes, 2-month old C57BL/6 mice were fed a high-fat diet for 16 weeks. Fasting and fed blood glucose levels were increased and NO plasma levels decreased. High-fat-diet-fed mice myocardium revealed endothelial nitric oxide synthase dysfunction, reduced mitochondrial activity and markers of mitochondrial biogenesis. The administration of 1 mg/kg (-)-epicatechin for 15 days by oral gavage shifted these endpoints towards control mice values. Results suggest that endothelial nitric oxide synthase mediates (-)-epicatechin-induced increases of indicators associated with mitochondrial biogenesis in endothelial cells. (-)-Epicatechin also counteracts the negative effects that high glucose or simulated type 2 diabetes has on endothelial nitric oxide synthase function. © The Author(s) 2016.

[Fractional exhaled nitric oxide in monitoring and therapeutic management of asthma].

PubMed

Melo, Bruno; Costa, Patrício; Afonso, Ariana; Machado, Vânia; Moreira, Carla; Gonçalves, Augusta; Gonçalves, Jean-Pierre

2014-01-01

Asthma is a chronic respiratory disease characterized by hyper-responsiveness and bronchial inflammation. The bronchial inflammation in these patients can be monitored by measuring the fractional exhaled nitric oxide. This study aims to determine fractional exhaled nitric oxide association with peak expiratory flow and with asthma control inferred by the Global Initiative for Asthma. Observational, analytical and cross-sectional study of children with asthma, 6-12 years-old, followed in the Outpatient Respiratory Pathology of Braga Hospital. Sociodemographic and clinical information were collected through a questionnaire. fractional exhaled nitric oxide and peak expiratory flow were determined by portable analyzer Niox Mino® and flow meter, respectively. The sample is constituted by 101 asthmatic children, 63 (62.4%) of males and 38 (37.6%) females. The mean age of participants in the sample is 9.18 (1.99) years. The logistic regression performed with the cutoff value obtained by ROC curve, revealed that fractional exhaled nitric oxide (b(FENO classes) = 0.85; χ(2)Wald (1) = 8.71; OR = 2.33; p = 0.003) has a statistical significant effect on the probability of changing level of asthma control. The odds ratio of going from "controlled" to "partly controlled/uncontrolled" is 2.33 per each level of fractional exhaled nitric oxide. The probability of an asthmatic children change their level of asthma control, from 'controlled' to 'partly controlled/uncontrolled', taking into account a change in their fractional exhaled nitric oxide level, increases 133%.

Expression of nitric oxide synthase-2 in the lungs decreases airway resistance and responsiveness.

PubMed

Hjoberg, Josephine; Shore, Stephanie; Kobzik, Lester; Okinaga, Shoji; Hallock, Arlene; Vallone, Joseph; Subramaniam, Venkat; De Sanctis, George T; Elias, Jack A; Drazen, Jeffrey M; Silverman, Eric S

2004-07-01

Individuals with asthma have increased levels of nitric oxide in their exhaled air. To explore its role, we have developed a regulatable transgenic mouse capable of overexpressing inducible nitric oxide synthase in a lung-specific fashion. The CC10-rtTA-NOS-2 mouse contains two transgenes, a reverse tetracycline transactivator under the control of the Clara cell protein promoter and the mouse nitric oxide synthase-2 (NOS-2) coding region under control of a tetracycline operator. Addition of doxycycline to the drinking water of CC10-rtTA-NOS-2 mice causes an increase in nitric oxide synthase-2 that is largely confined to the airway epithelium. The fraction of expired nitric oxide increases over the first 24 h from approximately 10 parts per billion to a plateau of approximately 20 parts per billion. There were no obvious differences between CC10-rtTA-NOS-2 mice, with or without doxycycline, and wild-type mice in lung histology, bronchoalveolar protein, total cell count, or count differentials. However, airway resistance was lower in CC10-rtTA-NOS-2 mice with doxycycline than in CC10-rtTA-NOS-2 mice without doxycycline or wild-type mice with doxycycline. Moreover, doxycycline-treated CC10-rtTA-NOS-2 mice were hyporesponsive to methacholine compared with other groups. These data suggest that increased nitric oxide in the airways has no proinflammatory effects per se and may have beneficial effects on pulmonary function.

Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort

PubMed Central

Gonzalez, Antonio; Hyde, Embriette; Sangwan, Naseer; Gilbert, Jack A.; Viirre, Erik

2016-01-01

ABSTRACT Nitrates, such as cardiac therapeutics and food additives, are common headache triggers, with nitric oxide playing an important role. Facultative anaerobic bacteria in the oral cavity may contribute migraine-triggering levels of nitric oxide through the salivary nitrate-nitrite-nitric oxide pathway. Using high-throughput sequencing technologies, we detected observable and significantly higher abundances of nitrate, nitrite, and nitric oxide reductase genes in migraineurs versus nonmigraineurs in samples collected from the oral cavity and a slight but significant difference in fecal samples. IMPORTANCE Recent work has demonstrated a potentially symbiotic relationship between oral commensal bacteria and humans through the salivary nitrate-nitrite-nitric oxide pathway (C. Duncan et al., Nat Med 1:546–551, 1995, http://dx.doi.org/10.1038/nm0695-546). Oral nitrate-reducing bacteria contribute physiologically relevant levels of nitrite and nitric oxide to the human host that may have positive downstream effects on cardiovascular health (V. Kapil et al., Free Radic Biol Med 55:93–100, 2013, http://dx.doi.org/10.1016/j.freeradbiomed.2012.11.013). In the work presented here, we used 16S rRNA Illumina sequencing to determine whether a connection exists between oral nitrate-reducing bacteria, nitrates for cardiovascular disease, and migraines, which are a common side effect of nitrate medications (U. Thadani and T. Rodgers, Expert Opin Drug Saf 5:667–674, 2006, http://dx.doi.org/10.1517/14740338.5.5.667). PMID:27822557

Ascorbic acid reduces noise-induced nitric oxide production in the guinea pig ear.

PubMed

Heinrich, Ulf-Rüdiger; Fischer, Ilka; Brieger, Jürgen; Rümelin, Andreas; Schmidtmann, Irene; Li, Huige; Mann, Wolf J; Helling, Kai

2008-05-01

Noise-induced hearing loss can be caused, among other causes, by increased nitric oxide (NO) production in the inner ear leading to nitroactive stress and cell destruction. Some studies in the literature suggest that the degree of hearing loss (HL) could be reduced in an animal model through ascorbic acid supplementation. To identify the effect of ascorbic acid on tissue-dependent NO content in the inner ear of the guinea pig, we determined the local NO production in the organ of Corti and the lateral wall separately 6 hours after noise exposure. Prospective animal study in guinea pigs. Over a period of 7 days, male guinea pigs were supplied with minimum (25 mg/kg body weight/day) and maximum (525 mg/kg body weight/day) ascorbic acid doses, and afterwards exposed to noise (90 dB sound pressure level for 1 hour). The acoustic-evoked potentials were recorded before and after noise exposure. The organ of Corti and the lateral wall were incubated differently for 6 hours in culture medium, and the degree of NO production was determined by chemiluminescence. Ascorbic acid treatment reduced the hearing threshold shift after noise exposure depending on concentration. When the maximum ascorbic acid dose was substituted, NO production was significantly reduced in the lateral wall after noise exposure and slightly reduced in the organ of Corti. Oral supplementation of the natural radical scavenger ascorbic acid reduces the NO-production rate in the inner ear in noisy conditions. This finding supports the concept of inner ear protection by ascorbic acid supplementation.

Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.

PubMed Central

Stamler, J S; Jaraki, O; Osborne, J; Simon, D I; Keaney, J; Vita, J; Singel, D; Valeri, C R; Loscalzo, J

1992-01-01

We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endothelium-derived relaxing factor-like properties. The single free cysteine of serum albumin, Cys-34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for approximately 0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S--NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosothiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains approximately 7 microM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-serum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at approximately 1 microM; 60 min after administration of NG-monomethyl-L-arginine at 50 mg/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by approximately 40% (greater than 95% of which were accounted for by S-nitrosoproteins, and approximately 80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be regulated for the maintenance of vascular tone. PMID:1502182

Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.

PubMed

Stamler, J S; Jaraki, O; Osborne, J; Simon, D I; Keaney, J; Vita, J; Singel, D; Valeri, C R; Loscalzo, J

1992-08-15

We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endothelium-derived relaxing factor-like properties. The single free cysteine of serum albumin, Cys-34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for approximately 0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S--NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosothiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains approximately 7 microM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-serum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at approximately 1 microM; 60 min after administration of NG-monomethyl-L-arginine at 50 mg/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by approximately 40% (greater than 95% of which were accounted for by S-nitrosoproteins, and approximately 80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be regulated for the maintenance of vascular tone.

Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

PubMed

Grassi, S; Pettorossi, V E

2000-01-01

In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a sufficient level for triggering potentiation. Once the synaptic efficacy has changed, it becomes a long-lasting phenomenon only through a subsequent action of platelet-activating factor.

Measurements and predictors of on-road ultrafine particle concentrations and associated pollutants in Los Angeles

NASA Astrophysics Data System (ADS)

Fruin, S.; Westerdahl, D.; Sax, T.; Sioutas, C.; Fine, P. M.

Motor vehicles are the dominant source of oxides of nitrogen (NO x), particulate matter (PM), and certain air toxics (e.g., benzene, 1,3-butadiene) in urban areas. On roadways, motor vehicle-related pollutant concentrations are typically many times higher than ambient concentrations. Due to high air exchange rates typical of moving vehicles, this makes time spent in vehicles on roadways a major source of exposure. This paper presents on-road measurements for Los Angeles freeways and arterial roads taken from a zero-emission electric vehicle outfitted with real-time instruments. The objective was to characterize air pollutant concentrations on roadways and identify the factors associated with the highest concentrations. Our analysis demonstrated that on freeways, concentrations of ultrafine particles (UFPs), black carbon, nitric oxide, and PM-bound polycyclic aromatic hydrocarbons (PM-PAH) are generated primarily by diesel-powered vehicles, despite the relatively low fraction (˜6%) of diesel-powered vehicles on Los Angeles freeways. However, UFP concentrations on arterial roads appeared to be driven primarily by proximity to gasoline-powered vehicles undergoing hard accelerations. Concentrations were roughly one-third of those on freeways. By using a multiple regression model for the freeway measurements, we were able to explain 60-70% of the variability in concentrations of UFP, black carbon, nitric oxide, and PM-PAH using measures of diesel truck density and hour of day (as an indicator of wind speed). Freeway concentrations of these pollutants were also well correlated with readily available annual average daily truck counts, potentially allowing improved population exposure estimates for epidemiology studies. Based on these roadway measurements and average driving time, it appears that 33-45% of total UFP exposure for Los Angeles residents occurs due to time spent traveling in vehicles.

Quercetin and its principal metabolites, but not myricetin, oppose lipopolysaccharide-induced hyporesponsiveness of the porcine isolated coronary artery

PubMed Central

Al-Shalmani, Salmin; Suri, Sunita; Hughes, David A; Kroon, Paul A; Needs, Paul W; Taylor, Moira A; Tribolo, Sandra; Wilson, Vincent G

2011-01-01

BACKGROUND AND PURPOSE Quercetin is anti-inflammatory in macrophages by inhibiting lipopolysaccharide (LPS)-mediated increases in cytokine and nitric oxide production but there is little information regarding the corresponding effect on the vasculature. We have examined the effect of quercetin, and its principal human metabolites, on inflammatory changes in the porcine isolated coronary artery. EXPERIMENTAL APPROACH Porcine coronary artery segments were incubated overnight at 37°C in modified Krebs-Henseleit solution with or without 1 µg·mL−1 LPS. Some segments were also co-incubated with quercetin-related flavonoids or Bay 11-7082, an inhibitor of NFκB. Changes in isometric tension of segments to vasoconstrictor and vasodilator agents were recorded. Nitrite content of the incubation solution was estimated using the Griess reaction, while inducible nitric oxide synthase was identified immunohistochemically. KEY RESULTS Lipopolysaccharide reduced, by 35–50%, maximal contractions to KCl and U46619, thromboxane A2 receptor agonist, and impaired endothelium-dependent relaxations to substance P. Nitrite content of the incubation medium increased 3- to 10-fold following exposure to LPS and inducible nitric oxide synthase was detected in the adventitia. Quercetin (0.1–10 µM) opposed LPS-induced changes in vascular responses, nitrite production and expression of inducible nitric oxide synthase. Similarly, 10 µM Bay 11-7082, 10 µM quercetin 3′-sulphate and 10 µM quercetin 3-glucuronide prevented LPS-induced changes, while myricetin (10 µM) was inactive. Myricetin (10 µM) prevented quercetin-induced modulation of LPS-mediated nitrite production. CONCLUSION AND IMPLICATIONS Quercetin, quercetin 3′-suphate and quercetin 3-glucuronide, exerted anti-inflammatory effects on the vasculature, possibly through a mechanism involving inhibition of NFκB. Myricetin-induced antagonism of the effect of anti-inflammatory action of quercetin merits further investigation. PMID:21375526

Nitric oxide acts as a positive regulator to induce metamorphosis of the ascidian Herdmania momus.

PubMed

Ueda, Nobuo; Degnan, Sandie M

2013-01-01

Marine invertebrates commonly have a biphasic life cycle in which the metamorphic transition from a pelagic larva to a benthic post-larva is mediated by the nitric oxide signalling pathway. Nitric oxide (NO) is synthesised by nitric oxide synthase (NOS), which is a client protein of the molecular chaperon heat shock protein 90 (HSP90). It is notable, then, that both NO and HSP90 have been implicated in regulating metamorphosis in marine invertebrates as diverse as urochordates, echinoderms, molluscs, annelids, and crustaceans. Specifically, the suppression of NOS activity by the application of either NOS- or HSP90-inhibiting pharmacological agents has been shown consistently to induce the initiation of metamorphosis, leading to the hypothesis that a negative regulatory role of NO is widely conserved in biphasic life cycles. Further, the induction of metamorphosis by heat-shock has been demonstrated for multiple species. Here, we investigate the regulatory role of NO in induction of metamorphosis of the solitary tropical ascidian, Herdmania momus. By coupling pharmacological treatments with analysis of HmNOS and HmHSP90 gene expression, we present compelling evidence of a positive regulatory role for NO in metamorphosis of this species, in contrast to all existing ascidian data that supports the hypothesis of NO as a conserved negative regulator of metamorphosis. The exposure of competent H. momus larvae to a NOS inhibitor or an NO donor results in an up-regulation of NOS and HSP90 genes. Heat shock of competent larvae induces metamorphosis in a temperature dependent manner, up to a thermal tolerance that approaches 35°C. Both larval/post-larval survival and the appearance of abnormal morphologies in H. momus post-larvae reflect the magnitude of up-regulation of the HSP90 gene in response to heat-shock. The demonstrated role of NO as a positive metamorphic regulator in H. momus suggests the existence of inter-specific adaptations of NO regulation in ascidian metamorphosis.

Methamphetamine- and 1-methyl-4-phenyl- 1,2,3, 6-tetrahydropyridine-induced dopaminergic neurotoxicity in inducible nitric oxide synthase-deficient mice.

PubMed

Itzhak, Y; Martin, J L; Ali, S F

1999-12-15

Previous studies have suggested a role for the retrograde messenger, nitric oxide (NO), in methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- induced dopaminergic neurotoxicity. Since evidence supported the involvement of the neuronal nitric oxide synthase (nNOS) isoform in the dopaminergic neurotoxicity, the present study was undertaken to investigate whether the inducible nitric oxide synthase (iNOS) isoform is also associated with METH- and MPTP-induced neurotoxicity. The administration of METH (5mg/kg x 3) to iNOS deficient mice [homozygote iNOS(-/-)] and wild type mice (C57BL/6) resulted in significantly smaller depletion of striatal dopaminergic markers in the iNOS(-/-) mice compared with the wild-type mice. METH-induced hyperthermia was also significantly lower in the iNOS(-/-) mice than in wild-type mice. In contrast to the outcome of METH administration, MPTP injections (20 mg/kg x 3) resulted in a similar decrease in striatal dopaminergic markers in iNOS(-/-) and wild-type mice. In the set of behavioral experiments, METH-induced locomotor sensitization was investigated. The acute administration of METH (1.0 mg/kg) resulted in the same intensity of locomotor activity in iNOS(-/-) and wild-type mice. Moreover, 68 to 72 h after the exposure to the high-dose METH regimen (5 mg/kg x 3), a marked sensitized response to a challenge injection of METH (1.0 mg/kg) was observed in both the iNOS(-/-) and wild-type mice. The finding that iNOS(-/-) mice were unprotected from MPTP-induced neurotoxicity suggests that the partial protection against METH-induced neurotoxicity observed was primarily associated with the diminished hyperthermic effect of METH seen in the iNOS(-/-) mice. Moreover, in contrast to nNOS deficiency, iNOS deficiency did not affect METH-induced behavioral sensitization. Copyright 1999 Wiley-Liss, Inc.

Nitric Oxide Acts as a Positive Regulator to Induce Metamorphosis of the Ascidian Herdmania momus

PubMed Central

Ueda, Nobuo; Degnan, Sandie M.

2013-01-01

Marine invertebrates commonly have a biphasic life cycle in which the metamorphic transition from a pelagic larva to a benthic post-larva is mediated by the nitric oxide signalling pathway. Nitric oxide (NO) is synthesised by nitric oxide synthase (NOS), which is a client protein of the molecular chaperon heat shock protein 90 (HSP90). It is notable, then, that both NO and HSP90 have been implicated in regulating metamorphosis in marine invertebrates as diverse as urochordates, echinoderms, molluscs, annelids, and crustaceans. Specifically, the suppression of NOS activity by the application of either NOS- or HSP90-inhibiting pharmacological agents has been shown consistently to induce the initiation of metamorphosis, leading to the hypothesis that a negative regulatory role of NO is widely conserved in biphasic life cycles. Further, the induction of metamorphosis by heat-shock has been demonstrated for multiple species. Here, we investigate the regulatory role of NO in induction of metamorphosis of the solitary tropical ascidian, Herdmania momus. By coupling pharmacological treatments with analysis of HmNOS and HmHSP90 gene expression, we present compelling evidence of a positive regulatory role for NO in metamorphosis of this species, in contrast to all existing ascidian data that supports the hypothesis of NO as a conserved negative regulator of metamorphosis. The exposure of competent H. momus larvae to a NOS inhibitor or an NO donor results in an up-regulation of NOS and HSP90 genes. Heat shock of competent larvae induces metamorphosis in a temperature dependent manner, up to a thermal tolerance that approaches 35°C. Both larval/post-larval survival and the appearance of abnormal morphologies in H. momus post-larvae reflect the magnitude of up-regulation of the HSP90 gene in response to heat-shock. The demonstrated role of NO as a positive metamorphic regulator in H. momus suggests the existence of inter-specific adaptations of NO regulation in ascidian metamorphosis. PMID:24019877

Possible Involvement of Nitric Oxide Modulatory Mechanisms in the Neuroprotective Effect of Centella asiatica Against Sleep Deprivation Induced Anxiety Like Behaviour, Oxidative Damage and Neuroinflammation.

PubMed

Chanana, Priyanka; Kumar, Anil

2016-04-01

Sleep deprivation (SD) is an experience of inadequate or poor quality of sleep that may produce significant alterations in multiple neural systems. Centella asiatica (CA) is a psychoactive medicinal herb with immense therapeutic potential. The present study was designed to explore the possible nitric oxide (NO) modulatory mechanism in the neuroprotective effect of CA against SD induced anxiety like behaviour, oxidative damage and neuroinflammation. Male laca mice were sleep deprived for 72 h, and CA (150 and 300 mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72-h SD exposure. Various behavioural (locomotor activity, elevated plus maze) and biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels and superoxide dismutase activity), neuroinflammation marker (TNF-alpha) were assessed subsequently. CA (150 and 300 mg/kg) treatment for 8 days significantly improved locomotor activity, anti-anxiety like effect and attenuated oxidative damage and TNF α level as compared to sleep-deprived 72-h group. Also while the neuroprotective effect of CA was increased by NO antagonists, it was diminished by NO agonists. The present study suggests that NO modulatory mechanism could be involved in the protective effect of CA against SD-induced anxiety-like behaviour, oxidative damage and neuroinflammation in mice. Copyright © 2016 John Wiley & Sons, Ltd.

Neuronal Nitric-Oxide Synthase Deficiency Impairs the Long-Term Memory of Olfactory Fear Learning and Increases Odor Generalization

ERIC Educational Resources Information Center

Pavesi, Eloisa; Heldt, Scott A.; Fletcher, Max L.

2013-01-01

Experience-induced changes associated with odor learning are mediated by a number of signaling molecules, including nitric oxide (NO), which is predominantly synthesized by neuronal nitric oxide synthase (nNOS) in the brain. In the current study, we investigated the role of nNOS in the acquisition and retention of conditioned olfactory fear. Mice…

Measurements of nitric oxide after a nuclear burst

NASA Technical Reports Server (NTRS)

Mcghan, M.; Shaw, A.; Megill, L. R.; Sedlacek, W.; Guthals, P. R.; Fowler, M. M.

1981-01-01

Measurements of ozone and nitric oxide in a nuclear cloud 7 days after the explosion are reported. No measurable increase above ambient density of either ozone or nitric oxide was found. Results from a chemistry model of the cloud do not agree with the measurement unless 'nonstandard' assumptions are made with regard to the operating chemical processes. A number of possible explanations of the results are discussed.

Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice

PubMed Central

Reece, Stephen T; Vogelzang, Alexis; Tornack, Julia; Bauer, Wolfgang; Zedler, Ulrike; Schommer-Leitner, Sandra; Stingl, Georg; Melchers, Fritz; Kaufmann, Stefan H E

2018-01-01

Abstract Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M. tuberculosis propagate hallmarks of disease if nitric oxide-mediated killing of bacteria is defective. PMID:29471332

Decreasing methylation of pectin caused by nitric oxide leads to higher aluminium binding in cell walls and greater aluminium sensitivity of wheat roots

PubMed Central

Sun, Chengliang; Lu, Lingli; Yu, Yan; Liu, Lijuan; Hu, Yan; Ye, Yiquan; Jin, Chongwei; Lin, Xianyong

2016-01-01

Nitric oxide (NO) is an important bioactive molecule involved in cell wall metabolism, which has been recognized as a major target of aluminium (Al) toxicity. We have investigated the effects of Al-induced NO production on cell wall composition and the subsequent Al-binding capacity in roots of an Al-sensitive cultivar of wheat (Triticum aestivum L. cv. Yang-5). We found that Al exposure induced NO accumulation in the root tips. Eliminating NO production with an NO scavenger (cPTIO) significantly alleviated the Al-induced inhibition of root growth and thus reduced Al accumulation. Elimination of NO, however, did not significantly affect malate efflux or rhizosphere pH changes under Al exposure. Levels of cell wall polysaccharides (pectin, hemicelluloses 1, and hemicelluloses 2) and pectin methylesterase activity, as well as pectin demethylation in the root apex, significantly increased under Al treatment. Exogenous cPTIO application significantly decreased pectin methylesterase activity and increased the degree of methylation of pectin in the root cell wall, thus decreasing the Al-binding capacity of pectin. These results suggest that the Al-induced enhanced production of NO decreases cell wall pectin methylation, thus increasing the Al-binding capacity of pectin and negatively regulating Al tolerance in wheat. PMID:26663393

Tissue injury and repair following cutaneous exposure of mice to sulfur mustard

PubMed Central

Joseph, Laurie B.; Composto, Gabriella; Heck, Diane E.

2016-01-01

In mouse skin, sulfur mustard is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of sulfur mustard and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and progrowth/pro–wound healing mediators, including cyclooxygenase-2 (COX-2), which generates prostanoids, inducible nitric oxide synthase (iNOS), which generates nitric oxide, fibroblast growth factor receptor 2 (FGFR2), and galectin-3. Characterization of the mediators regulating structural changes in the skin during sulfur mustard–induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. PMID:27371823

Tissue injury and repair following cutaneous exposure of mice to sulfur mustard.

PubMed

Joseph, Laurie B; Composto, Gabriella M; Heck, Diane E

2016-08-01

In mouse skin, sulfur mustard (SM) is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of SM and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and pro-growth/pro-wound healing mediators, including cyclooxygenase-2, which generates prostanoids, inducible nitric oxide synthase, which generates nitric oxide, fibroblast growth factor receptor 2, and galectin-3. Characterization of the mediators regulating structural changes in the skin during SM-induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. © 2016 New York Academy of Sciences.

Ocean Acidification Affects the Cytoskeleton, Lysozymes, and Nitric Oxide of Hemocytes: A Possible Explanation for the Hampered Phagocytosis in Blood Clams, Tegillarca granosa.

PubMed

Su, Wenhao; Rong, Jiahuan; Zha, Shanjie; Yan, Maocang; Fang, Jun; Liu, Guangxu

2018-01-01

An enormous amount of anthropogenic carbon dioxide (CO 2 ) has been dissolved into the ocean, leading to a lower pH and changes in the chemical properties of seawater, which has been termed ocean acidification (OA). The impacts of p CO 2 -driven acidification on immunity have been revealed recently in various marine organisms. However, the mechanism causing the reduction in phagocytosis still remains unclear. Therefore, the impacts of p CO 2 -driven OA at present and near-future levels (pH values of 8.1, 7.8, and 7.4) on the rate of phagocytosis, the abundance of cytoskeleton components, the levels of nitric oxide (NO), and the concentration and activity of lysozymes (LZM) of hemocytes were investigated in a commercial bivalve species, the blood clam ( Tegillarca granosa ). In addition, the effects of OA on the expression of genes regulating actin skeleton and nitric oxide synthesis 2 ( NOS2 ) were also analyzed. The results obtained showed that the phagocytic rate, cytoskeleton component abundance, concentration and activity of LZM of hemocytes were all significantly reduced after a 2-week exposure to the future OA scenario of a pH of 7.4. On the contrary, a remarkable increase in the concentration of NO compared to that of the control was detected in clams exposed to OA. Furthermore, the expression of genes regulating the actin cytoskeleton and NOS were significantly up-regulated after OA exposure. Though the mechanism causing phagocytosis seemed to be complicated based on the results obtained in the present study and those reported previously, our results suggested that OA may reduce the phagocytosis of hemocytes by (1) decreasing the abundance of cytoskeleton components and therefore hampering the cytoskeleton-mediated process of engulfment, (2) reducing the concentration and activity of LZM and therefore constraining the degradation of the engulfed pathogen through an oxygen-independent pathway, and (3) inducing the production of NO, which may negatively regulate immune responses.

Pulmonary neutrophil recruitment and bronchial reactivity in formaldehyde-exposed rats are modulated by mast cells and differentially by neuropeptides and nitric oxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lino dos Santos Franco, Adriana; Damazo, Amilcar Sabino; Post-Graduation in Morphology, UNIFESP, EPM, Sao Paulo

2006-07-01

We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose-response curves to methacholine (MCh). Local and systemic inflammatory phenomena were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL) fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found after FA inhalation as compared with naive rats. Also,more » FA exposure significantly increased the total cell numbers in BAL, in peripheral blood and in the spleen, but did not modify the counts in bone marrow. Capsaicin hindered the increase of leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80 and indomethacin were able to prevent the lung neutrophil influx after FA, but indomethacin had no effect on that of mononuclear cells. Following FA inhalation, the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO) synthase inhibitor L-NAME, significantly reduced the total cell number in BAL. Compound 48/80, L-NAME and SCG significantly prevented BHR to MCh after FA inhalation, whereas capsaicin was inactive in this regard. On the other hand, indomethacin exacerbated BHR. These data suggest that after FA inhalation, the resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory fibers and mast cell-derived mediators. The effect of NO seemed to be largely restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to the inflammatory response, therefore indicating that the mechanisms responsible for the changes of airway responsiveness caused by FA may be separate from those underlying its inflammatory lung effects.« less

Manganese enhances peroxynitrite and leukotriene E4 formation in bovine aortic endothelial cells exposed to arsenic.

PubMed

Bunderson, Melisa; Pereira, Flavia; Schneider, Mark C; Shaw, Pamela K; Coffin, J Douglas; Beall, Howard D

2006-01-01

Long-term exposure to arsenic in drinking water has been linked to cancer and other health effects, including cardiovascular disease. Arsenic in the environment is found in combination with a range of metals that could influence its toxicity. Manganese, in particular, is a metal that is typically found in conjunction with arsenic in contaminated groundwater. Peroxynitrite is a powerful oxidant formed from the reaction between nitric oxide and superoxide anion. Arsenic has been shown to increase the formation of peroxynitrite in bovine aortic endothelial cells (BAECs) and promote the formation of 3-nitrotyrosine (3-NY) in the atherosclerotic plaque of ApoE-/-/LDLr-/- mice. Arsenic exposure also increases leukotriene E4 (LTE4) formation in both the mice and BAECs, an effect that is partially reversed by the addition of Nomega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. In the present study, we investigated the effect of adding nontoxic concentrations of manganese along with arsenic to BAEC cultures. Manganese increased arsenic toxicity and enhanced peroxynitrite, 3-NY, and LTE4 formation in BAECs. Addition of LNAME reduced 3-NY formation induced by arsenic/manganese mixtures, but in contrast to its effect on arsenic alone, L-NAME actually increased LTE4 synthesis in BAECs treated with the arsenic/manganese combination. Overall, these data suggest that manganese may exacerbate the toxic effects of arsenic on the vascular system.

Enhanced biogenic emissions of nitric oxide and nitrous oxide following surface biomass burning

Treesearch

Iris C. Anderson; Joel S. Levine; Mark A. Poth; Philip J. Riggan

1988-01-01

Recent measurements indicate significantly enhanced biogenic soil emissions of both nitric oxide (NO) and nitrous oxide (N2O) following surface burning. These enhanced fluxes persisted for at least 6 months following the burn. Simultaneous measurements indicate enhanced levels of...

Nitric oxide enhances development of lateral roots in tomato (Solanum lycopersicum L.) under elevated carbon dioxide.

PubMed

Wang, Huan; Xiao, Wendan; Niu, Yaofang; Jin, Chongwei; Chai, Rushan; Tang, Caixian; Zhang, Yongsong

2013-01-01

Elevated carbon dioxide (CO₂) has been shown to enhance the growth and development of plants, especially of roots. Amongst them, lateral roots play an important role in nutrient uptake, and thus alleviate the nutrient limitation to plant growth under elevated CO₂. This paper examined the mechanism underlying CO₂ elevation-induced lateral root formation in tomato. The endogenous nitric oxide (NO) in roots was detected by the specific probe 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA). We suggest that CO₂ elevation-induced NO accumulation was important for lateral root formation. Elevated CO₂ significantly increased the activity of nitric oxide synthase in roots, but not nitrate reductase activity. Moreover, the pharmacological evidence showed that nitric oxide synthase rather than nitrate reductase was responsible for CO₂ elevation-induced NO accumulation. Elevated CO₂ enhanced the activity of nitric oxide synthase and promoted production of NO, which was involved in lateral root formation in tomato under elevated CO₂.

Acute electroacupuncture inhibits nitric oxide synthase expression in the spinal cord of neuropathic rats.

PubMed

Cha, Myeoung Hoon; Bai, Sun Joon; Lee, Kyung Hee; Cho, Zang Hee; Kim, Young-Bo; Lee, Hye-Jung; Lee, Bae Hwan

2010-02-01

To examine the effects of electroacupuncture stimulation on behavioral changes and neuronal nitric oxide synthase expression in the rat spinal cord after nerve injury. Under pentobarbital anesthesia, male Sprague-Dawley rats were subjected to neuropathic surgery by tightly ligating and cutting the left tibial and sural nerves. Behavioral responses to mechanical stimulation were tested for 2 weeks post-operatively. At the end of behavioral testing, electroacupuncture stimulation was applied to ST36 (Choksamni) and SP9 (Eumleungcheon) acupoints. Immunocytochemical staining was performed to investigate changes in the expression of neuronal nitric oxide synthase-immunoreactive neurons in the L4-5 spinal cord. Mechanical allodynia was observed by nerve injury. The mechanical allodynia was decreased after electroacupuncture stimulation. Neuronal nitric oxide synthase expression was also decreased in L4-5 spinal cord by electroacupuncture treatment. These results suggest that electroacupuncture relieves mechanical allodynia in the neuropathic rats possibly by the inhibition of neuronal nitric oxide synthase expression in the spinal cord.

Chemical kinetic models for combustion of hydrocarbons and formation of nitric oxide

NASA Technical Reports Server (NTRS)

Jachimowski, C. J.; Wilson, C. H.

1980-01-01

The formation of nitrogen oxides NOx during combustion of methane, propane, and a jet fuel, JP-4, was investigated in a jet stirred combustor. The results of the experiments were interpreted using reaction models in which the nitric oxide (NO) forming reactions were coupled to the appropriate hydrocarbon combustion reaction mechanisms. Comparison between the experimental data and the model predictions reveals that the CH + N2 reaction process has a significant effect on NO formation especially in stoichiometric and fuel rich mixtures. Reaction models were assembled that predicted nitric oxide levels that were in reasonable agreement with the jet stirred combustor data and with data obtained from a high pressure (5.9 atm (0.6 MPa)), prevaporized, premixed, flame tube type combustor. The results also suggested that the behavior of hydrocarbon mixtures, like JP-4, may not be significantly different from that of pure hydrocarbons. Application of the propane combustion and nitric oxide formation model to the analysis of NOx emission data reported for various aircraft gas turbines showed the contribution of the various nitric oxide forming processes to the total NOx formed.

Guanylyl cyclase-dependent chemotaxis of endothelial cells in response to nitric oxide gradients.

PubMed

Isenberg, Jeff S; Ridnour, Lisa A; Thomas, Douglas D; Wink, David A; Roberts, David D; Espey, Michael Graham

2006-03-15

Nitric oxide (NO) is an important regulator of angiogenesis and neovascularization. The nature of endothelial cell motility responses to NO was examined using a Boyden chamber method. NO generated via decomposition of either DEA/NO or DETA/NO produced increases in human umbilical vein endothelial cell (HUVEC) chemotaxis, which were completely abrogated by ODQ, a soluble guanylyl cyclase inhibitor. Measurements of NO either directly by chemiluminescence or its chemistry with diaminofluorescein revealed that chemotaxis was driven by subtle NO gradients between the lower and the upper wells in this system. In addition to diffusion and volatilization from the upper chambers, the data showed that HUVEC consumption of NO contributed to these sustained gradients. Comparison of DEA/NO- and DETA/NO-mediated responses suggested that the persistence of spatial NO gradients is as significant as the absolute magnitude of NO exposure per unit time. The findings suggest that subnanomolar NO gradients are sufficient to mobilize endothelial cell migration into hypoxic tissue during neovascularization events, such as in wound healing and cancer.

Antifungal effect of gaseous nitric oxide on mycelium growth, sporulation and spore germination of the postharvest horticulture pathogens, Aspergillus niger, Monilinia fructicola and Penicillium italicum.

PubMed

Lazar, E E; Wills, R B H; Ho, B T; Harris, A M; Spohr, L J

2008-06-01

To evaluate the antifungal activity of nitric oxide (NO) against the growth of the postharvest horticulture pathogens Aspergillus niger, Monilinia fructicola and Penicillium italicum under in vitro conditions. Different volumes of NO gas were injected into the Petri dish headspace to obtain the desired concentrations of 50-500 microl l(-1). The growth of the fungi was measured for 8 days of incubation in air at 25 degrees C. All concentrations of NO were found to produce an antifungal effect on spore germination, sporulation and mycelial growth of the three fungi, with the most effective concentration for A. niger and P. italicum being 100 and 500 microl l(-1) for M. fructicola. Short-term exposure to a low concentration of NO gas was able to inhibit the subsequent growth of A. niger, M. fructicola and P. italicum. NO gas has potential use as a natural fungicide to inhibit microbial growth on postharvest fruit and vegetables.

Nitric oxide in microgravity-induced orthostatic intolerance: relevance to spinal cord injury

NASA Technical Reports Server (NTRS)

Vaziri, N. D.; Purdy, R. E. (Principal Investigator)

2003-01-01

Prolonged exposure to microgravity results in cardiovascular deconditioning which is marked by orthostatic intolerance in the returning astronauts and recovering bed-ridden patients. Recent studies conducted in our laboratories at University of California, Irvine have revealed marked elevation of nitric oxide (NO) production in the kidney, heart, brain, and systemic arteries coupled with significant reduction of NO production in the cerebral arteries of microgravity-adapted animals. We have further demonstrated that the observed alteration of NO metabolism is primarily responsible for the associated cardiovascular deconditioning. Recovery from acute spinal cord injury (SCI) is frequently complicated by orthostatic intolerance that is due to the combined effects of the disruption of efferent sympathetic pathway and cardiovascular deconditioning occasioned by prolonged confinement to bed. In this presentation, I will review the nature of altered NO metabolism and its role in the pathogenesis of microgravity-induced cardiovascular deconditioning. The possible relevance of the new findings to orthostatic intolerance in patients with acute SCI and its potential therapeutic implications will be discussed.

The effects of two different doses of ultraviolet-A light exposure on nitric oxide metabolites and cardiorespiratory outcomes.

PubMed

Monaghan, Chris; McIlvenna, Luke C; Liddle, Luke; Burleigh, Mia; Weller, Richard B; Fernandez, Bernadette O; Feelisch, Martin; Muggeridge, David J; Easton, Chris

2018-05-01

The present study investigated different doses of ultraviolet-A (UV-A) light on plasma nitric oxide metabolites and cardiorespiratory variables. Ten healthy male participants completed three experimental conditions, 7 days apart. Participants were exposed to no light (CON); 10 J cm 2 (15 min) of UV-A light (UVA10) and 20 J cm 2 (30 min) of UV-A light (UVA20) in a randomized order. Plasma nitrite [NO 2 - ] and nitrate [NO 3 - ] concentrations, blood pressure (BP), and heart rate (HR) were recorded before, immediately after exposure and 30 min post-exposure. Whole body oxygen utilization ([Formula: see text]), resting metabolic rate (RMR) and skin temperature were recorded continuously. None of the measured parameters changed significantly during CON (all P > 0.05). [Formula: see text] and RMR were significantly reduced immediately after UVA10 (P < 0.05) despite no change in plasma [NO 2 - ] (P > 0.05). Immediately after exposure to UVA20, plasma [NO 2 - ] was higher (P = 0.014) and [Formula: see text] and RMR tended to be lower compared to baseline (P = 0.06). There were no differences in [NO 2 - ] or [Formula: see text] at the 30 min time point in any condition. UV-A exposure did not alter systolic BP, diastolic BP or MAP (all P > 0.05). UV-A light did not alter plasma [NO 3 - ] at any time point (all P > 0.05). This study demonstrates that a UV-A dose of 20 J cm 2 is necessary to increase plasma [NO 2 - ] although a smaller dose is capable of reducing [Formula: see text] and RMR at rest. Exposure to UV-A did not significantly reduce BP in this cohort of healthy adults. These data suggest that exposure to sunlight has a meaningful acute impact on metabolic function.

