Nitric oxide protects cultured rat hepatocytes from tumor necrosis factor-alpha-induced apoptosis by inducing heat shock protein 70 expression.
AuthorsKim YM,de Vera ME,Watkins SC,Billiar TR
JournalThe Journal of biological chemistry
PubMed ID8995451
Nitric oxide production and perivascular nitration in brain after carbon monoxide poisoning in the rat.
AuthorsIschiropoulos H, Beers MF, Ohnishi ST, Fisher D, Garner SE, Thom SR
JournalJ Clin Invest
PubMed ID8636405
'Nitric oxide is a short-lived free radical and physiological mediator which has the potential to cause cytotoxicity. Studies were conducted to investigate whether nitric oxide, and the potent oxidant peroxynitrite, were generated in brain during experimental carbon monoxide (CO) poisoning in the rat. Nitric oxide production was documented by electron ... More
Inhibition of amiloride-sensitive sodium-channel activity in distal lung epithelial cells by nitric oxide.
AuthorsDing JW, Dickie J, O'Brodovich H, Shintani Y, Rafii B, Hackam D, Marunaka Y, Rotstein OD
JournalAm J Physiol
PubMed ID9530173
'Distal lung epithelial cells (DLECs) play an active role in fluid clearance from the alveolus by virtue of their ability to actively transport Na+ from the alveolus to the interstitial space. The present study evaluated the ability of activated macrophages to modulate the bioelectric properties of DLECs. Low numbers of ... More
Contribution of sustained Ca2+ elevation for nitric oxide production in endothelial cells and subsequent modulation of Ca2+ transient in vascular smooth muscle cells in coculture.
AuthorsWang Y, Shin WS, Kawaguchi H, Inukai M, Kato M, Sakamoto A, Uehara Y, Miyamoto M, Shimamoto N, Korenaga R, Ando J, Toyo-oka T
JournalJ Biol Chem
PubMed ID8621428
'To elucidate the intracellular Ca2+ (Ca2+i ) transient responsible for nitric oxide (NO) production in endothelial cells (ECs) and the subsequent Ca2+i reduction in vascular smooth muscle cells (VSMCs), we administrated four agonists with different Ca2+i-mobilizing mechanisms for both cells in iso- or coculture. We monitored the Ca2+i of both ... More
Cardiac venous endothelial dysfunction after myocardial ischemia and reperfusion in dogs.
AuthorsLefer DJ, Nakanishi K, Vinten-Johansen J, Ma XL, Lefer AM
JournalAm J Physiol
PubMed ID1415612
'Endothelial dysfunction is a prominent occurrence in coronary arteries after myocardial ischemia and reperfusion. However, this has not been studied in coronary veins. Endothelium-dependent vasorelaxation was studied in cardiac venous rings obtained from dogs subjected to 60 min of coronary artery occlusion followed by 270 min of reperfusion, as well ... More
Endothelial dysfunction of hindquarter resistance vessels in experimental heart failure.
AuthorsDrexler H, Lu W
JournalAm J Physiol
PubMed ID1621825
'Local vascular alterations may contribute to increased peripheral vasoconstriction in chronic heart failure. To test whether endothelial dysfunction might be involved, the effect of acetylcholine, nitroglycerin, and NG-monomethyl-L-arginine (L-NMMA) was investigated in a constant-flow perfused hindquarter of rats with and without chronic heart failure (CHF) due to myocardial infarction. Changes ... More
Inhibition of nitric oxide synthase does not alter basal permeability of the blood-brain barrier.
AuthorsMayhan WG
JournalBrain Res
PubMed ID10650141
'The goal of the present study was to determine the role of basal synthesis/release of nitric oxide on the basal permeability characteristics of the blood-brain barrier to various sized molecules in vivo. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood-brain barrier was quantitated ... More
In the rat, endogenous nitric oxide modulates the response of the hypothalamic-pituitary-adrenal axis to interleukin-1 beta, vasopressin, and oxytocin.
AuthorsRivier C, Shen GH
JournalJ Neurosci
PubMed ID8158253
'Nitric oxide (NO) synthase (NOS), the enzyme responsible for NO formation, is found in hypothalamic neurons containing oxytocin (OT), vasopressin (VP), and to a lesser extent corticotropin-releasing factor (CRF). Because NO is reported to modulate endocrine activity, we have investigated the hypothesis that endogenous NO participates in ACTH released by ... More
N5-(1-Imino-3-butenyl)-L-ornithine. A neuronal isoform selective mechanism-based inactivator of nitric oxide synthase.
AuthorsBabu BR, Griffith OW
JournalJ Biol Chem
PubMed ID9535869
'Nitric oxide synthase (NOS) catalyzes the NADPH- and O2-dependent conversion of L-arginine to nitric oxide (NO) and citrulline; three isoforms, the neuronal (nNOS), endothelial, and inducible, have been identified. Because overproduction of NO is known to contribute to several pathophysiological conditions, NOS inhibitors are of interest as potential therapeutic agents. ... More
'Macrophage-colony stimulating factor (M-CSF) contributes to atherogenesis by regulating macrophage-derived foam cells in atherosclerotic lesions. Here we report that nitric oxide (NO) inhibits the expression of M-CSF in human vascular endothelial cells independent of guanylyl cyclase activation. The induction of M-CSF mRNA expression by either oxidized low density lipoprotein (ox-LDL) ... More
Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor/.NO through a radical reaction.
AuthorsAkaike T, Yoshida M, Miyamoto Y, Sato K, Kohno M, Sasamoto K, Miyazaki K, Ueda S, Maeda H
JournalBiochemistry
PubMed ID8422387
'A labile inorganic free radical, nitric oxide (.NO), is produced by nitric oxide synthase from the substrate L-arginine in various cells and tissues. It acts as an endothelium-derived relaxing factor (EDRF) or as a neurotransmitter in vivo. We investigated the reactivity of stable radical compounds, imidazolineoxyl N-oxides such as 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl ... More
Interleukin-4 stimulates cGMP production by IFN-gamma-activated human monocytes. Involvement of the nitric oxide synthase pathway.
