• Title/Summary/Keyword: Nitric Oxide formation

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Function and regulation of nitric oxide signaling in Drosophila

  • Sangyun Jeong
    • Molecules and Cells
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    • v.47 no.1
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    • pp.100006.1-100006.10
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    • 2024
  • Nitric oxide (NO) serves as an evolutionarily conserved signaling molecule that plays an important role in a wide variety of cellular processes. Extensive studies in Drosophila melanogaster have revealed that NO signaling is required for development, physiology, and stress responses in many different types of cells. In neuronal cells, multiple NO signaling pathways appear to operate in different combinations to regulate learning and memory formation, synaptic transmission, selective synaptic connections, axon degeneration, and axon regrowth. During organ development, elevated NO signaling suppresses cell cycle progression, whereas downregulated NO leads to an increase in larval body size via modulation of hormone signaling. The most striking feature of the Drosophila NO synthase is that various stressors, such as neuropeptides, aberrant proteins, hypoxia, bacterial infection, and mechanical injury, can activate Drosophila NO synthase, initially regulating cellular physiology to enable cells to survive. However, under severe stress or pathophysiological conditions, high levels of NO promote regulated cell death and the development of neurodegenerative diseases. In this review, I highlight and discuss the current understanding of molecular mechanisms by which NO signaling regulates distinct cellular functions and behaviors.

Impaired Endothelium-Dependent Relaxation is Mediated by Reduced Production of Nitric Oxide in the Streptozotocin-Induced Diabetic Rats

  • Park, Kyoung-Sook;Kim, Cuk-Seong;Kang, Sang-Won;Park, Jin-Bong;Kim, Kwang-Jin;Chang, Seok-Jong;Jeon, Byeong-Hwa
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.3
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    • pp.263-270
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    • 2000
  • To evaluate the involvement of nitric oxide production on the endothelium-dependent relaxation in diabetes, we have measured vascular and endothelial function and nitric oxide concentration, and the expression level of endothelial nitric oxide synthase in the streptozotocin-induced diabetic rats. Diabetic rats were induced by the injection of streptozotocin (50 mg/kg i.v.) in the Sprague-Dawley rats. Vasoconstrictor responses to norepinephrine (NE) showed that maximal contraction to norepinephrine $(10^{-5}\;M)$ was significantly enhanced in the aorta of diabetic rats. Endothelium-dependent relaxation induced by acetylcholine was markedly impaired in the aorta of diabetic rats, these responses were little improved by the pretreatment with indomethacin. However, endothelium-independent relaxation induced by nitroprusside was not altered in the diabetic rats. Plasma nitrite and nitrate $(NO_2/_3)$ levels in diabetic rats were significantly lower than in non-diabetic rats. Western blot analysis using a monoclonal antibody against endothelial cell nitric oxide synthase (eNOS) revealed that the protein level was lower in the aorta of diabetic rats than in non-diabetic rats. These data indicate that nitric oxide formation and eNOS expression is reduced in diabetes, and this would, in part, account for the impaired endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic rats.

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Impact of Physiological Stresses on Nitric Oxide Formation by Green Alga, Scenedesmus obliquus

  • Mallick, Nirupama;Mohn, Friedrich-Helmuth;Rai, Lalchand;Soeder, Carl-J.
    • Journal of Microbiology and Biotechnology
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    • v.10 no.3
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    • pp.300-306
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    • 2000
  • The rate of apparent nitric oxide (NO) release, as measured in the exhaust gas of green alga, Scenedesmus obliquus, depended on the light intensity and pH. It doubled after lowering the temperature from $25^{\circ}C{\;}to{\;}15^{\circ}C$ and strongly decreased from $35^{\circ}C{\;}to{\;}42^{\circ}C$. The Scenedesmus cells, deficient in nitrogen or phosphorus, demonstrated a significant increase in NO production following their transfer to nitrate- and phosphate-rich media. The addition of herbicides (DCMU and glyphosate) or toxic concentrations of $Cu^{2+}{\;}or{\;}Fe^{3+}$ produced strong NO peaks, resembling those that occurred after sudden darkening. An increase in the $Ni^{2+}$ concentration to 20 ppm resulted in a gradual increase of NO release from the initial ~1.5 ppbv to>20 ppbv, whereas $Cd^{2+}$ instantaneously suppressed the NO by the cultures of Scenedesmus was not altered by L-NNA, an inhibitor of nitric oxide synthase (NOS), or by its substrate, L-arginine. This seems to exclude the role of NOS in the NO formation under study. Accordingly, it can be assumed that the rate of NO formation is mainly a function of dynamic nitrite pool sizes and environmental factors significantly affect the NO production in algae.