Peroxisome proliferator-activated receptor-α agonists protect cortical neurons from inflammatory mediators and improve peroxisomal function.

PubMed

Gray, Elizabeth; Ginty, Mark; Kemp, Kevin; Scolding, Neil; Wilkins, Alastair

2011-04-01

Inflammation is known to cause significant neuronal damage and axonal injury in many neurological disorders. Among the range of inflammatory mediators, nitric oxide is a potent neurotoxic agent. Recent evidence has suggested that cellular peroxisomes may be important in protecting neurons from inflammatory damage. To assess the influence of peroxisomal activation on nitric oxide-mediated neurotoxicity, we investigated the effects of the peroxisomal proliferator-activated receptor (PPAR)-α agonist fenofibrate on cortical neurons exposed to a nitric oxide donor or co-cultured with activated microglia. Fenofibrate protected neurons and axons against both nitric oxide donor-induced and microglia-derived nitric oxide-induced toxicity. Moreover, cortical neurons treated with this compound showed a significant increase in gene expression of ABCD3 (the gene encoding for peroxisomal membrane protein-70), with a concomitant increase in protein levels of PPAR-α and catalase, which was associated with a functional increase in the activity of this enzyme. Collectively, these observations provide evidence that modulation of PPAR-α activity and peroxisomal function by fenofibrate attenuates nitric oxide-mediated neuronal and axonal damage, suggesting a new therapeutic approach to protect against neurodegenerative changes associated with neuroinflammation. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Caffeinated nitric oxide-releasing lozenge improves cycling time trial performance.

PubMed

Lee, J; Kim, H T; Solares, G J; Kim, K; Ding, Z; Ivy, J L

2015-02-01

Boosting nitric oxide production during exercise by various means has been found to improve exercise performance. We investigated the effects of a nitric oxide releasing lozenge with added caffeine (70 mg) on oxygen consumption during steady-state exercise and cycling time trial performance using a double-blinded randomized, crossover experimental design. 15 moderately trained cyclists (7 females and 8 males) were randomly assigned to ingest the caffeinated nitric oxide lozenge or placebo 5 min before exercise. Oxygen consumption and blood lactate were assessed at rest and at 50%, 65% and 75% maximal oxygen consumption. Exercise performance was assessed by time to complete a simulated 20.15 km cycling time-trial course. No significant treatment effects for oxygen consumption or blood lactate at rest or during steady-state exercise were observed. However, time-trial performance was improved by 2.1% (p<0.01) when participants consumed the nitric oxide lozenge (2,424±69 s) compared to placebo (2,476±78 s) and without a significant difference in rating of perceived exertion. These results suggest that acute supplementation with a caffeinated nitric oxide releasing lozenge may be a practical and effective means of improving aerobic exercise performance. © Georg Thieme Verlag KG Stuttgart · New York.

The role of nitric oxide in the reversal of hemorrhagic shock by oxotremorine.

PubMed

Gören, M Z; Akici, A; Karaalp, A; Aker, R; Oktay, S

2001-10-05

In the present study, the effect of the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methylester (L-NAME), on the antishock actions of oxotremorine was investigated in rats subjected to hemorrhagic shock under urethane anesthesia. L-citrulline production in the AV3V region, as an indicator of nitric oxide (NO) synthesis, was assayed by high-performance liquid chromatography (HPLC) with fluorescent detection throughout the experiment. The rats were pretreated with either intravenous (i.v.) physiological saline or L-NAME (2.5 mg/kg) before bleeding. L-NAME potentiated the reversal of hypotension by oxotremorine (25 microg/kg, i.v.). However, oxotremorine either alone or in combination with L-NAME did not produce any significant change in 60-min survival rate at this low dose. Analysis of microdialysis samples collected from the AV3V region showed that L-citrulline concentration increased during bleeding and that this increase was abolished by L-NAME pretreatment. These results may suggest that nitric oxide production contributes to hypotension in rats bled to shock since nitric oxide levels in the AV3V region increased in response to bleeding and nitric oxide synthase (NOS) inhibition abolished this increase and potentiated the oxotremorine-induced reversal of hypotension.

Direct hydride shift mechanism and stereoselectivity of P450nor confirmed by QM/MM calculations.

PubMed

Krámos, Balázs; Menyhárd, Dóra K; Oláh, Julianna

2012-01-19

Nitric oxide reductase (P450(nor)) found in Fusarium oxysporum catalyzes the reduction of nitric oxide to N(2)O in a multistep process. The reducing agent, NADH, is bound in the distal pocket of the enzyme, and direct hydride transfer occurs from NADH to the nitric oxide bound heme enzyme, forming intermediate I. Here we studied the possibility of hydride transfer from NADH to both the nitrogen and oxygen of the heme-bound nitric oxide, using quantum chemical and combined quantum mechanics/molecular mechanics (QM/MM) calculations, on two different protein models, representing both possible stereochemistries, a syn- and an anti-NADH arrangement. All calculations clearly favor hydride transfer to the nitrogen of nitric oxide, and the QM-only barrier and kinetic isotope effects are good agreement with the experimental values of intermediate I formation. We obtained higher barriers in the QM/MM calculations for both pathways, but hydride transfer to the nitrogen of nitric oxide is still clearly favored. The barriers obtained for the syn, Pro-R conformation of NADH are lower and show significantly less variation than the barriers obtained in the case of anti conformation. The effect of basis set and wide range of functionals on the obtained results are also discussed.

Molecular biological effects of selective neuronal nitric oxide synthase inhibition in ovine lung injury

PubMed Central

Westphal, Martin; Enkhbaatar, Perenlei; Wang, Jianpu; Pazdrak, Konrad; Nakano, Yoshimitsu; Hamahata, Atsumori; Jonkam, Collette C.; Lange, Matthias; Connelly, Rhykka L.; Kulp, Gabriela A.; Cox, Robert A.; Hawkins, Hal K.; Schmalstieg, Frank C.; Horvath, Eszter; Szabo, Csaba; Traber, Lillian D.; Whorton, Elbert; Herndon, David N.; Traber, Daniel L.

2010-01-01

Neuronal nitric oxide synthase is critically involved in the pathogenesis of acute lung injury resulting from combined burn and smoke inhalation injury. We hypothesized that 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, blocks central molecular mechanisms involved in the pathophysiology of this double-hit insult. Twenty-five adult ewes were surgically prepared and randomly allocated to 1) an uninjured, untreated sham group (n = 7), 2) an injured control group with no treatment (n = 7), 3) an injury group treated with 7-nitroindazole from 1-h postinjury to the remainder of the 24-h study period (n = 7), or 4) a sham-operated group subjected only to 7-nitroindazole to judge the effects in health. The combination injury was associated with twofold increased activity of neuronal nitric oxide synthase and oxidative/nitrosative stress, as indicated by significant increases in plasma nitrate/nitrite concentrations, 3-nitrotyrosine (an indicator of peroxynitrite formation), and malondialdehyde lung tissue content. The presence of systemic inflammation was evidenced by twofold, sixfold, and threefold increases in poly(ADP-ribose) polymerase, IL-8, and myeloperoxidase lung tissue concentrations, respectively (each P < 0.05 vs. sham). These molecular changes were linked to tissue damage, airway obstruction, and pulmonary shunting with deteriorated gas exchange. 7-Nitroindazole blocked, or at least attenuated, all these pathological changes. Our findings suggest 1) that nitric oxide formation derived from increased neuronal nitric oxide synthase activity represents a pivotal reactive agent in the patho-physiology of combined burn and smoke inhalation injury and 2) that selective neuronal nitric oxide synthase inhibition represents a goal-directed approach to attenuate the degree of injury. PMID:19965980

Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery.

PubMed

Lei, Chong; Berra, Lorenzo; Rezoagli, Emanuele; Yu, Binglan; Dong, Hailong; Yu, Shiqiang; Hou, Lihong; Chen, Min; Chen, Wensheng; Wang, Hongbing; Zheng, Qijun; Shen, Jie; Jin, Zhenxiao; Chen, Tao; Zhao, Rong; Christie, Emily; Sabbisetti, Venkata S; Nordio, Francesco; Bonventre, Joseph V; Xiong, Lize; Zapol, Warren M

2018-06-22

No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1-year after cardiac surgery. To determine whether administration of nitric oxide reduces the incidence of post-operative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass. 244 Patients undergoing elective, multiple valve replacement surgery mostly due to rheumatic fever were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24h post-operatively. Primary outcome: Oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated to a reduced post-operative acute kidney injury from 64% (control group) to 50% (nitric oxide) (RR, 95% CI; 0.78, 0.62-0.97;P=0.014). At 90-days, transition to stage 3 chronic kidney disease was reduced from 33% in the controls to 21% in the treatment group (RR, 95%CI; 0.64, 0.41 - 0.99;P=0.024); and at 1-year, from 31% to 18% (RR, 95% CI; 0.59, 0.36 - 0.96;P=0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30-days (RR, 95% CI; 0.40, 0.18 - 0.92;P=0.016, 90-days (RR, 95% CI; 0.40, 0.17 - 0.92;P=0.015 and 1-year (RR, 95% CI; 0.47, 0.20-1.10;P=0.041). In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease and major adverse kidney events at 30-days, 90-days, and 1-year. Clinical trial registered with ClinicalTrials.gov (NCT01802619).

Circadian variation in the effects of nitric oxide synthase inhibitors on body temperature, feeding and activity in rats.

PubMed

Kamerman, Peter; Mitchell, Duncan; Laburn, Helen

2002-02-01

We have investigated whether there is circadian variation in the effects of nitric oxide synthase inhibitors on body temperature, physical activity and feeding. We used nocturnally active Sprague-Dawley rats, housed at approximately 24 degrees C with a 12:12 h light:dark cycle (lights on 07:00 hours) and provided with food and water ad libitum. Nitric oxide synthesis was inhibited by intraperitoneal injection of the unspecific nitric oxide synthase inhibitor N-nitro- L-arginine methyl ester ( L-NAME, 100, 50, 25, 10 mg/kg), or the relatively selective inducible nitric oxide synthase inhibitor aminoguanidine (100, 50 mg/kg), during the day ( approximately 09:00 hours) or night ( approximately 21:00 hours). Body temperature and physical activity were measured using radiotelemetry, while food intake was calculated by weighing each animal's food before as well as 12 and 24 h after each injection. We found that daytime injection of L-NAME and aminoguanidine had no effect on daytime body temperature. However, daytime injection of both drugs did decrease nocturnal food intake ( P<0.05) and activity ( P<0.05). When injected at night, L-NAME reduced night-time body temperature ( P<0.01), activity ( P<0.05) and food intake ( P<0.05) in a dose-dependent manner, but night-time injection of aminoguanidine inhibited only night-time activity ( P<0.05). The effects of nitric oxide synthase inhibition on body temperature, feeding and activity therefore are primarily a consequence of inhibiting constitutively expressed nitric oxide synthase, and are subject to circadian variation.

Effects of resveratrol-related hydroxystilbenes on the nitric oxide production in macrophage cells: structural requirements and mechanism of action.

PubMed

Cho, Dong-Im; Koo, Na-Youn; Chung, Woon Jae; Kim, Tae-Sung; Ryu, Shi Yong; Im, Suhn Young; Kim, Kyeong-Man

2002-09-13

NF-kappaB that plays an important role in iNOS expression is one of the targets of various potential anti-inflammatory agents including resveratrol. Resveratrol contains a structural similarity with estrogen, and there has been speculation about resveratrol as estrogen agonist. In this study, the mechanism and structural requirements of resveratrol and related hydroxystilbenes for the inhibition of LPS-induced nitric oxide production were studied in macrophage cells (RAW 264.7 and J774) by comparing its effect on LPS-induced NF-kappaB translocation and nitric oxide production, and by considering the possibility of involvement of an estrogen receptor. LPS-induced nitric oxide production was inhibited only when cells were treated with resveratrol prior to stimulation with LPS, suggesting that resveratrol does not affect the enzyme itself. A higher concentration of resveratrol than needed for the inhibition of nitric oxide production was required for the inhibition of NF-kappaB mobilization or iNOS expression. Estrogen and diethylstilbesterol, an estrogen agonist, caused only weak inhibition of nitric oxide production, and the effects of resveratrol were not noticeably blocked by ICI-182780, an estrogen antagonist. Structure-activity analysis of resveratrol and nine hydroxystilbenes suggests that the structural balance between oxygen functional groups on the benzene rings is important for their activity. Our results suggest that resveratrol might act on other cellular targets as well as NF-kappaB at the initial stage of gene expression. Unique structural features of hydroxystilbenes are needed for suppression of nitric oxide production and it is unlikely that estrogen receptor is involved in it.

Copper Complex in Poly(vinyl chloride) as a Nitric Oxide-Generating Catalyst for the Control of Nitrifying Bacterial Biofilms.

PubMed

Wonoputri, Vita; Gunawan, Cindy; Liu, Sanly; Barraud, Nicolas; Yee, Lachlan H; Lim, May; Amal, Rose

2015-10-14

In this study, catalytic generation of nitric oxide by a copper(II) complex embedded within a poly(vinyl chloride) matrix in the presence of nitrite (source of nitric oxide) and ascorbic acid (reducing agent) was shown to effectively control the formation and dispersion of nitrifying bacteria biofilms. Amperometric measurements indicated increased and prolonged generation of nitric oxide with the addition of the copper complex when compared to that with nitrite and ascorbic acid alone. The effectiveness of the copper complex-nitrite-ascorbic acid system for biofilm control was quantified using protein analysis, which showed enhanced biofilm suppression when the copper complex was used in comparison to that with nitrite and ascorbic acid treatment alone. Confocal laser scanning microscopy (CLSM) and LIVE/DEAD staining revealed a reduction in cell surface coverage without a loss of viability with the copper complex and up to 5 mM of nitrite and ascorbic acid, suggesting that the nitric oxide generated from the system inhibits proliferation of the cells on surfaces. Induction of nitric oxide production by the copper complex system also triggered the dispersal of pre-established biofilms. However, the addition of a high concentration of nitrite and ascorbic acid to a pre-established biofilm induced bacterial membrane damage and strongly decreased the metabolic activity of planktonic and biofilm cells, as revealed by CLSM with LIVE/DEAD staining and intracellular adenosine triphosphate measurements, respectively. This study highlights the utility of the catalytic generation of nitric oxide for the long-term suppression and removal of nitrifying bacterial biofilms.

Modulation of the cyclooxygenase pathway via inhibition of nitric oxide production contributes to the anti-inflammatory activity of kaempferol.

PubMed

Mahat, Mahamad Yunnus A; Kulkarni, Nagaraj M; Vishwakarma, Santosh L; Khan, Farhin R; Thippeswamy, B S; Hebballi, Vijay; Adhyapak, Anjana A; Benade, Vijay S; Ashfaque, Saudagar Mohammad; Tubachi, Suraj; Patil, Basangouda M

2010-09-10

Kaempferol has been reported to inhibit nitric oxide synthase and cyclooxygenase enzymes in animal models. The present study was designed to investigate whether kaempferol modulates the cyclooxygenase pathway via inhibition of nitric oxide production, which in turn contributes to its anti-inflammatory activity. Investigations were performed using carrageenan induced rat air pouch model. Inflammation was assessed by measurement of nitrites (nitrite, a breakdown product of nitric oxide), prostaglandin-E(2) levels and cellular infiltration in the pouch fluid exudates. To assess the anti-inflammatory effect of the extract, rat air pouch linings were examined histologically. The levels of nitrite and prostaglandin-E(2) in pouch fluid were measured by using Griess assay and ELISA respectively. Cell counts and differential counts were performed using a Coulter counter and Wright-Giemsa stain respectively. Kaempferol when administered orally at 50 and 100mg/kg dose showed significant inhibition of carrageenan induced production of nitrite (40.12 and 59.74%, respectively) and prostaglandin-E(2) generation (64.23 and 78.55%, respectively). Infiltration of the cells into the rat granuloma air pouch was also significantly inhibited by kaempferol. Modulation of cyclooxygenase pathway via inhibition of nitric oxide synthesis significantly contributes to kaempferol's anti-inflammatory activity. The present study characterizes the effects and mechanisms of naturally occurring phenolic flavonoid kaempferol, on inducible nitric oxide synthase expression and nitric oxide production. These results partially explain the pharmacological efficacy of flavonoids in general and kaempferol in particular as anti-inflammatory compounds. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Quantitative RT-PCR Comparison of the Urea and Nitric Oxide Cycle Gene Transcripts in Adult Human Tissues

PubMed Central

Neill, Meaghan Anne; Aschner, Judy; Barr, Frederick; Summar, Marshall L.

2009-01-01

The urea cycle and nitric oxide cycle play significant roles in complex biochemical and physiologic reactions. These cycles have distinct biochemical goals including the clearance of waste nitrogen; the production of the intermediates ornithine, citrulline, and arginine for the urea cycle; and the production of nitric oxide for the nitric oxide pathway. Despite their disparate functions, the two pathways share two enzymes, argininosuccinic acid synthase and argininosuccinic acid lyase, and a transporter, citrin. Studying the gene expression of these enzymes is paramount in understanding these complex biochemical pathways. Here, we examine the expression of genes involved in the urea cycle and the nitric oxide cycle in a panel of eleven different tissue samples obtained from individual adults without known inborn errors of metabolism. In this study, the pattern of co-expressed enzymes provides a global view of the metabolic activity of the urea and nitric oxide cycles in human tissues. Our results show that these transcripts are differentially expressed in different tissues. The pattern of co-expressed enzymes provides a global view of the metabolic activity of the urea and nitric oxide cycles in human tissues. Using the co-expression profiles, we discovered that the combination of expression of enzyme transcripts as detected in our study, might serve to fulfill specific physiologic function(s) in tissue including urea production/nitrogen removal, arginine/citrulline production, nitric oxide production, and ornithine production. Our study reveals the importance of studying not only the expression profile of an enzyme of interest, but also studying the expression profiles of the other enzymes involved in a particular pathway so as to better understand the context of expression. The tissue patterns we observed highlight the variety of important functions they conduct and provide insight into many of the clinical observations from their disruption. PMID:19345634

Mediated electrochemical oxidation of organic wastes using a Co (III) mediator in a nitric acid based system

DOEpatents

Balazs, G. Bryan; Chiba, Zoher; Lewis, Patricia R.; Nelson, Norvell; Steward, G. Anthony

1999-01-01

An electrochemical cell with a Co(III) mediator and nitric acid electrolyte provides efficient destruction of organic and mixed wastes. The organic waste is concentrated in the anolyte reservoir, where the mediator oxidizes the organics and insoluble transuranic compounds and is regenerated at the anode until the organics are converted to CO.sub.2. The nitric acid is an excellent oxidant that facilitates the destruction of the organic components. The anode is not readily attacked by the nitric acid solution, thus the cell can be used for extended continual operation without electrode replacement.

[Studies on the oxidation reaction of octanol-2 with nitric acid by infrared spectroscopy].

PubMed

Zhang, G; Zhao, G; Wang, Y; Zhang, Q; Zhang, S; Lu, F

1998-04-01

In this paper, the reaction process of oxidation of octanol-2 with nitric acid has been studied by IR spectroscopy. It is found that the main components of non-sapoifiable matter are different in different oxidation degrees. The relation between oxidation products and the amount of nitric acid are investigated,the reaction mechanism has also been studied. Experimental results show that the oxidation process of octanol-2 is as follows: first, octanol-2 is oxidated to octanone-2, or to nitrate, nitrite and nitrile copmpounds, then these compounds are reoxidated to caproic acid in the meantime some by-products, such as valeric, enanthic acids are also found in oxidated products.

Nanoparticle (star polymer) delivery of nitric oxide effectively negates Pseudomonas aeruginosa biofilm formation.

PubMed

Duong, Hien T T; Jung, Kenward; Kutty, Samuel K; Agustina, Sri; Adnan, Nik Nik M; Basuki, Johan S; Kumar, Naresh; Davis, Thomas P; Barraud, Nicolas; Boyer, Cyrille

2014-07-14

Biofilms are increasingly recognized as playing a major role in human infectious diseases, as they can form on both living tissues and abiotic surfaces, with serious implications for applications that rely on prolonged exposure to the body such as implantable biomedical devices or catheters. Therefore, there is an urgent need to develop improved therapeutics to effectively eradicate unwanted biofilms. Recently, the biological signaling molecule nitric oxide (NO) was identified as a key regulator of dispersal events in biofilms. In this paper, we report a new class of core cross-linked star polymers designed to store and release nitric oxide, in a controlled way, for the dispersion of biofilms. First, core cross-linked star polymers were prepared by reversible addition-fragmentation chain transfer polymerization (RAFT) via an arm first approach. Poly(oligoethylene methoxy acrylate) chains were synthesized by RAFT polymerization, and then chain extended in the presence of 2-vinyl-4,4-dimethyl-5-oxazolone monomer (VDM) with N,N-methylenebis(acrylamide) employed as a cross-linker to yield functional core cross-linked star polymers. Spermine was successfully attached to the star core by reaction with VDM. Finally, the secondary amine groups were reacted with NO gas to yield NO-core cross-linked star polymers. The core cross-linked star polymers were found to release NO in a controlled, slow delivery in bacterial cultures showing great efficacy in preventing both cell attachment and biofilm formation in Pseudomonas aeruginosa over time via a nontoxic mechanism, confining bacterial growth to the suspended liquid.

Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses.

PubMed

Thakur, Tarun; Gulati, Kavita; Rai, Nishant; Ray, Arunabha

2017-09-01

The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH-sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200-250g) were exposed to either CPS or CUS for 14days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3-NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO-mediated signaling mechanisms may be involved during responses. Copyright © 2017. Published by Elsevier B.V.

Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells.

PubMed

Kim, Yong-Dae; Lantz-McPeak, Susan M; Ali, Syed F; Kleinman, Michael T; Choi, Young-Sook; Kim, Heon

2014-05-01

A major constituent of urban air pollution is diesel exhaust, a complex mixture of gases, chemicals, and particles. Recent evidence suggests that exposure to air pollution can increase the risk of a fatal stroke, cause cerebrovascular damage, and induce neuroinflammation and oxidative stress that may trigger neurodegenerative diseases, such as Parkinson's disease. The specific aim of this study was to determine whether ultrafine diesel exhaust particles (DEPs), the particle component of exhaust from diesel engines, can induce oxidative stress and effect dopamine metabolism in PC-12 cells. After 24 h exposure to DEPs of 200 nm or smaller, cell viability, ROS and nitric oxide (NO(2)) generation, and levels of dopamine (DA) and its metabolites, (dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)), were evaluated. Results indicated cell viability was not significantly changed by DEP exposure. However, ROS showed dramatic dose-dependent changes after DEP exposure (2.4 fold increase compared to control at 200 μg/mL). NO(2) levels were also dose-dependently increased after DEP exposure. Although not in a dose-dependent manner, upon DEP exposure, intracellular DA levels were increased while DOPAC and HVA levels decreased when compared to control. Results suggest that ultrafine DEPs lead to dopamine accumulation in the cytoplasm of PC-12 cells, possibly contributing to ROS formation. Further studies are warranted to elucidate this mechanism. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Characterizing low dose and dose rate effects in rodent and human neural stem cells exposed to proton and gamma irradiation.

PubMed

Tseng, Bertrand P; Lan, Mary L; Tran, Katherine K; Acharya, Munjal M; Giedzinski, Erich; Limoli, Charles L

2013-01-01

Past work has shown that exposure to gamma rays and protons elicit a persistent oxidative stress in rodent and human neural stem cells (hNSCs). We have now adapted these studies to more realistic exposure scenarios in space, using lower doses and dose rates of these radiation modalities, to further elucidate the role of radiation-induced oxidative stress in these cells. Rodent neural stem and precursor cells grown as neurospheres and human neural stem cells grown as monolayers were subjected to acute and multi-dosing paradigms at differing dose rates and analyzed for changes in reactive oxygen species (ROS), reactive nitrogen species (RNS), nitric oxide and superoxide for 2 days after irradiation. While acute exposures led to significant changes in both cell types, hNSCs in particular, exhibited marked and significant elevations in radiation-induced oxidative stress. Elevated oxidative stress was more significant in hNSCs as opposed to their rodent counterparts, and hNSCs were significantly more sensitive to low dose exposures in terms of survival. Combinations of protons and γ-rays delivered as lower priming or higher challenge doses elicited radioadaptive changes that were associated with improved survival, but in general, only under conditions where the levels of reactive species were suppressed compared to cells irradiated acutely. Protective radioadaptive effects on survival were eliminated in the presence of the antioxidant N-acetylcysteine, suggesting further that radiation-induced oxidative stress could activate pro-survival signaling pathways that were sensitive to redox state. Data corroborates much of our past work and shows that low dose and dose rate exposures elicit significant changes in oxidative stress that have functional consequences on survival.

Detection of Nitric Oxide by Electron Paramagnetic Resonance Spectroscopy

PubMed Central

Hogg, Neil

2010-01-01

Electron paramagnetic resonance (EPR) spectroscopy has been used in a number of ways to study nitric oxide chemistry and biology. As an intrinsically stable and relatively unreactive diatomic free radical, the challenges for detecting this species by EPR are somewhat different than those for transient radical species. This review gives a basic introduction to EPR spectroscopy and discusses its uses to assess and quantify nitric oxide formation in biological systems. PMID:20304044

Role of nitric oxide in progression and regression of atherosclerosis.

PubMed Central

Cooke, J P

1996-01-01

Endothelium-derived nitric oxide is a potent endogenous vasodilator that is derived from the metabolism of L-arginine. This endothelial factor inhibits circulating blood elements from interacting with the vessel wall. Platelet adherence and aggregation as well as monocyte adherence and infiltration are opposed by this paracrine substance. By virtue of these characteristics, endothelium-derived nitric oxide inhibits atherogenesis in animal models and may even induce regression. Images Figure 1. PMID:8686299

Investigation on Quantitative Structure Activity Relationships of a Series of Inducible Nitric Oxide.

PubMed

Sharma, Mukesh C; Sharma, S

2016-12-01

A series of 2-dihydro-4-quinazolin with potent highly selective inhibitors of inducible nitric oxide synthase activities was subjected to quantitative structure activity relationships (QSAR) analysis. Statistically significant equations with high correlation coefficient (r 2  = 0.8219) were developed. The k-nearest neighbor model has showed good cross-validated correlation coefficient and external validation values of 0.7866 and 0.7133, respectively. The selected electrostatic field descriptors the presence of blue ball around R1 and R4 in the quinazolinamine moiety showed electronegative groups favorable for nitric oxide synthase activity. The QSAR models may lead to the structural requirements of inducible nitric oxide compounds and help in the design of new compounds.

[State of mitochondrial respiration and calcium capacity in livers of rats with different resistance to hypoxia after injections of L-arginine].

PubMed

Kurhaliuk, N M

2001-01-01

In experiments on rats with different resistance to hypoxia are investigated processes of mitochondrial respiration, oxidative phosphorylation and calcium capacity in liver under precursor nitric oxide L-arginine (600 mg/kg) and blockator nitric oxide synthase L-NNA (35 mg/kg) injections. We are used next substrates of oxidation: 0.35 mM succinate, 1 mM alpha-ketoglutarate, 1 mM alpha-ketoglutarate and 2 mM malonic acid. Increasing of ADP-stimulation respiration states under exogenous L-arginine injection, decreasing efficacy of respiration processes (respiration control on Chance and ADP/O) under such substrates oxidation, testify to oxide energy support decreasing and reversing nitric oxide inhibit in such conditions. This will be used as mechanism cell regulation succinate dehydrogenase activity. It has shown that L-arginine injection increase calcium mitochondrial capacity low resistance to hypoxia rats using substrates of oxidation succinate and alpha-ketoglutarate to control meanings of high resistance rats. Effects of nitric oxide precursor influence on this processes limit NO-synthase inhibitor L-NNA.

Phosphine polymerization by nitric oxide: experimental characterization and theoretical predictions of mechanism.

PubMed

Zhao, Yi-Lei; Flora, Jason W; Thweatt, William David; Garrison, Stephen L; Gonzalez, Carlos; Houk, K N; Marquez, Manuel

2009-02-02

A yellow solid material [P(x)H(y)] has been obtained in the reaction of phosphine (PH(3)) and nitric oxide (NO) at room temperature and characterized by thermogravimetric analysis mass spectrometry (TGA-MS) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. In this work using complete basis set (CBS-QB3) methods a plausible mechanism has been investigated for phosphine polymerization in the presence of nitric oxide (NO). Theoretical explorations with the ab initio method suggest (a) instead of the monomer the nitric oxide dimer acts as an initial oxidant, (b) the resulting phosphine oxides (H(3)P=O <--> H(3)P(+)O(-)) in the gas phase draw each other via strong dipolar interactions between the P-O groups, and (c) consequently an autocatalyzed polymerization occurs among the phosphine oxides, forming P-P chemical bonds and losing water. The possible structures of polyhydride phosphorus polymer were discussed. In the calculations a series of cluster models was computed to simulate polymerization.

Oxidative damage mediated iNOS and UCP-2 upregulation in rat brain after sub-acute cyanide exposure: dose and time-dependent effects.

PubMed

Bhattacharya, Rahul; Singh, Poonam; John, Jebin Jacob; Gujar, Niranjan L

2018-04-03

Cyanide-induced chemical hypoxia is responsible for pronounced oxidative damage in the central nervous system. The disruption of mitochondrial oxidative metabolism has been associated with upregulation of uncoupling proteins (UCPs). The present study addresses the dose- and time-dependent effect of sub-acute cyanide exposure on various non-enzymatic and enzymatic oxidative stress markers and their correlation with inducible-nitric oxide synthase (iNOS) and uncoupling protein-2 (UCP-2) expression. Animals received (oral) triple distilled water (vehicle control), 0.25 LD50 potassium cyanide (KCN) or 0.50 LD50 KCN daily for 21 d. Animals were sacrificed on 7, 14 and 21 d post-exposure to measure serum cyanide and nitrite, and brain malondialdehyde (MDA), reduced glutathione (GSH), glutathione disulfide (GSSG), cytochrome c oxidase (CCO), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CA) levels, together with iNOS and UCP-2 expression, and DNA damage. The study revealed that a dose- and time-dependent increase in cyanide concentration was accompanied by corresponding CCO inhibition and elevated MDA levels. Decrease in GSH levels was not followed by reciprocal change in GSSG levels. Diminution of SOD, GPx, GR and CA activity was congruent with elevated nitrite levels and upregulation of iNOS and UCP-2 expression, without any DNA damage. It was concluded that long-term cyanide exposure caused oxidative stress, accompanied by upregulation of iNOS. The upregulation of UCP-2 further sensitized the cells to cyanide and accentuated the oxidative stress, which was independent of DNA damage.

JS-K, a Nitric Oxide Prodrug, Has Enhanced Cytotoxicity in Colon Cancer Cells with Knockdown of Thioredoxin Reductase 1

PubMed Central

Edes, Kornelia; Cassidy, Pamela; Shami, Paul J.; Moos, Philip J.

2010-01-01

Background The selenoenzyme thioredoxin reductase 1 has a complex role relating to cell growth. It is induced as a component of the cellular response to potentially mutagenic oxidants, but also appears to provide growth advantages to transformed cells by inhibiting apoptosis. In addition, selenocysteine-deficient or alkylated forms of thioredoxin reductase 1 have also demonstrated oxidative, pro-apoptotic activity. Therefore, a greater understanding of the role of thioredoxin reductase in redox initiated apoptotic processes is warranted. Methodology The role of thioredoxin reductase 1 in RKO cells was evaluated by attenuating endogenous thioredoxin reductase 1 expression with siRNA and then either inducing a selenium-deficient thioredoxin reductase or treatment with distinct redox challenges including, hydrogen peroxide, an oxidized lipid, 4-hydroxy-2-nonenol, and a nitric oxide donating prodrug. Thioredoxin redox status, cellular viability, and effector caspase activity were measured. Conclusions/Significance In cells with attenuated endogenous thioredoxin reductase 1, a stably integrated selenocysteine-deficient form of the enzyme was induced but did not alter either the thioredoxin redox status or the cellular growth kinetics. The oxidized lipid and the nitric oxide donor demonstrated enhanced cytotoxicity when thioredoxin reductase 1 was knocked-down; however, the effect was more pronounced with the nitric oxide prodrug. These results are consistent with the hypothesis that attenuation of the thioredoxin-system can promote apoptosis in a nitric oxide-dependent manner. PMID:20098717

Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1

PubMed Central

Otero, Miguel; Lago, Rocío; Lago, Francisca; Reino, Juan Jesús Gomez; Gualillo, Oreste

2005-01-01

The objective of the present study was to investigate the effect of leptin, alone or in combination with IL-1, on nitric oxide synthase (NOS) type II activity in vitro in human primary chondrocytes, in the mouse chondrogenic ATDC5 cell line, and in mature and hypertrophic ATDC5 differentiated chondrocytes. For completeness, we also investigated the signalling pathway of the putative synergism between leptin and IL-1. For this purpose, nitric oxide production was evaluated using the Griess colorimetric reaction in culture medium of cells stimulated over 48 hours with leptin (800 nmol/l) and IL-1 (0.025 ng/ml), alone or combined. Specific pharmacological inhibitors of NOS type II (aminoguanidine [1 mmol/l]), janus kinase (JAK)2 (tyrphostin AG490 and Tkip), phosphatidylinositol 3-kinase (PI3K; wortmannin [1, 2.5, 5 and 10 μmol/l] and LY294002 [1, 2.5, 5 and 10 μmol/l]), mitogen-activated protein kinase kinase (MEK)1 (PD098059 [1, 5, 10, 20 and 30 μmol/l]) and p38 kinase (SB203580 [1, 5, 10, 20 and 30 μmol/l]) were added 1 hour before stimulation. Nitric oxide synthase type II mRNA expression in ATDC5 chondrocytes was investigated by real-time PCR and NOS II protein expression was analyzed by western blot. Our results indicate that stimulation of chondrocytes with IL-1 results in dose-dependent nitric oxide production. In contrast, leptin alone was unable to induce nitric oxide production or expression of NOS type II mRNA or its protein. However, co-stimulation with leptin and IL-1 resulted in a net increase in nitric oxide concentration over IL-1 challenge that was eliminated by pretreatment with the NOS II specific inhibitor aminoguanidine. Pretreatment with tyrphostin AG490 and Tkip (a SOCS-1 mimetic peptide that inhibits JAK2) blocked nitric oxide production induced by leptin/IL-1. Finally, wortmannin, LY294002, PD098059 and SB203580 significantly decreased nitric oxide production. These findings were confirmed in mature and hypertrophic ATDC5 chondrocytes, and in human primary chondrocytes. This study indicates that leptin plays a proinflammatory role, in synergy with IL-1, by inducing NOS type II through a signalling pathway that involves JAK2, PI3K, MEK-1 and p38 kinase. PMID:15899045

Mobile phone radiation-induced free radical damage in the liver is inhibited by the antioxidants N-acetyl cysteine and epigallocatechin-gallate.

PubMed

Ozgur, Elcin; Güler, Göknur; Seyhan, Nesrin

2010-11-01

To investigate oxidative damage and antioxidant enzyme status in the liver of guinea pigs exposed to mobile phone-like radiofrequency radiation (RFR) and the potential protective effects of N-acetyl cysteine (NAC) and epigallocatechin-gallate (EGCG) on the oxidative damage. Nine groups of guinea pigs were used to study the effects of exposure to an 1800-MHz Global System for Mobile Communications (GSM)-modulated signal (average whole body Specific Absorption Rate (SAR) of 0.38 W/kg, 10 or 20 min per day for seven days) and treatment with antioxidants. Significant increases in malondialdehyde (MDA) and total nitric oxide (NO(x)) levels and decreases in activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and glutathione peroxidase (GSH-Px) were observed in the liver of guinea pigs after RFR exposure. Only NAC treatment induces increase in hepatic GSH-Px activities, whereas EGCG treatment alone attenuated MDA level. Extent of oxidative damage was found to be proportional to the duration of exposure (P < 0.05). Mobile phone-like radiation induces oxidative damage and changes the activities of antioxidant enzymes in the liver. The adverse effect of RFR may be related to the duration of mobile phone use. NAC and EGCG protect the liver tissue against the RFR-induced oxidative damage and enhance antioxidant enzyme activities.

Detection of Zn2+ release in nitric oxide treated cells and proteome: dependence on fluorescent sensor and proteomic sulfhydryl groups.

PubMed

Karim, Mohammad R; Petering, David H

2017-04-19

Nitric oxide (NO) is both an important regulatory molecule in biological systems and a toxic xenobiotic. Its oxidation products react with sulfhydryl groups and either nitrosylate or oxidize them. The aerobic reaction of NO supplied by diethylamine NONOate (DEA-NO) with pig kidney LLC-PK 1 cells and Zn-proteins within the isolated proteome was examined with three fluorescent zinc sensors, zinquin (ZQ), TSQ, and FluoZin-3 (FZ-3). Observations of Zn 2+ labilization from Zn-proteins depended on the specific sensor used. Upon cellular exposure to DEA-NO, ZQ sequestered about 13% of the proteomic Zn 2+ as Zn(ZQ) 2 and additional Zn 2+ as proteome·Zn-ZQ ternary complexes. TSQ, a sensor structurally related to ZQ with lower affinity for Zn 2+ , did not form Zn(TSQ) 2 . Instead, Zn 2+ mobilized by DEA-NO was exclusively bound as proteome·Zn-TSQ adducts. Analogous reactions of proteome with ZQ or TSQ in vitro displayed qualitatively similar products. Titration of native proteome with Zn 2+ in the presence of ZQ resulted in the sole formation of proteome·Zn-ZQ species. This result suggested that sulfhydryl groups are involved in non-specific proteomic binding of mobile Zn 2+ and that the appearance of Zn(ZQ) 2 after exposure of cells and proteome to DEA-NO resulted from a reduction in proteomic sulfhydryl ligands, favoring the formation of Zn(ZQ) 2 instead of proteome·Zn-ZQ. With the third sensor, FluoZin-3, neither Zn-FZ-3 nor proteome·Zn-FZ-3 was detected during the reaction of proteome with DEA-NO. Instead, it reacted independently with DEA-NO with a modest enhancement of fluorescence.