AuthorsKolb JP, Paul-Eugene N, Damais C, Yamaoka K, Drapier JC, Dugas B
JournalJ Biol Chem
PubMed ID7511593
'Resting human blood monocytes from some donors were found to produce a small amount of 3''-5'' guanine cyclic monophosphate (cGMP) in response to interleukin 4 (IL-4). A much higher response was observed when monocytes were preincubated with interferon (IFN-gamma), which alone was ineffective. Preincubation of monocytes with IL-4 led, in ... More
Studies on NG-methylarginine derivatives in myelin basic protein from developing and mutant mouse brain.
AuthorsRawal N, Lee YJ, Paik WK, Kim S
JournalBiochem J
PubMed ID1280107
'The amounts of NG-methylarginine derivatives in myelin basic protein (MBP) purified from dysmyelinating mutant and different stages of normal myelinating mouse brains have been studied by using h.p.l.c. with a highly sensitive post-column o-phthaldialdehyde derivative-formation method. All three naturally occurring derivatives (NG-monomethylarginine (MeArg), NGN''G-dimethylarginine [Me2(sym)Arg] and NGNG-dimethylarginine [Me2(asym)Arg]) were found ... More
Evidence for dual components in the non-adrenergic non-cholinergic relaxation in the rat gastric fundus: role of endogenous nitric oxide and vasoactive intestinal polypeptide.
AuthorsD'Amato M, Currò D, Montuschi P
JournalJ Auton Nerv Syst
PubMed ID1587995
'The effects of trypsin and arginine analogues, alone or in combination, on half-maximal non-adrenergic, non-cholinergic (NANC) relaxation elicited by different pulse trains of electrical field stimulation were studied in the rat gastric fundus in order to investigate further the relative contribution of peptides and NO. Trypsin (1 microM) partially inhibited ... More
Nitric oxide: an endogenous modulator of leukocyte adhesion.
AuthorsKubes P, Suzuki M, Granger DN
JournalProc Natl Acad Sci U S A
PubMed ID1675786
'The objective of this study was to determine whether endogenous nitric oxide (NO) inhibits leukocyte adhesion to vascular endothelium. This was accomplished by superfusing a cat mesenteric preparation with inhibitors of NO production, NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine methyl ester (L-NAME), and observing single (30-microns diameter) venules by intravital video microscopy. ... More
Inhibition of depolarization-induced nitric oxide synthase activation by NS-7, a phenylpyrimidine derivative, in primary neuronal culture.
AuthorsTatsumi S, Itoh Y, Ma FH, Higashira H, Ukai Y, Yoshikuni Y, Kimura K
JournalJ Neurochem
PubMed ID9422347
'Neuronal nitric oxide synthase (NOS) is considered to be involved in the pathogenesis of ischemic brain damage. In the present study, the effect of a novel neuroprotective phenylpyrimidine derivative, 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride (NS-7), on depolarization-stimulated NOS activity was examined in cultured neurons of mouse cerebral cortex. Various depolarizing stimuli such as ... More
Endothelium-dependent relaxation and L-arginine metabolism in genetic hypertension.
AuthorsLee L, Webb RC
JournalHypertension
PubMed ID1568761
'This study characterizes the effects of L-arginine and NG-monomethyl L-arginine on dilator responsiveness of vascular tissue from Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. Rings of abdominal aorta were suspended in tissue baths for measurement of isometric force. After contraction induced by phenylephrine, cumulative addition of acetylcholine, L-arginine, or A23187 ... More
Ca(2+)-mediated damage to rabbit gastric mucosal cells: modulation by nitric oxide.
AuthorsTepperman BL, Soper BD
JournalEur J Pharmacol
PubMed ID8666044
'Pertubations in cellular Ca2+ homeostasis can lead to oxidative stress whereas nitric oxide has been shown to inactivate oxygen radicals. Therefore the effects of inhibition of nitric oxide (NO) synthase activity on Ca2+-mediated disruption to rabbit dispersed gastric mucosal cells have been examined. Addition of the Ca2+ ionophore A23187 (3-25 ... More
Enzymatic methylation of heterogeneous nuclear ribonucleoprotein in isolated liver nuclei.
AuthorsRajpurohit R, Paik WK, Kim S
JournalBiochim Biophys Acta
PubMed ID1643091
'Protein N-methyltransferase activity has been studied in the rat liver nuclei, using recombinant heterogeneous nuclear ribonucleoprotein particle protein A1 and histone as the methyl acceptors. The hydrolysates of these two enzymatically [methyl-3H]-labeled proteins, however, yielded different patterns of methylated amino acids on HPLC analysis: NG-monomethylarginine (92%) and NG-NG-dimethyl (asymmetric) arginine ... More
Lymphocyte migration through monolayers of endothelial cell lines involves VCAM-1 signaling via endothelial cell NADPH oxidase.
AuthorsMatheny HE, Deem TL, Cook-Mills JM
JournalJ Immunol
PubMed ID10843714
'Lymphocytes migrate from the blood across endothelial cells to reach foreign substances sequestered in peripheral lymphoid organs and inflammatory sites. To study intracellular signaling in endothelial cells during lymphocyte migration, we used murine endothelial cell lines that promote lymphocyte migration and constitutively express VCAM-1. The maximum rate of resting splenic ... More
Inhibitory effect of nitric oxide on the replication of a murine retrovirus in vitro and in vivo.