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Coupling Efficiencies of m1, m3 and m5 Muscarinic Receptors to the Stimulation of Neuronal Nitric Oxide Synthase

  • Park, Sun-Hye;Lee, Seok-Yong;Cho, Tai-Soon
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.207-207
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    • 1996
  • Through molecular cloning, five muscarinic receptors have been identified. The muscarinic receptors can be generally grouped according to their coupling to either stimulation of phospholipase C (m1, m3, and m5) or the inhibition of adenylate cyclase (m2 and m4). Each m1, m3, and m5 receptors has the additional potential to couple to the activation of phospholipase A$_2$, C, and D, tyrosine kinase, and the mobilization of Ca$\^$2+/. However, the differences in coupling efficiencies to different second messenger systems between these receptors have not been studied well. Ectopic expression of each of these receptors in mammalian cells has provided the opportunity to evaluate the signal transduction of each in some detail. In this work we compared the coupling efficiencies of the m1, m3 and m5 muscarinic receptors expressed in chinese hamster ovary (CHO) cells to the Ca$\^$2+/ mobilization and the stimulation of neuronal nitric oxide synthase (nNOS). Because G protein/PLC/PI turnover/[(Ca$\^$2+/])i/NOS pathway was supposed as a main pathway for the production of nitric oxide via muscarinic receptors, we studied on ml, m3 and m5 receptors. Stimulation of guanylate cyclase activity in detector neuroblastoma cells was used as an index of generation nitric oxide (NO) in CHO cells. The agonist carbachol increased the cGMP formation and the intracellular [Ca$\^$2+/] in concentration dependent manner in three types of receptors and the increased cGMP formation was significantly attenuated by scavenger of NO or inhibitor of NOS. m5 receptors was most efficiently coupled to stimulation of nNOS, And, the coupling efficiencies to the stimulation of neuronal nitric oxide synthase in three types of receptors were parallel with them to the Ca$\^$2+/ mobilization.

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Studies on the Regulation of Nitric oxide Synthesis in Murine Mononuclear Phagocytes (마우스 단핵 탐식 세포에서 Nitric oxide 생성의 조절 기전에 관한 연구)

  • 최병기;김수응
    • Environmental Analysis Health and Toxicology
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    • v.15 no.3
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    • pp.69-80
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    • 2000
  • ADP-rubosylation may be involved in the process of macrophage activation. Nitric oxide (NO) has emerged as an important intracellular and interacellular regulatory molecule with function as diverse as vasodilation, neural communication or host defense. NO is derived from the oxidation of the terminal guanidino nitrogen atom of L-arginine by the NADPH -dependent enzyme, nitric oxide synthase (NOS) which is one of the three different isomers in mammalian tissues. Since NO can exert protective or regulatory functions in the cell at a low concentration while toxic effects at higher concentrations, its role may be tightly regulated in the cell. Therefore, this paper was focused on signal transduction pathway of NO synthesis, role of endogenous TGF-$\beta$ in NO production. effect of NO on superoxide formation. Costimulation of murine peritoneal macrophages with interferon-gamma (IFN-γ) and phorbol 12-myristate 13-acetate (PMA) increased both NO secretion and mRNA expression of inducible nitric oxide synthase (iNOS) when PMA abolished costimulation. Pretreatmnet of the cells with PMA abolished costimuation effects due to the depletion of protein kinase C (PKC) activities . The involvement of PKC in NO secretion could be further confirmed by PKC inhibitor, stauroprine, and phorbol ester derivative, phorbol 12,13-didecanoate. Addition of actinomycine D in IFN-γ plus PMA stimulated cells inhibited both NO secretion and mRNA expression of iNOS indication that PMA stabilizes mRNA of iNOS . Exogenous TGF-$\beta$ reduced NO secretion in IFN -γ stimulated murine macrophages. However addition of antisense oligodeoxynucleotide (ODN) to TGF-$\beta$ to this system recovered the ability of NO production and inhibited mRNA expression of TGF-$\beta$. ACAS interactive laser cytometry analysis showed that transportation of FITC -labeled antisense ODN complementary to TGF-$\beta$ mRNA could be observed within 5 min and reached maximal intensity in 30 min in the murine macrophage cells. NO released by activated macrophages inhibits superoxide formation in the same cells . This inhibition nay be related on NO-induced auto -adenosine diphosphate (ADP) -ribosylation . In addition, ADP-ribosylation may be involved in the process of macrophage activation .