Rapid cycling of reactive nitrogen in the marine boundary layer.

PubMed

Ye, Chunxiang; Zhou, Xianliang; Pu, Dennis; Stutz, Jochen; Festa, James; Spolaor, Max; Tsai, Catalina; Cantrell, Christopher; Mauldin, Roy L; Campos, Teresa; Weinheimer, Andrew; Hornbrook, Rebecca S; Apel, Eric C; Guenther, Alex; Kaser, Lisa; Yuan, Bin; Karl, Thomas; Haggerty, Julie; Hall, Samuel; Ullmann, Kirk; Smith, James N; Ortega, John; Knote, Christoph

2016-04-28

Nitrogen oxides are essential for the formation of secondary atmospheric aerosols and of atmospheric oxidants such as ozone and the hydroxyl radical, which controls the self-cleansing capacity of the atmosphere. Nitric acid, a major oxidation product of nitrogen oxides, has traditionally been considered to be a permanent sink of nitrogen oxides. However, model studies predict higher ratios of nitric acid to nitrogen oxides in the troposphere than are observed. A 'renoxification' process that recycles nitric acid into nitrogen oxides has been proposed to reconcile observations with model studies, but the mechanisms responsible for this process remain uncertain. Here we present data from an aircraft measurement campaign over the North Atlantic Ocean and find evidence for rapid recycling of nitric acid to nitrous acid and nitrogen oxides in the clean marine boundary layer via particulate nitrate photolysis. Laboratory experiments further demonstrate the photolysis of particulate nitrate collected on filters at a rate more than two orders of magnitude greater than that of gaseous nitric acid, with nitrous acid as the main product. Box model calculations based on the Master Chemical Mechanism suggest that particulate nitrate photolysis mainly sustains the observed levels of nitrous acid and nitrogen oxides at midday under typical marine boundary layer conditions. Given that oceans account for more than 70 per cent of Earth's surface, we propose that particulate nitrate photolysis could be a substantial tropospheric nitrogen oxide source. Recycling of nitrogen oxides in remote oceanic regions with minimal direct nitrogen oxide emissions could increase the formation of tropospheric oxidants and secondary atmospheric aerosols on a global scale.

Process for combined control of mercury and nitric oxide.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Livengood, C. D.; Mendelsohn, M. H.

Continuing concern about the effects of mercury in the environment may lead to requirements for the control of mercury emissions from coal-fired power plants. If such controls are mandated, the use of existing flue-gas cleanup systems, such as wet scrubbers currently employed for flue-gas desulfurization, would be desirable, Such scrubbers have been shown to be effective for capturing oxidized forms of mercury, but cannot capture the very insoluble elemental mercury (Hg{sup 0}) that can form a significant fraction of the total emissions. At Argonne National Laboratory, we have proposed and tested a concept for enhancing removal of Hg{sup 0}, as well as nitric oxide, through introduction of an oxidizing agent into the flue gas upstream of a scrubber, which readily absorbs the soluble reaction products. Recently, we developed a new method for introducing the oxidizing agent into the flue-gas stream that dramatically improved reactant utilization. The oxidizing agent employed was NOXSORB{trademark}, which is a commercial product containing chloric acid and sodium chlorate. When a dilute solution of this agent was introduced into a gas stream containing Hg{sup 0} and other typical flue-gas species at 300 F, we found that about 100% of the mercury was removed from the gas phase and recovered in process liquids. At the same time, approximately 80% of the nitric oxide was removed. The effect of sulfur dioxide on this process was also investigated and the results showed that it slightly decreased the amount of Hg{sup 0} oxidized while appearing to increase the removal of nitric oxide from the gas phase. We are currently testing the effects of variations in NOXSORB{trademark} concentration, sulfur dioxide concentration, nitric oxide concentration, and reaction time (residence time). Preliminary economic projections based on the results to date indicate that the chemical cost for nitric oxide oxidation could be less thanmore » $$5,000/ton removed, while for Hg{sup 0} oxidation it would be about $$20,000/lb removed.« less

Regulatory mechanism of the flavoprotein Tah18-dependent nitric oxide synthesis and cell death in yeast.

PubMed

Yoshikawa, Yuki; Nasuno, Ryo; Kawahara, Nobuhiro; Nishimura, Akira; Watanabe, Daisuke; Takagi, Hiroshi

2016-07-01

Nitric oxide (NO) is a ubiquitous signaling molecule involved in the regulation of a large number of cellular functions. The regulatory mechanism of NO generation in unicellular eukaryotic yeast cells is poorly understood due to the lack of mammalian and bacterial NO synthase (NOS) orthologues, even though yeast produces NO under oxidative stress conditions. Recently, we reported that the flavoprotein Tah18, which was previously shown to transfer electrons to the iron-sulfur cluster protein Dre2, is involved in NOS-like activity in the yeast Saccharomyces cerevisiae. On the other hand, Tah18 was reported to promote apoptotic cell death after exposure to hydrogen peroxide (H2O2). Here, we showed that NOS-like activity requiring Tah18 induced cell death upon treatment with H2O2. Our experimental results also indicate that Tah18-dependent NO production and cell death are suppressed by enhancement of the interaction between Tah18 and its molecular partner Dre2. Our findings indicate that the Tah18-Dre2 complex regulates cell death as a molecular switch via Tah18-dependent NOS-like activity in response to environmental changes. Copyright © 2016 Elsevier Inc. All rights reserved.

Estriol-induced fibrinolysis due to the activation of plasminogen to plasmin by nitric oxide synthesis in platelets.

PubMed

Jana, Pradipta; Maiti, Smarajit; Kahn, Nighat N; Sinha, Asru K

2015-04-01

Estriol, an oestrogen, at 0.6 nmol/l was reported to inhibit ADP-induced platelet aggregation through nitric oxide synthesis. As nitric oxide has been reported to cause fibrinolysis due to the activation of plasminogen to plasmin, the role of estriol as a fibrinolytic agent was investigated. Also, the mechanism of estriol-induced nitric oxide synthesis in anucleated platelets was investigated. The estriol-induced lysis of platelet-rich plasma (PRP) clot was determined by photography of the clot lysis and by the assay of fibrin degradation products in the lysate and was obtained by SDS-PAGE. Nitric oxide was determined by methemoglobin method. The platelet membrane protein was isolated from the platelets by using Triton X-100 (0.05% v/v). The binding of estriol to the protein was determined by Scatchard plot by using an ELISA for estriol. Estriol at 0.6 nmol/l was found to lyse the clotted PRP due to fibrinolysis that produced fibrin degradation products in the lysate. The amino acid analysis of the platelet membrane protein, which resembles with nitric oxide synthase (NOS) activity, was activated nearly 10-fold over the control in the presence of estriol and was identified to be a human serum albumin precursor (Mr. 69 kDa) that binds to estriol with Kd1 of 6.0 × 10 mol/l and 39 ± 2 molecules of estriol bound the NOS molecule. The estriol-induced nitric oxide is capable of inducing fibrinolysis of the clotted PRP. The binding of estriol to platelet membrane NOS activated the enzyme in the absence of DNA in the platelet.

A pentapeptide monocyte locomotion inhibitory factor protects brain ischemia injury by targeting the eEF1A1/endothelial nitric oxide synthase pathway.

PubMed

Zhang, Yuefan; Chen, Jun; Li, Fan; Li, Dong; Xiong, Qinhui; Lin, Yang; Zhang, Dazhi; Wang, Xiao-Fan; Yang, Pengyuan; Rui, Yao-Cheng

2012-10-01

Ischemic stroke is a major cause of death worldwide but lacks viable treatment or treatment targets. Monocyte locomotion inhibitory factor (MLIF) is a small heat-stable pentapeptide produced by Entamoeba histolytica in axenic culture, which is supposed to protect the brain from ischemic injury; the mechanism, however, remains unknown. In this study, we further investigated the mechanism underlying the protective role of MLIF in brain ischemia. A middle cerebral artery occlusion model in rats was used for detecting the effect of MLIF in the brain ischemia in vivo. To identify targets of MLIF in brain endothelial cells, we performed immunoprecipitation of biotin-conjugated MLIF and mass spectrometry. MLIF can protect the brain from ischemic injury in vivo, yielding decreased ischemic volume, prolonged survival, and improved neurological outcome. In vitro studies showed that MLIF displayed protective effects through inhibition of expression of pathological inflammatory adhesion molecules and enhancing endothelial nitric oxide synthase expression and nitric oxide release in the cerebrovascular endothelium. The target screening experiments demonstrated binding of MLIF to the ribosomal protein translation elongation factor eEF1A1. MLIF enhanced endothelial nitric oxide synthase expression through stabilization of endothelial nitric oxide synthase mRNA, and eEF1A1 was shown to be necessary for this enhanced expression. Knockdown of eEF1A1 or inhibition of endothelial nitric oxide synthase attenuated MLIF-mediated inhibition of adhesion molecule expression. In this study, we identified a new potential pharmacologically targetable mechanism underlying MLIF's protective effects in brain ischemia through the eEF1A1/endothelial nitric oxide synthase pathway.

Pulmonary Hypertension in Lambs Transfused with Stored Blood is Prevented by Breathing Nitric Oxide

PubMed Central

Baron, David M.; Yu, Binglan; Lei, Chong; Bagchi, Aranya; Beloiartsev, Arkadi; Stowell, Christopher P.; Steinbicker, Andrea U.; Malhotra, Rajeev; Bloch, Kenneth D.; Zapol, Warren M.

2012-01-01

Background During extended storage, erythrocytes undergo functional changes. These changes reduce the viability of erythrocytes leading to release of oxyhemoglobin, a potent scavenger of nitric oxide. We hypothesized that transfusion of ovine packed erythrocytes (PRBC) stored for prolonged periods would induce pulmonary vasoconstriction in lambs, and that reduced vascular nitric oxide concentrations would increase this vasoconstrictor effect. Methods We developed a model of autologous stored blood transfusion in lambs (n=36). Leukoreduced blood was stored for either 2 days (fresh PRBC) or 40 days (stored PRBC). Fresh or stored PRBC were transfused into donors instrumented for awake hemodynamic measurements. Hemodynamic effects of PRBC transfusion were also studied after infusion of NG-nitro-L-arginine methyl-ester (25 mg/kg) or during inhalation of nitric oxide (80 ppm). Results Cell-free hemoglobin levels were higher in the supernatant of stored PRBC than in supernatant of fresh PRBC (Mean±SD, 148±20 versus 41±13 mg/dl, respectively, P<0.001). Pulmonary artery pressure during transfusion of stored PRBC transiently increased from 13±1 to 18±1 mmHg (P<0.001) and was associated with increased plasma hemoglobin concentrations. NG-nitro-L-arginine methyl-ester potentiated the increase in pulmonary arterial pressure induced by transfusing stored PRBC, whereas inhalation of nitric oxide prevented the vasoconstrictor response. Conclusions Our results suggest that patients with reduced vascular nitric oxide levels due to endothelial dysfunction may be more susceptible to adverse effects of transfusing blood stored for prolonged periods. These patients might benefit from transfusion of fresh PRBC, when available, or inhaled nitric oxide supplementation to prevent the pulmonary hypertension associated with transfusion of stored PRBC. PMID:22293717

Iron(II) porphyrins induced conversion of nitrite into nitric oxide: A computational study.

PubMed

Zhang, Ting Ting; Liu, Yong Dong; Zhong, Ru Gang

2015-09-01

Nitrite reduction to nitric oxide by heme proteins was reported as a protective mechanism to hypoxic injury in mammalian physiology. In this study, the pathways of nitrite reduction to nitric oxide mediated by iron(II) porphyrin (P) complexes, which were generally recognized as models for heme proteins, were investigated by using density functional theory (DFT). In view of two type isomers of combination of nitrite and Fe(II)(P), N-nitro- and O-nitrito-Fe(II)-porphyrin complexes, and two binding sites of proton to the different O atoms of nitrite moiety, four main pathways for the conversion of nitrite into nitric oxide mediated by iron(II) porphyrins were proposed. The results indicate that the pathway of N-bound Fe(II)(P)(NO2) isomer into Fe(III)(P)(NO) and water is similar to that of O-bound isomer into nitric oxide and Fe(III)(P)(OH) in both thermodynamical and dynamical aspects. Based on the initial computational studies of five-coordinate nitrite complexes, the conversion of nitrite into NO mediated by Fe(II)(P)(L) complexes with 14 kinds of proximal ligands was also investigated. Generally, the same conclusion that the pathways of N-bound isomers are similar to those of O-bound isomer was obtained for iron(II) porphyrin with ligands. Different effects of ligands on the reduction reactions were also found. It is notable that the negative proximal ligands can improve reactive abilities of N-nitro-iron(II) porphyrins in the conversion of nitrite into nitric oxide compared to neutral ligands. The findings will be helpful to expand our understanding of the mechanism of nitrite reduction to nitric oxide by iron(II) porphyrins. Copyright © 2015 Elsevier Inc. All rights reserved.

Nitric oxide contributes to substance P-induced increases in lung rapidly adapting receptor activity in guinea-pigs.

PubMed Central

Joad, J P; Kott, K S; Bonham, A C

1997-01-01

1. Substance P induces fluid flux via nitric oxide, and fluid flux stimulates lung rapidly adapting receptors (RARs). We therefore proposed that nitric oxide contributes to substance P-evoked increases in RAR activity. Since substance P decreases dynamic compliance (Cdyn), which can stimulate RARs, we also determined whether nitric oxide contributed to substance P-induced effects on pulmonary function. 2. In anaesthetized guinea-pigs, the effects of substance P on RAR activity, Cdyn, pulmonary resistance (RL), and arterial blood pressure were measured before and after i.v. infusion of NG-methyl-L-arginine (L-NMMA; a nitric oxide synthase inhibitor), or L-NMMA followed by L-arginine (a nitric oxide precursor which reverses the effects of L-NMMA). 3. Substance P-evoked increases in RAR activity were blunted by L-NMMA (P = 0.006) but not by L-NMMA-L-arginine (P = 0.42). 4. Substance P-evoked decreases in Cdyn were slightly inhibited by L-NMMA (P = 0.02) and slightly enhanced by L-NMMA-L-arginine (P = 0.004). However, at the time at which L-NMMA maximally reduced substance P-induced RAR stimulation (the first 30 s), it did not change substance P-induced decreases in Cdyn. 5. Substance P-evoked increases in RL were not changed by L-NMMA (P = 0.10) and were enhanced by L-NMMA-L-arginine (P = 0.03). 6. L-NMMA-evoked increases in mean arterial blood pressure were reversed by L-arginine. Substance P-evoked decreases in mean arterial blood pressure were not changed by L-NMMA or by L-NMMA-L-arginine. 7. We conclude that nitric oxide contributes to substance P-evoked increases in RAR activity and that the increases are most probably independent of decreases in Cdyn. PMID:9379417

Enhanced nitric oxide generation from nitric oxide synthases as the cause of increased peroxynitrite formation during acute restraint stress: Effects on carotid responsiveness to angiotensinergic stimuli in type-1 diabetic rats.

PubMed

Moreira, Josimar D; Pernomian, Larissa; Gomes, Mayara S; Moreira, Rafael P; do Prado, Alejandro F; da Silva, Carlos H T P; de Oliveira, Ana M

2016-07-15

Diabetes mellitus is associated with reactive oxygen and nitrogen species accumulation. Behavioral stress increases nitric oxide production, which may trigger a massive impact on vascular cells and accelerate cardiovascular complications under oxidative stress conditions such as Diabetes. For this study, type-1 Diabetes mellitus was induced in Wistar rats by intraperitoneal injection of streptozotocin. After 28 days, cumulative concentration-response curves for angiotensin II were obtained in endothelium-intact carotid rings from diabetic rats that underwent to acute restraint stress for 3h. The contractile response evoked by angiotensin II was increased in carotid arteries from diabetic rats. Acute restraint stress did not alter angiotensin II-induced contraction in carotid arteries from normoglycaemic rats. However acute stress combined with Diabetes increased angiotensin II-induced contraction in carotid rings. Western blot experiments and the inhibition of nitric oxide synthases in functional assays showed that neuronal, endothelial and inducible nitric oxide synthase isoforms contribute to the increased formation of peroxynitrite and contractile hyperreactivity to angiotensin II in carotid rings from stressed diabetic rats. In summary, these findings suggest that the increased superoxide anion generation in carotid arteries from diabetic rats associated to the increased local nitric oxide synthases expression and activity induced by acute restrain stress were responsible for exacerbating the local formation of peroxynitrite and the contraction induced by angiotensin II. Copyright © 2016 Elsevier B.V. All rights reserved.

Mediated electrochemical oxidation of organic wastes using a Co (III) mediator in a nitric acid based system

DOEpatents

Balazs, G.B.; Chiba, Z.; Lewis, P.R.; Nelson, N.; Steward, G.A.

1999-06-15

An electrochemical cell with a Co(III) mediator and nitric acid electrolyte provides efficient destruction of organic and mixed wastes. The organic waste is concentrated in the anolyte reservoir, where the mediator oxidizes the organics and insoluble transuranic compounds and is regenerated at the anode until the organics are converted to CO[sub 2]. The nitric acid is an excellent oxidant that facilitates the destruction of the organic components. The anode is not readily attacked by the nitric acid solution, thus the cell can be used for extended continual operation without electrode replacement. 2 figs.

Contemporary approaches to modulating the nitric oxide-cGMP pathway in cardiovascular disease

PubMed Central

Kraehling, Jan R.; Sessa, William C.

2017-01-01

Endothelial cells lining the vessel wall control important aspects of vascular homeostasis. In particular, the production of endothelium-derived nitric oxide and activation of soluble guanylate cyclase promotes endothelial quiescence and governs vasomotor function and proportional remodeling of blood vessels. Here, we discuss novel approaches to improve endothelial nitric oxide generation and preserve its bioavailability. We also discuss therapeutic opportunities aimed at activation of soluble guanylate cyclase for multiple cardiovascular indications. PMID:28360348

Monoclonal L-citrulline immunostaining reveals nitric oxide-producing vestibular neurons

NASA Technical Reports Server (NTRS)

Holstein, G. R.; Friedrich, V. L. Jr; Martinelli, G. P.

2001-01-01

Nitric oxide is an unstable free radical that serves as a novel messenger molecule in the central nervous system (CNS). In order to understand the interplay between classic and novel chemical communication systems in vestibular pathways, the staining obtained using a monoclonal antibody directed against L-citrulline was compared with the labeling observed using more traditional markers for the presence of nitric oxide. Brainstem tissue from adult rats was processed for immunocytochemistry employing a monoclonal antibody directed against L-citrulline, a polyclonal antiserum against neuronal nitric oxide synthase, and/or NADPH-diaphorase histochemistry. Our findings demonstrate that L-citrulline can be fixed in situ by vascular perfusion, and can be visualized in fixed CNS tissue sections by immunocytochemistry. Further, the same vestibular regions and cell types are labeled by NADPH-diaphorase histochemistry, by the neuronal nitric oxide synthase antiserum, and by our anti-L-citrulline antibody. Clusters of L-citrulline-immunoreactive neurons are present in subregions of the vestibular nuclei, including the caudal portion of the inferior vestibular nucleus, the magnocellular portion of the medial vestibular nucleus, and the large cells in the ventral tier of the lateral vestibular nucleus. NADPH-diaphorase histochemical staining of these neurons clearly demonstrated their multipolar, fusiform and globular somata and long varicose dendritic processes. These results provide support for the suggestion that nitric oxide serves key roles in both vestibulo-autonomic and vestibulo-spinal pathways.

Evidence for involvement of nitric oxide and GABAB receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex

PubMed Central

Roenker, Nicole L.; Gudelsky, Gary A.; Ahlbrand, Rebecca; Horn, Paul S.; Richtand, Neil M.

2012-01-01

Systemic administration of NMDA receptor antagonists elevates extracellular glutamate within prefrontal cortex. The cognitive and behavioral effects of NMDA receptor blockade have direct relevance to symptoms of schizophrenia, and recent studies demonstrate an important role for nitric oxide and GABAB receptors in mediating the effects of NMDA receptor blockade on these behaviors. We sought to extend those observations by directly measuring the effects of nitric oxide and GABAB receptor mechanisms on MK-801-induced glutamate release in the prefrontal cortex. Systemic MK-801 injection (0.3 mg/kg) to male Sprague-Dawley rats significantly increased extracellular glutamate levels in prefrontal cortex, as determined by microdialysis. This effect was blocked by pretreatment with the nitric oxide synthase inhibitor L-NAME (60 mg/kg). Reverse dialysis of the nitric oxide donor SNAP (0.5 – 5 mM) directly into prefrontal cortex mimicked the effect of systemic MK-801, dose-dependently elevating cortical extracellular glutamate. The effect of MK-801 was also blocked by systemic treatment with the GABAB receptor agonist baclofen (5 mg/kg). In combination, these data suggest increased nitric oxide formation is necessary for NMDA antagonist-induced elevations of extracellular glutamate in the prefrontal cortex. Additionally, the data suggest GABAB receptor activation can modulate the NMDA antagonist-induced increase in cortical glutamate release. PMID:22579658

Pu-erh Tea Reduces Nitric Oxide Levels in Rats by Inhibiting Inducible Nitric Oxide Synthase Expression through Toll-Like Receptor 4

PubMed Central

Xu, Yang; Wang, Guan; Li, Chunjie; Zhang, Min; Zhao, Hang; Sheng, Jun; Shi, Wei

2012-01-01

Pu-erh tea undergoes a unique fermentation process and contains theabrownins, polysaccharides and caffeine; although it is unclear about which component is associated with the down regulation of nitric oxide levels or how this process is mediated. To address this question we examined the effects of pu-erh tea on nitric oxide synthase (NOS) genes. Cohorts of rats were separately given four-week treatments of water as control, pu-erh tea, or the tea components: theabrownins, caffeine or polysaccharides. Five experimental groups were injected with lipopolysaccharides (LPS) to induce nitric oxide (NO) production, while the corresponding five control groups were injected with saline as a negative control. The serum and liver NO concentrations were examined and the NOS expression of both mRNA and protein was measured in liver. The results showed that the rats which were fed pu-erh tea or polysaccharides had lower levels of NO which corresponded with the down-regulation of inducible nitric oxide synthase (iNOS) expression. We further demonstrate that this effect is mediated through reduction of Toll-like receptor 4 (TLR4) signaling. Thus we find that the polysaccharide components in pu-erh tea reduce NO levels in an animal model by inhibiting the iNOS expression via signaling through TLR4. PMID:22837686

The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics.

PubMed

Divakaran, Sanjay; Loscalzo, Joseph

2017-11-07

The use of nitroglycerin in the treatment of angina pectoris began not long after its original synthesis in 1847. Since then, the discovery of nitric oxide as a biological effector and better understanding of its roles in vasodilation, cell permeability, platelet function, inflammation, and other vascular processes have advanced our knowledge of the hemodynamic (mostly mediated through vasodilation of capacitance and conductance arteries) and nonhemodynamic effects of organic nitrate therapy, via both nitric oxide-dependent and -independent mechanisms. Nitrates are rapidly absorbed from mucous membranes, the gastrointestinal tract, and the skin; thus, nitroglycerin is available in a number of preparations for delivery via several routes: oral tablets, sublingual tablets, buccal tablets, sublingual spray, transdermal ointment, and transdermal patch, as well as intravenous formulations. Organic nitrates are commonly used in the treatment of cardiovascular disease, but clinical data limit their use mostly to the treatment of angina. They are also used in the treatment of subsets of patients with heart failure and pulmonary hypertension. One major limitation of the use of nitrates is the development of tolerance. Although several agents have been studied for use in the prevention of nitrate tolerance, none are currently recommended owing to a paucity of supportive clinical data. Only 1 method of preventing nitrate tolerance remains widely accepted: the use of a dosing strategy that provides an interval of no or low nitrate exposure during each 24-h period. Nitric oxide's important role in several cardiovascular disease mechanisms continues to drive research toward finding novel ways to affect both endogenous and exogenous sources of this key molecular mediator. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Treatment of micro air bubbles in rat adipose tissue at 25 kPa altitude exposures with perfluorocarbon emulsions and nitric oxide.

PubMed

Randsøe, Thomas; Hyldegaard, O

2014-01-01

Perfluorocarbon emulsions (PFC) and nitric oxide (NO) releasing agents have on experimental basis demonstrated therapeutic properties in treating and preventing the formation of venous gas embolism as well as increased survival rate during decompression sickness from diving. The effect is ascribed to an increased solubility and transport capacity of respiratory gases in the PFC emulsion and possibly enhanced nitrogen washout through NO-increased blood flow rate and/or the removal of endothelial micro bubble nuclei precursors. Previous reports have shown that metabolic gases (i.e., oxygen in particular) and water vapor contribute to bubble growth and stabilization during altitude exposures. Accordingly, we hypothesize that the administration of PFC and NO donors upon hypobaric pressure exposures either (1) enhance the bubble disappearance rate through faster desaturation of nitrogen, or in contrast (2) promote bubble growth and stabilization through an increased oxygen supply. In anesthetized rats, micro air bubbles (containing 79% nitrogen) of 4-500 nl were injected into exposed abdominal adipose tissue. Rats were decompressed in 36 min to 25 kPa (~10,376 m above sea level) and bubbles studied for 210 min during continued oxygen breathing (FIO2 = 1). Rats were administered PFC, NO, or combined PFC and NO. In all groups, most bubbles grew transiently, followed by a stabilization phase. There were no differences in the overall bubble growth or decay between groups or when compared with previous data during oxygen breathing alone at 25 kPa. During extreme altitude exposures, the contribution of metabolic gases to bubble growth compromises the therapeutic effects of PFC and NO, but PFC and NO do not induce additional bubble growth.

Nitric oxide: A new possible biomarker in heart failure? Relationship with pulmonary hypertension secondary to left heart failure.

PubMed

Bonafede, Roberto Jorge; Calvo, Juan Pablo; Fausti, Julia María Valeria; Puebla, Sonia; Gambarte, Adolfo Juan; Manucha, Walter

Heart failure (HF) is a growing medical problem and it is of interest to study new biomarkers for better characterisation. In this sense, nitric oxide, reactive oxygen species (ROS), NADPH, and superoxide dismutase (SOD) were evaluated, along with their possible predictive value in patients with HF. An analysis was also performed on the potential differences between patients with and without secondary pulmonary hypertension (SPH), considered to have a worse prognosis. A significant decrease of nitric oxide and SOD was noted in HF, whereas ROS and NADPH were increased. These results agree with the pathophysiological changes characteristic of HF. It was also demonstrated that in patients with HF and SPH that nitric oxide and SOD were decreased when compared to HF without SPH, whereas ROS and NADPH were increased. Therefore, our results suggest that nitric oxide, ROS, NADPH, and SOD, could be considered as possible markers in HF, and could also characterise patients with SPH. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Satellite observations of the nitric oxide dayglow Implications for the behavior of mesospheric and lower-thermospheric odd nitrogen

NASA Technical Reports Server (NTRS)

Frederick, J. E.; Serafino, G. N.

1985-01-01

The solar backscattered ultraviolet spectral radiometer on the Nimbus 7 satellite routinely measures fluorescence emissions from the nitric oxide (1, 4) gamma band that are imposed on the large Rayleigh-scattered signal in the wavelength range 255-256 nm. The gamma band feature, when isolated from the background radiance, provide information on the seasonal and latitudinal variations in the nitric oxide column abundance over the altitude region from 40 to 45 km upward through the thermosphere. At latitudes from 30 deg to 45 deg in the Northern Hemisphere the measurements show an annual cycle with maximum nitric oxide abundance in summer. The Southern Hemisphere pattern is qualitatively similar to this, although the amplitude of the seasonal variation is substantially smaller. The most prominent feature of the data base is a large maximum in nitric oxide emission that develops poleward of 45 deg latitude in both Hemispheres during late autumn and early winter. These maxima dissipate rapidly as spring approaches and are no longer evident in the data for Northern Hemisphere March and Southern Hemisphere September.

Inflammatory response and endothelial dysfunction in the hearts of mice co-exposed to SO2 , NO2 , and PM2.5.

PubMed

Zhang, Yingying; Ji, Xiaotong; Ku, Tingting; Sang, Nan

2016-12-01

SO 2 , NO 2 , and PM 2.5 are typical air pollutants produced during the combustion of coal. Increasing evidence indicates that air pollution has contributed to the development and progression of heart-related diseases over the past decades. However, little experimental data and few studies of SO 2 , NO 2 , and PM 2.5 co-exposure in animals exist; therefore, the relevant mechanisms underlying this phenomenon are unclear. An important characteristic of air pollution is that co-exposure persists at a low concentration throughout a lifetime. In the present study, we treated adult mice with SO 2 , NO 2 , and PM 2.5 at various concentrations (0.5 mg/m 3 SO 2 , 0.2 mg/m 3 NO 2 6 h/d, with intranasal instillation of 1 mg/kg PM 2.5 every other day during these exposures; or 3.5 mg/m 3 SO 2 , 2 mg/m 3 NO 2 6 h/d, and 10 mg/kg PM 2.5 for 28 d). Blood pressure (BP), heart rate (HR), histopathological damage, and inflammatory and endothelial cytokines in the heart were assessed. The results indicate that co-exposure caused endothelial dysfunction by elevating endothelin-1 (ET-1) expression and repressing the endothelial nitric oxide synthase (eNOS) level as well as stimulating the inflammatory response by increasing the levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Additionally, these alterations were confirmed by histological staining. Furthermore, we observed decreased BP and increased HR after co-exposure. Our results indicate that co-exposure to SO 2 , NO 2 , and PM 2.5 may be a major risk factor for cardiac disease and may induce injury to the hearts of mammals and contribute to heart disease. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1996-2005, 2016. © 2015 Wiley Periodicals, Inc.

Nitric oxide functions as a signal in plant disease resistance.

PubMed

Delledonne, M; Xia, Y; Dixon, R A; Lamb, C

1998-08-06

Recognition of an avirulent pathogen triggers the rapid production of the reactive oxygen intermediates superoxide (O2-) and hydrogen peroxide (H2O2). This oxidative burst drives crosslinking of the cell wall, induces several plant genes involved in cellular protection and defence, and is necessary for the initiation of host cell death in the hypersensitive disease-resistance response. However, this burst is not enough to support a strong disease-resistance response. Here we show that nitric oxide, which acts as a signal in the immune, nervous and vascular systems, potentiates the induction of hypersensitive cell death in soybean cells by reactive oxygen intermediates and functions independently of such intermediates to induce genes for the synthesis of protective natural products. Moreover, inhibitors of nitric oxide synthesis compromise the hypersensitive disease-resistance response of Arabidopsis leaves to Pseudomonas syringae, promoting disease and bacterial growth. We conclude that nitric oxide plays a key role in disease resistance in plants.

Nitric oxide is a mediator of methamphetamine (METH)-induced neurotoxicity. In vitro evidence from primary cultures of mesencephalic cells.

PubMed

Sheng, P; Cerruti, C; Ali, S; Cadet, J L

1996-10-31

METH is a monoaminergic toxic that destroys dopamine terminals in vivo. Oxidative mechanisms associated with DA metabolism are thought to play an important role in its toxic effects. These ideas were supported by the demonstration that CuZn-superoxide dismutase (CuZnSOD) transgenic mice were protected against the toxic effects of the drug. In the present study, we sought to determine if nitric oxide (NO) production was also involved in METH-induced neurotoxicity using primary cultures obtained from fetal rat mesencephalon. METH caused dose- and time-dependent cell death in vitro. Blockade of nitric oxide (NO) formation with several nitric oxide (NO) synthase blockers attenuated METH-mediated toxicity. Moreover, inhibition of ADP-ribosylation with nicotinamide and benzamide also provided protection against the toxicity of the drug. These results, together with our previous results in transgenic mice, support a role for free radicals in METH-induced toxic effects.

Hydroxycarboxylic acids and salts

DOEpatents

Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N

2015-02-24

Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

Methylparaben induces malformations and alterations on apoptosis, oxidant-antioxidant status, ccnd1 and myca expressions in zebrafish embryos.

PubMed

Ateş, Perihan Seda; Ünal, İsmail; Üstündağ, Ünsal Veli; Alturfan, Ahmet Ata; Yiğitbaşı, Türkan; Emekli-Alturfan, Ebru

2018-03-01

Methylparabens (MP) are widely used as preservatives in cosmetics, pharmacy, and food industry. Although acute toxicity studies in animals indicated that parabens are not significantly toxic, the effects of chronic exposure under sublethal doses are still unknown and the number of related studies is limited. Our aim was to evaluate the effects of MP on the development of zebrafish embryos focusing on development, locomotor activity, oxidant-antioxidant status, apoptosis, and ccnd1 and myca expressions. The expressions of ccnd1 and myca were determined by RT-PCR. Lipid peroxidation (LPO), nitric oxide (NO), and glutathione-S-transferase (GST) activities were determined spectrophotometrically. Apoptosis was determined using acridine orange staining. Locomotor activity was measured using touch-evoked movement test. MP exposure increased malformations, LPO, apoptosis, ccnd1 and myca expressions, and decreased GST activities and NO levels compared with the control group. Our findings will lead to further understanding of the mechanism of MP toxicity, and merit further research. © 2018 Wiley Periodicals, Inc.

Antimicrobial Activity of Nitric Oxide-Releasing Ti-6Al-4V Metal Oxide

PubMed Central

Reger, Nina A.; Meng, Wilson S.; Gawalt, Ellen S.

2017-01-01

Titanium and titanium alloy materials are commonly used in joint replacements, due to the high strength of the materials. Pathogenic microorganisms can easily adhere to the surface of the metal implant, leading to an increased potential for implant failure. The surface of a titanium-aluminum-vanadium (Ti-6Al-4V) metal oxide implant material was functionalized to deliver an small antibacterial molecule, nitric oxide. S-nitroso-penicillamine, a S-nitrosothiol nitric oxide donor, was covalently immobilized on the metal oxide surface using self-assembled monolayers. Infrared spectroscopy was used to confirm the attachment of the S-nitrosothiol donor to the Ti-Al-4V surface. Attachment of S-nitroso-penicillamine resulted in a nitric oxide (NO) release of 89.6 ± 4.8 nmol/cm2 under physiological conditions. This low concentration of nitric oxide reduced Escherichia coli and Staphylococcus epidermidis growth by 41.5 ± 1.2% and 25.3 ± 0.6%, respectively. Combining the S-nitrosothiol releasing Ti-6Al-4V with tetracycline, a commonly-prescribed antibiotic, increased the effectiveness of the antibiotic by 35.4 ± 1.3%, which allows for lower doses of antibiotics to be used. A synergistic effect of ampicillin with S-nitroso-penicillamine-modified Ti-6Al-4V against S. epidermidis was not observed. The functionalized Ti-6Al-4V surface was not cytotoxic to mouse fibroblasts. PMID:28635681

METHOD OF ISOTOPE CONCENTRATION

DOEpatents

Taylor, T.I.; Spindel, W.

1960-02-01

A method of concentrating N/sup 15/ in a liquid is described. Gaseous nitric oxide and at least one liquid selected from the group consisting of the aqueous oxyacids and oxides of nitrogen, wherein the atomic ratio of oxygen to nitrogen is greater than unity, are brought into intimate contact to cause an enrichment of the liquid and a depletion of the gas in N/sup 15/. The liquid is, thereafter, reacted with sulfur dioxide to produce a gas contuining nitric oxide. The gas contuining nitric oxide is then continuously passed in countercurrent contact with the liquid to cause further enrichment of the liquid.

Contemporary Approaches to Modulating the Nitric Oxide-cGMP Pathway in Cardiovascular Disease.

PubMed

Kraehling, Jan R; Sessa, William C

2017-03-31

Endothelial cells lining the vessel wall control important aspects of vascular homeostasis. In particular, the production of endothelium-derived nitric oxide and activation of soluble guanylate cyclase promotes endothelial quiescence and governs vasomotor function and proportional remodeling of blood vessels. Here, we discuss novel approaches to improve endothelial nitric oxide generation and preserve its bioavailability. We also discuss therapeutic opportunities aimed at activation of soluble guanylate cyclase for multiple cardiovascular indications. © 2017 American Heart Association, Inc.

Mechanisms of Persistence of the Ammonia-Oxidizing Bacteria Nitrosomonas to the Biocide Free Nitrous Acid.

PubMed

Laloo, Andrew E; Wei, Justin; Wang, Dongbo; Narayanasamy, Shaman; Vanwonterghem, Inka; Waite, David; Steen, Jason; Kaysen, Anne; Heintz-Buschart, Anna; Wang, Qilin; Schulz, Benjamin; Nouwens, Amanda; Wilmes, Paul; Hugenholtz, Philip; Yuan, Zhiguo; Bond, Philip L

2018-05-01

Free nitrous acid (FNA) exerts a broad range of antimicrobial effects on bacteria, although susceptibility varies considerably among microorganisms. Among nitrifiers found in activated sludge of wastewater treatment processes (WWTPs), nitrite-oxidizing bacteria (NOB) are more susceptible to FNA compared to ammonia-oxidizing bacteria (AOB). This selective inhibition of NOB over AOB in WWTPs bypasses nitrate production and improves the efficiency and costs of the nitrogen removal process in both the activated sludge and anaerobic ammonium oxidation (Anammox) system. However, the molecular mechanisms governing this atypical tolerance of AOB to FNA have yet to be understood. Herein we investigate the varying effects of the antimicrobial FNA on activated sludge containing AOB and NOB using an integrated metagenomics and label-free quantitative sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) metaproteomic approach. The Nitrosomonas genus of AOB, on exposure to FNA, maintains internal homeostasis by upregulating a number of known oxidative stress enzymes, such as pteridine reductase and dihydrolipoyl dehydrogenase. Denitrifying enzymes were upregulated on exposure to FNA, suggesting the detoxification of nitrite to nitric oxide. Interestingly, proteins involved in stress response mechanisms, such as DNA and protein repair enzymes, phage prevention proteins, and iron transport proteins, were upregulated on exposure to FNA. In addition enzymes involved in energy generation were also upregulated on exposure to FNA. The total proteins specifically derived from the NOB genus Nitrobacter was low and, as such, did not allow for the elucidation of the response mechanism to FNA exposure. These findings give us an understanding of the adaptive mechanisms of tolerance within the AOB Nitrosomonas to the biocidal agent FNA.