AuthorsAkarid K, Sinet M, Desforges B, Gougerot-Pocidalo MA
JournalJ Virol
PubMed ID7474119
'Nitric oxide (NO) exerts microbicidal effects on a broad spectrum of pathogens, including viruses, but its antiretrovirus properties have not yet been described. The purpose of this study was to determine whether NO inhibits murine Friend leukemia virus (FV) replication in vitro and to what extent NO may play a ... More
Multiple catalytic functions of brain nitric oxide synthase. Biochemical characterization, cofactor-requirement, and the role of N omega-hydroxy-L-arginine as an intermediate.
AuthorsKlatt P, Schmidt K, Uray G, Mayer B
JournalJ Biol Chem
PubMed ID7686905
'Brain NO (nitric oxide) synthase contains FAD, FMN, heme, and tetrahydrobiopterin as prosthetic groups and represents a multi-functional oxidoreductase catalyzing oxidation of L-arginine to NO and L-citrulline, formation of H2O2, and reduction of cytochrome c. We show that substrate analogues and inhibitors interacting with the heme block both the reductive ... More
Inhibition of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase blocks hypoxia-mediated down-regulation of endothelial nitric oxide synthase.
AuthorsLaufs U, Fata VL, Liao JK
JournalJ Biol Chem
PubMed ID9395516
'Hypoxia induces vasoconstriction, in part, by down-regulating endothelial cell nitric oxide synthase (ecNOS) expression. Previous studies indicate that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors improve endothelium-dependent relaxation by increasing ecNOS activity. To determine whether HMG CoA reductase inhibitors can prevent hypoxia-mediated down-regulation of ecNOS function and expression, human endothelial cells ... More
Endothelin-1 production by rat inner medullary collecting duct: effect of nitric oxide, cGMP, and immune cytokines.
AuthorsKohan DE, Padilla E
JournalAm J Physiol
PubMed ID8141330
'Nitric oxide (NO), guanosine 3'',5''-cyclic monophosphate (cGMP), and endothelin-1 (ET-1) inhibit collecting duct sodium reabsorption. Because the inner medullary collecting duct (IMCD) synthesizes NO and ET-1, we examined NO and cGMP regulation of IMCD ET-1 production. S-nitroso-N-acetylpenicillamine (SNAP, 6 h) increased NO and cGMP and modestly reduced ET-1 release in ... More
A fluorometric assay for the measurement of nitrite in biological samples.
AuthorsMisko TP, Schilling RJ, Salvemini D, Moore WM, Currie MG
JournalAnal Biochem
PubMed ID7504409
'The increasing importance of nitric oxide synthase has been underscored by the elucidation of its role in a growing number of normal and pathophysiological processes. Therefore, techniques for detection of nitrite/nitrate, oxidation products of the enzymatic conversion of arginine to citrulline and nitric oxide, should serve as useful tools in ... More
Electron transfer in the nitric-oxide synthases. Characterization of L-arginine analogs that block heme iron reduction.
AuthorsAbu-Soud HM, Feldman PL, Clark P, Stuehr DJ
JournalJ Biol Chem
PubMed ID7528212
'Heme iron reduction in the nitric-oxide synthases (NOSs) requires calmodulin binding and is associated with increased NO synthesis and NADPH oxidation (Abu-Soud, H. M., and Stuehr, D. J. (1993) Proc. Natl. Acad. Sci., U. S. A. 90, 10769-10772). Here, we examined how L-arginine and the analogs N omega-methyl-L-arginine (NMA), N ... More
Nitric oxide mediates Kupffer cell-induced reduction of mitochondrial energization in hepatoma cells: a comparison with oxidative burst.
AuthorsKurose I, Miura S, Fukumura D, Yonei Y, Saito H, Tada S, Suematsu M, Tsuchiya M
JournalCancer Res
PubMed ID8388320
'The metabolic changes in rat hepatoma cell line, AH70 cells, after coculturing with Kupffer cells were visualized using a silicon-intensified target camera and subsequent processing with a computer-assisted digital imaging processor. In cocultured tumor cells, nonactivated Kupffer cells reduced mitochondrial energization as indicated by the decrease in the fluorescence intensity ... More
Portacaval shunting and hyperammonemia stimulate the uptake of L-[3H] arginine but not of L-[3H]nitroarginine into rat brain synaptosomes.
AuthorsRao VL, Audet RM, Butterworth RF
JournalJ Neurochem
PubMed ID8978744
'Elevated activities of nitric oxide synthase (NOS) have been reported previously in the brains of portacaval-shunted (PCS) rats, a model of chronic hepatic encephalopathy (HE). As L-arginine availability for nitric oxide synthesis depends on a specific uptake mechanism in neurons, we studied the kinetics of L-[3H]-arginine uptake into synaptosomes prepared ... More
Measurement of nitric oxide and peroxynitrite generation in the postischemic heart. Evidence for peroxynitrite-mediated reperfusion injury.
AuthorsWang P, Zweier JL
JournalJ Biol Chem
PubMed ID8910581
'Altered nitric oxide (NO.) production is a critical factor in tissue reperfusion injury; however, controversy remains regarding these alterations and how they cause injury. Since superoxide (O-2) generation is triggered during the early period of reperfusion the cytotoxic oxidant peroxynitrite (ONOO-) could be formed, but it is not known if ... More
Calcium regulates estrogen increase in permeability of cultured CaSki epithelium by eNOS-dependent mechanism.
AuthorsGorodeski GI
JournalAm J Physiol Cell Physiol
PubMed ID11029297
'Estrogen increases baseline transepithelial permeability across CaSki cultures and augments the increase in permeability in response to hypertonic gradients. In estrogen-treated cells, lowering cytosolic calcium abrogated the hypertonicity-induced augmented increase in permeability and decreased baseline permeability to a greater degree than in estrogen-deprived cells. Steady-state levels of cytosolic calcium in ... More
Apolipoprotein E inhibits platelet aggregation through the L-arginine:nitric oxide pathway. Implications for vascular disease.