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Durability of Photocatalytic Cement after Nitric Oxide-Wet-Dry Cycling

  • Lee, Bo Yeon;Kurtis, Kimberly E.
    • Journal of the Korea Institute of Building Construction
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    • v.14 no.4
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    • pp.359-368
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    • 2014
  • Photocatalytic cement has been receiving attention due to its high oxidation power that reduces nitrogen oxide, thus contributing to a clean atmospheric environment. However, there has not yet been a thorough investigation on the effect of photocatalytic reactions on the durability of cementitious material, the parent material. In this study, photocatalytic cement samples were exposed to nitric oxide gas and UV along with cycles of wetting and drying to simulate environmental conditions. The surface of samples was characterized mechanically, chemically, and visually during the cycling. The results indicate that that the photocatalytic efficiency decreased with continued NO oxidation. The pits found from SEM indicated that chemical deterioration, such as acid attack or leaching, did occur. However, this was not confirmed by X-ray diffraction. The hardness was not affected, probably due to the formation of CSH as evidenced by the XRD pattern. In conclusion, it was found that photocatalysis could alter cementitious materials both chemically and mechanically, which could further affect long-term durability.

The Effect of Hydrogen Peroxide on Inducible Nitric Oxide Synthase Expression in Murine Macrophage RA W264.7 Cells (Murine macrophage RAW264.7에서 과산화수소가 유발형 산화질소 합성효소의 발현에 미치는 영향)

  • Ahn, Joong-Hyun;Song, Jeong-Sup
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.2
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    • pp.172-183
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    • 1999
  • Background: Nitric oxide is a short-lived effector molecule derived from L-arginine by the nitric oxide synthase(NOS). Nitric oxide plays a role in a number of physiologic and pathophysiologic functions including host defense, edema formation, and regulation of smooth muscle tone. Some kinds of cells including macrophage are known to produce large quantities of nitric oxide in response to inflammatory stimuli such as interleukin-$1\beta$(IL-$1\beta$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), interferon-$\gamma$(IFN-$\gamma$) and lipopolysaccharide(LPS). Reactive oxygen species are also known to be important in the pathogenesis of acute cell and tissue injury such as acute lung injury model Methods: Using the RA W264.7 cells, we have examined the ability of oxidant hydrogen peroxide($H_2O_2$) to stimulate nitric oxide production and inducible NOS mRNA expression. Also, we have examined the effects of NOS inhibitors and antioxidants on $H_2O_2$ induced nitric oxide production. Results: Stimulation of RAW264.7 cells with combinations of 100 ng/ml IL-$1\beta$, 100 ng/ml TNF-$\alpha$, and 100 U/ml IFN-$\gamma$ or 100 U/ml IFN-$\gamma$ and $1{\mu}g/ml$ LPS induced the synthesis of nitric oxide as measured by the oxidation products nitrite($NO_2^-$) and nitrate($NO_3^-$). Addition of $250 {\mu}M-2$ mM $H_2O_2$ to the cytokines significantly augmented the synthesis of $NO_2^-$ and $NO_3^-$(p<0.05). When cells were incubated with increasing concentrations of $H_2O_2$ in the presence of IL-$1\beta$, TNF-$\alpha$ and IFN-$\gamma$ at constant level, the synthesis of $NO_2^-$ and $NO_3^-$ was dose-dependently increased(p<0.05). $N^G$-nitro-L-arginine methyl ester(L-NAME), dose dependently, significantly inhibited the formation of $NO_2^-$ and $NO_3^-$ in cells stimulated with LPS, IFN-$\gamma$ and $H_2O_2$ at constant level(p<0.05). Catalase significantly inhibited the $H_2O_2$-induced augmentation of cytokine-induced $NO_2^-$ and $NO_3^-$ formation(p<0.05). But, boiled catalase did not produce a significant inhibition in comparison with the native enzyme. Another antioxidant 2-mercaptoethanol and orthophenanthroline dose-dependently suppressed $NO_2^-$ and $NO_3^-$ synthesis(p<0.05). Northern blotting demonstrated that H:02 synergistically stimulated the cytokine-induced iNOS mRNA expression in RA W264.7. Conclusion: These results suggest that $H_2O_2$ contributes to inflammatory process by augmenting the iNOS expression and nitric oxide synthesis induced by cytokines.