21 CFR 862.3080 - Breath nitric oxide test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... fractional nitric oxide concentration in expired breath aids in evaluating an asthma patient's response to anti-inflammatory therapy, as an adjunct to established clinical and laboratory assessments of asthma...

Biomarkers of human cardiopulmonary response after short-term exposures to medical laser generated particulate matter from simulated procedures: a pilot study

PubMed Central

Lopez, Ramon; Farber, Mark O.; Wong, Vincent; Lacey, Steven E.

2016-01-01

Objective We conducted an exposure chamber study in humans using a simulated clinical procedure lasing porcine tissue to demonstrate evidence of effects of exposure to laser generated particulate matter (LGPM). Methods We measured pre- and post-exposure changes in exhaled nitric oxide (eNO), spirometry, heart rate variability (HRV), and blood markers of inflammation in five volunteers. Results Change in pre- and post-exposure measurements of eNO and spirometry were unremarkable. Neutrophil and lymphocyte counts increased and fibrinogen levels decreased in four of the five subjects. Measures of HRV showed decreases in the standard deviation of normal between beat intervals and sequential five-minute intervals. Conclusion These data represent the first evidence of human physiologic response to LGPM exposure. Further exploration of coagulation effects and HRV are warranted. PMID:27465102

AIR POLLUTION INFLUENCES ON EXHALED NITRIC OXIDE AMONG PEOPLE WITH TYPE II DIABETES.

PubMed

Peng, Cheng; Luttmann-Gibson, Heike; Zanobetti, Antonella; Cohen, Allison; De Souza, Celine; Coull, Brent A; Horton, Edward S; Schwartz, Joel; Koutrakis, Petros; Gold, Diane R

2016-04-01

In a population with type 2 diabetes mellitus (T2DM), we examined associations of short-term air pollutant exposures with pulmonary inflammation, measured as fraction of exhaled pulmonary nitric oxide (FeNO). Sixty-nine Boston Metropolitan residents with T2DM completed up to 5 bi-weekly visits with 321 offline FeNO measurements. We measured ambient concentrations of particle mass, number and components at our stationary central site. Ambient concentrations of gaseous air pollutants were obtained from state monitors. We used linear models with fixed effects for participants, adjusting for 24-hour mean temperature, 24-hour mean water vapor pressure, season, and scrubbed room NO the day of the visit, to estimate associations between FeNO and interquartile range increases in exposure. Interquartile increases in the 6-hour averages of black carbon (BC) (0.5 μg/m 3 ) and particle number (PN) (1,000 particles/cm 3 ) were associated with increases in FeNO of 3.84% (95% CI 0.60% to 7.18%) and 9.86 % (95% CI 3.59% to 16.52%), respectively. We also found significant associations of increases in FeNO with increases in 24-hour moving averages of BC, PN and nitrogen oxides (NOx). Recent studies have focused on FeNO as a marker for eosinophilic pulmonary inflammation in asthmatic populations. This study adds support to the relevance of FeNO as a marker for pulmonary inflammation in diabetic populations, whose underlying chronic inflammatory status is likely to be related to innate immunity and proinflammatory adipokines.

Acute hyperbilirubinaemia induces presynaptic neurodegeneration at a central glutamatergic synapse

PubMed Central

Haustein, Martin D; Read, David J; Steinert, Joern R; Pilati, Nadia; Dinsdale, David; Forsythe, Ian D

2010-01-01

There is a well-established link between hyperbilirubinaemia and hearing loss in paediatrics, but the cellular mechanisms have not been elucidated. Here we used the Gunn rat model of hyperbilirubinaemia to investigate bilirubin-induced hearing loss. In vivo auditory brainstem responses revealed that Gunn rats have severe auditory deficits within 18 h of exposure to high bilirubin levels. Using an in vitro preparation of the auditory brainstem from these rats, extracellular multi-electrode array recording from the medial nucleus of the trapezoid body (MNTB) showed longer latency and decreased amplitude of evoked field potentials following bilirubin exposure, suggestive of transmission failure at this synaptic relay. Whole-cell patch-clamp recordings confirmed that the electrophysiological properties of the postsynaptic MNTB neurons were unaffected by bilirubin, with no change in action potential waveforms or current–voltage relationships. However, stimulation of the trapezoid body was unable to elicit large calyceal EPSCs in MNTB neurons of hyperbilirubinaemic rats, indicative of damage at a presynaptic site. Multi-photon imaging of anterograde-labelled calyceal projections revealed axonal staining and presynaptic profiles around MNTB principal neuron somata. Following induction of hyperbilirubinaemia the giant synapses were largely destroyed. Electron microscopy confirmed loss of presynaptic calyceal terminals and supported the electrophysiological evidence for healthy postsynaptic neurons. MNTB neurons express high levels of neuronal nitric oxide synthase (nNOS). Nitric oxide has been implicated in mechanisms of bilirubin toxicity elsewhere in the brain, and antagonism of nNOS by 7-nitroindazole protected hearing during bilirubin exposure. We conclude that bilirubin-induced deafness is caused by degeneration of excitatory synaptic terminals in the auditory brainstem. PMID:20937712

Acute hyperbilirubinaemia induces presynaptic neurodegeneration at a central glutamatergic synapse.

PubMed

Haustein, Martin D; Read, David J; Steinert, Joern R; Pilati, Nadia; Dinsdale, David; Forsythe, Ian D

2010-12-01

There is a well-established link between hyperbilirubinaemia and hearing loss in paediatrics, but the cellular mechanisms have not been elucidated. Here we used the Gunn rat model of hyperbilirubinaemia to investigate bilirubin-induced hearing loss. In vivo auditory brainstem responses revealed that Gunn rats have severe auditory deficits within 18 h of exposure to high bilirubin levels. Using an in vitro preparation of the auditory brainstem from these rats, extracellular multi-electrode array recording from the medial nucleus of the trapezoid body (MNTB) showed longer latency and decreased amplitude of evoked field potentials following bilirubin exposure, suggestive of transmission failure at this synaptic relay. Whole-cell patch-clamp recordings confirmed that the electrophysiological properties of the postsynaptic MNTB neurons were unaffected by bilirubin, with no change in action potential waveforms or current-voltage relationships. However, stimulation of the trapezoid body was unable to elicit large calyceal EPSCs in MNTB neurons of hyperbilirubinaemic rats, indicative of damage at a presynaptic site. Multi-photon imaging of anterograde-labelled calyceal projections revealed axonal staining and presynaptic profiles around MNTB principal neuron somata. Following induction of hyperbilirubinaemia the giant synapses were largely destroyed. Electron microscopy confirmed loss of presynaptic calyceal terminals and supported the electrophysiological evidence for healthy postsynaptic neurons. MNTB neurons express high levels of neuronal nitric oxide synthase (nNOS). Nitric oxide has been implicated in mechanisms of bilirubin toxicity elsewhere in the brain, and antagonism of nNOS by 7-nitroindazole protected hearing during bilirubin exposure. We conclude that bilirubin-induced deafness is caused by degeneration of excitatory synaptic terminals in the auditory brainstem.

Longitudinal Effects of Air Pollution on Exhaled Nitric Oxide: The Children’s Health Study

PubMed Central

Berhane, Kiros; Zhang, Yue; Salam, Muhammad T.; Eckel, Sandrah P.; Linn, William S.; Rappaport, Edward B.; Bastain, Theresa M; Lurmann, Fred; Gilliland, Frank D.

2015-01-01

OBJECTIVES To assess the effects of long-term variations in ambient air pollutants on longitudinal changes in exhaled nitric oxide (FeNO), a potentially useful biomarker of eosinophilic airway inflammation, based on data from the southern California Children’s Health Study. METHODS Based on a cohort of 1,211 schoolchildren from 8 Southern California communities with FeNO measurements in 2006/07 and 2007/08, regression models adjusted for short-term effects of air pollution were fitted to assess the association between changes in annual long-term exposures and changes in FeNO. RESULTS Increases in annual average concentrations of 24-hr average NO2 and PM2.5 (scaled to the interquartile range (IQR) of 1.8 ppb and 2.4 μg/m3, respectively) were associated with a 2.29 ppb (CI=[0.36,4.21]; p =0.02) and a 4.94 ppb (CI=[1.44,8.47]; p = 0.005) increase in FeNO, respectively, after adjustments for short term effects of the respective pollutants. In contrast, changes in annual averages of PM10 and O3 were not significantly associated with changes in FeNO. These findings did not differ significantly by asthma status. CONCLUSIONS Changes in annual average exposure to current levels of ambient air pollutants are significantly associated with changes in FeNO levels in children, independent of short-term exposures and asthma status. Use of this biomarker in population-based epidemiologic research has great potential for assessing the impact of changing real world mixtures of ambient air pollutants on children’s respiratory health. PMID:24696513

Exhaled nitric oxide levels in school children in relation to IgE sensitisation and window pane condensation.

PubMed

Janson, Christer; Kalm-Stephens, Pia; Foucard, Tony; Norbäck, Dan; Alving, Kjell; Nordvall, S Lennart

2005-08-01

A positive relation between exhaled nitric oxide (NO) levels and allergen exposure has been found in some studies whereas there is less information on how non-allergen environmental factors influences exhaled NO. To study the relationship between exhaled NO levels in schoolchildren in relation to IgE sensitisation and allergenic and non-allergenic environmental factors. This study comprised 374 schoolchildren (13-14 years of age) who performed exhaled NO-measurements and skin prick tests. Exposure to allergens, respiratory infections, environmental tobacco smoke and home window pane condensation, the latter an indicator of high humidity and poor ventilation was evaluated through questionnaires. In IgE-sensitised children sensitisation to pets was a more important determinant of exhaled NO than sensitisation to pollen. Higher NO levels were found in cat-sensitised children with a cat or other furred pets at home compared to cat-sensitised children without pets (geometric mean, 24.0 vs. 13.9 ppb, P=0.03). Significantly higher exhaled NO levels were found in non-sensitised children that reported having a cold (5.7 vs. 3.8 ppb, P<0.001) or lived in homes with window pane condensation (7.1 vs. 4.4 ppb, P=0.01) than in non-sensitised children without a cold and window pane condensation, respectively. These associations were not found in children that were sensitised to inhalation allergens. Allergen exposure seems to be the most important determinant for exhaled NO levels in IgE-sensitised children whereas in non-sensitised children NO levels were associated with respiratory infections and home window pane condensation.

Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells.

PubMed Central

Kelley, T J; Drumm, M L

1998-01-01

It has been reported that exhaled nitric oxide levels are reduced in cystic fibrosis (CF) patients. We have examined the inducible isoform of nitric oxide synthase (iNOS) in the airways by immunostaining and found that iNOS is constitutively expressed in the airway epithelia of non-CF mouse and human tissues but essentially absent in the epithelium of CF airways. We explored potential consequences of lost iNOS expression and found that iNOS inhibition significantly increases mouse nasal trans-epithelial potential difference, and hindered the ability of excised mouse lungs to prevent growth of Pseudomonas aeruginosa. The absence of continuous nitric oxide production in epithelial cells of CF airways may play a role in two CF-associated characteristics: hyperabsorption of sodium and susceptibility to bacterial infections. PMID:9739054

Possible involvement of nitric oxide in pilocarpine induced seminal emission in rats.

PubMed

Tomé, A R; da Silva, J C; Souza, A A; Mattos, J P; Vale, M R; Rao, V S

1999-12-01

Intraperitoneal injection of pilocarpine (0.75-3.0 mg/kg) caused a dose-related seminal emission in adult male rats. The seminal emission response to 3 mg/kg of pilocarpine was greatly reduced in atropinized (5 and 10 mg/kg, SC) animals, suggesting a cholinomimetic effect. Nw-nitro-L-arginine methyl ester (5, 10, and 20 mg/kg, SC), a nitric oxide synthesis inhibitor, also inhibited the pilocarpine-induced seminal emission, which was reversed by L-arginine (600 mg/kg, SC) or by coinjection of sodium nitroprusside (0.5 mg/kg, SC). Urine analysis for levels of nitric oxide metabolites, nitrate/nitrite (NO3-/NO2-), showed marked alterations in accordance with the drug treatments. The results suggest that nitric oxide mediates the inhibitory neurotransmission responsible for seminal emission in pilocarpine stimulated rats.

Role of nitric oxide in in vitro contractile activity of the third compartment of the stomach in llamas.

PubMed

Van Hoogmoed, L; Rakestraw, P C; Snyder, J R; Harmon, F A

1998-09-01

To determine the role of nitric oxide and an apamin-sensitive nonadrenergic-noncholinergic inhibitory transmitter in in vitro contractile activity of the third compartment in llamas. Isolated strips of third compartment of the stomach from 5 llamas. Strips were mounted in tissue baths containing oxygenated Kreb's buffer solution and connected to a polygraph chart recorder to measure contractile activity. Atropine, guanethidine, and indomethacin were added to tissue baths to inhibit muscarinic receptors, adrenoreceptors, and prostaglandin synthesis. Responses to electrical field stimulation following addition of the nitric oxide antagonist Nwo-nitro-L-arginine methyl ester (L-NAME) and apamin were evaluated. Electrical field stimulation (EFS) resulted in a reduction in the amplitude and frequency of contractile activity, followed by rebound contraction when EFS was stopped. Addition of L-NAME resulted in a significant reduction in inhibition of contractile activity. Addition of apamin also resulted in a significant reduction in inhibitory contractile activity at most stimulation frequencies. The combination of L-NAME and apamin resulted in a significant reduction in inhibition at all frequencies. Nitric oxide and a transmitter acting via an apamin-sensitive mechanism appear to be involved in inhibition of contractile activity of the third compartment in llamas. Results suggest that nitric oxide plays an important role in mediating contractile activity of the third compartment in llamas. Use of nitric oxide synthase inhibitors may have a role in the therapeutic management of llamas with lesions of the third compartment.

Improvement of Tissue Survival of Skin Flaps by 5α-Reductase Inhibitors: Possible Involvement of Nitric Oxide and Inducible Nitric Oxide Synthase

PubMed Central

Karimi, Ali Asghar; Ajami, Marjan; Asadi, Yasin; Aboutaleb, Nahid; Gorjipour, Fazel; Malekloo, Roya; Pazoki-Toroudi, Hamidreza

2015-01-01

Background: Skin flap grafting is a popular approach for reconstruction of critical skin and underlying soft tissue injuries. In a previous study, we demonstrated the beneficial effects of two 5α-reductase inhibitors, azelaic acid and finasteride, on tissue survival in a rat model of skin flap grafting. In the current study, we investigated the involvement of nitric oxide and inducible nitric oxide synthase (iNOS) in graft survival mediated by these agents. Methods: A number of 42 male rats were randomly allocated into six groups: 1, normal saline topical application; 2, azelaic acid (100 mg/flap); 3, finasteride (1 mg/flap); 4, injection of L-NG-nitroarginine methyl ester (L-NAME) (i.p., 20 mg/kg); 5, L-NAME (20 mg/kg, i.p.) + azelaic acid (100 mg/flap, topical); 6, L-NAME (20 mg/kg, i.p.) + finasteride (1 mg/flap, topical). Tissue survival, level of nitric oxide, and iNOS expression in groups were measured. Results: Our data revealed that azelaic acid and finasteride significantly increased the expression of iNOS protein and nitric oxide (NO) levels in graft tissue (P < 0.05). These increases in iNOS expression and NO level were associated with higher survival of the graft tissue. Conclusion: It appears that alterations of the NO metabolism are implicated in the azelaic acid- and finasteride-mediated survival of the skin flaps. PMID:25864816

Domestic airborne black carbon and exhaled nitric oxide in children in NYC

PubMed Central

Cornell, Alexandra G.; Chillrud, Steven N.; Mellins, Robert B.; Acosta, Luis M.; Miller, Rachel L.; Quinn, James W.; Yan, Beizhan; Divjan, Adnan; Olmedo, Omar E.; Lopez-Pintado, Sara; Kinney, Patrick L.; Perera, Frederica P.; Jacobson, Judith S.; Goldstein, Inge F.; Rundle, Andrew G.; Perzanowski, Matthew S.

2012-01-01

Differential exposure to combustion by-products and allergens may partially explain the marked disparity in asthma prevalence (3%–18%) among New York City neighborhoods. Subclinical changes in airway inflammation can be measured by fractional exhaled nitric oxide (FeNO). FeNO could be used to test independent effects of these environmental exposures on airway inflammation. Seven and eight year-old children from neighborhoods with lower (range 3–9%, n=119) and higher (range 11–18%, n=121) asthma prevalence participated in an asthma case-control study. During home visits, FeNO was measured, and samples of bed dust (allergens) and air (black carbon) were collected. Neighborhood built-environment characteristics were assessed for the 500m surrounding participants’ homes. Airborne black carbon concentrations in homes correlated with neighborhood asthma prevalence (P<0.001) and neighborhood densities of truck routes (P<0.001) and buildings burning residual oil (P<0.001). FeNO concentrations were higher among asthmatics with compared to asthmatics without frequent wheeze (≥4 times/year) (P=0.002). FeNO concentrations correlated with domestic black carbon among children without seroatopy (P=0.012) and with dust mite allergen among children with seroatopy (P=0.020). The association between airborne black carbon in homes and both neighborhood asthma prevalence and FeNO suggest that further public health interventions on truck emissions standards and residual oil use are warranted. PMID:22377682

Nitric Oxide Induces Ca2+-independent Activity of the Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII)*

PubMed Central

Coultrap, Steven J.; Bayer, K. Ulrich

2014-01-01

Both signaling by nitric oxide (NO) and by the Ca2+/calmodulin (CaM)-dependent protein kinase II α isoform (CaMKIIα) are implicated in two opposing forms of synaptic plasticity underlying learning and memory, as well as in excitotoxic/ischemic neuronal cell death. For CaMKIIα, these functions specifically involve also Ca2+-independent autonomous activity, traditionally generated by Thr-286 autophosphorylation. Here, we demonstrate that NO-induced S-nitrosylation of CaMKIIα also directly generated autonomous activity, and that CaMKII inhibition protected from NO-induced neuronal cell death. NO induced S-nitrosylation at Cys-280/289, and mutation of either site abolished autonomy, indicating that simultaneous nitrosylation at both sites was required. Additionally, autonomy was generated only when Ca2+/CaM was present during NO exposure. Thus, generation of this form of CaMKIIα autonomy requires simultaneous signaling by NO and Ca2+. Nitrosylation also significantly reduced subsequent CaMKIIα autophosphorylation specifically at Thr-286, but not at Thr-305. A previously described reduction of CaMKII activity by S-nitrosylation at Cys-6 was also observed here, but only after prolonged (>5 min) exposure to NO donors. These results demonstrate a novel regulation of CaMKII by another second messenger system and indicate its involvement in excitotoxic neuronal cell death. PMID:24855644

Nitric oxide measurements in hTERT-RPE cells and subcellular fractions exposed to low levels of red light

NASA Astrophysics Data System (ADS)

Wigle, Jeffrey C.; Castellanos, Cherry C.; Denton, Michael L.; Holwitt, Eric A.

2014-02-01

Cells in a tissue culture model for laser eye injury exhibit increased resistance to a lethal pulse of 2.0-μm laser radiation if the cells are first exposed to 2.88 J/cm2 of red light 24 hr prior to the lethal laser exposure. Changes in expression of various genes associated with apoptosis have been observed, but the biochemical link between light absorption and gene expression remains unknown. Cytochome c oxidase (CCOX), in the electron transport chain, is the currentlyhypothesized absorber. Absorption of the red light by CCOX is thought to facilitate displacement of nitric oxide (NO) by O2 in the active site, increasing cellular respiration and intracellular ATP. However, NO is also an important regulator and mediator of numerous physiological processes in a variety of cell and tissue types that is synthesized from l-arginine by NO synthases. In an effort to determine the relative NO contributions from these competing pathways, we measured NO levels in whole cells and subcellular fractions, with and without exposure to red light, using DAF-FM, a fluorescent dye that stoichiometrically reacts with NO. Red light induced a small, but consistently reproducible, increase in fluorescence intensity in whole cells and some subcellular fractions. Whole cells exhibited the highest overall fluorescence intensity followed by (in order) cytosolic proteins, microsomes, then nuclei and mitochondria.

The Nitric Acid Oxidation of Selected Alcohols and Ketones.

ERIC Educational Resources Information Center

Field, Kurt W.; And Others

1985-01-01

Shows that nitric acid can be used as a rapid, versatile, and economical oxidant for selected organic substances. The experiments (with background information, procedures, and results provided) require one three-hour laboratory period but could serve as open-ended projects since substrates not described could be oxidized. (JN)

Modulatory role of dietary Chlorella vulgaris powder against arsenic-induced immunotoxicity and oxidative stress in Nile tilapia (Oreochromis niloticus).

PubMed

Zahran, Eman; Risha, Engy

2014-12-01

Arsenic intoxicant have long been regarded as an impending carcinogenic, genotoxic, and immunotoxic heavy metal to human and animals as well. In this respect, we evaluated biomarkers of the innate immune response and oxidative stress metabolism in gills and liver of Nile tilapia (Oreochromis niloticus) after arsenic exposure, and the protective role of Chlorella vulgaris (Ch) dietary supplementation were elucidated. Protective role of C. vulgaris (Ch), as supplementary feeds (5% and 10% of the diet) was studied in Nile tilapia (O. niloticus) against arsenic induced toxicity (NaAsO2 at 7 ppm) for 21 days exposure period. A significant down-regulation in innate immune response; including, respiratory burst, lysozyme, and bactericidal activity followed due to deliberately As(+3) exposure. Similarly, oxidative stress response; like nitric oxide (NO), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels were significantly decreased. Combined treatment of Ch and As(+3) significantly enhanced the innate immune response and antioxidant activity. Strikingly, Ch supplementation at 10% has been considered the optimum for Nile tilapia since it exhibited enhancement of innate immune response and antioxidant activity over the level 5%, and even better than that of control level. Thus, our results concluded that dietary Ch supplementation could protect Nile tilapia against arsenic induced immunosuppression and oxidative stresses. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bio-Physicochemical Interactions of Engineered Nanomaterials in in Vitro Cell Culture Model

DTIC Science & Technology

2014-10-11

are the important factors to study their toxicity . To investigate the potential role of oxidative stress as a mechanism of toxicity , reactive oxygen...of oxidative stress as a mechanism of toxicity , reactive oxygen species (ROS), nitric oxide (NO) lactate dehydrogenase (LDH) level and reduction in...potential role of oxidative stress as a mechanism of toxicity , reactive oxygen species (ROS), nitric oxide (NO), lactate dehydrogenase (LDH) level

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abraham, W.M.; Kim, C.S.; King, M.M.

The airway effects of a 4-hr exposure (via a Plexiglas hood) to 1.6 ppm nitric acid vapor were evaluated in seven normal and seven allergic sheep, i.e., animals that have a history of reacting with bronchospasm to inhalation challenge with Ascaris suum antigen. The nitric acid vapor was generated by ultrasonic nebulization of a 2% nitric acid solution. Airway effects were assessed by measuring the change in specific pulmonary flow resistance before and after a standard inhalation challenge with 2.5% carbachol aerosol. Nitric acid exposure did not produce bronchoconstriction in either group. Pre-exposure increases in specific pulmonary flow resistance aftermore » carbachol inhalation were 68% (SD+/- 13%) and 82% (SD+/- 35%) for the normal and allergic sheep, respectively. Within 24 hr, the largest post-exposure increases in specific pulmonary flow resistance for the normal and allergic sheep were 108% (SD+/- 51%(P<.06)) and 175% (SD+/- 87% (p<.02)), respectively. We conclude that a short-term exposure to nitric acid vapor at levels below the industrial threshold limit (2 ppm), produces airway hyperreactivity to aerosolized carbachol in allergic sheep.« less

Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacNaughton, W.K.; Wallace, J.L.; Cirino, G.

1989-01-01

The role that nitric oxide, an endothelium-derived relaxing factor, may play in the regulation of gastric mucosal defense was investigated by assessing the potential protective actions of this factor against the damage caused by ethanol in an ex vivo chamber preparation of the rat stomach. Topical application of glyceryl trinitrate and sodium nitroprusside, which have been shown to release nitric oxide, markedly reduced the area of 70% ethanol-induced hemorrhagic damage. Topical application of a 0.01% solution of authentic nitric oxide also significantly reduced the severity of mucosal damage. Pretreatment with indomethacin precluded the involvement of endogenous prostaglandins in the protectivemore » effects of these agents. The protective effects of NO were transient, since a delay of 5 minutes between NO administration and ethanal administration resulted in a complete loss of the protective activity. The protection against ethanol afforded by 10 ug/ml nitroprusside could be completely reversed by intravenous infusion of either 1% methylene blue or 1 mM hemoglobin, both of which inhibit vasodilation induced by nitric oxide. Intravenous infusion of 1% methylene blue significantly increased the susceptibility of the mucosa to damage induced by topical 20% ethanol.« less

Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling

As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-inducedmore » inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by “Biotin-switch” method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. - Highlights: • Flavone inhibits proliferation and induces apoptosis in MCF-7 cells. • Flavone decreases nitric oxide production by inhibiting NOS enzymatic activity in breast cancer cells. • Flavone down-regulates protein S-nitrosylation.« less

The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock.

PubMed

Ozkan, Seda; Ikizceli, Ibrahim; Sözüer, Erdoğan Mütevelli; Avşaroğullari, Levent; Oztürk, Figen; Muhtaroğlu, Sebahattin; Akdur, Okhan; Küçük, Can; Durukan, Polat

2008-10-01

To demonstrate the effect of piracetam on changes in brain tissue and serum nitric oxide levels in dogs submitted to hemorrhagic shock. The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was induced in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was induced and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment and at 60, 120 and 180 minutes for nitric oxide analysis. For histopathological examination, brain tissue samples were obtained at the end of the experiment. The observed improvement in blood pressure and pulse rates in Group III was more than in Group II. Nitric oxide levels were increased in Group I; however, no correlation between piracetam and nitric oxide levels was determined. It was seen that recovery in brain damage in Group III was greater than in the control group. Piracetam, added to the treatment, may ecrease ischemic damage in hemorrhagic shock.

Rapamycin inhibits oxidative/nitrosative stress and enhances angiogenesis in high glucose-treated human umbilical vein endothelial cells: Role of autophagy.

PubMed

Rezabakhsh, Aysa; Ahmadi, Mahdi; Khaksar, Majid; Montaseri, Azadeh; Malekinejad, Hassan; Rahbarghazi, Reza; Garjani, Alireza

2017-09-01

Chronic hyperglycemia is a potent risk factor of abnormal angiogenesis with various tissue diseases. Autophagy, as an alternative cell response, is mostly generated by a vast array of insults. Applying autophagic response contributes to normal cell retrieval circumstance during various insults. We aimed to show whether stimulation/inhibition of autophagy could reduce or exacerbate oxidative status and angiogenic potential in endothelial cells after exposure to 30mM glucose. HUVECs were incubated with the combined regime of 100nM Rapamycin and 30mM glucose over a period of 72h. The effect of rapamycin on cell viability, malondialdehyde levels, and nitric oxide were monitored by convenient assays. Intracellular ROS level was measured by flow cytometric analysis and DCFDA. HUVECs migration and angiogenic properties were assessed using scratch test and tubulogenesis assay. The expression of autophagic modulators LC3, Becline-1 and P62 was measured by using western blotting. Data showed 30mM glucose reduced cell viability, migration and in vitro tubulogenesis and level of ROS and nitric oxide were found to increased (p<0.05). Rapamycin had potential to increase cell survival and significantly decreased the total levels of oxidative stress markers after cell exposure to 30mM glucose (p<0.05). Rapamycin potentially improved the detrimental effect of 30mM glucose on cell migration and tubulogenesis capacity (p<0.05). Effective autophagic response was stimulated by rapamycin by increasing beclin-1, and the LC3-II/I ratio and reducing intracellular P62 level (p<0.05), resulting in the improvement of cell health and function. Together, rapamycin protected HUVECs from damages caused by high glucose concentration. This effect was possibly mediated by autophagy-dependent pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cucumber (Cucumis sativus L.) Nitric Oxide Synthase Associated Gene1 (CsNOA1) Plays a Role in Chilling Stress

PubMed Central

Liu, Xingwang; Liu, Bin; Xue, Shudan; Cai, Yanlinq; Qi, Wenzhu; Jian, Chen; Xu, Shuo; Wang, Ting; Ren, Huazhong

2016-01-01

Nitric oxide (NO) is a gaseous signaling molecule in plants, transducing information as a result of exposure to low temperatures. However, the underlying molecular mechanism linking NO with chilling stress is not well understood. Here, we functionally characterized the cucumber (Cucumis sativus L.) nitric oxide synthase-associated gene, NITRIC OXIDE ASSOCIATED 1 (CsNOA1). Expression analysis of CsNOA1, using quantitative real-time PCR, in situ hybridization, and a promoter::β-glucuronidase (GUS) reporter assay, revealed that it is expressed mainly in the root and shoot apical meristem (SAM), and that expression is up-regulated by low temperatures. A CsNOA1-GFP fusion protein was found to be localized in the mitochondria, and ectopic expression of CsNOA1 in the A. thaliana noa1 mutant partially rescued the normal phenotype. When overexpressing CsNOA1 in the Atnoa1 mutant under normal condition, no obvious phenotypic differences was observed between its wild type and transgenic plants. However, the leaves from mutant plant grown under chilling conditions showed hydrophanous spots and wilting. Physiology tolerance markers, chlorophyll fluorescence parameter (Fv/Fm), and electrolyte leakage, were observed to dramatically change, compared mutant to overexpressing lines. Transgenic cucumber plants revealed that the gene is required by seedlings to tolerate chilling stress: constitutive over-expression of CsNOA1 led to a greater accumulation of soluble sugars, starch, and an up-regulation of Cold-regulatory C-repeat binding factor3 (CBF3) expression as well as a lower chilling damage index (CI). Conversely, suppression of CsNOA1 expression resulted in the opposite phenotype and a reduced NO content compared to wild type plants. Those results suggest that CsNOA1 regulates cucumber seedlings chilling tolerance. Additionally, under normal condition, we took several classic inhibitors to perform, and detect endogenous NO levels in wild type cucumber seedling. The results suggest that generation of endogenous NO in cucumber leaves occurs largely independently in the (CsNOA1) and nitrate reductase (NR) pathway. PMID:27891134

Yomogin, an inhibitor of nitric oxide production in LPS-activated macrophages.

PubMed

Ryu, J H; Lee, H J; Jeong, Y S; Ryu, S Y; Han, Y N

1998-08-01

In activated macrophages the inducible form of nitric oxide synthase (i-NOS) generates high amounts of toxic mediator, nitric oxide (NO) which contributes to the circulatory failure associated with septic shock. A sesquiterpene lactone compound (yomogin) isolated from medicinal plant Artemisia princeps Pampan inhibited the production of NO in LPS-activated RAW 264.7 cells by suppressing i-NOS enzyme expression. Thus, yomogin may be a useful candidate for the development of new drugs to treat endotoxemia and inflammation accompanied by the overproduction of NO.

Effects of nitro-heterocyclic derivatives against Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes.

PubMed

Petri e Silva, Simone Carolina Soares; Palace-Berl, Fanny; Tavares, Leoberto Costa; Soares, Sandra Regina Castro; Lindoso, José Angelo Lauletta

2016-04-01

Leishmaniasis is an overlooked tropical disease affecting approximately 1 million people in several countries. Clinical manifestation depends on the interaction between Leishmania and the host's immune response. Currently available treatment options for leishmaniasis are limited and induce severe side effects. In this research, we tested nitro-heterocyclic compounds (BSF series) as a new alternative against Leishmania. Its activity was measured in Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes using MTT colorimetric assay. Additionally, we assessed the phosphatidylserine exposure by promastigotes, measured by flow cytometry, as well as nitric oxide production, measured by Griess' method. The nitro-heterocyclic compounds (BSF series) showed activity against L. (L.) infantum promastigotes, inducting the phosphatidylserine exposition by promastigotes, decreasing intracellular amastigotes and increasing oxide nitric production. The selectivity index was more prominent to Leishmania than to macrophages. Compared to amphotericin b, our compounds presented higher IC50, however the selectivity index was more specific to parasite than to amphotericin b. In conclusion, these nitro-heterocyclic compounds showed to be promising as an anti-Leishmania drug, in in vitro studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases

PubMed Central

Forte, Maurizio; Damato, Antonio; Ambrosio, Mariateresa; Puca, Annibale A.; Sciarretta, Sebastiano; Frati, Giacomo; Vecchione, Carmine

2016-01-01

Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases. PMID:27651855

Nitric oxide-induced interstrand cross-links in DNA.

PubMed

Caulfield, Jennifer L; Wishnok, John S; Tannenbaum, Steven R

2003-05-01

The DNA damaging effects of nitrous acid have been extensively studied, and the formation of interstrand cross-links have been observed. The potential for this cross-linking to occur through a common nitrosating intermediate derived from nitric oxide is investigated here. Using a HPLC laser-induced fluorescence (LIF) system, the amount of interstrand cross-link formed on nitric oxide treatment of the 5'-fluorescein-labeled oligomer ATATCGATCGATAT was determined. This self-complimentary sequence contains two 5'-CG sequences, which is the preferred site for nitrous acid-induced cross-linking. Nitric oxide was delivered to an 0.5 mM oligomer solution at 15 nmol/mL/min to give a final nitrite concentration of 652 microM. The resulting concentration of the deamination product, xanthine, in this sample was found to be 211 +/- 39 nM, using GC/MS, and the amount of interstrand cross-link was determined to be 13 +/- 2.5 nM. Therefore, upon nitric oxide treatment, the cross-link is found at approximately 6% of the amount of the deamination product. Using this system, detection of the cross-link is also possible for significantly lower doses of nitric oxide, as demonstrated by treatment of the same oligomer with NO at a rate of 18 nmol/mL/min resulting in a final nitrite concentration of 126 microM. The concentration of interstrand cross-link was determined to be 3.6 +/- 0.1 nM in this sample. Therefore, using the same dose rate, when the total nitric oxide concentration delivered drops by a factor of approximately 5, the concentration of cross-link drops by a factor of about 4-indicating a qausi-linear response. It may now be possible to predict the number of cross-links in a small genome based on the number of CpG sequences and the yield of xanthine derived from nitrosative deamination.

BIOCHEMISTRY OF MOBILE ZINC AND NITRIC OXIDE REVEALED BY FLUORESCENT SENSORS

PubMed Central

Pluth, Michael D.; Tomat, Elisa; Lippard, Stephen J.

2010-01-01

Biologically mobile zinc and nitric oxide (NO) are two prominent examples of inorganic compounds involved in numerous signaling pathways in living systems. In the past decade, a synergy of regulation, signaling, and translocation of these two species has emerged in several areas of human physiology, providing additional incentive for developing adequate detection systems for Zn(II) ions and NO in biological specimens. Fluorescent probes for both of these bioinorganic analytes provide excellent tools for their detection, with high spatial and temporal resolution. We review the most widely used fluorescent sensors for biological zinc and nitric oxide, together with promising new developments and unmet needs of contemporary Zn(II) and NO biological imaging. The interplay between zinc and nitric oxide in the nervous, cardiovascular, and immune systems is highlighted to illustrate the contributions of selective fluorescent probes to the study of these two important bioinorganic analytes. PMID:21675918

Nitric Oxide in the Crustacean Brain: Regulation of Neurogenesis and Morphogenesis in the Developing Olfactory Pathway

PubMed Central

Benton, J.L.; Sandeman, D.C.; Beltz, B.S.

2009-01-01

Nitric oxide (NO) plays major roles during development and in adult organisms. We examined the temporal and spatial patterns of nitric oxide synthase (NOS) appearance in the embryonic lobster brain to localize sources of NO activity; potential NO targets were identified by defining the distribution of NO-induced cGMP. Staining patterns are compared with NOS and cyclic 3,5 guanosine monophosphate (cGMP) distribution in adult lobster brains. Manipulation of NO levels influences olfactory glomerular formation and stabilization, as well as levels of neurogenesis among the olfactory projection neurons. In the first 2 days following ablation of the lateral antennular flagella in juvenile lobsters, a wave of increased NOS immunoreactivity and a reduction in neurogenesis occur. These studies implicate nitric oxide as a developmental architect and also support a role for this molecule in the neural response to injury in the olfactory pathway. PMID:17948307

Understanding the Latitude Structure of Nitric Oxide in the Mesosphere and Lower Thermosphere

NASA Technical Reports Server (NTRS)

Fuller-Rowell, T.J.

1997-01-01

The goal of the proposed work was to understand the latitude structure of nitric oxide in the mesosphere and lower thermosphere. The problem was portrayed by a clear difference between predictions of the nitric oxide distribution from chemical/dynamical models and data from observations made by the Solar Mesosphere Explorer (SMEE) in the early to mid eighties. The data exhibits a flat latitude structure of NO, the models tend to produce at equatorial maximum. The first task was to use the UARS-HALOE data to confirm the SME observations. The purpose of this first phase was to verify the UARS-NO structure is consistent with the SME data. The next task was to determine the cause of the discrepancy between modeled and observed nitric oxide latitude structure. The result from the final phase indicated that the latitude structure in the Photo-Electron (PE) production rate was the most important.

Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

PubMed

Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

2015-12-15

Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. Copyright © 2015 Elsevier B.V. All rights reserved.

Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries.

PubMed

Fricchione, Gregory; Stefano, George B

2005-05-01

Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

Mycobacterial glycolipids di-O-acylated trehalose and tri-O-acylated trehalose downregulate inducible nitric oxide synthase and nitric oxide production in macrophages.

PubMed

Espinosa-Cueto, Patricia; Escalera-Zamudio, Marina; Magallanes-Puebla, Alejandro; López-Marín, Luz María; Segura-Salinas, Erika; Mancilla, Raúl

2015-06-23

Tuberculosis (TB) remains a serious human health problem that affects millions of people in the world. Understanding the biology of Mycobacterium tuberculosis (Mtb) is essential for tackling this devastating disease. Mtb possesses a very complex cell envelope containing a variety of lipid components that participate in the establishment of the infection. We have previously demonstrated that di-O-acylated trehalose (DAT), a non-covalently linked cell wall glycolipid, inhibits the proliferation of T lymphocytes and the production of cytokines. In this work we show that DAT and the closely related tri-O-acylated trehalose (TAT) inhibits nitric oxide (NO) production and the inducible nitric oxide synthase (iNOS) expression in macrophages (MØ). These findings show that DAT and TAT are cell-wall located virulence factors that downregulate an important effector of the immune response against mycobacteria.