AuthorsRiddell DR, Graham A, Owen JS
JournalJ Biol Chem
PubMed ID8995232
'We have previously reported that plasma apolipoprotein (apo) E-containing high density lipoprotein particles have a potent anti-platelet action, apparently by occupying saturable binding sites in the cell surface. Here we show that purified apoE (10-50 microg/ml), complexed with phospholipid vesicles (dimyristoylphosphatidylcholine, DMPC), suppresses platelet aggregation induced by ADP, epinephrine, or ... More
Nonstructural 3 protein of hepatitis C virus triggers an oxidative burst in human monocytes via activation of NADPH oxidase.
AuthorsBureau C, Bernad J, Chaouche N, Orfila C, Béraud M, Gonindard C, Alric L, Vinel JP, Pipy B
JournalJ Biol Chem
PubMed ID11304537
'It has been shown that oxidative stress occurs in chronic hepatitis C. Release of reactive oxygen species (ROS) from sequestered phagocytes and activated resident macrophages represents the predominant component of oxidative stress in the liver. However, little is known about the ability of the monocyte to produce ROS in response ... More
Endothelin-stimulated capacitative calcium entry in enteric glial cells: synergistic effects of protein kinase C activity and nitric oxide.
'Depletion of intracellular calcium stores by agonist stimulation is coupled to calcium influx across the plasma membrane, a process termed capacitative calcium entry. Capacitative calcium entry was examined in cultured guinea pig enteric glial cells exposed to endothelin 3. Endothelin 3 (10 nM) caused mobilization of intracellular calcium stores followed ... More
Quantification of superoxide radical formation in intact vascular tissue using a Cypridina luciferin analog as an alternative to lucigenin.
AuthorsSkatchkov MP, Sperling D, Hink U, Anggard E, Münzel T
JournalBiochem Biophys Res Commun
PubMed ID9675145
'Lucigenin has been frequently used for the chemiluminescent detection of superoxide (*O-2) in intact tissue. More recent studies, however, revealed that lucigenin per se causes formation of *O-2 raising doubt about this probe to detect reliably *O-2. We therefore tested a more recently described chemiluminescence probe (2-methyl-6-phenyl-3,7-dihydroimidazol[1,2-alpha]pyrazine-3-one (CLA)) to estimate ... More
Endothelin increases cyclic GMP levels in LLC-PK1 porcine kidney epithelial cells via formation of an endothelium-derived relaxing factor-like substance.
AuthorsIshii K, Warner TD, Sheng H, Murad F
JournalJ Pharmacol Exp Ther
PubMed ID1662272
'The effect of endothelin (ET) on cyclic GMP levels in cultured porcine kidney epithelial cells, LLC-PK1, was investigated. ET-1 or ET-3, but not big ET-1 or ET C-terminal hexapeptide 16-21, elevated cyclic GMP levels in a concentration-dependent manner with an EC50 value of about 5 x 10(-10) M. This effect ... More
Nitric oxide-dependent efflux of cGMP in rat cerebellar cortex: an in vivo microdialysis study.
AuthorsLuo D, Leung E, Vincent SR
JournalJ Neurosci
PubMed ID7506765
'The stimulation of excitatory amino acid receptors in the cerebellar cortex results in the Ca2+/calmodulin-dependent activation of nitric oxide synthase. This leads to an increase in tissue levels of cGMP following the interaction of nitric oxide with soluble guanylyl cyclase. The cerebellar cortex has the highest levels of nitric oxide ... More
Contribution of nitric oxide synthase to luminol-dependent chemiluminescence generated by phorbol-ester-activated Kupffer cells.
AuthorsWang JF, Komarov P, Sies H, de Groot H
JournalBiochem J
PubMed ID1718262
'Phorbol 12-myristate 13-acetate-induced luminol chemiluminescence in rat Kupffer cells was doubled by the addition of L-arginine and significantly (up to 70%) inhibited by NG-nitro-L-arginine and NG-monomethyl-L-arginine, competitive inhibitors of L-arginine-dependent nitric oxide (NO) formation. The release of superoxide anion (O2-) by NADPH oxidase was neither affected by L-arginine nor by ... More
Is there a role for nitric oxide in regulation of T cell secretion of IL-2?
AuthorsMarcinkiewicz J, Grabowska A, Chain BM
JournalJ Immunol
PubMed ID8648104
'Nitric oxide (NO) can have both effector (cytotoxic) and regulatory roles in immune function. In this study, we have re-examined the potential role of nitric oxide in mediating the macrophage-dependent suppression of IL-2 synthesis. In our model, TNP-specific CD4+ T cells are cocultured with Ag and either peritoneal or alveolar ... More
Human monocytes induce a carcinoma cell line to secrete high amounts of nitric oxide.
AuthorsKonur A, Krause SW, Rehli M, Kreutz M, Andreesen R
JournalJ Immunol
PubMed ID8757334
'Nitric oxide (NO) is a short-lived pleiotropic mediator with a multitude of biologic functions. The inducible form of NO synthase (iNOS) is responsible for the discontinuous production of high amounts of NO and is important for the cytotoxic capacity of macrophages in rodents, whereas NO production by human macrophages or ... More
Nitric oxide production by cultured aortic endothelial cells in response to thiol depletion and replenishment.
AuthorsMurphy ME, Piper HM, Watanabe H, Sies H
JournalJ Biol Chem
PubMed ID1918052
'The requirements and influence of thiols on the production of nitric oxide (NO) were examined in cultured porcine aortic endothelial cells. NO production was diminished when cells were pretreated with thiol-depleting agents (IC50: N-ethylmaleimide, 30 microM; 1-chloro-2,4-dinitrobenzene, 200 microM; diamide, 1.5 mM; diethyl maleate, 20 mM). The depletion of glutathione ... More
Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells.