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A Study on Nitric Oxide Formation & Reduction in Industrial Burner (I) -NO Concetration-Distribution in Double Swirling Diffusion Flame by LIF- (산업용 고부하버너 연소에서의 $NO_x$ 형성 및 저감에 관한 연구(I)-레이저 유도 형광법(LIF)를 이용한 이중선회 확산화염의 NO 농도 분포 측정-)

  • 박경석;김경수
    • Journal of Energy Engineering
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    • v.10 no.4
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    • pp.379-386
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    • 2001
  • This experimental study deals with on Nitric Oxide Formation & Reduction in Industrial Bunner. In this study, Laser-induced fluorescence (LIF) techniques have been used for quantitative measurements of Nitric Oxide. The NO A-X (0, 0) Vibrational band around 226 nm was excited using a XeCl excimer-pumped dye laser. And on-line excitation used $P_{21}+Q_1(14.5)/R_{12}+Q_2(20.5)/P_1(23.5)$ transition, for minimizing the other interferential effect. The measurements were taken NO concentration distribution in double swirling diffusion flame. In this swirl burner, NO concentration in downstream fo the flame decrease as primary/secondary air ratio increases.

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Saururus chinenesis Extracts Scavenge Reactive Oxygen Species and Modulate Nitric Oxide Production in Raw 264.7 Macrophages

  • Oh, Jang-Hee;Shon, Hee-Kyoung;Oh, Moon-You;Chung, An-Sik
    • Toxicological Research
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    • v.18 no.2
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    • pp.117-127
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    • 2002
  • Saururus chinensis Baill has been used in Korean folk medicine for the treatment of various diseases such as edema, Jaundice, and furuncle. The components of this plant were extracted into four fraction. Among the four fraction, hexane and ethyl acetate fraction were highly toxic to 3T3 mouse embryo fibroblast and Raw 264.7 mouse macrophage, but n-butanol and residue fraction did not show any toxic effect to those cell lines. n-Butanol and residue fraction exhibited antioxidant effects on hydro-gen peroxide, hydroxyl radical, and superoxide anion directly in vitro and in the 3T3 fibroblasts. All the four fractions inhibited lipid peroxidation measured by thiobarbituric acid reactive substances (TBARS) formation. In addition, n-butanol and residue fraction showed inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide production, and also down-regulated inducible nitric oxide synthase (iNOS) mRNA transcription 6 h after LPS stimulation in Raw 204.7 cells. Only n-butanol fraction, which mainly consists of flavonoids, inhibited NF-kB activation by decreasing IkBa degradation 90 min after LPS stimulation. horn the results, it is suggested that this plant could be a good candidate material for drug development based on its antioxidant and/or anti-inflammatory constituents.

Luteolin and Chicoric Acid, Two Major Constituents of Dandelion Leaf, Inhibit Nitric Oxide and Lipid Peroxide Formation in Lipopolysaccharide-Stimulated RAW 264.7 Cells

  • Park, Chung-Mu;Park, Ji-Young;Song, Young-Sun
    • Preventive Nutrition and Food Science
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    • v.15 no.2
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    • pp.92-97
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    • 2010
  • Luteolin and chicoric acid are the most abundant phytochemicals in dandelion (Taraxacum officinale) leaf. In this study, four kinds of extraction methods [hot water, ambient temperature (AT) water, ethanol, and methanol] were applied to analyze the contents of both phytochemicals and verify their anti-inflammatory and antioxidative activities. The methanol extract showed the most potent nitric oxide (NO) inhibitory effect. The luteolin and chicoric acid concentrations were 3.42 and $12.86\;{\mu}g/g$ dandelion leaf in the methanol extract. The NO-suppressive effect of luteolin and chicoric acid was identified in a dose-dependent manner with $IC_{50}$ values of $21.2\;{\mu}M$ and $283.6\;{\mu}M$, respectively, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells without cytotoxicity. Malondialdehyde (MDA) concentration, as an index for free radical injury on cell membrane, was also dose-dependently inhibited by the two compounds. The suppressive effect was further examined using mRNA and protein expression levels, which were attributable to the inhibition of inducible nitric oxide synthase (iNOS). These results suggest that two phytochemicals in dandelion leaf, luteolin and chicoric acid, may play an important role in the amelioration of LPS-induced oxidative stress and inflammation.