The Polar Night Nitric Oxide Experiment

NASA Image and Video Library

2017-12-08

The Polar Night Nitric Oxide or PolarNOx experiment from Virginia Tech is launched aboard a NASA Black Brant IX sounding rocket at 8:45 a.m. EST, Jan. 27, from the Poker Flat Research Range in Alaska. PolarNOx is measuring nitric oxide in the polar night sky. Nitric oxide in the polar night sky is created by auroras. Under appropriate conditions it can be transported to the stratosphere where it may destroy ozone resulting in possible changes in stratospheric temperature and wind and may even impact the circulation at Earth’s surface. Credit: NASA/Wallops/Jamie Adkins NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Nitric Oxide Ameliorates Zinc Oxide Nanoparticles Phytotoxicity in Wheat Seedlings: Implication of the Ascorbate–Glutathione Cycle

PubMed Central

Tripathi, Durgesh K.; Mishra, Rohit K.; Singh, Swati; Singh, Samiksha; Vishwakarma, Kanchan; Sharma, Shivesh; Singh, Vijay P.; Singh, Prashant K.; Prasad, Sheo M.; Dubey, Nawal K.; Pandey, Avinash C.; Sahi, Shivendra; Chauhan, Devendra K.

2017-01-01

The present study investigates ameliorative effects of nitric oxide (NO) against zinc oxide nanoparticles (ZnONPs) phytotoxicity in wheat seedlings. ZnONPs exposure hampered growth of wheat seedlings, which coincided with reduced photosynthetic efficiency (Fv/Fm and qP), due to increased accumulation of zinc (Zn) in xylem and phloem saps. However, SNP supplementation partially mitigated the ZnONPs-mediated toxicity through the modulation of photosynthetic activity and Zn accumulation in xylem and phloem saps. Further, the results reveal that ZnONPs treatments enhanced levels of hydrogen peroxide and lipid peroxidation (as malondialdehyde; MDA) due to severely inhibited activities of the following ascorbate–glutatione cycle (AsA–GSH) enzymes: ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase, and its associated metabolites ascorbate and glutathione. In contrast to this, the addition of SNP together with ZnONPs maintained the cellular functioning of the AsA–GSH cycle properly, hence lesser damage was noticed in comparison to ZnONPs treatments alone. The protective effect of SNP against ZnONPs toxicity on fresh weight (growth) can be reversed by 2-(4carboxy-2-phenyl)-4,4,5,5-tetramethyl- imidazoline-1-oxyl-3-oxide, a NO scavenger, and thus suggesting that NO released from SNP ameliorates ZnONPs toxicity. Overall, the results of the present study have shown the role of NO in the reducing of ZnONPs toxicity through the regulation of accumulation of Zn as well as the functioning of the AsA–GSH cycle. PMID:28220127

Inhibition of Cryptococcus neoformans replication by nitrogen oxides supports the role of these molecules as effectors of macrophage-mediated cytostasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alspaugh, J.A.; Granger, D.L.

Activated macrophages are able to inhibit the replication of intracellular microbes and tumor cells. In the murine system, this cytostatic effect is associated with the oxidation of L-arginine to L-citrulline, nitrite, and nitrate and is thought to be mediated by an intermediate of this reaction, possibly nitric oxide (NO.). By exposing replicating Cryptococcus neoformans cells to conditions under which NO. is chemically generated, we have observed a cytostatic effect similar to that caused by activated murine macrophages. Nitric oxide is formed as a decomposition product of nitrite salts in acidic, aqueous solutions. Although C. neoformans replicates well in the presencemore » of high nitrite concentrations at physiologic pH, its growth in acidic media can be inhibited by the addition of low concentrations of sodium nitrite. The degree of cytostasis is dependent on both the pH and the nitrite concentration of the NO. generating solution. The cytostatic effector molecule appears to be a gas since, in addition to inhibiting C. neoformans replication in solution, it is able to exert its inhibitory effect across a gas-permeable but ion-impermeable membrane. At high nitrite concentrations, a fungicidal effect occurs. We propose that the growth inhibition of C. neoformans upon exposure to chemically generated NO. or some related oxide of nitrogen represents a cell-free system simulating the cytostatic effect of activated murine macrophages.« less

Putative free radical-scavenging activity of an extract of Cineraria maritima in preventing selenite-induced cataractogenesis in Wistar rat pups

PubMed Central

Anitha, Thirugnanasambandhar Sivasubramanian; Muralidharan, Arumugam Ramachandran; Annadurai, Thangaraj; Jesudasan, Christdas Arul Nelson; Thomas, Philip Aloysius

2013-01-01

Purpose To investigate the possible free radical-scavenging activity of an extract of Cineraria maritima on selenite-induced cataractous lenses in Wistar rat pups. Methods In the present study, Wistar rat pups were divided into three experimental groups. On P10, Group I (control) rat pups received an intraperitoneal injection of 0.89% saline. Rats in groups II (selenite-challenged, untreated) and III (selenite-challenged, C. maritima treated) received a subcutaneous injection of sodium selenite (19 μmol/kg bodyweight); Group III rat pups also received an intraperitoneal injection of the extract of C. maritima (350 mg/kg bodyweight) once daily P9–14. Both eyes of each pup were examined from P16 until P30. Cytochemical localization of nitroblue tetrazolium salts and generation of superoxide, hydroxyl, and nitric oxide levels were measured. The expression of the inducible nitric oxide synthase gene was evaluated with reverse transcription-PCR. Immunoblot analysis was also performed to confirm the differential expression of the inducible nitric oxide synthase protein. Results Subcutaneous injection of sodium selenite led to severe oxidative damage in the lenticular tissues, shown by increased formation of formazan crystals, elevated generation of superoxide, hydroxyl, and nitric oxide radicals, and elevated inducible nitric oxide synthase gene and protein expression that possibly contributed to the opacification of the lens and thus cataract formation. When rat pups were treated with intraperitoneal administration of the extract of C. maritima, the generation of free radicals as well as the messenger ribonucleic acid and protein expression of inducible nitric oxide synthase were maintained at near normal levels. Conclusions The data generated by this study suggest that an ethanolic extract of C. maritima possibly prevents cataractogenesis in a rat model by minimizing free radical generation. PMID:24357923

Method for combined removal of mercury and nitrogen oxides from off-gas streams

DOEpatents

Mendelsohn, Marshall H [Downers Grove, IL; Livengood, C David [Lockport, IL

2006-10-10

A method for removing elemental Hg and nitric oxide simultaneously from a gas stream is provided whereby the gas stream is reacted with gaseous chlorinated compound to convert the elemental mercury to soluble mercury compounds and the nitric oxide to nitrogen dioxide. The method works to remove either mercury or nitrogen oxide in the absence or presence of each other.

Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis.

PubMed

Hyde, Embriette R; Andrade, Fernando; Vaksman, Zalman; Parthasarathy, Kavitha; Jiang, Hong; Parthasarathy, Deepa K; Torregrossa, Ashley C; Tribble, Gena; Kaplan, Heidi B; Petrosino, Joseph F; Bryan, Nathan S

2014-01-01

The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO) homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria.

Metagenomic Analysis of Nitrate-Reducing Bacteria in the Oral Cavity: Implications for Nitric Oxide Homeostasis

PubMed Central

Hyde, Embriette R.; Andrade, Fernando; Vaksman, Zalman; Parthasarathy, Kavitha; Jiang, Hong; Parthasarathy, Deepa K.; Torregrossa, Ashley C.; Tribble, Gena; Kaplan, Heidi B.; Petrosino, Joseph F.; Bryan, Nathan S.

2014-01-01

The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO) homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria. PMID:24670812

Associations of oxidative stress and inflammatory biomarkers with chemically-characterized air pollutant exposures in an elderly cohort

PubMed Central

Zhang, Xian; Staimer, Norbert; Gillen, Daniel L.; Tjoa, Tomas; Schauer, James J.; Shafer, Martin M.; Hasheminassab, Sina; Pakbin, Payam; Vaziri, Nosratola D.; Sioutas, Constantinos; Delfino, Ralph J.

2016-01-01

Background Exposure to air pollution has been associated with cardiorespiratory morbidity and mortality. However, the chemical constituents and pollution sources underlying these associations remain unclear. Method We conducted a cohort panel study involving 97 elderly subjects living in the Los Angeles metropolitan area. Airway and circulating biomarkers of oxidative stress and inflammation were measured weekly over 12 weeks and included, exhaled breath condensate malondialdehyde (EBC MDA), fractional exhaled nitric oxide (FeNO), plasma oxidized low-density lipoprotein (oxLDL), and plasma interleukin-6 (IL-6). Exposures included 7-day personal nitrogen oxides (NOX), daily criteria-pollutant data, five-day average particulate matter (PM) measured in three size-fractions and characterized by chemical components including transition metals, and in vitro PM oxidative potential (dithiothreitol and macrophage reactive oxygen species). Associations between biomarkers and pollutants were assessed using linear mixed effects regression models. Results We found significant positive associations of airway oxidative stress and inflammation with traffic-related air pollutants, ultrafine particles and transition metals. Positive but nonsignificant associations were observed with PM oxidative potential. The strongest associations were observed among PM variables in the ultrafine range (PM <0.18 μm). It was estimated that an interquartile increase in 5-day average ultrafine polycyclic aromatic hydrocarbons was associated with a 6.3% (95% CI: 1.1%, 11.6%) increase in EBC MDA and 6.7% (95% CI: 3.4%, 10.2%) increase in FeNO. In addition, positive but nonsignificant associations were observed between oxLDL and traffic-related pollutants, ultrafine particles and transition metals while plasma IL-6 was positively associated with 1-day average traffic-related pollutants. Conclusion Our results suggest that exposure to pollutants with high oxidative potential (traffic-related pollutants, ultrafine particles, and transition metals) may lead to increased airway oxidative stress and inflammation in elderly adults. This observation was less clear with circulating biomarkers. PMID:27336235

Off-Target Effect of Sildenafil on Postsurgical Erectile Dysfunction: Alternate Pathways and Localized Delivery System.

PubMed

Salmasi, Amirali; Lee, Geun Taek; Patel, Neal; Goyal, Ritu; Dinizo, Michael; Kwon, Young Suk; Modi, Part K; Faiena, Izak; Kim, Hee-Jin; Lee, Nara; Hannan, Johanna L; Kohn, Joachim; Kim, Isaac Yi

2016-12-01

There is no consensus on the best oral phosphodiesterase type 5 inhibitor (PDE5I) for patients undergoing penile rehabilitation after surgical nerve injury. To determine the mechanism of PDE5I on cultured neuronal cells and the effectiveness of local drug delivery using nanospheres (NSPs) to sites of nerve injury in a rat model of bilateral cavernous nerve injury (BCNI). The effects of sildenafil, tadalafil, and vardenafil on cyclic adenosine monophosphate, cyclic guanosine monophosphate, and cell survival after exposure to hypoxia and H 2 O 2 were measured in PC12, SH-SY5Y, and NTERA-2 (NT2) cell cultures. The effects of phosphodiesterase type 4 inhibitor (PDE4I) and PDE5I on neuronal cell survival were evaluated. Male rats underwent BCNI and were untreated (BCNI), immediately treated with application of empty NSPs (BCNI + NSP), NSPs containing sildenafil (Sild + NSP), or NSPs containing rolipram (Rol + NSP). Viability of neuronal cells was measured. Intracavernous pressure changes after cavernous nerve electrostimulation and expression of neurofilament, nitric oxide synthase, and actin in mid-shaft of penis were analyzed 14 days after injury. Sildenafil and rolipram significantly decreased cell death after exposure to H 2 O 2 and hypoxia in PC12, SH-SY5Y, and NT2 cells. PC12 cells did not express PDE5 and knockdown of PDE4 significantly increased cell viability in PC12, SH-SY5Y, and NT2 cells exposed to hypoxia. The ratio of intracavernous pressure to mean arterial pressure and expression of penile neurofilament, nitric oxide synthase, and actin were significantly higher in the Sild + NSP and Rol + NSP groups than in the BCNI and BCNI + NSP groups. Limitations included analysis in only two PDE families using only a single dose. Sildenafil showed the most profound neuroprotective effect compared with tadalafil and vardenafil. Sildenafil- or rolipram-loaded NSP delivery to the site of nerve injury prevented erectile dysfunction and led to increased neurofilament, nitric oxide synthase, smooth muscle content in rat penile tissue after BCNI. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Titanium Dioxide Nanoparticle Integrated Concrete: An Assessment of Nanoparticle Release When Exposed to UV Radiation and Wet Weather Conditions

DTIC Science & Technology

2016-03-23

polystyrene tubes . This procedure was repeated 30 times to simulate an annual exposure to acidic precipitation weathering. The average annual number...with diluted nitric acid in a 10 mL test tube . This sample was used for the ICP-AES analysis. The remainder of the sample solution was acid...Water at a Semiconducter Electrode. Nature 238 9. Gamer AO, Leibold E, van Ravenzwaay B. 2006. The in vitro absorption of microfine zinc oxide and

Nitric oxide

Integrated Risk Information System (IRIS)

Nitric oxide ; CASRN 10102 - 43 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

75 FR 43535 - NIH Consensus Development Conference on Inhaled Nitric Oxide Therapy for Premature Infants

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

... problems with long-term lung health, brain development, and brain function. Nitric oxide is a chemical... and brain development and function. Since its approval, researchers have examined expanding the use of...

Immunotoxicity of bisphenol S and F are similar to that of bisphenol A during zebrafish early development.

PubMed

Qiu, Wenhui; Shao, Haiyang; Lei, Penghui; Zheng, Chunmiao; Qiu, Cunxin; Yang, Ming; Zheng, Yi

2018-03-01

Bisphenol S (BPS) and bisphenol F (BPF) have been increasingly used as alternatives to bisphenol A (BPA) owing to health concerns. The present study aims to evaluate the impact of these two BPA analogs on oxidative stress and the immune system during zebrafish embryonic and larval development. Environmentally relevant levels of BPS and BPF exposure could increase reactive oxygen species (ROS) content, nitric oxide (NO) content, nitric oxide synthase (NOS) activity, and the expression of immunity-related genes in concentration dependent manners during the early developmental stages in zebrafish. At a concentration of 100 μg/L, BPS and BPF showed similar effects on the immune toxicity of zebrafish as that of BPA. Moreover, BPS and BPF induced both erα and nf-κb expression, and antagonists of estrogen receptor and NF-κB blocked the effects on immunity-related gene expression, providing evidence that the two pathways mediate the actions of BPS and BPF on fish immune response and functions. Thus we conclude that the presence of BPS and BPF in the environment, similar to BPA, may also pose risks to ecosystem and human health and cannot be widely used without limitations and precautions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of intermittent fasting on age-related changes on Na,K-ATPase activity and oxidative status induced by lipopolysaccharide in rat hippocampus.

PubMed

Vasconcelos, Andrea Rodrigues; Kinoshita, Paula Fernanda; Yshii, Lidia Mitiko; Marques Orellana, Ana Maria; Böhmer, Ana Elisa; de Sá Lima, Larissa; Alves, Rosana; Andreotti, Diana Zukas; Marcourakis, Tania; Scavone, Cristoforo; Kawamoto, Elisa Mitiko

2015-05-01

Chronic neuroinflammation is a common characteristic of neurodegenerative diseases, and lipopolysaccharide (LPS) signaling is linked to glutamate-nitric oxide-Na,K-ATPase isoforms pathway in central nervous system (CNS) and also causes neuroinflammation. Intermittent fasting (IF) induces adaptive responses in the brain that can suppress inflammation, but the age-related effect of IF on LPS modulatory influence on nitric oxide-Na,K-ATPase isoforms is unknown. This work compared the effects of LPS on the activity of α1,α2,3 Na,K-ATPase, nitric oxide synthase gene expression and/or activity, cyclic guanosine monophosphate, 3-nitrotyrosine-containing proteins, and levels of thiobarbituric acid-reactive substances in CNS of young and older rats submitted to the IF protocol for 30 days. LPS induced an age-related effect in neuronal nitric oxide synthase activity, cyclic guanosine monophosphate, and levels of thiobarbituric acid-reactive substances in rat hippocampus that was linked to changes in α2,3-Na,K-ATPase activity, 3-nitrotyrosine proteins, and inducible nitric oxide synthase gene expression. IF induced adaptative cellular stress-response signaling pathways reverting LPS effects in rat hippocampus of young and older rats. The results suggest that IF in both ages would reduce the risk for deficits on brain function and neurodegenerative disorders linked to inflammatory response in the CNS. Copyright © 2015 Elsevier Inc. All rights reserved.

Gene variations of nitric oxide synthase regulate the effects of a saturated fat rich meal on endothelial function

USDA-ARS?s Scientific Manuscript database

Objective: Endothelial nitric oxide synthase gene variations have been linked to a higher risk for cardiovascular diseases by unknown mechanisms. Our aim was to determine if two SNPs located in NOS3 (E298D and i19342) interfere with microvascular endothelial function (MEF) and/or oxidative stress du...

Real time and in vivo monitoring of nitric oxide by electrochemical sensors--from dream to reality.

PubMed

Zhang, Xueji

2004-09-01

Nitric oxide is a key intercellular messenger in the human and animal bodies. The identification of nitric oxide (NO) as the endothelium-derived relaxing factor (EDRF) has driven an enormous effort to further elucidate the chemistry, biology and therapeutic actions of this important molecule. It has found that nitric oxide is involved in many disease states such as such as chronic heart failure, stroke, impotent (erectile dysfunction). The bioactivity of nitric oxide intrinsically linked to its diffusion from its site production to the sites of action. Accurate reliable in real time detection of NO in various biological systems is therefore crucial to understanding its biological role. However, the instability of NO in aqueous solution and its high reactivity with other molecules can cause difficulties for its measurement depending on the detection method employed. Although a variety of methods have been described to measure NO in aqueous environments, it is now generally accepted that electrochemical (amperometric) detection using NO-specific electrodes is the most reliable and sensitive technique available for real-time in situ detection of NO. In 1992 the first commercial NO electrode-based amperometric detection system was developed by WPI. The system has been used successfully for a number of years in a wide range of research applications, both in vitro and in vivo. Recently, many new electrochemical nitric sensors have been invented and commercialized. Here we describe some of the background principles in NO sensors design, methodology and their applications.

Decomposition of nitric oxide in a hot nitrogen stream to synthesize air for hypersonic wind tunnel combustion testing

NASA Technical Reports Server (NTRS)

Zumdieck, J. F.; Zlatarich, S. A.

1974-01-01

A clean source of high enthalpy air was obtained from the exothermic decomposition of nitric oxide in the presence of strongly heated nitrogen. A nitric oxide jet was introduced into a confined coaxial nitrogen stream. Measurements were made of the extent of mixing and reaction. Experimental results are compared with one- and two-dimensional chemical kinetics computations. Both analyses predict much lower reactivity than was observed experimentally. Inlet nitrogen temperatures above 2400 K were sufficient to produce experimentally a completely reacted gas stream of synthetic air.

In vitro inducible nitric oxide synthesis inhibitory active constituents from Fraxinus rhynchophylla.

PubMed

Kim, N Y; Pae, H O; Ko, Y S; Yoo, J C; Choi, B M; Jun, C D; Chung, H T; Inagaki, M; Higuchi, R; Kim, Y C

1999-10-01

Bioassay-guided fractionation of an H2O extract of the barks of Fraxinus rhynchophylla has furnished two inducible nitric oxide synthase (iNOS) inhibitory compounds, ferulaldehyde (1) and scopoletin (3) together with a coumarin, fraxidin (2). Compounds 1 and 3 showed inhibition of nitric oxide (NO) synthesis in a dose-dependent manner by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). The inhibition of NO synthesis of 1 was reflected in the decreased amount of iNOS protein, as determined by Western blotting.

Thiopental inhibits nitric oxide production in rat aorta.

PubMed

Castillo, C; Asbun, J; Escalante, B; Villalón, C M; López, P; Castillo, E F

1999-12-01

We studied whether thiopental affects endothelial nitric oxide dependent vasodilator responses and nitrite production (an indicator of nitric oxide production) elicited by acetylcholine, histamine, and A23187 in rat aorta (artery in which nitric oxide is the main endothelial relaxant factor). In addition, we evaluated the barbiturate effect on nitric oxide synthase (NOS) activity in both rat aorta and kidney homogenates. Thiopental (10-100 microg/mL) reversibly inhibited the endothelium-dependent relaxation elicited by acetylcholine, histamine, and A23187. On the contrary, this anesthetic did not modify the endothelium-independent but cGMP-dependent relaxation elicited by sodium nitroprusside (1 nM - 1 microM) and nitroglycerin (1 nM - 1 microM), thus excluding an effect of thiopental on guanylate cyclase of vascular smooth muscle. Thiopental (100 microg/mL) inhibited both basal (87.8+/-14.3%) and acetylcholine- or A23187-stimulated (78.6+/-3.9 and 39.7+/-5.6%, respectively) production of nitrites in aortic rings. In addition the barbiturate inhibited (100 microg/mL) the NOS (45+/-4 and 42.8+/-9%) in aortic and kidney homogenates, respectively (measured as 14C-labeled citrulline production). In conclusion, thiopental inhibition of endothelium-dependent relaxation and nitrite production in aortic rings strongly suggests an inhibitory effect on NOS. Thiopental inhibition of the NOS provides further support to this contention.

The Effect of Vitamin D3 Alone and Mixed With IFN-γ on Tachyzoites of Toxoplasma gondii (RH Strain) Proliferation and Nitric Oxide (NO) Production in Infected Macrophages of BALB/C Mice.

PubMed

Ghaffarifar, F; Abdolah Pour, M; Sharifi, Z; Dalimi Asl, A; Al-Kawaz, E

2010-09-01

Toxoplasma gondii is an obligatory interacelullar parasite that infects nucleated cells in its intermediate hosts. The aim of the present study was to determine the effect of vitamin D3 on the multiplication of T. gondii in peritoneal macrophage of Balb/c mice and nitric oxide production by macrophages. According to usage of vitamin D3 (one dose or seven doses) and INFγ in vitro and in vivo, this study was divided into four experiments. In all experiments, the macrophages were collected from peritoneum and cultured in RPMI-1640. Then the supernatants were collected after 24 h and their nitric oxide was measure. After 96 h, the macrophages were collected and stained and the number of tachyzoites was measured. The first experiment (the mice were infected with tachyzoites and after 2 h, got one dose vitamin D3 intraperitonealy) showed the best results. The mean of tachyzoites per macrophages was 2.37, and mean±SD of nitric oxide was 187.8±9. High-level production of nitric oxide may be related to the only one injection of vitamin D3. The injection in long time might suppress the immune system.

A variant of the endothelial nitric oxide synthase gene (NOS3) associated with AMS susceptibility is less common in the Quechua, a high altitude Native population.

PubMed

Wang, Pei; Ha, Alice Y N; Kidd, Kenneth K; Koehle, Michael S; Rupert, Jim L

2010-01-01

Endothelial nitric oxide synthase (eNOS) is a vascular enzyme that produces nitric oxide, a transient signaling molecule that by vasodilatation regulates blood flow and pressure. Nitric oxide is believed to play roles in both short-term acclimatization and long-term evolutionary adaptation to environmental hypoxia. Several laboratories, including ours, have shown that variants in NOS3 (the gene encoding eNOS) are overrepresented in individuals with altitude-related illnesses such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS), suggesting that NOS3 genotypes contribute to altitude tolerance. To further test our hypothesis that the G allele at the G894T polymorphism in NOS3 (dbSNP number: rs1799983; protein polymorphism Glu298Asp) is beneficial in hypoxic environments, we compared frequencies of this allele in an altitude-adapted Amerindian population, Quechua of the Andean altiplano, with those in a lowland Amerindian population, Maya of the Yucatan Peninsula. While common in both populations, the G allele was significantly more frequent in the highlanders. Taken together, our data suggest that this variant in NOS3, which has been previously associated with higher levels of nitric oxide, contributes to both acclimatization and adaptation to altitude.

Expression of the Nitric Oxide Synthase 2 Gene Is Not Essential for Early Control of Mycobacterium tuberculosis in the Murine Lung

PubMed Central

Cooper, Andrea M.; Pearl, John E.; Brooks, Jason V.; Ehlers, Stefan; Orme, Ian M.

2000-01-01

The interleukin-12 and gamma interferon (IFN-γ) pathway of macrophage activation plays a pivotal role in controlling tuberculosis. In the murine model, the generation of supplementary nitric oxide by the induction of the nitric oxide synthase 2 (NOS2) gene product is considered the principal antimicrobial mechanism of IFN-γ-activated macrophages. Using a low-dose aerosol-mediated infection model in the mouse, we have investigated the role of nitric oxide in controlling Mycobacterium tuberculosis in the lung. In contrast to the consequences of a systemic infection, a low dose of bacteria introduced directly into the lungs of mice lacking the NOS2 gene is controlled almost as well as in intact animals. This is in contrast to the rapid progression of disease in mice lacking IFN-γ or a key member of the IFN signaling pathway, interferon regulatory factor 1. Thus while IFN-γ is pivotal in early control of bacterial growth in the lung, this control does not completely depend upon the expression of the NOS2 gene. The absence of inducible nitric oxide in the lung does, however, result in increased polymorphonuclear cell involvement and eventual necrosis in the pulmonary granulomas of the infected mice lacking the NOS2 gene. PMID:11083808

Isosorbide 5 mononitrate administration increases nitric oxide blood levels and reduces proteinuria in IgA glomerulonephritis patients with abnormal urinary endothelin/cyclic GMP ratio.

PubMed

Roccatello, D; Mengozzi, G; Ferro, M; Cesano, G; Polloni, R; Mosso, R; Bonetti, G; Inconis, T; Paradisi, L; Sena, L M

1995-09-01

An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by electron paramagnetic resonance, significantly increased after isosorbide administration (p < 0.01) and decreased after drug discontinuation in both groups. Nitric oxide levels were significantly related with those of the effective renal plasma flow (p < 0.02), but not with the glomerular filtration rate. Proteinuria levels significantly decreased after drug administration (p < 0.009) in group 1 and returned to baseline levels thereafter, except two cases showing persisting low levels. Values of filtration fraction in the same group decreased after iso5M administration (p < 0.02 compared to basal levels). These results may possibly be related to the counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.

Modulation of the behavioral and electrical responses to the repellent DEET elicited by the pre-exposure to the same compound in Blattella germanica

PubMed Central

Mougabure-Cueto, Gastón A.; González-Audino, Paola A.

2016-01-01

Insects under different stimuli from the environment modify behavioural responses due to changes in the sensitivity of neurons at the peripheral and/or at the central level of the nervous system. This phenomenon is called neuronal plasticity, and sensory adaptation is an example of it. An insect repellent is a chemical that produces oriented movements of the insects away from its source. In this work we studied the modulation of the behavioural and electrical response to the repellent N, N-diethyl-3-methylbenzamide (DEET) in males of the German cockroach B. germanica produced by previous exposure to the same repellent. Methods. We determined repellency using a circular arena, one half of which was treated with DEET. The time spent by insects in each half of the arena was measured, and a repellency coefficient (RC) was calculated. The RCs of pre-exposed and non-pre-exposed insects were compared. To determine a possible role of nitric oxide in the modulation of the response to DEET after pre-exposure, the nitric oxide donor S-nitroso-acetyl-cysteine (SNAC) was applied on cockroaches’ antennae. The electrical activity of the cockroaches’ antennae in response to DEET was recorded using electroantennogram (EAG) technique. The response to DEET was recorded also after a long stimulation with the same repellent, and after topical application of SNAC and dbcGMP (a cGMP analogue) on the antennae. Results. We found that previous exposure of B. germanica males to the repellent DEET produced an increase of the repellency at the behavioural level, measured as RC. A possible role of nitric oxide (NO) in the transduction pathway of this phenomenon is suggested, since treatment of the cockroaches with the NO donor SNAC also produced an increase of the repellency elicited by DEET. On the other hand, the response of the cockroaches’ antennae exposed to DEET was determined electrophysiologically. The electrical activity in response to DEET decreased when the insects’ antennae were stimulated with a long pulse of the repellent. The activity of the antennae was restored after 10 min. Treatment of the antennae either with SNAC or dbGMPc also produced a decrease in the response of the antennae to the repellent. Discussion.The previous exposure to a chemical stimulus can modify the behaviour associated to the same stimulus, increasing or decreasing the behavioural response. In the case of DEET we found that pre-exposure increased DEET repellency in male cockroaches. We also found NO involvement in a similar phenomenon. On the other hand, the test showed that DEET is perceived by insects’ antennae as an odour. A long exposure of the antennae to DEET caused a transient decrease in the response of the antennae to the same compound. The same effect was achieved by treating the antennae with SNAC or dbcGMP, suggesting the involvement of the NO/cGMP system in the transduction pathway of the sensory adaptation phenomenon elicited by an odour in this species. PMID:27375967

Modulation of the behavioral and electrical responses to the repellent DEET elicited by the pre-exposure to the same compound in Blattella germanica.

PubMed

Sfara, Valeria; Mougabure-Cueto, Gastón A; González-Audino, Paola A

2016-01-01

Insects under different stimuli from the environment modify behavioural responses due to changes in the sensitivity of neurons at the peripheral and/or at the central level of the nervous system. This phenomenon is called neuronal plasticity, and sensory adaptation is an example of it. An insect repellent is a chemical that produces oriented movements of the insects away from its source. In this work we studied the modulation of the behavioural and electrical response to the repellent N, N-diethyl-3-methylbenzamide (DEET) in males of the German cockroach B. germanica produced by previous exposure to the same repellent. Methods. We determined repellency using a circular arena, one half of which was treated with DEET. The time spent by insects in each half of the arena was measured, and a repellency coefficient (RC) was calculated. The RCs of pre-exposed and non-pre-exposed insects were compared. To determine a possible role of nitric oxide in the modulation of the response to DEET after pre-exposure, the nitric oxide donor S-nitroso-acetyl-cysteine (SNAC) was applied on cockroaches' antennae. The electrical activity of the cockroaches' antennae in response to DEET was recorded using electroantennogram (EAG) technique. The response to DEET was recorded also after a long stimulation with the same repellent, and after topical application of SNAC and dbcGMP (a cGMP analogue) on the antennae. Results. We found that previous exposure of B. germanica males to the repellent DEET produced an increase of the repellency at the behavioural level, measured as RC. A possible role of nitric oxide (NO) in the transduction pathway of this phenomenon is suggested, since treatment of the cockroaches with the NO donor SNAC also produced an increase of the repellency elicited by DEET. On the other hand, the response of the cockroaches' antennae exposed to DEET was determined electrophysiologically. The electrical activity in response to DEET decreased when the insects' antennae were stimulated with a long pulse of the repellent. The activity of the antennae was restored after 10 min. Treatment of the antennae either with SNAC or dbGMPc also produced a decrease in the response of the antennae to the repellent. Discussion.The previous exposure to a chemical stimulus can modify the behaviour associated to the same stimulus, increasing or decreasing the behavioural response. In the case of DEET we found that pre-exposure increased DEET repellency in male cockroaches. We also found NO involvement in a similar phenomenon. On the other hand, the test showed that DEET is perceived by insects' antennae as an odour. A long exposure of the antennae to DEET caused a transient decrease in the response of the antennae to the same compound. The same effect was achieved by treating the antennae with SNAC or dbcGMP, suggesting the involvement of the NO/cGMP system in the transduction pathway of the sensory adaptation phenomenon elicited by an odour in this species.

Oral treatment with herbal formula B401 alleviates penile toxicity in aging mice with manganism.

PubMed

Hsu, Chih-Hsiang; Lin, Ching-Lung; Wang, Sheue-Er; Sheu, Shuenn-Jyi; Chien, Chiang-Ting; Wu, Chung-Hsin

2015-01-01

The present study aims to elucidate the roles of nitric oxide synthase activity, oxidative stress, inflammation, and apoptosis in penile toxicity of aging mice associated with excess manganese (Mn) treatment and to investigate the effect of oral treatment with the herbal formula B401 in this respect. ICR strain mice were divided into two groups: the vehicle (sham group) and the B401 (50 mg/kg) group. The mice were orally treated for 5 days; then a high single dose of MnCl2 (100 mg/kg) was given by intraperitoneal injection to the mice. One day after MnCl2 treatment, corpora cavernosal tissues of both Mn-treated mice and their controls were simultaneously sampled to examine their immunohistochemical staining and Western blot analysis. Nitric oxide (NO) production, levels of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), expression levels of factors governing angiogenesis (vascular endothelial growth factor), oxidative stress (catalase, superoxide dismutase 2,4-hydroxynonenal), inflammation (tumor necrosis factor alpha), apoptosis (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein [Bax], cleaved poly(adenosine diphosphate-ribose) polymerase [c-PARP], cytochrome C, caspase-12, and caspase-3) were evaluated in penile corpus cavernosum of the mice. We found that penile toxicity in the mice was enhanced under excess Mn treatment through reduction of NOS activity and increase in oxidative stress, inflammation, and apoptosis in the penile cavernous tissue. Furthermore, the penile toxicity in mice with manganism was alleviated by oral B401 treatment through enhancement of both nitric oxide synthesis and angiogenesis, with simultaneous reduction of oxidative stress, inflammation, and apoptosis in penile corpus cavernosum. We suggest that the herbal formula B401 may serve as a potential dietotherapeutic supplement for penile toxicity or dysfunction in aging males.

Current Practices and Attitudes Regarding Use of Inhaled Nitric Oxide in the NICU

PubMed Central

Kayton, Allyson; Timoney, Paula; Vargo, Lyn; Perez, Jose A.

2018-01-01

Background: Excessive supplemental oxygen exposure in the neonatal intensive care unit (NICU) can be associated with oxygen-related toxicities, which can lead to negative clinical consequences. Use of inhaled nitric oxide (iNO) can be a successful strategy for avoiding hyperoxia in the NICU. iNO selectively produces pulmonary vasodilation and has been shown to improve oxygenation parameters across the spectrum of disease severity, from mild to very severe, in neonates with hypoxic respiratory failure associated with persistent pulmonary hypertension of the newborn. Purpose: An online survey was conducted among members of the National Association of Neonatal Nurse Practitioners to gain insight into the level of understanding and knowledge among neonatal nurse practitioners (NNPs) about optimizing supplemental oxygen exposure and the use of iNO in the NICU setting. Results: Of 937 NNP respondents, 51% reported that their healthcare team typically waits until the fraction of inspired oxygen level is 0.9 or more before adding iNO in patients not responding to oxygen ventilation alone. Among respondents with 1 or more iNO-treated patients per month, only 35% reported they know the oxygenation index level at which iNO should be initiated. Less than 20% of NNPs reported perceived benefits associated with early initiation of iNO for preventing progression to use of extracorporeal membrane oxygenation or reducing the length of hospital stay, and about one-third of respondents reported they believe early iNO use minimizes hyperoxia. Implications for Practice: More education is needed for NNPs regarding the negative effects of oxidative stress in neonates. Implications for Research: Additional clinical trials investigating the most beneficial strategies for avoiding neonatal hyperoxia are warranted. PMID:29465446

Cinnamon extract ameliorates ionizing radiation-induced cellular injury in rats.

PubMed

Azab, Khaled Sh; Mostafa, Abdel-Halem A; Ali, Ehab M M; Abdel-Aziz, Mohamed A S

2011-11-01

The present study aimed to investigate the protective role of cinnamon extract against inflammatory and oxidative injuries in gamma irradiated rats. Rats were subjected to fractionated doses of gamma radiation. Cinnamon extract were daily administrated before starting irradiation and continued after radiation exposure. The results obtained revealed that the administration of cinnamon extract to irradiated rats significantly ameliorated the changes induced in liver antioxidant system; catalase, superoxide dismutase and glutathione peroxidase activities as well as reduced glutathione concentration. The liver's lipid peroxidation and protein oxidation indices were significantly decreased when compared with their equivalent values in irradiated rats. Furthermore, the changes induces in xanthine oxidoreductase system were significantly diminished. In addition, the changes in liver nitric oxide contents, serum tumor necrosis factor alpha and C-reactive protein levels were markedly improved. In conclusion, the administration of cinnamon extract might provide substantial protection against radiation-induced oxidative and inflammatory damages. Copyright © 2011 Elsevier Inc. All rights reserved.

Nitric oxide mediates insect cellular immunity via phospholipase A2 activation

USDA-ARS?s Scientific Manuscript database

After infection or invasion is recognized, biochemical mediators act in signaling insect immune functions. These include biogenic amines, insect cytokines, eicosanoids and nitric oxide (NO). Treating insects or isolated hemocyte populations with different mediators often leads to similar results. Se...

Arginine, citrulline and nitric oxide metabolism in sepsis

USDA-ARS?s Scientific Manuscript database

Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

BIOGENIC NITRIC OXIDE EMISSIONS FROM CROPLAND SOILS

EPA Science Inventory

Emissions of nitric oxide (NO) were determined during late spring and summer 1995 and the spring of 1996 from four agricultural soils on which four different crops were grown. These agricultural soils were located at four different sites throughout North Carolina. Emission rates ...

Swimming pool exposure is associated with autonomic changes and increased airway reactivity to a beta-2 agonist in school aged children: A cross-sectional survey.

PubMed

Cavaleiro Rufo, João; Paciência, Inês; Silva, Diana; Martins, Carla; Madureira, Joana; Oliveira Fernandes, Eduardo de; Padrão, Patrícia; Moreira, Pedro; Delgado, Luís; Moreira, André

2018-01-01

Endurance swimming exercises coupled to disinfection by-products exposure has been associated with increased airways dysfunction and neurogenic inflammation in elite swimmers. However, the impact of swimming pool exposure at a recreational level on autonomic activity has never been explored. Therefore, this study aimed to investigate how swimming pool attendance is influencing lung and autonomic function in school-aged children. A total of 858 children enrolled a cross sectional survey. Spirometry and airway reversibility to beta-2 agonist, skin-prick-tests and exhaled nitric oxide measurements were performed. Pupillometry was used to evaluate autonomic nervous function. Children were classified as current swimmers (CS), past swimmers (PS) and non-swimmers (NS), according to the amount of swimming practice. Current swimmers group had significantly lower maximum and average pupil constriction velocities when compared to both PS and NS groups (3.8 and 5.1 vs 3.9 and 5.3 vs 4.0 and 5.4 mm/s, p = 0.03 and p = 0.01, respectively). Moreover, affinity to the beta-2 agonist and levels of exhaled nitric oxide were significantly higher in CS when compared to NS (70 vs 60 mL and 12 vs 10 ppb, p<0.01 and p = 0.03, respectively). A non-significant trend for a higher risk of asthma, atopic eczema and allergic rhinitis was found with more years of swimming practice, particularly in atopic individuals (β = 1.12, 1.40 and 1.31, respectively). After case-case analysis, it was possible to observe that results were not influenced by the inclusion of individuals with asthma. Concluding, swimming pool attendance appears to be associated with autonomic changes and increased baseline airway smooth muscle constriction even in children without asthma.