AuthorsStuehr DJ, Nathan CF
JournalJ Exp Med
PubMed ID2497225
'A metabolic pathway of activated macrophages (M phi) involving oxidation of the guanido nitrogens of L-arginine is required for inhibition of growth and respiration of some target cells. The goal of this study was to identify the M phi metabolite(s) that induce these injuries. The stable products of the L-arginine ... More
'Indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase are part of the anti-tumor and antimicrobial activities of mononuclear phagocytes induced by interferon-gamma (IFN gamma). As IDO is a heme-containing enzyme and NO, the product of nitric oxide synthase-initiated arginine degradation, is a regulator of heme enzymes, we investigated whether NO is ... More
Lung injury after deposition of IgA immune complexes. Requirements for CD18 and L-arginine.
AuthorsMulligan MS, Warren JS, Smith CW, Anderson DC, Yeh CG, Rudolph AR, Ward PA
JournalJ Immunol
PubMed ID1374449
'Acute lung injury produced by deposition of IgA immune complexes is complement-dependent, neutrophil-independent, oxygen radical-mediated, and may be a result of the formation of the hydroxyl radical (HO) generated directly or indirectly from activated lung macrophages. The current studies were designed to evaluate further the pathophysiologic events that occur after ... More
EPR characterization of molecular targets for NO in mammalian cells and organelles.
AuthorsHenry Y, Lepoivre M, Drapier JC, Ducrocq C, Boucher JL, Guissani A
JournalFASEB J
PubMed ID8397130
'Nitric oxide is synthesized in mammalian cells from L-arginine or from pharmaceutical drugs. It forms paramagnetic complexes with some metalloproteins, inhibiting key enzymes in DNA synthesis, mitochondrial respiration, iron metabolism, etc. This article reviews how electron paramagnetic resonance spectroscopy helps to detect unambiguously such specific molecular targets for NO in ... More
Approaches toward selective inhibition of nitric oxide synthase.
AuthorsMarletta MA
JournalJ Med Chem
PubMed ID7518001
Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis.
'The bioavailability of nitric oxide (NO) in the human coronary circulation at rest and after acetylcholine (ACH)-induced vasodilation was investigated in 32 patients with angiographically normal coronary arteries. The effects of intracoronary L-NG monomethyl arginine (L-NMMA) were investigated at rest and after ACH, sodium nitroprusside, and adenosine. L-NMMA (64 mumol/min) ... More
Nitric oxide regulates interleukin 1 bioactivity released from murine macrophages.
AuthorsHill JR, Corbett JA, Kwon G, Marshall CA, McDaniel ML
JournalJ Biol Chem
PubMed ID8798439
'The bioactivity of interleukin-1 (IL-1), a major proinflammatory cytokine, can be modulated by a variety of factors including inhibitors of IL-1 production and release and receptor blockade by IL-1 receptor antagonist and by binding to nonsignaling soluble receptors. This study demonstrates that the free radical nitric oxide (NO) is also ... More
Glutamate receptors induce a burst of superoxide via activation of nitric oxide synthase in arginine-depleted neurons.
AuthorsCulcasi M, Lafon-Cazal M, Pietri S, Bockaert J
JournalJ Biol Chem
PubMed ID7513691
'We have previously shown in cultured cerebellar granule neurons (Lafon-Cazal, M., Pietri, S., Culcasi, M., and Bockaert, J. (1993) Nature 364, 535-537) that upon N-methyl-D-aspartate stimulation, a nitric oxide synthase (NOS)-independent, arachidonic acid-dependent generation of superoxide free radicals (O2-.) is observed after a lag time of 10-15 min. Using the ... More
Optical difference spectrophotometry as a probe of rat brain nitric oxide synthase heme-substrate interaction.
AuthorsMcMillan K, Masters BS
JournalBiochemistry
PubMed ID7691172
'NO synthase (NOS) is a family of enzymes that catalyzes the NADPH-dependent formation of NO and citrulline from L-arginine and molecular oxygen. The reaction involves an initial hydroxylation of L-arginine to form the isolable intermediate NG-hydroxy-L-arginine (NOHArg). The subsequent incorporation of a second atom of oxygen during the metabolism of ... More
Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo.
AuthorsRees DD, Palmer RM, Schulz R, Hodson HF, Moncada S
JournalBr J Pharmacol
PubMed ID1706208
'1. Three analogues of L-arginine were characterized as inhibitors of endothelial nitric oxide (NO) synthase by measuring their effect on the endothelial NO synthase from porcine aortae, on the vascular tone of rings of rat aorta and on the blood pressure of the anaesthetized rat. 2. NG-monomethyl-L-arginine (L-NMMA), N-iminoethyl-L-ornithine (L-NIO) ... More
Comparison of spectrophotometric and biological assays for nitric oxide (NO) and endothelium-derived relaxing factor (EDRF): nonspecificity of the diazotization reaction for NO and failure to detect EDRF.
AuthorsTracey WR, Linden J, Peach MJ, Johns RA
JournalJ Pharmacol Exp Ther
PubMed ID2319475
'Endothelium-derived relaxing factor has been tentatively identified as nitric oxide (NO) partially on the basis of chemical assays. In the present study, saline solutions that were either bubbled continuously for 30 min with NO (NO/X) or prepared using 25 ml of NO/ml (NO/25) produced equivalent relaxations of segments of rabbit ... More
Synthesis of L-thiocitrulline, L-homothiocitrulline, and S-methyl-L-thiocitrulline: a new class of potent nitric oxide synthase inhibitors.
AuthorsNarayanan K, Griffith OW
JournalJ Med Chem
PubMed ID7512141
'Nitric oxide synthase catalyzes the NADPH- and O2-dependent conversion of L-arginine to L-citrulline and nitric oxide. L-Thiocitrulline, L-homothiocitrulline, and S-methyl-L-thiocitrulline, novel citrulline analogs, have been synthesized and are shown to be potent inhibitors of both the constitutive brain and the inducible smooth muscle isoforms of nitric oxide synthase. Although many ... More
Coinduction of nitric oxide synthase and argininosuccinate synthetase in a murine macrophage cell line. Implications for regulation of nitric oxide production.
AuthorsNussler AK, Billiar TR, Liu ZZ, Morris SM
JournalJ Biol Chem
PubMed ID7507106
'In macrophages and other cell types, bacterial lipopolysaccharide and certain cytokines stimulate nitric oxide (NO) production via expression of the inducible isoform of nitric oxide synthase (NOS). Citrulline, which is the coproduct of NOS-catalyzed metabolism of arginine, can be recycled to arginine by the action of argininosuccinate synthetase and argininosuccinate ... More
Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons.
AuthorsArancio O, Kiebler M, Lee CJ, Lev-Ram V, Tsien RY, Kandel ER, Hawkins RD
JournalCell
PubMed ID8978607
'Nitric oxide (NO) has been proposed to act as a retrograde messenger during long-term potentiation (LTP) in the CA1 region of hippocampus, but the inaccessibility of the presynaptic terminal has prevented a definitive test of this hypothesis. Because both sides of the synapse are accessible in cultured hippocampal neurons, we ... More
Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta.
AuthorsGeng YJ, Wu Q, Muszynski M, Hansson GK, Libby P
JournalArterioscler Thromb Vasc Biol
PubMed ID8548421
'Recent studies have documented evidence for the death of smooth muscle cells (SMCs) within advanced human atheroma. These lesions contain macrophages and T lymphocytes in addition to SMCs. We therefore investigated whether interferon-gamma (IFN-gamma), a cytokine secreted by T lymphocytes, or interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), ... More
Nitric oxide and human skin blood flow responses to acetylcholine and ultraviolet light.
AuthorsWarren JB
JournalFASEB J
PubMed ID7509761
'Nitric oxide (NO) is a potent endogenous vasodilator of large blood vessels but its role in the physiological and pathological control of the human microcirculation is not known. This study was designed to assess whether NO contributes to the control of blood flow in the human skin microcirculation in vivo. ... More
Macrophage-stimulating protein inhibits induction of nitric oxide production by endotoxin- or cytokine-stimulated mouse macrophages.
AuthorsWang MH, Cox GW, Yoshimura T, Sheffler LA, Skeel A, Leonard EJ
JournalJ Biol Chem
PubMed ID7514598
'Human serum macrophage-stimulating protein (MSP) is a disulfide-linked heterodimer that induces motile and phagocytic activity of mouse resident peritoneal macrophages. In this work, we found that MSP blocked the increase in macrophage nitric oxide synthase mRNA, as well as the associated increase in nitric oxide production, that occurred in response ... More
Modulation of airway smooth muscle beta-adrenoceptor function by a muscarinic agonist.
AuthorsGrandordy BM, Mak JC, Barnes PJ
JournalLife Sci
PubMed ID7904709
'We have investigated the effect of a muscarinic agonist and protein kinase C (PKC) activation on beta-adrenoceptors and their coupling to adenylyl cyclase in bovine tracheal smooth muscle. There was a significant reduction in maximum binding capacity of [125I]iodocyanopindolol ([125I]ICYP) after exposure to carbachol and 4 beta-phorbol 12 beta-myristate 13 ... More
On the substrate specificity of nitric oxide synthase.
AuthorsHecker M, Walsh DT, Vane JR
JournalFEBS Lett
PubMed ID1721880
'Nitric oxide (.NO) synthase (NOS) activity in subcellular fractions from cultured endothelial cells (EC) and lipopolysaccharide-activated J774.2 monocyte/macrophages was investigated by monitoring the .NO-mediated increase in intracellular cyclic GMP in LLC-PK1 pig kidney epithelial cells. The constitutive NOS in EC (NOSc) was largely membrane-bound, whereas the inducible NOS in J774.2 ... More
NO in hydra feeding response.
AuthorsColasanti M, Lauro GM, Venturini G
JournalNature
PubMed ID7535383
Nitric oxide synthases in mammals.
AuthorsKnowles RG, Moncada S
JournalBiochem J
PubMed ID7510950
Nitric oxide: a new paradigm for second messengers.
AuthorsKerwin JF, Lancaster JR, Feldman PL
JournalJ Med Chem
PubMed ID7473563
Nitric oxide synthesis and action in an invertebrate brain.
AuthorsElphick MR, Green IC, O'Shea M
JournalBrain Res
PubMed ID7690676
Nitric oxide (NO) is synthesized in mammalian neurons by Ca2+/calmodulin activated NO synthase and functions as a signalling molecule by activating soluble guanylyl cyclases in target cells. We demonstrate here that both NO synthase and NO-activated guanylyl cyclase are present in the brain of the locust Schistocerca gregaria. Our observations ... More
N omega-hydroxy-L-arginine: a novel arginine analog capable of causing vasorelaxation in bovine intrapulmonary artery.
AuthorsWallace GC, Gulati P, Fukuto JM
JournalBiochem Biophys Res Commun
PubMed ID2018542
This study describes the effects of N omega-hydroxy-L-arginine (NOHA) on endothelium dependent and endothelium independent relaxation of bovine pulmonary artery. These results are consistent with the hypothesis that NOHA is a biosynthetic intermediate in the production of nitric oxide from arginine. N omega-Hydroxy-L-arginine causes both endothelium dependent and endothelium independent ... More
S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control.
A dynamic cycle exists in which haemoglobin is S-nitrosylated in the lung when red blood cells are oxygenated, and the NO group is released during arterial-venous transit. The vasoactivity of S-nitrosohaemoglobin is promoted by the erythrocytic export of S-nitrosothiols. These findings highlight newly discovered allosteric and electronic properties of haemoglobin ... More
Effect of 3-morpholinosydnonimine (SIN-1), NG-nitro-L-arginine (NNA) and NG-monomethyl-L-arginine (NMMA) on isolated anaphylactic guinea-pig hearts.