Longitudinal effects of air pollution on exhaled nitric oxide: the Children's Health Study.

PubMed

Berhane, Kiros; Zhang, Yue; Salam, Muhammad T; Eckel, Sandrah P; Linn, William S; Rappaport, Edward B; Bastain, Theresa M; Lurmann, Fred; Gilliland, Frank D

2014-07-01

To assess the effects of long-term variations in ambient air pollutants on longitudinal changes in exhaled nitric oxide (FeNO), a potentially useful biomarker of eosinophilic airway inflammation, based on data from the southern California Children's Health Study. Based on a cohort of 1211 schoolchildren from eight Southern California communities with FeNO measurements in 2006-2007 and 2007-2008, regression models adjusted for short-term effects of air pollution were fitted to assess the association between changes in annual long-term exposures and changes in FeNO. Increases in annual average concentrations of 24-h average NO2 and PM2.5 (scaled to the IQR of 1.8 ppb and 2.4 μg/m(3), respectively) were associated with a 2.29 ppb (CI 0.36 to 4.21; p=0.02) and a 4.94 ppb (CI 1.44 to 8.47; p=0.005) increase in FeNO, respectively, after adjustments for short-term effects of the respective pollutants. In contrast, changes in annual averages of PM10 and O3 were not significantly associated with changes in FeNO. These findings did not differ significantly by asthma status. Changes in annual average exposure to current levels of ambient air pollutants are significantly associated with changes in FeNO levels in children, independent of short-term exposures and asthma status. Use of this biomarker in population-based epidemiological research has great potential for assessing the impact of changing real world mixtures of ambient air pollutants on children's respiratory health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Antimicrobial efficacy and wound-healing property of a topical ointment containing nitric-oxide-loaded zeolites

PubMed Central

Ercan, Utku K.; Bhattacharyya, Aparna; Samuels, Joshua; Sedlak, Jason; Trikha, Ritika; Barbee, Kenneth A.; Weingarten, Michael S.

2014-01-01

Topical delivery of nitric oxide (NO) through a wound dressing has the potential to reduce wound infections and improve healing of acute and chronic wounds. This study characterized the antibacterial efficacy of an ointment containing NO-loaded, zinc-exchanged zeolite A that releases NO upon contact with water. The release rate of NO from the ointment was measured using a chemiluminescence detection system. Minimum bactericidal concentration assays were performed using five common wound pathogens, including Gram-negative bacteria (Escherichia coli and Acinetobacter baumannii), Gram-positive bacteria (Staphylococcus epidermidis and meticillin-resistant Staphylococcus aureus) and a fungus (Candida albicans). The time dependence of antimicrobial activity was characterized by performing log-reduction assays at four time points after 1–8 h ointment exposure. The cytotoxicity of the ointment after 24 h was assessed using cultured 3T3 fibroblast cells. Minimum microbicidal concentrations (MMCs) for bacterial organisms (5×107 c.f.u.) ranged from 50 to 100 mg ointment (ml media)−1; the MMC for C. albicans (5×104 c.f.u.) was 50 mg ointment (ml media)−1. Five to eight log reductions in bacterial viability and three log reductions in fungal viability were observed after 8 h exposure to NO–zeolite ointment compared with untreated organisms. Fibroblasts remained viable after 24 h exposure to the same concentration of NO–zeolite ointment as was used in antimicrobial tests. In parallel studies, full-thickness cutaneous wounds on Zucker obese rats healed faster than wounds treated with a control ointment. These data indicate that ointment containing NO-loaded zeolites could potentially be used as a broad-spectrum antimicrobial wound-healing dressing. PMID:24196133

Coronary endothelial function and vascular smooth muscle proliferation are programmed by early-gestation dexamethasone exposure in sheep

PubMed Central

Volk, Kenneth A.; Roghair, Robert D.; Jung, Felicia; Scholz, Thomas D.; Lamb, Fred S.

2010-01-01

Exposure of the early-gestation ovine fetus to exogenous glucocorticoids induces changes in postnatal cardiovascular physiology. We sought to characterize coronary artery vascular function in this model by elucidating the contribution of nitric oxide and reactive oxygen species to altered coronary vascular reactivity and examining the proliferative potential of coronary artery vascular smooth muscle cells. Dexamethasone (dex, 0.28 mg·kg−1·day−1 for 48 h) was administered to pregnant ewes at 27–28-day gestation (term 145 days). Coronary arteries were isolated from 1- to 2-wk-old dex-exposed offspring and aged-matched controls. Compared with controls, coronary arteries from dex-exposed lambs demonstrated enhanced vasoconstriction to endothelin-1 and ACh that was abolished by endothelial removal or preincubation with the nitric oxide synthase inhibitor l-NNA, membrane-permeable superoxide dismutase + catalase, or apamin + charybdotoxin, but not indomethacin. The rate of coronary vascular smooth muscle cell (VSMC) proliferation was also significantly greater in dex-exposed lambs. Protein levels of the proliferating cell nuclear antigen were increased and α-smooth muscle actin decreased in dex-exposed coronary VSMC, consistent with a proliferative state. Finally, expression of the NADPH oxidase Nox 4, but not Nox 1, mRNA was also decreased in coronary VSMC from dex-exposed lambs. These findings suggest an important interaction exists between early-gestation glucocorticoid exposure and reactive oxygen species that is associated with alterations in endothelial function and coronary VSMC proliferation. These changes in coronary physiology are consistent with those associated with the development of atherosclerosis and may provide an important link between an adverse intrauterine environment and increased risk for coronary artery disease. PMID:20335378

Effect of streptavidin-biotin on endothelial vasoregulation and leukocyte adhesion.

PubMed

Chan, Bernard P; Reichert, William M; Truskey, George A

2004-08-01

The current study examines whether the adhesion promoting arginine-glycine-aspartate-streptavidin mutant (RGD-SA) also affects two important endothelial cell (EC) functions in vitro: vasoregulation and leukocyte adhesion. EC adherent to surfaces via fibronectin (Fn) or Fn plus RGD-SA were subjected to laminar shear flow and media samples were collected over a period of 4h to measure the concentration of nitric oxide (NO), prostacyclin (PGI(2)), and endothelin-1 (ET-1). Western blot analysis was used to quantify the levels of endothelial-derived nitric oxide synthase (eNOS) and cyclooxygenase II (COX II). In a separate set of experiments, fluorescent polymorphonuclear leukocyte (PMN) adhesion to EC was quantified for EC with and without exposure to flow preconditioning. When cell adhesion was supplemented with the SA-biotin system, flow-induced production of NO and PGI(2) increased significantly relative to cells adherent on Fn alone. Previous exposure of EC to shear flow also significantly decreased PMN attachment to SA-biotin supplemented EC, but only after 2h of exposure to shear flow. The observed decrease in PMN-EC adhesion was negated by NG-nitro-L-arginine methyl ester (L-NAME), an antagonist of NO synthesis, but not by indomethacin, an inhibitor to PGI(2) synthesis, indicating the induced effect of PMN-EC interaction is primarily NO-dependent. Results from this study suggest that the use of SA-biotin to supplement EC adhesion encourages vasodilation and PMN adhesion in vitro under physiological shear-stress conditions. We postulate that the presence of SA-biotin more efficiently transmits the shear-stress signal and amplifies the downstream events including the NO and PGI(2) release and leukocyte-EC inhibition. These results may have ramifications for reducing thrombus-induced vascular graft failure.

Nitric oxide, can it be only good? Increasing the antioxidant properties of nitric oxide in hepatocytes by YC-1 compound.

PubMed

Aharoni-Simon, Michal; Anavi, Sarit; Beifuss, Uwe; Madar, Zecharia; Tirosh, Oren

2012-12-01

The aim of the study was to evaluate the effect of Nitric oxide (NO) on redox changes and fat accumulation in hepatocytes. AML-12 hepatocytes were exposed to the NO donor Diethylenetriamine-NONOate (DETA-NO). DETA-NO led to a dose- and time-dependent increase in lipid accumulation in the cells, measured by Nile red fluorescence. Exposure of the cells to 1mM DETA-NO for 24h increased reactive oxygen species production, mainly peroxides. At the same time, NO induced elevation of reduced glutathione (GSH) and a mild activation of the antioxidant transcription factors Hypoxia-inducible factor 1α (HIF1α) and NF-E2 related factor 2 (Nrf-2). We used 100 μM YC-1 to inhibit HIF1α activity and induce activation of soluble Guanylate Cyclase (sGC). YC-1 alone did not affect fat accumulation, and only moderately increased the expression of Nrf-2-targeted genes Heme oxygenase 1 (Hmox1), NAD(P)H dehydrogenase (quinone 1) (Nqo1) and Glutathione S-transferase α1 (Gstα1). However, YC-1 abolished the negative effect of NO on fat accumulation when administered together. Strikingly, YC-1 potentiated the effect of NO on Nrf-2 activation, thus increasing dramatically the antioxidant properties of NO. Moreover, YC-1 intensified the effect of NO on the expression of peroxisome-proliferator-activated receptor-gamma co-activator 1α (PGC1α) and mitochondrial biogenesis markers. This study suggests that YC-1 may shift the deleterious effects of NO into the beneficial ones, and may improve the antioxidant properties of NO. 2012 Elsevier Inc. All rights reserved

Combined effect of IL-17 and blockade of nitric oxide biosynthesis on haematopoiesis in mice.

PubMed

Krstić, A; Santibanez, J F; Okić, I; Mojsilović, S; Kocić, J; Jovcić, G; Milenković, P; Bugarski, D

2010-05-01

The study was undertaken to extend our investigation concerning both the in vivo activity of interleukin (IL)-17 and the specific role of nitric oxide (NO) in IL-17-induced effects in the process of haematopoiesis. CBA mice were simultaneously treated with IL-17 and/or nitric oxide synthase (NOS) inhibitor, l-NAME, for 5 days and changes within various haematopoietic cell lineages in bone marrow, spleen and peripheral blood were analysed. Findings showed that administration of both IL-17 and l-NAME stimulated increase in net haematopoiesis in normal mice. IL-17-enhanced myelopoiesis was characterized by stimulation of both femoral and splenic haematopoietic progenitor cells and morphologically recognizable granulocytes. Additionally, IL-17 induced alterations in the frequency of erythroid progenitor cells in both bone marrow and spleen, accompanied with their mobilization to the peripheral blood. As a consequence of these changes in the erythroid cell compartments, significant reticulocytosis was observed, which evidenced that in IL-17-treated mice effective erythropoiesis occurred. Exposure of mice to NOS inhibitor also increased the number of both granulocyte-macrophage and erythroid progenitors in bone marrow and spleens, and these alterations were followed by the mobilization of erythroid progenitors and elevated content of reticulocytes in peripheral blood. The specific role of NO in IL-17-induced haematopoiesis was demonstrated only in the IL-17-reducing effect on bone marrow late stage erythroid progenitors, CFU-E. The results demonstrated the involvement of both IL-17 and NO in the regulation of haematopoietic cell activity in various haematopoietic compartments. They further suggest that IL-17 effects are differentially mediated depending on the haematopoietic microenvironments.

Protective effects of intermittent hydrostatic pressure on osteoarthritic chondrocytes activated by bacterial endotoxin in vitro.

PubMed

Lee, Mel S; Ikenoue, Takashi; Trindade, Michael C D; Wong, Neal; Goodman, Stuart B; Schurman, David J; Smith, R Lane

2003-01-01

The role of continuous passive motion (CPM) in the management of septic arthritis and inflammatory arthritis remains of interest. CPM produces cyclic variations in intraarticular pressure that facilitates transport of fluid, nutrients, and solutes within and/or across the joint and stimulates chondrocyte metabolism. However, the precise mechanisms mediating the responses of chondrocytes to joint motion remain unclear. This study tested the hypothesis that dynamic mechanical loading counteracts effects of bacterial lipopolysaccharide (LPS), an inflammatory mediator, on chondrocyte metabolism. Intermittent hydrostatic pressure (IHP) (10 MPa for 4 h) was applied to human chondrocytes pretreated with LPS (1 microg/ml for 18 h). LPS activation of chondrocytes decreased mRNA signal levels of type II collagen by 67% and aggrecan by 56% and increased nitric oxide by 3.1-fold, monocyte chemotactic protein-1 mRNA signal levels by 6.5-fold, and matrix metalloproteinase-2 mRNA signal levels by 1.3-fold. Application of IHP to LPS-activated chondrocytes decreased nitric oxide synthase mRNA signal levels and nitric oxide levels in the culture medium. Exposure of LPS-activated chondrocytes to IHP upregulated type II collagen and aggrecan mRNA signal levels by 1.7-fold, relative to chondrocytes activated by LPS and maintained without loading. In addition, application of IHP decreased the upregulation in signal levels of monocyte chemotactic factor-1 and matrix metalloproteinase-2 following LPS activation by 45% and 15%, respectively. These data show that mechanical loading counteract effects of inflammatory agents, such as bacterial LPS, and suggest that postinfection sequelae are influenced by the presence or absence of joint loading.

The bovine paranasal sinuses: Bacterial flora, epithelial expression of nitric oxide and potential role in the in-herd persistence of respiratory disease pathogens.

PubMed

Murray, Gerard M; O'Neill, Rónan G; Lee, Alison M; McElroy, Máire C; More, Simon J; Monagle, Aisling; Earley, Bernadette; Cassidy, Joseph P

2017-01-01

The bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99) and of cattle submitted for post-mortem examination (PME: n = 34) were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (BPIV-3). Overall, the paranasal sinuses were either predominantly sterile or did not contain detectable microbes (83.5%: 94.9% of clinically normal and 50.0% of cattle submitted for PME). Bacteria, including BRD causing pathogens, were identified in relatively small numbers of cattle (<10%). While serology indicated widespread exposure of both clinically normal and cattle submitted for PME to BPIV-3 and BRSV (seroprevalences of 91.6% and 84.7%, respectively), PCR identified BPIV-3 in only one animal. To further explore these findings we investigated the potential role of the antimicrobial molecule nitric oxide (NO) within paranasal sinus epithelium using immunohistochemistry. Expression of the enzyme responsible for NO synthesis, inducible nitric oxide synthase (iNOS), was detected to varying degrees in 76.5% of a sub-sample of animals suggesting production of this compound plays a similar protective role in the bovine sinus as it does in humans.

Effects of clopidogrel on inflammatory cytokines and adhesion molecules in human endothelial cells: Role of nitric oxide mediating pleiotropic effects.

PubMed

Cerda, Alvaro; Pavez, Monica; Manriquez, Victor; Luchessi, Andre Ducati; Leal, Pamela; Benavente, Felipe; Fajardo, Cristina Moreno; Salazar, Luis; Hirata, Mario Hiroyuki; Hirata, Rosario Dominguez Crespo

2017-08-01

Clopidogrel is commonly used in prevention and treatment of atherothrombosis. Some previous studies have suggested a pleiotropic effect of clopidogrel; however, when this drug causes platelet-independent effects on endothelial function remains unclear. To evaluate the influence of clopidogrel on inflammatory biomarkers and adhesion molecules in human endothelial cells and the role of nitric oxide (NO) in this process. TNF-α-induced human umbilical vein endothelial cells (HUVEC) were exposed to clopidogrel. Gene expression and protein expression of ICAM-1, P-selectin, IL-8, IL-6, and MCP-1 were evaluated by qPCR, flux cytometry, or milliplex technology. Expression of endothelial nitric oxide synthase (NOS3) and NO release were also evaluated. Influence of clopidogrel was further evaluated in NOS3 downregulated HUVEC by RNAi. Clopidogrel at 20 μmol/L induced NO release in HUVEC after 24-hours treatment. Gene expressions of inflammatory markers IL-8 and MCP1 were reduced after clopidogrel treatment (P<.05); however, only MCP-1 remained reduced at protein level. IL-6 was not modified by clopidogrel treatment. Gene expression and protein expression of ICAM-1 were diminished by 24-hours clopidogrel exposure, whereas P-selectin was not modified. NOS3 downregulated HUVEC model revealed that ICAM-1 modification by clopidogrel is dependent of this via, whereas MCP-1 is modulated in an NO-independent form. Our results support new evidence for pleiotropic effects of clopidogrel on inflammation and endothelial function. Reduction in ICAM-1 and MCP-1 in human endothelium is an important extent of the use of this drug for treatment of cardiovascular diseases, and NO has an important role in this process. © 2017 John Wiley & Sons Ltd.

17β-Estradiol reduces nitric oxide production in the Guinea pig cochlea.

PubMed

Heinrich, U-R; Brieger, J; Striedter, C; Fischer, I; Schmidtmann, I; Li, H; Mann, W J; Helling, K

2013-11-01

Intense noise exposure and the application of ototoxic substances result in increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO). In order to reduce the free NO concentration in the inner ear under pathological conditions, the use of natural cytoprotective substances such as 17β-estradiol is a promising therapeutic concept. In male guinea pigs the organ of Corti and the lateral wall were isolated from the cochlea and afterwards incubated for 6 h in cell-culture medium. 17β-Estradiol was adjusted in 2 concentrations to organ cultures of the right ears (12 animals per concentration). The left ears were used as controls. The NO production was quantified in the supernatant by chemiluminescence after incubation. Depending on the concentration, 17β-estradiol reduced NO in the organ of Corti by 43% (p=0.015) and 46% (p=0.026), respectively. In the lateral wall, the NO concentration was reduced by 24%, but without statistical significance (p=0.86). However, when analyzing the association between the 2 cochlear regions for each animal separately, the NO concentrations were lower in nearly all 17β-estradiol-treated ears compared to controls. In order to demonstrate the flexibility of the organ culture system, the NO donor DETA NONOate and the nitric oxide synthase inhibitors L-NAME and L-NMMA were applied. The electron microscopic analysis revealed a well-preserved cochlear cell morphology after incubation. The ability of 17β-estradiol to influence the NO production preferentially in the organ of Corti might offer new therapeutic perspectives for inner ear protection. © Georg Thieme Verlag KG Stuttgart · New York.

A screening method for cardiovascular active compounds in marine algae.

PubMed

Agatonovic-Kustrin, S; Kustrin, E; Angove, M J; Morton, D W

2018-05-18

The interaction of bioactive compounds from ethanolic extracts of selected marine algae samples, separated on chromatographic plates, with nitric/nitrous acid was investigated. The nature of bioactive compounds in the marine algae extracts was characterised using UV absorption spectra before and after reaction with diluted nitric acid, and from the characteristic colour reaction after derivatization with anisaldehyde. It was found that diterpenes from Dictyota dichotoma, an edible brown algae, and sterols from green algae Caulerpa brachypus, bind nitric oxide and may act as a nitric oxide carrier. Although the carotenoid fucoxanthin, found in all brown marine algae also binds nitric oxide, the bonds between nitrogen and the fucoxanthin molecule are much stronger. Further studies are required to evaluate the effects of diterpenes from Dictyota dichotoma and sterols from green algae Caulerpa brachypus to see if they have beneficial cardiovascular effects. The method reported here should prove useful in screening large numbers of algae species for compounds with cardiovascular activity. Copyright © 2018 Elsevier B.V. All rights reserved.

Study of the Genes and Mechanism Involved in the Radioadaptive Response

NASA Technical Reports Server (NTRS)

Dasgupta, Pushan R.

2009-01-01

The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor secreted by the cells that inhibits radioadaptation leading to the upregulation of some genes which initiates the response.

Cylinder-averaged histories of nitrogen oxide in a DI diesel with simulated turbocharging

NASA Astrophysics Data System (ADS)

Donahue, Ronald J.; Borman, Gary L.; Bower, Glenn R.

1994-10-01

An experimental study was conducted using the dumping technique (total cylinder sampling) to produce cylinder mass-averaged nitric oxide histories. Data were taken using a four stroke diesel research engine employing a quiescent chamber, high pressure direct injection fuel system, and simulated turbocharging. Two fuels were used to determine fuel cetane number effects. Two loads were run, one at an equivalence ratio of 0.5 and the other at a ratio of 0.3. The engine speed was held constant at 1500 rpm. Under the turbocharged and retarded timing conditions of this study, nitric oxide was produced up to the point of about 85% mass burned. Two different models were used to simulate the engine mn conditions: the phenomenological Hiroyasu spray-combustion model, and the three dimensional, U.W.-ERO modified KIVA-2 computational fluid dynamic code. Both of the models predicted the correct nitric oxide trend. Although the modified KIVA-2 combustion model using Zeldovich kinetics correctly predicted the shapes of the nitric oxide histories, it did not predict the exhaust concentrations without arbitrary adjustment based on experimental values.

Does pharmaconutrition with L-arginine and/or alpha-tocopherol improve the gut barrier in bile duct ligated rats?

PubMed

Tuncyurek, P; Sari, M; Firat, O; Mutaf, I; Gulter, C; Tunger, A; Yuce, G; Yilmaz, M; Makay, O; Dayangac, M; Ersin, S

2006-01-01

Nitric oxide supplementation and antioxidant therapy modulate gut barrier function, but the relationships between enhanced nitric oxide production, antioxidant administration, and biliary obstruction remain unclear. We evaluated the role of nitric oxide and alpha-tocopherol supplementation in bile duct ligated rats. Fifty male Wistar albino rats underwent sham operation (group I; control animals) or bile duct ligation (groups II, III, IV, and V). The ligation groups received the following regimens: standard pellet diet (group II), pellet diet plus intramuscularly administered alpha-tocopherol (group III), and L-arginine-enriched pellet diet without (group IV) or with (group V) alpha-tocopherol. Nitric oxide, malondialdehyde, and alpha-tocopherol concentrations were assessed at the end of 3 weeks. Liver and intestinal samples were scored histologically. Mesenteric lymph node and liver cultures were assessed for bacterial translocation. The liver malondialdehyde concentration was highest in group III. The nitric oxide content in the liver was higher in groups III and V, as were the blood alpha-tocopherol levels. Bacterial translocation was evident following bile duct ligation, but did not differ among the treatment groups. Intestinal histology revealed that group III had the lowest villus height, that group V had the least villus count, and that group II had the highest mucous cell count. The fibrosis scores were higher in groups IV and V. An obvious effect of alpha-tocopherol (with or without L-arginine) on the gut barrier could not be demonstrated. Moreover, the L-arginine-enriched diet promoted fibrosis in the liver. Thus, while biliary duct obstruction triggers bacterial translocation, nitric oxide and/or alpha-tocopherol supplementation did not seem to improve the gut barrier in our model. Copyright 2006 S. Karger AG, Basel.

[Participation of nitric oxide and arachidonic acid metabolites via cytochrome - P450 in the regulation of arterial blood pressure].

PubMed

Sánchez-Mendoza, M Alicia; Martínez-Ayala, Sonia O; Hernández-Hernández, José A; Zúñiga-Sosa, Leonor; Pastelín-Hernández, Gustavo; Escalante-Acosta, Bruno A

2003-01-01

Nitric oxide and cytochrome P450 arachidonic acid metabolites participate in blood pressure regulation. The synthesis of these autacoids leads to arterial hypertension. However, it is not known whether there is an interaction between them. Therefore, we studied the modulatory effect of nitric oxide and cytochrome P450-arachidonic acid metabolites, their interaction on blood pressure, and the renal content of cytochrome P450. Male Wistar rats were divided: 1) control, 2) L-NAME (100 mg/kg/d p.o.), 3) L-NAME + SnCl2 (10 mg/kg/d i.p.), and 4) L-NAME + dexamethasone (1 mg/kg/d s.c.). We measured blood pressure and collected urine and blood for nitric oxide measurement. NO2 was quantified by HPLC. Blood pressure was: control, 97 +/- 7 mmHg; L-NAME, 151 +/- 4.6 mmHg; L-NAME + SnCl2, 133 +/- 3 mmHg, and L-NAME + dexamethasone 152 +/- 4.5 mmHg. Urine nitrite concentration was: 1) 1.832 +/- 0.32, 2) 1.031 +/- 0.23, 3) 1.616 +/- 0.33, and 4) 1.244 +/- 0.33 mumol/mL, while the concentration in blood was: 1) 0.293 +/- 0.06, 2) 0.150 +/- 0.05, 3) 0.373 +/- 0.13, and 4) 0.373 +/- 0.07 mumol/mL. L-NAME + SnCl2 decreased cytochrome P450 renal content, and L-NAME + dexamethasone showed a similar response. In conclusion, both, nitric oxide and CYP-arachidonic acid metabolites play a role in the regulation of blood pressure. Nitric oxide also partially regulates renal cytochrome P450 content.

Nitric oxide synthase expression in foetal placentas of cows with retained fetal membranes.

PubMed

Shixin, Fu; Li, Zhang; Chunhai, Luo; Chuang, Xu; Cheng, Xia; Zhe, Wang; Xiaobing, Li

2011-10-01

The objectives of this study were to investigate relationship of retained fetal membranes (RFM) to expression of NOS and NOS mRNA and to analyze pathohistological changes and the distribution of nitric oxide synthase (NOS) in foetal placentas of cows with RFM. Twenty cows were assigned to two groups, a control group (no retained fetal membranes, NRFM, n = 10) and a diseased group (RFM, n = 10). The endpoint method was used to detect the nitric oxide (NO) content and nitric oxide synthase (NOS) activity in foetal placental tissue fluid and the fluorescent quantitation PCR was used to measure the expression of NOS mRNA. Immunohistochemistry and hematoxylin-eosin staining were used to observe pathohistological changes. Tissue from RFM cows showed fibronecrosis of the chorionic villi, and a decreased number of trophoblastic cells. The majority of trophoblastic cells displayed vacuolar degeneration. Interstitium vessels were distended and congested. Expression of induced nitric oxide synthase (iNOS) protein and iNOS mRNA was significantly higher (P < 0.05) in the cytoplasm of placental villus trophoblastic cells in the RFM group. But expression of endothelial nitric oxide synthase (eNOS) protein and eNOS mRNA was significantly lower (P<0.05) in the RFM group. The NO content and NOS activity of cows with RFM were significantly higher (P < 0.05). A high expression of iNOS protein and iNOS mRNA in the cow foetal placenta could produce high content of NO, which might inhibit uterine contraction. So over expression of iNOS protein and iNOS mRNA might be an important agent of retained fetal membranes in cows, and it may be a potential diagnosis biomarker. Copyright © 2010 Elsevier Ltd. All rights reserved.

Use-dependent loss of active sympathetic neurogenic vasodilation after nitric oxide synthase inhibition in conscious rats. Evidence for the presence of preformed stores of nitric oxide-containing factors

NASA Technical Reports Server (NTRS)

Davisson, R. L.; Shaffer, R. A.; Johnson, A. K.; Lewis, S. J.

1996-01-01

In this study, we examined whether air-jet stress-induced active sympathetic hindlimb vasodilation in conscious rats involves the release of preformed stores of nitric oxide-containing factors. We determined the effects of repeated episodes of air-jet stress (six episodes given 5 minutes apart) on mean arterial pressure and vascular resistances in the mesenteric bed and intact and sympathetically denervated hindlimb beds of conscious rats treated with saline or the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mumol/kg IV). In saline-treated rats, air-jet stress produced alerting behavior, minor changes in blood pressure, pronounced mesenteric vaso-constriction, and immediate and marked vasodilation in the sympathetically intact hindlimb but a minor vasodilation in the sympathetically denervated hindlimb. Each air-jet stress produced virtually identical responses. In L-NAME-treated rats, the first air-jet stress produced vasodilator responses in the sympathetically intact and sympathetically denervated hindlimbs that were similar to those in the saline-treated rats. However, each subsequent air-jet stress produced progressively smaller vasodilator responses in the sympathetically intact but not the sympathetically denervated hindlimb. There was no loss of air-jet stress-induced alerting behavior or mesenteric vasoconstriction, suggesting that L-NAME did not interfere with the central processing of the air-jet or the resultant changes in autonomic nerve activity. The progressive diminution of air-jet stress-induced vasodilation in the intact hindlimb of L-NAME-treated rats may be due to the use-dependent depletion of preformed stores of nitric oxide-containing factors that cannot be replenished in the absence of nitric oxide synthesis.

Study of plasma-chemical NO-containing gas flow for treatment of wounds and inflammatory processes.

PubMed

Pekshev, Alexander V; Shekhter, Anatoly B; Vagapov, Andrey B; Sharapov, Nikolay A; Vanin, Anatoly F

2018-02-28

This work is aimed at exhaustive and detailed study of chemical, physical and physico-chemical characteristics of NO-containing gas flow (NO-CGF) generated by a plasma-chemical generator of Plason device, which has been used in medical practice for more than 15 years for effectively healing wound and inflammatory conditions with exogenous nitric oxide (NO-therapy). Data was obtained on spatial structure of the gas flow, and values of its local parameters in axial and radial directions, such as nitric oxide content, velocity, temperature and mass flow density of nitric oxide, providing altogether the effectiveness of treatment by the exogenous NO-therapy method, were determined experimentally and by computations. It was demonstrated that plasma-chemical synthesis of NO from atmospheric air in a low direct current (DC) arc provides a high mass flow of nitric oxide at the level of 1.6-1.8 mg/s, while in the area of impact of NO-CGF on the biological tissue, on its axis, NO content is 400-600 ppm, flow velocity about 5 m/s, nitric oxide mass flow density 0.25-0.40 mg/(s·cm 2 ), temperature 40-60 °C. Tendencies were determined for designing new devices for further experimental biological and medical research in the field of NO-therapy: lowering the temperature of NO-CGF to ambient temperature will enable variation, in experiments, of the affecting flow parameters in a wide range up to their maximum values: NO content up to 2000 ppm, velocity up to 20 m/s, nitric oxide mass flow density up to 2.5 mg/(s·cm 2 ). Copyright © 2017. Published by Elsevier Inc.

Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling.

PubMed

Sorokin, Andrey

2016-01-01

The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.

Domain-Specific Partitioning of Uterine Artery Endothelial Connexin43 and Caveolin-1.

PubMed

Ampey, Bryan C; Morschauser, Timothy J; Ramadoss, Jayanth; Magness, Ronald R

2016-10-01

Uterine vascular adaptations facilitate rises in uterine blood flow during pregnancy, which are associated with gap junction connexin (Cx) proteins and endothelial nitric oxide synthase. In uterine artery endothelial cells (UAECs), ATP activates endothelial nitric oxide synthase in a pregnancy (P)-specific manner that is dependent on Cx43 function. Caveolar subcellular domain partitioning plays key roles in ATP-induced endothelial nitric oxide synthase activation and nitric oxide production. Little is known regarding the partitioning of Cx proteins to caveolar domains or their dynamics with ATP treatment. We observed that Cx43-mediated gap junction function with ATP stimulation is associated with Cx43 repartitioning between the noncaveolar and caveolar domains. Compared with UAECs from nonpregnant (NP) ewes, levels of ATP, PGI2, cAMP, NOx, and cGMP were 2-fold higher (P<0.05) in pregnant UAECs. In pregnant UAECs, ATP increased Lucifer yellow dye transfer, a response abrogated by Gap27, but not Gap 26, indicating involvement of Cx43, but not Cx37. Confocal microscopy revealed domain partitioning of Cx43 and caveolin-1. In pregnant UAECs, LC/MS/MS analysis revealed only Cx43 in the caveolar domain. In contrast, Cx37 was located only in the noncaveolar pool. Western analysis revealed that ATP increased Cx43 distribution (1.7-fold; P=0.013) to the caveolar domain, but had no effect on Cx37. These data demonstrate rapid ATP-stimulated repartitioning of Cx43 to the caveolae, where endothelial nitric oxide synthase resides and plays an important role in nitric oxide-mediated increasing uterine blood flow during pregnancy. © 2016 American Heart Association, Inc.

Changes in Adenosine Triphosphate and Nitric Oxide in the Urothelium of Patients with Benign Prostatic Hyperplasia and Detrusor Underactivity.

PubMed

Cho, Kang Jun; Koh, Jun Sung; Choi, Jinbong; Kim, Joon Chul

2017-12-01

We investigated changes in the levels of adenosine triphosphate and nitric oxide in the urothelium of men with detrusor underactivity and benign prostatic hyperplasia. We prospectively enrolled in study 30 men who planned to undergo surgical treatment for benign prostatic hyperplasia. The 15 patients with a bladder contractility index less than 100 were assigned to the detrusor underactivity group while the 15 with a bladder contractility index more than 100 were assigned to the no detrusor underactivity group. Bladder mucosal specimens were collected at surgical prostate resection, and adenosine triphosphate and endothelial nitric oxide synthase were analyzed in these specimens. The levels of adenosine triphosphate and endothelial nitric oxide synthase were compared between the 2 groups. The correlation of urodynamic parameters with adenosine triphosphate and endothelial nitric oxide synthase was assessed in all patients. Mean ± SEM endothelial nitric oxide synthase did not significantly differ between the detrusor underactivity and no underactivity groups (3.393 ± 0.969 vs 1.941 ± 0.377 IU/ml, p = 0.247). However, the mean level of adenosine triphosphate in the detrusor underactivity group was significantly lower than in the no detrusor underactivity group (1.289 ± 0.320 vs 9.262 ± 3.285 pmol, p = 0.011). In addition, in all patients adenosine triphosphate positively correlated with the bladder contractility index (r = 0.478, p = 0.018) and with detrusor pressure on maximal flow (r = 0.411, p = 0.046). Adenosine triphosphate was significantly decreased in the urothelium in men with detrusor underactivity and benign prostatic hyperplasia, reflecting the change in detrusor function. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Omanakuttan, Athira; Bose, Chinchu; Pandurangan, Nanjan

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlyingmore » the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′ ,7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. - Highlights: • Ecdysterone significantly enhances cell migration in a dose dependent manner. • Ecdysterone augments cell spreading during the initial phase of cell migration through actin cytoskeletal rearrangement. • Ecdysterone enhances cell proliferation in a nitric oxide dependent manner. • Ecdysterone enhances nitric oxide production via activation of EGFR and phosphorylation of ERK.« less

Gestational Obstructive Sleep Apnea: Biomarker Screening Models and Lack of Postpartum Resolution.

PubMed

Street, Linda M; Aschenbrenner, Carol A; Houle, Timothy T; Pinyan, Clark W; Eisenach, James C

2018-04-15

To measure prevalence and severity of third trimester obstructive sleep apnea and evaluate postpartum resolution. To assess a novel biomarker for screening for obstructive sleep apnea in pregnancy. This prospective observational study was performed at Wake Forest School of Medicine obstetrics clinics between April 2014 and December 2015. Fractional exhaled nitric oxide measurements and sleep studies were obtained and compared at 32 0/7 to 35 6/7 weeks gestation and postpartum. Exhaled nitric oxide and risk factors for the development of gestational sleep apnea were evaluated for predictive ability independently and in screening models. Of 76 women enrolled, 73 performed valid sleep studies in pregnancy and 65 had an additional valid study 6 to 15 weeks postpartum. Twenty-four women (37%) had gestational sleep apnea compared with 23 (35%) with postpartum sleep apnea ( P > .99). Eight of 11 women (73%) retested 6 to 8 months postpartum had persistent sleep apnea. Exhaled nitric oxide had moderate discrimination screening for sleep apnea in pregnancy (area under the receiver operating characteristic curve = 0.64). A model utilizing exhaled nitric oxide, pregnancy-specific screening, and Mallampati score improved ability to identify women at risk for gestational sleep apnea (sensitivity = 46%, specificity = 91% and likelihood ratio = 5.11, area under receiver operating characteristic curve = 0.75). Obstructive sleep apnea is common in the early postpartum period and often persisted at least 6 months. Exhaled nitric oxide as a sole biomarker to screen for sleep apnea in pregnancy has only modest discrimination. Combined with additional parameters sensitivity and specificity improved. Registry: ClinicalTrials.gov, Identifier: NCT02100943, Title: Exhaled Nitric Oxide as a Biomarker of Gestational Obstructive Sleep Apnea and Persistence Postpartum, URL: https://clinicaltrials.gov/ct2/show/NCT02100943. © 2018 American Academy of Sleep Medicine.

Possible involvement of nitric oxide (NO) signaling pathway in the antidepressant-like effect of MK-801(dizocilpine), a NMDA receptor antagonist in mouse forced swim test.

PubMed

Dhir, Ashish; Kulkarni, S K

2008-03-01

L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) is an important signaling pathway involved in depression. With this information, the present study aimed to study the involvement of this signaling pathway in the antidepressant-like action of MK-801 (dizocilpine; N-methyl-d-aspartate receptor antagonist) in the mouse forced-swim test. Total immobility period was recorded in mouse forced swim test for 6 min. MK-801 (5-25 microg/kg., ip) produced a U-shaped curve in reducing the immobility period. The antidepressant-like effect of MK-801 (10 microg/kg, ip) was prevented by pretreatment with L-arginine (750 mg/kg, ip) [substrate for nitric oxide synthase (NOS)]. Pretreatment of mice with 7-nitroindazole (7-NI) (25 mg/kg, ip) [a specific neuronal nitric oxide synthase inhibitor] produced potentiation of the action of subeffective dose of MK-801 (5 microg/kg, ip). In addition, treatment of mice with methylene blue (10 mg/kg, ip) [direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase] potentiated the effect of MK-801 (5 microg/kg, ip) in the forced-swim test. Further, the reduction in the immobility period elicited by MK-801 (10 microg/kg, ip) was also inhibited by pretreatment with sildenafil (5 mg/kg, ip) [phosphodiesterase 5 inhibitor]. The various modulators used in the study and their combination did not produce any changes in locomotor activity per se and in combination with MK-801. MK-801 however, at higher doses (25 microg/kg, ip) produced hyperlocomotion. The results demonstrated the involvement of nitric oxide signaling pathway in the antidepressant-like effect of MK-801 in mouse forced-swim test.

The peripheral administration of a nitric oxide donor potentiates the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice.