AuthorsPallapies D, Thelen K, Dembinska-Kiec A, Simmet T, Peskar BA
JournalAgents Actions Suppl
PubMed ID1632288
In isolated perfused ovalbumin-sensitized guinea-pig hearts modulating effects of nitric oxide (NO) on cardiac function and eicosanoid release were investigated. While the NO-donor SIN-1 exhibited a protective effect during cardiac anaphylaxis, inhibition of NO biosynthesis by NNA or NMMA aggravated anaphylactic changes of cardiac functions. Exogenous and endogenous NO seems ... More
NG-monomethyl-L-arginine causes nitric oxide synthesis in isolated arterial rings: trouble in paradise.
AuthorsArcher SL, Hampl V
JournalBiochem Biophys Res Commun
PubMed ID1445303
Arginine analogs are commonly used as inhibitors of the synthesis of endothelium-derived relaxing factor, nitric oxide. However, their effect on nitric oxide levels is rarely measured. Using a chemiluminescence assay for nitric oxide, we found that NG-monomethyl-L-arginine enhanced, rather than reduced, nitric oxide synthesis in pulmonary arterial and aortic rings. ... More
Flow cytometric analysis of nitric oxide production in human neutrophils using dichlorofluorescein diacetate in the presence of a calmodulin inhibitor.
Dichlorofluorescein (DCFH) oxidation assay measures hydrogen peroxide (H2O2), which is a derivative of superoxide anion. We found that a calmodulin antagonist, W-13, which is known to inhibit superoxide anion generation enhanced the capacity of human neutrophils to oxidize DCFH. To investigate this discrepancy we studied the role of nitric oxide ... More
Loss and degradation of enzyme-bound heme induced by cellular nitric oxide synthesis.
AuthorsKim YM, Bergonia HA, Müller C, Pitt BR, Watkins WD, Lancaster JR
JournalJ Biol Chem
PubMed ID7890697
We report here that, like nonheme iron, protein-bound intracellular heme iron is also a target for destruction by endogenously produced nitric oxide (NO). In isolated rat hepatocytes NO synthesis results in substantial (approximately 60%) and comparable loss of catalase and cytochrome P450 as well as total microsomal heme, and decreased ... More
Differential distribution of nitric oxide synthase between cell fractions isolated from the rat gastric mucosa.
AuthorsBrown JF, Tepperman BL, Hanson PJ, Whittle BJ, Moncada S
JournalBiochem Biophys Res Commun
PubMed ID1374239
Cells isolated from the rat gastric mucosa were resolved into two fractions on a percoll density gradient, and into five fractions using counterflow centrifugation (elutriation). Ca(2+)-dependent nitric oxide synthase (NOS) activity was found in the high density percoll fraction but not in the parietal cell enriched low density fraction. This ... More
7-Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti-nociceptive activity in the mouse without increasing blood pressure.
7-Nitro indazole (7-NI) inhibits mouse cerebellar nitric oxide synthase (NOS) in vitro with an IC50 of 0.47 microM. Following i.p. administration in mice, 7-NI (10-50 mg kg-1) produces dose-related anti-nociception as evidenced by an inhibition of late phase (15-30 min) but not early phase (0-5 min) hindpaw licking time following ... More
Cytochrome P450 catalyzes the oxidation of N omega-hydroxy-L-arginine by NADPH and O2 to nitric oxide and citrulline.
AuthorsBoucher JL, Genet A, Vadon S, Delaforge M, Henry Y, Mansuy D
JournalBiochem Biophys Res Commun
PubMed ID1530643
Rat liver microsomes catalyze the oxidative denitration of N omega-hydroxy-L-arginine (NOHA) by NADPH and O2 with formation of citrulline and nitrogen oxides like NO and NO2-. Besides NO2- and citrulline, whose simultaneous formation is linear for at least 20 min, the formation of NO could be detected under the form ... More
Improved nitric oxide detection using 2,3-diaminonaphthalene and its application to the evaluation of novel nitric oxide synthase inhibitors.
AuthorsNakatsubo N, Kojima H, Sakurai K, Kikuchi K, Nagoshi H, Hirata Y, Akaike T, Maeda H, Urano Y, Higuchi T, Nagano T
JournalBiol Pharm Bull
PubMed ID9881632
A specific and sensitive detection method for nitric oxide (NO) in living cells and tissue culture systems is required in the search for novel NO synthase (NOS) inhibitors. We have improved a fluorometric determination with 2,3-diaminonaphthalene (DAN) by the addition of 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (PTIO) as an oxidant to form NO2 from ... More
Endotoxin and TNF alpha directly stimulate nitric oxide formation in cultured rat hepatocytes from chronically endotoxemic rats.
AuthorsPittner RA, Spitzer JA
JournalBiochem Biophys Res Commun
PubMed ID1599481
We examined the effects of endotoxin on nitric oxide formation in isolated rat hepatocytes in primary culture. Endotoxin was administered either in vivo, by continuous infusion for 30 or 3 h, or in vitro, on cultured cells. The spontaneous production of nitrites in hepatocytes from in vivo ET-infused rats was ... More
Synthesis of prostaglandin H synthase-2 by human alveolar macrophages in response to lipopolysaccharide is inhibited by decreased cell oxidant tone.
AuthorsHempel SL, Monick MM, He B, Yano T, Hunninghake GW
JournalJ Biol Chem
PubMed ID7528741
We previously demonstrated that lipopolysaccharide (LPS) increases expression of the prostaglandin H synthase-2 (PGHS-2) gene (Hempel, S.L., Monick, M.M., and Hunninghake, G.W. (1994) J. Clin. Invest. 93, 391-396). In this study, the expression of the PGHS-2 gene in response to changes in cell oxidant tone was studied. During LPS exposure, ... More
Identification of arginine as a precursor of endothelium-derived relaxing factor.