PubMed

Hervera, Arnau; Leánez, Sergi; Negrete, Roger; Pol, Olga

2009-10-01

Several works reveal that nitric oxide could enhance the peripheral antinociception induced by opioids during acute inflammation. Nonetheless, the role of nitric oxide in the local antinociceptive effects of delta-opioid receptor (DOR) agonists during chronic peripheral inflammation is not known. The aim of this study is to evaluate whether nitric oxide would enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice. Chronic inflammatory pain was induced by the subplantar administration of complete Freund's adjuvant (CFA; 30 microl) and thermal hyperalgesia assessed by plantar test. In C57BL/6J mice, we evaluated the local antinociceptive effects of a DOR agonist, [D-Pen2,5]-enkephalin (DPDPE) and a nitric oxide donor, DETA NONOate DETA/NO 2,2'-(hydroxynitrosohydrazino) Bis-Ethanamine (NOC-18) alone or combined (DPDPE plus NOC-18) at 1, 4, 7, and 10 days after CFA injection. The reversibility of the peripheral antinociceptive effects of DPDPE, alone or combined with NOC-18, was assessed with the local administration of selective (naltrindole) and non-selective (naloxone methiodide) DOR antagonists. The local administration of DPDPE or NOC-18 alone dose-dependently inhibited the thermal hyperalgesia induced by peripheral inflammation. Moreover, the co-administration of NOC-18 with DPDPE significantly increased the antinociceptive effects produced by DPDPE from 1 to 10 days of CFA-induced inflammatory pain (P < 0.05). These effects were completely blocked by naltrindole and naloxone methiodide. Our results demonstrate that nitric oxide might enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain by interaction with peripheral DOR, representing a useful strategy for an efficient antinociceptive treatment of peripheral inflammatory pain.

The effect of a selective neuronal nitric oxide synthase inhibitor 3-bromo 7-nitroindazole on spatial learning and memory in rats.

PubMed

Gocmez, Semil Selcen; Yazir, Yusufhan; Sahin, Deniz; Karadenizli, Sabriye; Utkan, Tijen

2015-04-01

Since the discovery of nitric oxide (NO) as a neuronal messenger, its way to modulate learning and memory functions is subject of intense research. NO is an intercellular messenger in the central nervous system and is formed on demand through the conversion of L-arginine to L-citrulline via the enzyme nitric oxide synthase (NOS). Neuronal form of nitric oxide synthase may play an important role in a wide range of physiological and pathological conditions. Therefore the aim of this study was to investigate the effects of chronic 3-bromo 7-nitroindazole (3-Br 7-NI), specific neuronal nitric oxide synthase (nNOS) inhibitor, administration on spatial learning and memory performance in rats using the Morris water maze (MWM) paradigm. Male rats received either 3-Br 7-NI (20mg/kg/day) or saline via intraperitoneal injection for 5days. Daily administration of the specific neuronal nitric oxide synthase (nNOS) inhibitor, 3-Br 7-NI impaired the acquisition of the MWM task. 3-Br 7-NI also impaired the probe trial. The MWM training was associated with a significant increase in the brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus. BDNF mRNA expression in the hippocampus did not change after 3-Br 7-NI treatment. L-arginine significantly reversed behavioural parameters, and the effect of 3-Br 7-NI was found to be NO-dependent. There were no differences in locomotor activity and blood pressure in 3-Br 7-NI treated rats. Our results may suggest that nNOS plays a key role in spatial memory formation in rats. Copyright © 2015 Elsevier Inc. All rights reserved.

Human nitric oxide biomarker as potential NO donor in conjunction with superparamagnetic iron oxide @ gold core shell nanoparticles for cancer therapeutics.

PubMed

Singh, Nimisha; Patel, Khushbu; Sahoo, Suban K; Kumar, Rajender

2018-03-01

Nitric oxide releasing superparamagnetic (Fe 3 O 4 -Au@NTHP) nanoparticles were synthesized by conjugation of human biomarker of nitric oxide, N-nitrosothioproline with iron oxide-gold (Fe 3 O 4 -Au) core shell nanoparticles. The structure and morphology of the prepared nanoparticles were confirmed by ATR-FTIR, HR-TEM, EDAX, XPS, DLS and VSM measurements. N-nitrosothioproline is a natural molecule and nontoxic to humans. Thus, the core shell nanoparticles prepared were highly biocompatible. The prepared Fe 3 O 4 -Au@NTHP nanoparticles also provided an excellent release of nitric oxide in dark and upon light irradiation for cancer treatment. The amount of NO release was controllable with the wavelength of light and time of irradiation. The developed nanoparticles provided efficient cellular uptake and good cytotoxicity in picomolar range when tested on HeLa cancerous cells. These nanoparticles on account of their controllable NO release can also be used to release small amount of NO for killing cancerous cells without any toxic effect. Furthermore, the magnetic and photochemical properties of these nanoparticles provides dual platform for magneto therapy and phototherapy for cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Increase in exhaled nitric oxide is associated with bronchial hyperresponsiveness among apprentices.

PubMed

Tossa, Paul; Paris, Christophe; Zmirou-Navier, Denis; Demange, Valérie; Acouetey, Dovi-Stéphanie; Michaely, Jean-Pierre; Bohadana, Abraham

2010-09-15

Airway inflammation is a hallmark of asthma. Several studies have validated the use of the fractional concentration of exhaled nitric oxide (Fe(NO)) as a surrogate marker of airway inflammation in asthma. We examined how the change in Fe(NO) levels, since the beginning of occupational exposure, could be associated with the incidence of bronchial hyperresponsiveness (BHR) among baker, pastry maker, and hairdresser apprentices during their 2-year training. A standardized questionnaire was administered; skin prick tests for common and specific occupational allergens were done; methacholine challenge and measurement of Fe(NO) were performed 6, 12, and 15 months after the first examination. Of 441 apprentices initially included, 351 completed the study. The increase in Fe(NO), since the beginning of exposure, was associated with the incidence of BHR (odds ratio, 2.00 [95% confidence interval, 1.21-3.32] per unit increase in log parts per billion) both in atopic and nonatopic subjects. The average increase in Fe(NO) was similar in atopic and nonatopic subjects and was unrelated to past or current smoking habits, sex, or training track. Atopy in bakers/pastry makers and sensitization to alkaline persulfates in hairdressers were also independently associated with the incidence of BHR. BHR occurred sooner among bakers/pastry makers than among hairdressers, but its incidence leveled off later. Our results suggest that measurement of Fe(NO), a simple and reproducible test, could be useful in the screening of BHR in workers newly exposed to agents known to cause occupational asthma.

Nitric oxide releasing plasma polymer coating with bacteriostatic properties and no cytotoxic side effects.

PubMed

Michl, Thomas D; Coad, Bryan R; Doran, Michael; Osiecki, Michael; Kafshgari, Morteza Hasanzadeh; Voelcker, Nicolas H; Hüsler, Amanda; Vasilev, Krasimir; Griesser, Hans J

2015-04-25

We report a stable plasma polymer coating, using isopentyl nitrite as a volatile precursor, which releases nitric oxide at bacteriostatic concentrations when contacted with water, inhibiting bacterial growth without cytotoxic side effects to human mesenchymal stem/stromal cells.

Nitric oxide gamma and delta band emission at twilight

NASA Technical Reports Server (NTRS)

Feldman, P. D.; Takacs, P. Z.

1974-01-01

Nitric oxide twilight emission above 140 km in the gamma- and delta-bands was observed with a rocket-borne spectrophotometer. The relative intensity of the two band systems indicates that the emission is produced predominantly by the chemiluminescent preassociation of oxygen and nitrogen atoms.

EXAMINING THE TEMPORAL VARIABILITY OF AMMONIA AND NITRIC OXIDE EMISSIONS FROM AGRICULTURAL PROCESSES

EPA Science Inventory

This paper examines the temporal variability of airborne emissions of ammonia from livestock operations and fertilizer application and nitric oxide from soils. In the United States, the livestock operations and fertilizer categories comprise the majority of the ammonia emissions...

Apigenin attenuates diabetes-associated cognitive decline in rats via suppressing oxidative stress and nitric oxide synthase pathway

PubMed Central

Mao, Xiao-Yuan; Yu, Jing; Liu, Zhao-Qian; Zhou, Hong-Hao

2015-01-01

Our present investigation aimed to determine the neuroprotection of apigenin (API) against diabetes-associated cognitive decline (DACD) a diabetic rat model and exploring its potential mechanism. Diabetic rat model was induced by intraperitoneal injection of streptozotocin. All experiment animals treated with vehicle or API by doses of 10, 20 and 40 mg/kg for seven weeks. Firstly, the body weight and blood glucose levels were detected. We used Morris water maze test to evaluate learning and memory function. The oxidative indicators (malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)), cNOS, iNOS, caspase-3 and caspase-9 were measured in cerebral cortex and hippocampus using corresponding commercial kits. API can increase body weight, reduce the blood glucose levels, and improve the cognitive function in rats induced by diabetes. API decrease the MDA content, and increase SOD activity and GSH level of diabetic animals in the cerebral cortex and hippocampus of diabetic rats. Meanwhile, constitutive nitric oxide synthase (cNOS), inducible nitric oxide synthase (iNOS), caspase-3/9 were markedly exhibited in the cerebral cortex and hippocampus of diabetic rats. In summary, our current work discloses that API attenuates DACD in rats via suppressing oxidative stress, nitric oxide and apoptotic cascades synthase pathway. PMID:26629041

The role of nitric oxide pathway in arginine transport and growth of IPEC-1 cells.

PubMed

Xiao, Hao; Zeng, Liming; Shao, Fangyuan; Huang, Bo; Wu, Miaomiao; Tan, Bie; Yin, Yulong

2017-05-02

L-Arginine itself and its metabolite-nitric oxide play great roles in intestinal physiology. However, the molecular mechanism underlying nitric oxide pathway regulating L-Arginine transport and cell growth is not yet fully understood. We report that inhibition of nitric oxide synthase (NOS) significantly induced cell apoptosis (p < 0.05), and promoted the rate of Arginine uptake and the expressions of protein for CAT-2 and y+LAT-1 (p < 0.05), while reduced protein expression of CAT-1. And NOS inhibition markedly decreased the activation of mammalian target of rapamycin (mTOR) and PI3K-Akt pathways by Arginine in the IPEC-1 cells (p < 0.05). Taken together, these data suggest that inhibition of NO pathway by L-NAME induces a negative feedback increasing of Arginine uptake and CAT-2 and y+LAT-1 protein expression, but promotes cell apoptosis which involved inhibiting the activation of mTOR and PI3K-Akt pathways.

Effect of PDT-treated apoptotic cells on macrophages

NASA Astrophysics Data System (ADS)

Song, Sheng; Xing, Da; Zhou, Fei-fan; Chen, Wei R.

2009-02-01

Recently, the long-term immunological effects of photodynamic therapy have attracted much attention. PDT induced immune response was mainly initiated through necrotic cells and apoptotic cells, as well as immune cells such as macrophages. Nitric oxide (NO) as an important regulatory factor in signal transfer between cells has been wildly studied for generation, development, and metastasis of tumors. NO synthase is a key enzyme in nitric oxide synthesis. However, inducible nitric oxide synthase (iNOS) is usually activated under pathological conditions, such as stress and cancer, which can produce high levels of nitric oxide and contribute to tumor cytotoxicity. In addition, increased NO production by iNOS has been associated with the host immune response and cell apoptosis, which play an important role in many carcinogenesis and anti-carcinoma mechanisms. This study focuses on the NO production in macrophages, induced by mouse breast carcinoma apoptotic cells treated by PDT in vitro, and on the effects of immune response induced by apoptotic cells in tumor cells growth.

Reference models for thermospheric NO

NASA Technical Reports Server (NTRS)

Barth, C. A.

1989-01-01

Nitric oxide has been measured with an ultraviolet spectrometer on the polar-orbiting satellite Solar Mesosphere Explorer (SME) for the period January 1982 to August 1986. The nitric oxide database contains densities at all latitudes sorted into 5 degree bins and at altitudes between 100 and 140 km sorted into 3.3 km-bins. The largest densities occur at latitudes in the auroral zones where the density varies as a function of geomagnetic activity. Variations of a factor of 10 occur between times of intense activity and quiet times. At low latitudes, the nitric oxide density at 110 km varies from a mean value of 3 times 10(exp 7) molecules per cubic cm in January 1982 to a mean value of 4 times 10(exp 6) molecules per cubic cm during solar minimum conditions in 1986. In addition, the low-latitude nitric oxide density varies plus or minus 50 percent with a period of 27 days during times of high solar activity.

Ferulic acid and its water-soluble derivatives inhibit nitric oxide production and inducible nitric oxide synthase expression in rat primary astrocytes.

PubMed

Kikugawa, Masaki; Ida, Tomoaki; Ihara, Hideshi; Sakamoto, Tatsuji

2017-08-01

We recently reported that two water-soluble derivatives of ferulic acid (1-feruloyl glycerol, 1-feruloyl diglycerol) previously developed by our group exhibited protective effects against amyloid-β-induced neurodegeneration in vitro and in vivo. In the current study, we aimed to further understand this process by examining the derivatives' ability to suppress abnormal activation of astrocytes, the key event of neurodegeneration. We investigated the effects of ferulic acid (FA) derivatives on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in rat primary astrocytes. The results showed that these compounds inhibited NO production and iNOS expression in a concentration-dependent manner and that the mechanism underlying these effects was the suppression of the nuclear factor-κB pathway. This evidence suggests that FA and its derivatives may be effective neuroprotective agents and could be useful in the treatment of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.

The nitric oxide prodrug JS-K and its structural analogues as cancer therapeutic agents.

PubMed

Maciag, Anna E; Saavedra, Joseph E; Chakrapani, Harinath

2009-09-01

Nitric oxide (NO) prodrugs of the diazeniumdiolate class are routinely used as reliable sources of nitric oxide in chemical and biological laboratory settings. O(2)-(2,4-dinitrophenyl) diazeniumdiolates, which are derivatized forms of ionic diazeniumdiolates, have been found to show potent anti-proliferative activity in a variety of cancer cells, presumably through the effects of NO. One important member of this class of diazeniumdiolates, O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K), has shown promise as a novel cancer therapeutic agent in a number of animal models. This review describes the developments in chemical and biochemical characterization and structure-activity relationship of JS-K and its analogues. In addition, some molecular mechanistic insights into the observed anti-proliferative activity of JS-K are discussed. Finally, a structural motif is presented for O(2)-(aryl) diazeniumdiolate nitric oxide prodrugs that show potency comparable with that of JS-K.

Endomembrane H-Ras Controls Vascular Endothelial Growth Factor-induced Nitric-oxide Synthase-mediated Endothelial Cell Migration*

PubMed Central

Haeussler, Dagmar J.; Pimentel, David R.; Hou, Xiuyun; Burgoyne, Joseph R.; Cohen, Richard A.; Bachschmid, Markus M.

2013-01-01

We demonstrate for the first time that endomembrane-delimited H-Ras mediates VEGF-induced activation of endothelial nitric-oxide synthase (eNOS) and migratory response of human endothelial cells. Using thiol labeling strategies and immunofluorescent cell staining, we found that only 31% of total H-Ras is S-palmitoylated, tethering the small GTPase to the plasma membrane but leaving the function of the large majority of endomembrane-localized H-Ras unexplained. Knockdown of H-Ras blocked VEGF-induced PI3K-dependent Akt (Ser-473) and eNOS (Ser-1177) phosphorylation and nitric oxide-dependent cell migration, demonstrating the essential role of H-Ras. Activation of endogenous H-Ras led to recruitment and phosphorylation of eNOS at endomembranes. The loss of migratory response in cells lacking endogenous H-Ras was fully restored by modest overexpression of an endomembrane-delimited H-Ras palmitoylation mutant. These studies define a newly recognized role for endomembrane-localized H-Ras in mediating nitric oxide-dependent proangiogenic signaling. PMID:23548900

Intake of red wine increases the number and functional capacity of circulating endothelial progenitor cells by enhancing nitric oxide bioavailability.

PubMed

Huang, Po-Hsun; Chen, Yung-Hsiang; Tsai, Hsiao-Ya; Chen, Jia-Shiong; Wu, Tao-Cheng; Lin, Feng-Yen; Sata, Masataka; Chen, Jaw-Wen; Lin, Shing-Jong

2010-04-01

Red wine (RW) consumption has been associated with a reduction of cardiovascular events, but limited data are available on potential mediating mechanisms. This study tested the hypothesis that intake of RW may promote the circulating endothelial progenitor cell (EPC) level and function through enhancement of nitric oxide bioavailability. Eighty healthy, young subjects were randomized and assigned to consume water (100 mL), RW (100 mL), beer (250 mL), or vodka (30 mL) daily for 3 weeks. Flow cytometry was used to quantify circulating EPC numbers, and in vitro assays were used to evaluate EPC functions. After RW ingestion, endothelial function determined by flow-mediated vasodilation was significantly enhanced; however, it remained unchanged after water, beer, or vodka intake. There were significantly increased numbers of circulating EPC (defined as KDR(+)CD133(+), CD34(+)CD133(+), CD34(+)KDR(+)) and EPC colony-forming units only in the RW group (all P<0.05). Only RW ingestion significantly enhanced plasma levels of nitric oxide and decreased asymmetrical dimethylarginine (both P<0.01). Incubation of EPC with RW (but not beer or ethanol) and resveratrol in vitro attenuated tumor necrosis factor-alpha-induced EPC senescence and improved tumor necrosis factor-alpha-suppressed EPC functions and tube formation. Incubation with nitric oxide donor sodium nitroprusside significantly ameliorated the inhibition of tumor necrosis factor-alpha on EPC proliferation, but incubation with endothelial nitric oxide synthase inhibitor l-NAME and PI3K inhibitor markedly attenuated the effect of RW on EPC proliferation. The intake of RW significantly enhanced circulating EPC levels and improved EPC functions by modifying nitric oxide bioavailability. These findings may help explain the beneficial effects of RW on the cardiovascular system. This study demonstrated that a moderate intake of RW can enhance circulating levels of EPC in healthy subjects by increasing nitric oxide availability. Direct incubation of EPC with RW and resveratrol can modify the functions of EPC, including attenuation of senescence and promotion of EPC adhesion, migration, and tube formation. These data suggest that RW ingestion may alter the biology of EPC, and these alterations may contribute to its unique cardiovascular-protective effect.

Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial.

PubMed

Bondonno, Catherine P; Yang, Xingbin; Croft, Kevin D; Considine, Michael J; Ward, Natalie C; Rich, Lisa; Puddey, Ian B; Swinny, Ewald; Mubarak, Aidilla; Hodgson, Jonathan M

2012-01-01

Flavonoids and nitrates in fruits and vegetables may protect against cardiovascular disease. Dietary flavonoids and nitrates can augment nitric oxide status via distinct pathways, which may improve endothelial function and lower blood pressure. Recent studies suggest that the combination of flavonoids and nitrates can enhance nitric oxide production in the stomach. Their combined effect in the circulation is unclear. Here, our objective was to investigate the independent and additive effects of flavonoid-rich apples and nitrate-rich spinach on nitric oxide status, endothelial function, and blood pressure. A randomized, controlled, crossover trial with healthy men and women (n=30) was conducted. The acute effects of four energy-matched treatments (control, apple, spinach, and apple+spinach), administered in random order, were compared. Measurements included plasma nitric oxide status, assessed by measuring S-nitrosothiols+other nitrosylated species (RXNO) and nitrite, blood pressure, and endothelial function, measured as flow-mediated dilatation of the brachial artery. Results are means and 95% CI. Relative to control, all treatments resulted in higher RXNO (control, 33 nmol/L, 26, 42; apple, 51 nmol/L, 40, 65; spinach, 86 nmol/L, 68, 110; apple+spinach, 69 nmol/L, 54, 88; P<0.01) and higher nitrite (control, 35 nmol/L, 27, 46; apple, 69 nmol/L, 53, 90; spinach, 99 nmol/L, 76, 129; apple+spinach, 80 nmol/L, 61, 104; P<0.01). Compared to control, all treatments resulted in higher flow-mediated dilatation (P<0.05) and lower pulse pressure (P<0.05), and apple and spinach resulted in lower systolic blood pressure (P<0.05). No significant effect was observed on diastolic blood pressure. The combination of apple and spinach did not result in additive effects on nitric oxide status, endothelial function, or blood pressure. In conclusion, flavonoid-rich apples and nitrate-rich spinach can independently augment nitric oxide status, enhance endothelial function, and lower blood pressure acutely, outcomes that may benefit cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular and biochemical responses of hypoxia exposure in Atlantic croaker collected from hypoxic regions in the northern Gulf of Mexico.

PubMed

Rahman, Md Saydur; Thomas, Peter

2017-01-01

A major impact of global climate change has been the marked increase worldwide in the incidence of coastal hypoxia (dissolved oxygen, DO<2.0 mg l-1). However, the extent of hypoxia exposure to motile animals such as fish collected from hypoxic waters as well as their molecular and physiological responses to environmental hypoxia exposure are largely unknown. A suite of potential hypoxia exposure biomarkers was evaluated in Atlantic croaker collected from hypoxic and normoxic regions in the northern Gulf of Mexico (nGOM), and in croaker after laboratory exposure to hypoxia (DO: 1.7 mg l-1). Expression of hypoxia-inducible factor-α, hif-α; neuronal nitric oxide synthase, nNOS; and insulin-like growth factor binding protein, igfbp mRNAs and protein carbonyl (PC, an oxidative stress indicator) content were elevated several-fold in brain and liver tissues of croaker collected from nGOM hypoxic sites. All of these molecular and biochemical biomarkers were also upregulated ~3-10-fold in croaker brain and liver tissues within 1-2 days of hypoxia exposure in controlled laboratory experiments. These results suggest that hif-αs, nNOS and igfbp-1 transcripts and PC contents are useful biomarkers of environmental hypoxia exposure and some of its physiological effects, making them important components for improved assessments of long-term impacts of environmental hypoxia on fish populations.

Role of nitric oxide and KATP channel in the protective effect mediated by nicorandil in bile duct ligation-induced liver fibrosis in rats.

PubMed

Mohamed, Yasmin S; Ahmed, Lamiaa A; Salem, Hesham A; Agha, Azza M

2018-05-01

Liver fibrosis is one of the most serious conditions affecting patients worldwide. In the present study, the role of nitric oxide and KATP channel was investigated for the first time in the possible protection mediated by nicorandil in bile duct ligation-induced liver fibrosis in rats. Nicorandil (3 mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed marked improvement in liver function tests, hepatic oxidative stress and inflammatory markers as well as inducible and endothelial nitric oxide synthase protein expressions. Furthermore, nicorandil administration led to significant decrement of phosphorylated protein kinase C, fibrosis and hepatic stellate cells activation as indicated by decreased alpha smooth muscle actin expression. Oral co-administration of glibenclamide (5 mg/kg/day) (a KATP channel blocker) with nicorandil mostly showed similar improvement though not reaching to that of nicorandil group. However, co-adminstration of L-NAME (15 mg/kg/day) (an inhibitor of nitric oxide synthase) completely abolished the protective effects of nicorandil and produced more or less similar results to that of untreated bile duct ligated group. In conclusion, nicorandil is an effective therapy against the development of bile duct ligation-induced liver fibrosis in rats where nitric oxide plays a more prominent role in the protective effect of nicorandil than KATP channel opening. Copyright © 2018 Elsevier Inc. All rights reserved.

Functional Nitric Oxide Nutrition to Combat Cardiovascular Disease.

PubMed

Bryan, Nathan S

2018-03-17

To reveal the mechanisms of nitric oxide (NO) production in humans and how lifestyle, drug therapy, and hygienic practices can decrease NO production. Furthermore, to show how functional nitric oxide nutrition can overcome these limitations to restore endogenous NO production and combat cardiovascular disease. Research over the past decade has revealed that inorganic nitrate and nitrite found naturally in green leafy vegetables and other vegetables such as beets can provide the human body with a source of bioactive nitric oxide. NO is one of the most important molecules produced within the cardiovascular system that maintains normal blood pressure and prevents inflammation, immune dysfunction, and oxidative stress, hallmarks of cardiovascular disease. This pathway is dependent upon the amount of inorganic nitrate and nitrite in the foods we eat, the presence of oral nitrate-reducing bacteria, and sufficient stomach acid production. The concept of food being medicine and medicine being food has lost its place in the practice and implementation of modern medicine over the past century. Certain dietary patterns and specific foods are known to confer very significant protective effects for many human diseases, including cardiovascular disease, the number one killer of men and women in the developed world. However, identification of single or multiple bioactive molecules that are responsible for these effects has escaped scientists and nutritionists for many years. This review will highlight the biochemical, physiological, and epidemiological basis for functional nitric oxide nutrition that can be safely and effectively utilized in patients.

Investigating the sensitivity of nitric oxide infrared emissions to electron impact

NASA Astrophysics Data System (ADS)

Campbell, L.; Brunger, M. J.; Allan, M.

2008-05-01

Integral cross sections for low energy electron excitation of the 0→1, 0→2 and 0→3 vibrational modes in nitric oxide have quite recently become available [Trevisan et al. PRA 71, 052714 (2005)]. In this study we adapt our recent work [Campbell and Brunger GRL, in press (2007)], to look at the effect of these new cross sections on the production of nitric oxide infrared radiation. Predictions from our model are compared with measurements from Espy et al. [Planet. Space Sci. 36, 543 (1988)], with the inclusion of the new cross sections improving the agreement of the shape of the spectrum with the measurements.

Delivery of nitric oxide to the interior of mammalian cell by carbon nanotube: MD simulation.

PubMed

Raczyński, Przemysław; Górny, Krzysztof; Dawid, Aleksander; Gburski, Zygmunt

2014-07-15

Computer simulations have been performed to study the nanoindentation of phospholipid bilayer by the single-walled armchair carbon nanotube, filled with the nitric oxide molecules. The process has been simulated by means of molecular dynamics (MD) technique at physiological temperature T = 310 K with a constant pulling velocity of the nanotube. The force acting on the nanotube during membrane penetration has been calculated. We show that the indentation by carbon nanotube does not permanently destroy the membrane structure (self-sealing of the membrane occurs). The mobility of nitric oxide molecules during the membrane nanoindentation is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

The production of nitric oxide in the troposphere as a result of solid-rocket-motor afterburning

NASA Technical Reports Server (NTRS)

Stewart, R. B.; Gomberg, R. I.

1976-01-01

As part of an ongoing assessment of the environmental effects of solid-rocket-motor operations in the troposphere, estimates were made of the nitric oxide produced in the troposphere by the space shuttle and Titan 3-C boosters. Calculations were made with the low-altitude plume computer program and included the effects of coupled finite-rate chemistry and turbulent mixing. A recent measurement of nitric oxide taken in the effluent cloud of a Titan 3-C booster is compared with calculations made with this computer code. The various chemical reactions of the exhaust gases are listed in tabular form.

Simulation of nitrous oxide and nitric oxide emissions from tropical primary forests in the Costa Rican Atlantic Zone

Treesearch

Shuguanga Liu; William A. Reiners; Michael Keller; Davis S. Schimel

2000-01-01

Nitrous oxide (N2O) and nitric oxide (NO) are important atmospheric trace gases participating in the regulation of global climate and environment. Predictive models on the emissions of N2O and NO emissions from soil into the atmosphere are required. We modified the CENTURY model (Soil Sci. Soc. Am. J., 51 (1987) 1173) to simulate the emissions of N2O and NO from...

Nitrification inhibition by hexavalent chromium Cr(VI)--Microbial ecology, gene expression and off-gas emissions.

PubMed

Kim, Young Mo; Park, Hongkeun; Chandran, Kartik

2016-04-01

The goal of this study was to investigate the responses in the physiology, microbial ecology and gene expression of nitrifying bacteria to imposition of and recovery from Cr(VI) loading in a lab-scale nitrification bioreactor. Exposure to Cr(VI) in the reactor strongly inhibited nitrification performance resulting in a parallel decrease in nitrate production and ammonia consumption. Cr(VI) exposure also led to an overall decrease in total bacterial concentrations in the reactor. However, the fraction of ammonia oxidizing bacteria (AOB) decreased to a greater extent than the fraction of nitrite oxidizing bacteria (NOB). In terms of functional gene expression, a rapid decrease in the transcript concentrations of amoA gene coding for ammonia oxidation in AOB was observed in response to the Cr(VI) shock. In contrast, transcript concentrations of the nxrA gene coding for nitrite oxidation in NOB were relatively unchanged compared to Cr(VI) pre-exposure levels. Therefore, Cr(VI) exposure selectively and directly inhibited activity of AOB, which indirectly resulted in substrate (nitrite) limitation to NOB. Significantly, trends in amoA expression preceded performance trends both during imposition of and recovery from inhibition. During recovery from the Cr(VI) shock, the high ammonia concentrations in the bioreactor resulted in an irreversible shift towards AOB populations, which are expected to be more competitive in high ammonia environments. An inadvertent impact during recovery was increased emission of nitrous oxide (N2O) and nitric oxide (NO), consistent with recent findings linking AOB activity and the production of these gases. Therefore, Cr(VI) exposure elicited multiple responses on the microbial ecology, gene expression and both aqueous and gaseous nitrogenous conversion in a nitrification process. A complementary interrogation of these multiple responses facilitated an understanding of both direct and indirect inhibitory impacts on nitrification. Copyright © 2016 Elsevier Ltd. All rights reserved.

Wildland smoke exposure values and exhaled breath indicators in firefighters.

PubMed

Miranda, Ana Isabel; Martins, Vera; Cascão, Pedro; Amorim, Jorge Humberto; Valente, Joana; Borrego, Carlos; Ferreira, António Jorge; Cordeiro, Carlos Robalo; Viegas, Domingos Xavier; Ottmar, Roger

2012-01-01

Smoke from forest fires contains significant amounts of gaseous and particulate pollutants. Firefighters exposed to wildland fire smoke can suffer from several acute and chronic adverse health effects. Consequently, exposure data are of vital importance for the establishment of cause/effect relationships between exposure to smoke and firefighter health effects. The aims of this study were to (1) characterize the relationship between wildland smoke exposure and medical parameters and (2) identify health effects pertinent to wildland forest fire smoke exposure. In this study, firefighter exposure levels of carbon monoxide (CO), nitrogen dioxide (NO₂), and volatile organic compounds (VOC) were measured in wildfires during three fire seasons in Portugal. Personal monitoring devices were used to measure exposure. Firefighters were also tested for exhaled nitric oxide (eNO) and CO before and after their firefighting activities. Data indicated that exposure levels during firefighting activities were beyond limits recommended by the Occupational Exposure Standard (OES) values. Medical tests conducted on the firefighters also indicated a considerable effect on measured medical parameters, with a significant increase in CO and decrease in NO in exhaled air of majority of the firefighters.

[Geomagnetic field variations in the human prenatal period and cancer in adults].

PubMed

Iamshanov, V A

2007-01-01

Our earlier evidence pointed to a relationship between geomagnetic field (GMF) variations in pre- and early postnatal periods and appearance in the future of oncopathology in these patients. It appears to contribute to risk for such malignancies in adults as breast, lung, liver, bladder, kidney, prostate, hypophysis cancer, ovarian carcinoma, skin melanoma, Hodgkin's disease, lymphoma, and probably stomach cancer. No link was detected between esophageal, thyroid, colorectal cancer or cervical carcinoma, on the one hand, and GMF variations in prenatal period, on the other. It is suggested that low intensity of GMF is associated with increased death of macrophages and other granulocytes as well as nitric oxide formation both in fetal and maternal organism. The latter factor induces genes responsible for detoxication. In adults, under normal or disturbed GMF conditions, detoxication processes take care of excessive blood-nitric oxide. Both in fetus and mother, due to high GMF intensity, granulocyte decay is inhibited thus causing nitric oxide levels to fall. As a consequence, detoxication fails. That accounts for excessive blood-nitric oxide formation at adult stage when GMF intensity is low or normal. Nitric oxide causes certain nitrosamines to form, which are tissue-specific carcinogens. Therefore, the lower level of GMF oscillations was in pre- and early postnatal periods than in more late terms tumors appeared (for example, the negative correlation for breast cancer took place).

Antidepressant-like effect of folic acid: Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway.

PubMed

Brocardo, Patrícia de Souza; Budni, Josiane; Lobato, Kelly Ribas; Kaster, Manuella Pinto; Rodrigues, Ana Lúcia S

2008-11-19

Antidepressant-like activity of folic acid in forced swimming test and in the tail suspension test was demonstrated previously by our group. In this study we investigated the involvement of N-methyl-d-aspartate (NMDA) receptors and l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate pathway in its antidepressant-like effect in the forced swimming test in mice. The antidepressant-like effect of folic acid (10 nmol/site, i.c.v.) was prevented by the pretreatment of mice with NMDA (0.1 pmol/site, i.c.v.), l-arginine (750 mg/kg, i.p., substrate for nitric oxide synthase), S-nitroso-N-acetyl-penicillamine (SNAP, 25 microg/site, i.c.v, a NO donor) or sildenafil (5 mg/kg, i.p., phosphodiesterase 5 inhibitor). The administration of 7-nitroindazole (25 and 50 mg/kg, i.p., a specific neuronal nitric oxide synthase (nNOS) inhibitor) or methylene blue (20 mg/kg, i.p., direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase) in combination with a sub-effective dose of folic acid (1 nmol/site, i.c.v.) reduced the immobility time in the FST as compared with either drug alone. Together the results suggest that the antidepressant-like effect of folic acid in the forced swimming test is dependent on an inhibition of either NMDA receptors or NO and cGMP synthesis.

The effect of nitric oxide releasing cream on healing pressure ulcers

PubMed Central

Saidkhani, Vahid; Asadizaker, Marziyeh; Khodayar, Mohammad Javad; Latifi, Sayed Mahmoud

2016-01-01

Background: Pressure ulcer is one of the main concerns of nurses in medical centers around the world, which, if untreated, causes irreparable problems for patients. In recent years, nitric oxide (NO) has been proposed as an effective method for wound healing. This study was conducted to determine the effect of nitric oxide on pressure ulcer healing. Materials and Methods: In this clinical trial, 58 patients with pressure ulcer at hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences were homogenized and later divided randomly into two groups of treatment (nitric oxide cream; n = 29) and control (placebo cream; n = 29). In this research, the data collection tool was the Pressure Ulcer Scale for Healing (PUSH). At the outset of the study (before using the cream), the patients' ulcers were examined weekly in terms of size, amount of exudates, and tissue type using the PUSH tool for 3 weeks. By integrating these three factors, wound healing was determined. Data were analyzed using SPSS. Results: Although no significant difference was found in terms of the mean of score size, the amount of exudates, and the tissue type between the two groups, the mean of total score (healing) between the two groups was statistically significant (P = 0.04). Conclusions: Nitric oxide cream seems to accelerate wound healing. Therefore, considering its easy availability and cost-effectiveness, it can be used for treating pressure ulcers in the future. PMID:27186212

Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: Essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hien, Tran Thi; Kim, Nak Doo; Pokharel, Yuba Raj

2010-08-01

We previously showed that ginsenosides increase nitric oxide (NO) production in vascular endothelium and that ginsenoside Rg3 (Rg3) is the most active one among ginseng saponins. However, the mechanism for Rg3-mediated nitric oxide production is still uncertain. In this study, we determined whether Rg3 affects phosphorylation and expression of endothelial nitric oxide synthase (eNOS) in ECV 304 human endothelial cells. Rg3 increased both the phosphorylation and the expression of eNOS in a concentration-dependent manner and a maximal effect was found at 10 {mu}g/ml of Rg3. The enzyme activities of phosphatidylinositol 3-kinase (PI3-kinase), c-Jun N-terminal kinase (JNK), and p38 kinase weremore » enhanced as were estrogen receptor (ER)- and glucocorticoid receptor (GR)-dependent reporter gene transcriptions in Rg3-treated endothelial cells. Rg3-induced eNOS phosphorylation required the ER-mediated PI3-kinase/Akt pathway. Moreover, Rg3 activates AMP-activated protein kinase (AMPK) through up-regulation of CaM kinase II and Rg3-stimulated eNOS phosphorylation was reversed by AMPK inhibition. The present results provide a mechanism for Rg3-stimulated endothelial NO production.« less

Substantial Effect of Melanin Influencing Factors on In vitro Melanogenesis in Muzzle Melanocytes of Differently Colored Hanwoo.

PubMed

Amna, Touseef; Park, Kyoung Mi; Cho, In-Kyung; Choi, Tae Jeong; Lee, Seung Soo; Seo, Kang-Seok; Hwang, Inho

2012-07-01

The present study was designed to investigate the effect of α-melanocyte-stimulating hormone (α-MSH), nitric oxide (NO) and L-cysteine on melanin production and expression of related genes MC1R, Tyr, Tyrp-1 and Tyrp-2 in muzzle melanocytes of differently colored three native Hanwoo cattle. Muzzle samples were taken from black, brindle and brown Hanwoo and purified melanocytes were cultured with α-MSH, nitric oxide and L-cysteine at 100 nM, 50 µM and 0.07 mg/ml of media respectively. The amounts of total melanin, eumelanin and mRNA expression at Tyr, Tyrp-1, Tyrp-2 and MC1R levels were quantified. α-MSH and nitric oxide significantly increased (p<0.05) the amount of total melanin in black and brindle whereas eumelanin production in brown Hanwoo muzzle melanocytes. On the contrary, L-cysteine greatly (p<0.05) depressed the eumelanin production in black color but increased in brown. Simultaneously, up regulation of Tyr by nitric oxide and α-MSH and down regulation of Tyr, Tyrp-2 and MC1R genes by L-cysteine were observed in muzzle melanocytes of all three phenotypes. The results of this study revealed nitric oxide and α-MSH contribute hyper-pigmentation by enhancing eumelanogenesis whereas L-cysteine contributes to pheomelanin production in different colored Hanwoo muzzle melanocytes.

Substantial Effect of Melanin Influencing Factors on In vitro Melanogenesis in Muzzle Melanocytes of Differently Colored Hanwoo

PubMed Central

Amna, Touseef; Park, Kyoung Mi; Cho, In-Kyung; Choi, Tae Jeong; Lee, Seung Soo; Seo, Kang-Seok; Hwang, Inho

2012-01-01

The present study was designed to investigate the effect of α-melanocyte-stimulating hormone (α-MSH), nitric oxide (NO) and L-cysteine on melanin production and expression of related genes MC1R, Tyr, Tyrp-1 and Tyrp-2 in muzzle melanocytes of differently colored three native Hanwoo cattle. Muzzle samples were taken from black, brindle and brown Hanwoo and purified melanocytes were cultured with α-MSH, nitric oxide and L-cysteine at 100 nM, 50 µM and 0.07 mg/ml of media respectively. The amounts of total melanin, eumelanin and mRNA expression at Tyr, Tyrp-1, Tyrp-2 and MC1R levels were quantified. α-MSH and nitric oxide significantly increased (p<0.05) the amount of total melanin in black and brindle whereas eumelanin production in brown Hanwoo muzzle melanocytes. On the contrary, L-cysteine greatly (p<0.05) depressed the eumelanin production in black color but increased in brown. Simultaneously, up regulation of Tyr by nitric oxide and α-MSH and down regulation of Tyr, Tyrp-2 and MC1R genes by L-cysteine were observed in muzzle melanocytes of all three phenotypes. The results of this study revealed nitric oxide and α-MSH contribute hyper-pigmentation by enhancing eumelanogenesis whereas L-cysteine contributes to pheomelanin production in different colored Hanwoo muzzle melanocytes. PMID:25049660

Caveolin versus calmodulin. Counterbalancing allosteric modulators of endothelial nitric oxide synthase.

PubMed

Michel, J B; Feron, O; Sase, K; Prabhakar, P; Michel, T

1997-10-10

Nitric oxide is synthesized in diverse mammalian tissues by a family of calmodulin-dependent nitric oxide synthases. The endothelial isoform of nitric oxide synthase (eNOS) is targeted to the specialized signal-transducing membrane domains termed plasmalemmal caveolae. Caveolin, the principal structural protein in caveolae, interacts with eNOS and leads to enzyme inhibition in a reversible process modulated by Ca2+-calmodulin (Michel, J. B., Feron, O., Sacks, D., and Michel, T. (1997) J. Biol. Chem. 272, 15583-15586). Caveolin also interacts with other structurally distinct signaling proteins via a specific region identified within the caveolin sequence (amino acids 82-101) that appears to subserve the role of a "scaffolding domain." We now report that the co-immunoprecipitation of eNOS with caveolin is completely and specifically blocked by an oligopeptide corresponding to the caveolin scaffolding domain. Peptides corresponding to this domain markedly inhibit nitric oxide synthase activity in endothelial membranes and interact directly with the enzyme to inhibit activity of purified recombinant eNOS expressed in Escherichia coli. The inhibition of purified eNOS by the caveolin scaffolding domain peptide is competitive and completely reversed by Ca2+-calmodulin. These studies establish that caveolin, via its scaffolding domain, directly forms an inhibitory complex with eNOS and suggest that caveolin inhibits eNOS by abrogating the enzyme's activation by calmodulin.

Nitric oxide-induced calcium release: activation of type 1 ryanodine receptor by endogenous nitric oxide.

PubMed

Kakizawa, Sho; Yamazawa, Toshiko; Iino, Masamitsu

2013-01-01

Ryanodine receptors (RyRs), located in the sarcoplasmic/endoplasmic reticulum (SR/ER) membrane, are required for intracellular Ca2+ release that is involved in a wide range of cellular functions. In addition to Ca2+-induced Ca2+ release in cardiac cells and voltage-induced Ca2+ release in skeletal muscle cells, we recently identified another mode of intracellular Ca2+ mobilization mediated by RyR, i.e., nitric oxide-induced Ca2+ release (NICR), in cerebellar Purkinje cells. NICR is evoked by neuronal activity, is dependent on S-nitrosylation of type 1 RyR (RyR1) and is involved in the induction of long-term potentiation (LTP) of cerebellar synapses. In this addendum, we examined whether peroxynitrite, which is produced by the reaction of nitric oxide with superoxide, may also have an effect on the Ca2+ release via RyR1 and the cerebellar LTP. We found that scavengers of peroxynitrite have no significant effect either on the Ca2+ release via RyR1 or on the cerebellar LTP. We also found that an application of a high concentration of peroxynitrite does not reproduce neuronal activity-dependent Ca2+ release in Purkinje cells. These results support that NICR is induced by endogenous nitric oxide produced by neuronal activity through S-nitrosylation of RyR1.

Long-term exposure to traffic-related air pollution and progression of carotid artery atherosclerosis: a prospective cohort study

PubMed Central

Gan, Wen Qi; Allen, Ryan W; Brauer, Michael; Davies, Hugh W; Mancini, G B John; Lear, Scott A

2014-01-01

Objectives Epidemiological studies have demonstrated associations between long-term exposure to traffic-related air pollution and coronary heart disease (CHD). Atherosclerosis is the principal pathological process responsible for CHD events, but effects of traffic-related air pollution on progression of atherosclerosis are not clear. This study aimed to investigate associations between long-term exposure to traffic-related air pollution and progression of carotid artery atherosclerosis. Setting Healthy volunteers in metropolitan Vancouver, Canada. Participants and outcome measures 509 participants aged 30–65 years were recruited and followed for approximately 5 years. At baseline and end of follow-up, participants underwent carotid artery ultrasound examinations to assess atherosclerosis severity, including carotid intima-media thickness, plaque area, plaque number and total area. Annual change of each atherosclerosis marker during the follow-up period was calculated as the difference between these two measurements divided by years of follow-up. Living close to major roads was defined as ≤150 m from a highway or ≤50 m from a major road. Residential exposures to traffic-related air pollutants including black carbon, fine particles, nitrogen dioxide and nitric oxide were estimated using high-resolution land-use regression models. The data were analysed using general linear models adjusting for various covariates. Results At baseline, there were no significant differences in any atherosclerosis markers between participants living close to and those living away from major roads. After follow-up, the differences in annual changes of these markers between these two groups were small and not statistically significant. Also, no significant associations were observed with concentrations of traffic-related air pollutants including black carbon, fine particles, nitrogen dioxide and nitric oxide. Conclusions This study did not find significant associations between traffic-related air pollution and progression of carotid artery atherosclerosis in a region with lower levels and smaller contrasts of ambient air pollution. PMID:24710134

Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters.

PubMed

Sarnat, Jeremy A; Golan, Rachel; Greenwald, Roby; Raysoni, Amit U; Kewada, Priya; Winquist, Andrea; Sarnat, Stefanie E; Dana Flanders, W; Mirabelli, Maria C; Zora, Jennifer E; Bergin, Michael H; Yip, Fuyuen

2014-08-01

Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response. We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in the subjects' private vehicles. Biomarker measurements were conducted before, during, and immediately after the commutes and in 3 hourly intervals after commutes. At measurement time points within 3h after the commute, we observed mild to pronounced elevations relative to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative stress initiation, as well as decreases relative to baseline levels in the time-domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic dysfunction. We did not observe any detectable changes in lung function measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter or other systemic biomarkers of vascular injury. Water soluble organic carbon was associated with changes in eNO at all post-commute time-points (p<0.0001). Our results point to measureable changes in pulmonary and autonomic biomarkers following a scripted 2-h highway commute. Copyright © 2014 Elsevier Inc. All rights reserved.

Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters

PubMed Central

Sarnat, Jeremy A.; Golan, Rachel; Greenwald, Roby; Raysoni, Amit U.; Kewada, Priya; Winquist, Andrea; Sarnat, Stefanie E.; Flanders, W. Dana; Mirabelli, Maria C.; Zora, Jennifer E.; Bergin, Michael H.; Yip, Fuyuen

2015-01-01

Background Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. Objectives: We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response. Methods We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in the subjects’ private vehicles. Biomarker measurements were conducted before, during, and immediately after the commutes and in 3 hourly intervals after commutes. Results At measurement time points within 3 h after the commute, we observed mild to pronounced elevations relative to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative stress initiation, as well as decreases relative to baseline levels in the time-domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic dysfunction. We did not observe any detectable changes in lung function measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter or other systemic biomarkers of vascular injury. Water soluble organic carbon was associated with changes in eNO at all post-commute time-points (p < 0.0001). Conclusions Our results point to measureable changes in pulmonary and autonomic biomarkers following a scripted 2-h highway commute. PMID:24906070

The Role of Nitric Oxide in Modulating Retinal, Choroidal, and Anterior Uveal Blood Flows in the Domestic Piglet

DTIC Science & Technology

1993-11-17

that are substituted at the quanidino nitrogens are competitive Inhibitors of nitric ox!de synthase in a dOS&<lependent and enantiomerically specific...by nitric oxide. We were able to reduce basal chorc»dal and ante nor wea blood 99 flOYI by 47% and 43%, respectively, by enantiomeric specific...Atthough competitive blockade of NOS by L-NAME is enantiomerically specKle, It Is possible that there Is an allosteric binding site for these arginine

Reducing Dangerous Effects of Unsymmetrical Dimethyl Hydrazine as a Liquid Propellant by Addition of Hydroxyethylhydrazine, Part II, Performance with Several Oxidizers

NASA Astrophysics Data System (ADS)

Keshavarz, Mohammad Hossein; Ramadan, Alireza; Mousaviazar, Ali; Zali, Abbas; Shokrollahi, Arash

2011-07-01

This work continues the study of suitable binary liquid mixtures of unsymmetrical dimethylhydrazine (UDMH) and hydroxyethylhydrazine (HEH) to reduce the harmful effects of pure UDMH. The synthesized HEH was mixed with UDMH up to 40 wt% of HEH to study the performance and properties of binary liquid mixtures of UDMH/HEH. The existence of strong hydrogen bonding between HEH and UDMH provides low-volatile mixtures of these hydrazine derivatives. The addition of HEH significantly reduces the vapor pressure of UDMH, thus reducing the known UDMH health risk to inhalation exposure. Specific impulse was used to study performance of binary mixture UDMH/HEH with respect to pure UDMH. A binary mixture of UDMH/HEH reacts spontaneously in contact with nitrogen tetroxide, red fuming nitric acid (RFNA), and inhibited red fuming nitric acid (IRFNA).

Review of Federal Reference Method for Ozone: Nitric Oxide-Chemiluminescence:Supplemental Material for CASAC AMMS

EPA Science Inventory

ApproachPer suggestion made by CASAC AMMS members during the April 3, 2014 conference call on the Review of Federal Reference Method for Ozone: Nitric Oxide-Chemiluminescence, ORD has performed additional data analysis activities to explain and mitigate scatter observed in the co...

INDUCTION OF NITRIC OXIDE SYNTHASE AND ASSOCIATED TOXICITY IN LIVERS OF HARDHEAD CATFISH, ARIUS FELIS, FROM CONTROL AND EPIZOOTIC SITES

EPA Science Inventory

Earlier work with a live channel catfish (Ictalurus punctatus) pathogen, Edwardsiella ictaluri, demonstrated the induction of nitric oxide synthase (NOS) in the head kidney, paralleling enteric septicemia (Hawke et al. 1981; Schoor and Plumb 1994). However, another study exposing...

Estimates of nitric oxide production for lifting spacecraft reentry

NASA Technical Reports Server (NTRS)

Park, C.

1971-01-01

The amount of nitric oxide which may be produced by heating of air during an atmospheric reentry of a lifting spacecraft is estimated by three different methods. Two assume nitrogen fixation by the process of sudden freezing, and the third is a computer calculation using chemical rate equations.

Efficacy and residue analysis of nitric oxide fumigation of strawberries for control of Drosophila suzukii

USDA-ARS?s Scientific Manuscript database

Nitric oxide (NO) has been demonstrated as an effective fumigant against various insect pests on postharvest products under ultralow oxygen (ULO) conditions. NO showed efficacy against all life stages of insect pests with varied fumigation time and temperature, and had feasible cost-effectiveness to...

Detoxification of nitric oxide by Fusarium verticillioides is linked to denitrification

USDA-ARS?s Scientific Manuscript database

Nitric oxide (NO) is a potent cellular signaling molecule and a byproduct of nitrogen metabolism. High concentrations of NO are a form of nitrosative stress, and to alleviate this stress, organisms utilize flavohemoglobins to convert NO into nontoxic nitrate ions. We have investigated the capacity o...

Review of Federal Reference Method for Ozone: Nitric Oxide-Chemiluminescence

EPA Science Inventory

•The proposed new FRM measurement principle for ozone is based on quantitative measurement of the chemiluminescence emission from the gas-phase reaction of ozone in an air sample with nitric oxide (NO).•The chemiluminescence from the NO-O3 reaction (with excess NO) is p...

DEPENDENCE OF NITRIC OXIDE EMISSIONS ON VEHICLE LOAD: RESULTS FROM THE GTRP INSTRUMENTED VEHICLE PROGRAM

EPA Science Inventory

The presentation discussed the dependence of nitric oxide (NO) emissions on vehicle load, bases on results from an instrumented-vehicle program. The accuracy and feasibility of modal emissions models depend on algorithms to allocate vehicle emissions based on a vehicle operation...

ENVIRONMENTAL VARIABLES CONTROLLING NITRIC OXIDE EMISSIONS FROM AGRICULTURAL SOILS IN THE SOUTHEAST UNITED STATES

EPA Science Inventory

Fluxes of nitric oxide (NO) were measured during the summer of 1994 (12 July to 11 August) in the Upper Coastal Plain of North Carolina in a continuing effort to characterize NO emissions from intensively managed agricultural soils in the southeastern United States. Previous work...

Procedures of laboratory nitric oxide fumigation for pest control

USDA-ARS?s Scientific Manuscript database

Nitric oxide (NO) is a newly discovered fumigant and has the potential to be a safe and effective alternative for postharvest pest control. As NO reacts with oxygen spontaneously to produce nitrogen dioxide, NO fumigation must be conducted under ultralow oxygen (ULO) atmosphere and therefore has com...

Nitric oxide detoxification by Fusarium verticillioides involves flavohemoglobins and the denitrification pathway

USDA-ARS?s Scientific Manuscript database

Nitric oxide (NO) is a highly mobile and potent signaling molecule, yet as a free radical it can also cause nitrosative stress to cells. To alleviate negative effects from excessive accumulation of endogenous NO or from potential exogenous sources, flavohemoglobin proteins can convert NO into nonto...

Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism

EPA Science Inventory

The adaptive mechanisms that protect brain metabolism during and after hypoxia, for instance, during hypoxic preconditioning, are coordinated in part by nitric oxide (NO). We tested the hypothesis that acute transient hypoxia stimulates NO synthase (NOS)-activated mechanisms of m...

21 CFR 862.3080 - Breath nitric oxide test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Breath nitric oxide test system. 862.3080 Section 862.3080 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test...

21 CFR 862.3080 - Breath nitric oxide test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Breath nitric oxide test system. 862.3080 Section 862.3080 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test...

21 CFR 862.3080 - Breath nitric oxide test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Breath nitric oxide test system. 862.3080 Section 862.3080 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test...

21 CFR 862.3080 - Breath nitric oxide test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Breath nitric oxide test system. 862.3080 Section 862.3080 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test...

Efficacy and safety of nitric oxide fumigation for controlling codling moth in apples

USDA-ARS?s Scientific Manuscript database

Nitric oxide (NO) fumigation under ultralow oxygen (ULO) conditions was studied for its efficacy in controlling codling moth and effects on postharvest quality of apples. NO fumigation was effective against eggs and larvae of different sizes on artificial diet in 48 h treatments. Small larvae were...

Oxidized LDL at low concentration promotes in-vitro angiogenesis and activates nitric oxide synthase through PI3K/Akt/eNOS pathway in human coronary artery endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Shan; Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong; Wong, Siu Ling

Research highlights: {yields} Low-concentration oxidized LDL enhances angiogenesis through nitric oxide (NO). {yields} Oxidized LDL increases intracellular NO levels via eNOS phosphorylation. {yields} Akt/PI3K signaling mediates oxidized LDL-induced eNOS phosphorylation. -- Abstract: It has long been considered that oxidized low-density lipoprotein (oxLDL) causes endothelial dysfunction and is remarkably related to the development of atherosclerosis. However, the effect of oxLDL at very low concentration (<10 {mu}g/ml) on the endothelial cells remains speculative. Nitric oxide (NO) has a crucial role in the endothelial cell function. In this study, we investigated the effect of oxLDL at low concentration on NO production and proliferation,more » migration, tube formation of the human coronary artery endothelial cells (HCAEC). Results showed that oxLDL at 5 {mu}g/ml enhanced HCAEC proliferation, migration and tube formation. These phenomena were accompanied by an increased intracellular NO production. L-NAME (a NOS inhibitor), LY294002 and wortmannin (PI3K inhibitors) could abolish oxLDL-induced angiogenic effects and prevent NO production in the HCAEC. The phosphorylation of Akt, PI3K and eNOS were up-regulated by oxLDL, which was attenuated by LY294002. Our results suggested that oxLDL at low concentration could promote in-vitro angiogenesis and activate nitric oxide synthesis through PI3K/Akt/eNOS pathway in HCAEC.« less

Repeated exposure to iron oxide nanoparticles causes testicular toxicity in mice.

PubMed

Sundarraj, Kiruthika; Manickam, Vijayprakash; Raghunath, Azhwar; Periyasamy, Madhivadhani; Viswanathan, Mangala Priya; Perumal, Ekambaram

2017-02-01

The aim of this study was to determine whether repeated exposure to iron oxide nanoparticles (Fe 2 O 3 -NPs) could be toxic to mice testis. Fe 2 O 3 -NPs (25 and 50 mg/kg) were intraperitoneally administered into mice once a week for 4 weeks. Our study showed that Fe 2 O 3 -NPs have the ability to cross the blood-testis barrier to get into the testis. The findings showed that exposure resulted in the accumulation of Fe 2 O 3 -NPs which was evidenced from the iron content and accumulation in the testis. Furthermore, 25 and 50 mg/kg Fe 2 O 3 -NPs administration increased the reactive oxygen species, lipid peroxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels with a concomitant decrease in the levels of antioxidants-superoxide dismutase, catalase, glutathione, and vitamin C. Increased expression of Bax, cleaved-caspase-3, and cleaved-PARP confirms apoptosis. Serum testosterone levels increased with increased concentration of Fe 2 O 3 -NPs exposure. In addition, the histopathological lesions like vacuolization, detachment, and sloughing of germ cells were also observed in response to Fe 2 O 3 -NPs treatment. The data from our study entailed that testicular toxicity caused by Fe 2 O 3 -NPs exposure may be associated with Fe 2 O 3 -NPs accumulation leading to oxidative stress and apoptosis. Therefore, precautions should be taken in the safe use of Fe 2 O 3 -NPs to avoid complications in the fertility of males. Further research will unravel the possible molecular mechanisms on testicular toxicity of Fe 2 O 3 -NPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 594-608, 2017. © 2016 Wiley Periodicals, Inc.

Garlic extracts prevent oxidative stress, hypertrophy and apoptosis in cardiomyocytes: a role for nitric oxide and hydrogen sulfide

PubMed Central

2012-01-01

Background In ancient times, plants were recognized for their medicinal properties. Later, the arrival of synthetic drugs pushed it to the backstage. However, from being merely used for food, plants are now been widely explored for their therapeutic value. The current study explores the potential of skin and flesh extracts from a hard-necked Rocambole variety of purple garlic in preventing cardiomyocyte hypertrophy and cell death. Methods Norepinephrine (NE) was used to induce hypertrophy in adult rat cardiomyocytes pretreated with garlic skin and flesh extracts. Cell death was measured as ratio of rod to round shaped cardiomyocytes. Fluorescent probes were used to measure apoptosis and oxidative stress in cardiomyocytes treated with and without extracts and NE. Pharmacological blockade of nitric oxide (NO) and hydrogen sulfide (H2S) were used to elucidate the mechanism of action of garlic extracts. Garlic extract samples were also tested for alliin and allicin concentrations. Results Exposure of cardiomyocytes to NE induced an increase in cell size and cell death; this increase was significantly prevented upon treatment with garlic skin and flesh extracts. Norepinephrine increased apoptosis and oxidative stress in cardiomyocytes which was prevented upon pretreatment with skin and flesh extracts; NO, and H2S blockers significantly inhibited this beneficial effect. Allicin and alliin concentration were significantly higher in garlic flesh extract when compared to the skin extract. Conclusion These results suggest that both skin and flesh garlic extracts are effective in preventing NE induced cardiomyocyte hypertrophy and cell death. Reduction in oxidative stress may also play an important role in the anti-hypertrophic and anti-apoptotic properties of garlic extracts. These beneficial effects may in part be mediated by NO and H2S. PMID:22931510

Therapeutic Role of Resveratrol and Quercetin on Aortic Fibroblasts of Psammomys obesus After Oxidative Stress by Hydrogen Peroxide.

PubMed

Boumaza, Saliha; Belkebir, Aicha; Neggazi, Samia; Sahraoui, Hamid; Berdja, Sihem; Smail, Leila; Benazzoug, Yasmina; Kacimi, Ghoti; Aouichat Bouguerra, Souhila

In our study, we propose to analyze the effects of resveratrol (RES) and quercetin (QRC) on proliferation markers, oxidative stress, apoptosis, and inflammation of aortic fibroblasts of Psammomys obesus after induced oxidative stress by hydrogen peroxide (H2O2). Fibroblasts were incubated in RES 375 μM and QRC 0.083 μM for 24 hours after exposure to H2O2 1.2 mM for 6 hours. We performed the proliferation rate, cells viability, morphological analyses, cytochrome c, Akt, ERK1/2, and p38 MAPK quantification. The redox status was achieved by proportioning of malondialdehyde, nitric monoxide, advanced oxidation protein products, carbonyl proteins, catalase, and superoxide dismutase activity. The inflammation was measured by TNFα, MCP1, and NF-kB assay. The extracellular matrix (ECM) remodeling was performed by SDS-PAGE. Stressed fibroblasts showed a decrease of cell proliferation and viability, hypertrophy and oncosis, chromatin hypercondensation and increase of cytochrome c release characteristic of apoptosis, activation of ERK1/2 and Akt pathway, and decreases in p38 MAPK pathways marking the cellular resistance. The redox state was disrupted by increased malondialdehyde, nitric monoxide, advanced oxidation protein products, carbonyl protein production, catalase and superoxide dismutase activity, and a decreased production of proteins including collagens. Inflammation state was marked by MCP-1, TNFα, and NF-kB increase. Treatment of fibroblasts stressed by RES and QRC inverted the oxidative stress situation decreasing apoptosis and inflammation, and improving the altered redox status and rearrangement of disorders observed in extracellular matrix. H2O2 induced biochemical and morphological alterations leading to apoptosis. An improved general condition is observed after treatment with RES and QRC; this explains the antioxidant and antiapoptotic effects of polyphenols.

Statins and nitric oxide donors affect thrombospondin 1-induced chemotaxis.

PubMed

Seymour, Keri; Stein, Jeffrey; Han, Xuan; Maier, Kristopher G; Gahtan, Vivian

2014-01-01

Thrombospondin 1 (TSP-1) induces vascular smooth muscle cell (VSMC) migration and intimal hyperplasia. Statins and nitric oxide (NO) donors decrease intimal hyperplasia. We previously showed that statins (long-term exposure) and NO donors inhibit TSP-1-induced VSMC chemotaxis. (1) Pretreatment with short-term statin will inhibit TSP-1-induced VSMC chemotaxis and (2) NO donors will enhance statin inhibition of TSP-1-induced or platelet-derived growth factor (PDGF)-induced VSMC chemotaxis. We examined these treatment effects on TSP-1-induced VSMC chemotaxis: (1) long-term (20 hours) versus short-term (20 minutes) pravastatin, (2) diethylenetriamine NONOate (DETA/NO) or S-nitroso-N-acetylpenicillamine (SNAP) in combination with pravastatin, and (3) comparison of TSP-1 to PDGF as a chemoattractant. Pravastatin (long term or short term) inhibited TSP-1-induced chemotaxis. Diethylenetriamine NONOate and SNAP impeded statin inhibition of TSP-1-induced chemotaxis. Platelet-derived growth factor and TSP-1 had opposite effects on DETA/NO-pravastatin treatment. Short-term statin pretreatment inhibited TSP-1-induced VSMC chemotaxis, suggesting a pleiotropic effect. High-dose NO reversed statin inhibition of TSP-1-induced chemotaxis, suggesting NO and statin combination therapies warrant further study. © The Author(s) 2014.

Fluid flow stimulates rapid and continuous release of nitric oxide in osteoblasts

NASA Technical Reports Server (NTRS)

Johnson, D. L.; McAllister, T. N.; Frangos, J. A.

1996-01-01

Interstitial fluid flow may mediate skeletal remodeling in response to mechanical loading. Because nitric oxide (NO) has been shown to be an osteoblast mitogen and inhibitor of osteoclastic resorption, we investigated and characterized the role of fluid shear on the release of NO in osteoblasts. Rat calvarial cells in a stationary culture produced undetectable levels of NO. Fluid shear stress (6 dyn/cm2) rapidly increased NO release rate to 9.8 nmol.h-1.mg protein-1 and sustained this production for 12 h of exposure to flow. Cytokine treatment also induced NO synthesis after a 12-h lag phase of zero production, followed by a production rate of 0.6 nmol.h-1.mg protein-1. Flow-induced NO production was blocked by the NO synthase (NOS) inhibitor NG-amino-L-arginine, but not by dexamethasone, which suggests that the flow stimulated a constitutive NOS isoform. This is the first time that a functional constitutively present NOS isoform has been identified in osteoblasts. Moreover, fluid flow represents the most potent stimulus of NO release in osteoblasts reported to date. Fluid flow-induced NO production may therefore play a primary role in bone maintenance and remodeling.

Intermittent hydrostatic pressure inhibits shear stress-induced nitric oxide release in human osteoarthritic chondrocytes in vitro.

PubMed

Lee, Mel S; Trindade, Michael C D; Ikenoue, Takashi; Schurman, David J; Goodman, Stuart B; Smith, R Lane

2003-02-01

To test the effects of intermittent hydrostatic pressure (IHP) on nitric oxide (NO) release induced by shear stress and matrix macromolecule gene expression in human osteoarthritic chondrocytes in vitro. Chondrocytes isolated from cartilage samples from 9 patients with osteoarthritis were cultured and exposed to either shear stress or an NO donor. Nitrite concentration was measured using the Griess reaction. Matrix macromolecule mRNA signal levels were determined using reverse-transcriptase polymerase chain reaction and quantified by imaging analysis software. Exposure to shear stress upregulated NO release in a dose and time-dependent manner. Application of IHP inhibited shear stress induced NO release but did not alter NO release from chondrocytes not exposed to shear stress. Shear stress induced NO or addition of an NO donor (sodium nitroprusside) was associated with decreased mRNA signal levels for the cartilage matrix proteins, aggrecan, and type II collagen. Intermittent hydrostatic pressure blocked the inhibitory effects of sodium nitroprusside but did not alter the inhibitory effects of shear stress on cartilage macromolecule gene expression. Our data show that shear stress and IHP differentially alter chondrocyte metabolism and suggest that a balance of effects between different loading forces preserve cartilage extracellular matrix in vivo.

Androstenediol inhibits the trauma-hemorrhage-induced increase in caspase-3 by downregulating the inducible nitric oxide synthase pathway.

PubMed

Kiang, Juliann G; Peckham, Russell M; Duke, Leah E; Shimizu, Tomoharu; Chaudry, Irshad H; Tsokos, George C

2007-03-01

Soft tissue trauma and hemorrhage (T-H) diminishes various aspects of liver function, while it increases hepatic nitrate/nitrite, inducible nitric oxide synthase (iNOS), and endothelin-1 levels. Treatment with androstenediol (AED) inhibits the T-H-induced alterations of the above parameters. We sought to identify the molecular events underlying the beneficial effect of AED. Exposure of rats to T-H significantly increased the caspase-3 activity and protein, whereas treatment with AED significantly limited these increases. AED treatment also suppressed the T-H-induced increase in iNOS by effectively altering the levels of key transcription factors involved in the regulation of iNOS expression. Immunoprecipitation and immunoblotting analyses indicate that T-H increased apoptosome formation, and AED treatment significantly decreased it. Modulating the iNOS protein by transfecting cells with iNOS gene or small interfering RNA further confirmed the correlation between iNOS and caspase-3. Our data indicate that AED limits caspase-3 expression by suppressing the expression of transcription factors involved in the production of iNOS, resulting in decreased apoptosome. AED can potentially be a useful adjuvant for limiting liver apoptosis following T-H shock.

Mechanisms for impaired effector function in alveolar macrophages from marijuana and cocaine smokers.

PubMed

Roth, Michael D; Whittaker, Katherine; Salehi, Ken; Tashkin, Donald P; Baldwin, Gayle C

2004-02-01

Lung macrophages provide a first line of host defense against inhaled pathogens and their function is impaired in the lungs of inhaled substance abusers. In order to investigate the mechanism for this impairment, alveolar macrophages (AM) were recovered from nonsmokers (NS), regular tobacco smokers (TS), marijuana smokers (MS), or crack cocaine smokers (CS), and evaluated for their production of nitric oxide (NO) and the role of NO as an antimicrobial effector molecule. AM from NS and TS efficiently killed Staphylococcus aureus and their antibacterial activity correlated closely with the production of nitrite and the expression of mRNA encoding for inducible nitric oxide synthase (iNOS). In contrast, AM collected from MS and CS exhibited limited antimicrobial activity that was not affected by an inhibitor of iNOS, or associated with expression of iNOS. Treatment with either granulocyte/macrophage colony-stimulating factor (GM-CSF) or interferon-gamma restored the ability of these cells to produce NO and to kill bacteria. These findings confirm a significant role for NO as an antibacterial effector molecule used by normal human AM and suggest that this host defense mechanism is suppressed by habitual exposure to inhaled marijuana or crack cocaine in vivo.

Fact and Fiction of Nitrous Oxide Production By Nitrification

NASA Astrophysics Data System (ADS)

Stein, L. Y.; Kozlowski, J.; Stieglmeier, M.; Klotz, M. G.; Schleper, C.

2014-12-01

An accepted dogma in nitrification research is that ammonia-oxidizing bacteria (AOB) produce a modicum of nitrous oxide (N2O) during nitritation via incomplete oxidation of hydroxylamine, and substantially more at low oxygen concentrations via nitrifier denitrification.The nitrifier denitrification pathway involves the reduction of nitrite to N2O via nitric oxide and was thought to require activities of a copper-containing nitrite reductase (NirK) and nitric oxide reductase (NorB); inventory encoded in most, but not all AOB genome sequences. The discovery of nirK genes in ammonia-oxidizing Thaumarchaeota (AOA) resulted in a slew of publications stating that AOA must also perform nitrifier denitrification and, due to their high abundance, must control the majority of nitrification-linked N2O emissions. Prior to a publication by Stieglmeier et al. (2014), which definitively showed a lack of nitrifier denitrification by two axenic AOA cultures, other researchers relied on enrichment cultures, negative data, and heavy inferencing without direct demonstration of either a functional pathway or involvement of specific genes or enzymes. AOA genomes lack recognizable nitric oxide reductases and thermophilic AOA also lack nirK genes. Physiological and microrespirometry experiments with axenic AOB and AOA cultures allowed us to demonstrate that: 1) AOB produce N2O via nitrifier denitrification even though some lack annotated nirK and/or norB genes; 2) nitrifier denitrification by AOB is reliant on nitric oxide but ammonia oxidation is not; 3) ammonia oxidation by AOA is reliant on production of nitric oxide; 4) AOA are incapable of generating N2O via nitrifier denitrification; 5) N2O production by AOA is from chemical interactions between NO and media components, most likely not by enzyme activity. Our results reveal operation of different N oxide transformation pathways in AOB and AOA governed by different environmental controls and involving different mechanisms of N2O production. Critical controls on these mechanisms are levels of oxygen and ammonium. Future calculations of relative contributions of AOB and AOA to N2O emissions must take into account physiological, enzymatic, and environmental differences between these two nitrifying microorganisms.

Brief Exposure to Secondhand Smoke Reversibly Impairs Endothelial Vasodilatory Function

PubMed Central

2014-01-01

Introduction: We sought to determine the effects of brief exposures to low concentrations of tobacco secondhand smoke (SHS) on arterial flow-mediated dilation (FMD, a nitric oxide-dependent measure of vascular endothelial function), in a controlled animal model never before exposed to smoke. In humans, SHS exposure for 30min impairs FMD. It is important to gain a better understanding of the acute effects of exposure to SHS at low concentrations and for brief periods of time. Methods: We measured changes in FMD in rats exposed to a range of real-world levels of SHS for durations of 30min, 10min, 1min, and 4 breaths (roughly 15 s). Results: We observed a dose-response relationship between SHS particle concentration over 30min and post-exposure impairment of FMD, which was linear through the range typically encountered in smoky restaurants and then saturated at higher concentrations. One min of exposure to SHS at moderate concentrations was sufficient to impair FMD. Conclusions: Brief SHS exposure at real-world levels reversibly impairs FMD. Even 1min of SHS exposure can cause reduction of endothelial function. PMID:24302638

Ozone-Induced Injury and Oxidative Stress in Bronchiolar Epithelium Are Associated with Altered Pulmonary Mechanics

PubMed Central

Sunil, Vasanthi R.

2013-01-01

In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3h) resulted in rapid (within 3h) and persistent (up to 72h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24h post-exposure. Ozone also induced the appearance of 8-hydroxy-2′-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3–24h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase-1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning. PMID:23492811

Research and Development of Hazardous/Toxic Waste Analytical Screening Procedures. Available Field Methods for Rapid Screening of Hazardous Waste Materials at Waste Sites (Class A Poisons).

DTIC Science & Technology

1982-01-01

bromide is listed as a positive interference. Nitric oxide and nitrogen dioxide can be detected by using the Draeger nitrous fumes detector tube. A... fumes exhibit a delay from the time of exposure to the onset of symptoms. This time delay would not be conducive for a rapid field screening test. It...Dangerous when strongly heated, emits highly toxic fumes . THRESHOLD LIMIT VALUE: No information available PHYSIOLOGICAL EFFECTS: A. Intensely irritating to

The production of nitric oxide in the coeliac ganglion modulates the effect of cholinergic neurotransmission on the rat ovary during the preovulatory period.

PubMed

Delsouc, María B; Della Vedova, María C; Ramírez, Darío; Delgado, Silvia M; Casais, Marilina

2018-05-01

The aim of the present work was to investigate whether the nitric oxide produced by the nitric oxide/nitric oxide synthase (NO/NOS) system present in the coeliac ganglion modulates the effects of cholinergic innervation on oxidative status, steroidogenesis and apoptotic mechanisms that take place in the rat ovary during the first proestrous. An ex vivo Coeliac Ganglion- Superior Ovarian Nerve- Ovary (CG-SON-O) system was used. Cholinergic stimulation of the CG was achieved by 10 -6  M Acetylcholine (Ach). Furthermore, 400 μM Aminoguanidine (AG) - an inhibitor of inducible-NOS was added in the CG compartment in absence and presence of Ach. It was found that Ach in the CG compartment promotes apoptosis in ovarian tissue, probably due to the oxidative stress generated. AG in the CG compartment decreases the release of NO and progesterone, and increases the release of estradiol from the ovary. The CG co-treatment with Ach and AG counteracts the effects of the ganglionic cholinergic agonist on ovarian oxidative stress, increases hormone production and decreases Fas mRNA expression. These results suggest that NO is an endogenous modulator of cholinergic neurotransmission in CG, with implication in ovarian steroidogenesis and the apoptotic mechanisms that take place in the ovary during the preovulatory period in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

Nitric oxide protects anterior pituitary cells from cadmium-induced apoptosis.

PubMed

Poliandri, Ariel H B; Velardez, Miguel O; Cabilla, Jimena P; Bodo, Cristian C A; Machiavelli, Leticia I; Quinteros, Alnilan F; Duvilanski, Beatriz H

2004-11-01

Cadmium (Cd2+) is a potent toxic metal for both plants and animals. Chronic exposure to low doses of Cd2+ results in damage to several organs. We have previously reported that Cd2+ induces apoptosis in anterior pituitary cells by a caspase- and oxidative stress-dependent mechanism. Nitric oxide (NO) synthesis is affected by Cd2+ in several systems. NO has been shown to be either cytoprotective or cytotoxic in many systems. The aim of this study was to evaluate the possible participation of NO in the cytotoxic effect of Cd2+ on rat anterior pituitary cells. Cell viability was evaluated by mitochondrial dehydrogenase activity assay and confirmed by microscopy, studying nuclear morphology. Here we show that DETA NONOate ((Z)-1-[2 (2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate), a long-term NO donor, at concentrations below 0.5 mM, reduces nuclear condensation and fragmentation and reverses the decrease in cellular activity induced by Cd2+. Cd2+, by itself, induced NO synthesis, and inhibition of this synthesis enhanced Cd2+ cytotoxicity. NO also prevented caspase-3 activation and lipidic peroxidation induced by Cd2+. The NO/cGMP pathway does not seem to be involved in the cytoprotective effect of NO. These results indicate that NO has a cytoprotective role in Cd2+ -induced apoptosis, suggesting that endogenous NO could have a physiological role in protecting anterior pituitary cells.

Long-term treatment of anterior pituitary cells with nitric oxide induces programmed cell death.

PubMed

Velardez, Miguel Omar; Poliandri, Ariel Hernán; Cabilla, Jimena Paula; Bodo, Cristian Carlos Armando; Machiavelli, Leticia Inés; Duvilanski, Beatriz Haydeé

2004-04-01

Nitric oxide (NO) plays a complex role in modulating programmed cell death. It can either protect the cell from apoptotic death or mediate apoptosis, depending on its concentration and the cell type and/or status. In this study, we demonstrate that long-term exposition to NO induces cell death of anterior pituitary cells from Wistar female rats. DETA NONOate (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, 1 mm], a NO donor that releases NO for an extended period of time, decreased cellular viability and prolactin release from primary cultures of anterior pituitary cells. Morphological studies showed an increase in the number of cells with chromatin condensation and nuclear fragmentation at 24 and 48 h after DETA/NO exposure. DNA internucleosomal fragmentation was also observed at the same time. Reversibility of the NO effect on cellular viability and prolactin release was observed only when the cells were incubated with DETA/NO for less than 6 h. Most apoptotic cells were immunopositive for prolactin, suggesting a high susceptibility of lactotrophs to the effect of NO. The cytotoxic effect of NO is dependent of caspase-9 and caspase-3, but seems to be independent of oxidative stress or nitrosative stress. Our results show that the exposition of anterior pituitary cells to NO for long periods induces programmed cell death of anterior pituitary cells.