AuthorsSakuma I, Stuehr DJ, Gross SS, Nathan C, Levi R
JournalProc Natl Acad Sci U S A
PubMed ID3263652
Nitric oxide (NO) is a major endothelium-derived relaxing factor (EDRF) released in response to vasodilating amines, peptides, proteins, ionophores, and nucleotides. EDRF is an important regulator of smooth muscle tone and platelet aggregation and adhesion. Histamine and acetylcholine relax the intact norepinephrine-constricted guinea pig pulmonary artery by an EDRF-dependent mechanism ... More
Inhibition of renal nitric oxide synthesis with NG-monomethyl-L-arginine and NG-nitro-L-arginine.
AuthorsNaess PA, Kirkebøen KA, Christensen G, Kiil F
JournalAm J Physiol
PubMed ID1535755
In barbiturate-anesthetized dogs, the effects of intrarenal infusion of the two selective inhibitors of nitric oxide synthesis, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (NO-Arg), were compared. Basal renal blood flow (RBF) was reduced by 15 +/- 2% after L-NMMA at 0.28 mumol/ml, by 20 +/- 3% after NO-Arg at 0.07 mumol/ml, and ... More
Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway.
AuthorsBingisser RM, Tilbrook PA, Holt PG, Kees UR
JournalJ Immunol
PubMed ID9637481
Nitric oxide (NO) has been invoked as an important pathogenic factor in a wide range of immunologically mediated diseases. The present study demonstrates that macrophage-derived NO may conversely function to fine tune T cell-mediated inflammation via reversible dephosphorylation of intracellular signaling molecules, which are involved in the control of T ... More
Cloning and characterization of a brain-specific cationic amino acid transporter.
rCAT3 (rat cationic amino acid transporter 3), a cDNA that encodes a novel member of the murine CAT family was isolated. The protein encoded by rCAT3 contained 619 amino acids, 53-58% of which were identical with those of the murine CAT family proteins previously described (mouse CAT1, CAT2a, CAT2b, and ... More
Cyclic AMP-elevating agents induce an inducible type of nitric oxide synthase in cultured vascular smooth muscle cells. Synergism with the induction elicited by inflammatory cytokines.
AuthorsKoide M, Kawahara Y, Nakayama I, Tsuda T, Yokoyama M
JournalJ Biol Chem
PubMed ID7693710
In cultured vascular smooth muscle cells, interferon gamma (IFN-gamma) induced the accumulation of nitrite, a stable metabolite of nitric oxide, in a dose- and time-dependent manner. In parallel with this reaction, this cytokine increased the mRNA and protein levels of an inducible macrophage-type of nitric oxide synthase (iNOS). Forskolin, a ... More
Inhibitors of brain nitric oxide synthase. Binding kinetics, metabolism, and enzyme inactivation.
AuthorsKlatt P, Schmidt K, Brunner F, Mayer B
JournalJ Biol Chem
PubMed ID7507482
Nitric oxide (NO) is synthesized from L-arginine by different NO synthase isozymes, which are inhibited by the substrate analogs NG-methyl- and NG-nitro-L-arginine. We studied binding of 3H-labeled NG-nitro-L-arginine to purified brain NO synthase and compared the data with results obtained in enzyme kinetic experiments. Binding data revealed a single binding ... More
Protective effects of inhibitors of nitric oxide synthase in immune complex-induced vasculitis.
AuthorsMulligan MS, Moncada S, Ward PA
JournalBr J Pharmacol
PubMed ID1281719
1. The ability of analogues of L-arginine (N-iminoethyl-L-ornithine (L-NIO), NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-L-arginine (L-NNA)) to protect against inflammatory injury induced by activated neutrophils was investigated in rats following intradermal or intrapulmonary deposition of immune complexes. 2. The descending order of potency for protective effects of these ... More
Changes in mechanisms of monocyte/macrophage-mediated cytotoxicity during culture. Reactive oxygen intermediates are involved in monocyte-mediated cytotoxicity, whereas reactive nitrogen intermediates are employed by macrophages in tumor cell killing.
AuthorsMartin JH, Edwards SW
JournalJ Immunol
PubMed ID8385686
Freshly isolated human blood monocytes were spontaneously cytotoxic toward K562 tumor cells. During culture of the monocytes in vitro cytotoxicity decreased during the first 48 h but tumoricidal competence was restored after 3 to 4 days in vitro. These changes were accompanied by changes in both reactive oxygen intermediate generating ... More
Neurogenic nitric oxide (NO) in the regulation of cerebroarterial tone.
AuthorsToda N, Okamura T
JournalJ Chem Neuroanat
PubMed ID8811415
Sympathetic vasoconstrictor nerves are commonly recognized to mainly control the vascular smooth muscle tone, thus alters regional vascular resistance and blood flow. In contrast to peripheral organs and tissues, regulation by sympathetic nerves of blood flow in the brain is not so evident, and conversely vasodilator innervation is expected to ... More
Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase.
AuthorsLiao JK, Shin WS, Lee WY, Clark SL
JournalJ Biol Chem
PubMed ID7529227
The atherogenic effects of low-density lipoprotein (LDL) may be mediated, in part, by its effect(s) on endothelial-derived nitric oxide (NO). To determine whether LDL can modulate NO production by changing NO synthase expression, we treated human saphenous vein endothelial cells with increasing concentrations of native or oxidized LDL (0-100 micrograms/ml) ... More
Synthesis of nitrogen oxides from L-arginine by macrophage cytosol: requirement for inducible and constitutive components.
Cytosols prepared from murine peritoneal macrophages and the RAW 264 macrophage cell line catalyzed conversion of L-arginine to the labile vaso-relaxant nitric oxide and its accumulating endproducts, nitrite and nitrate. This activity required previous exposure of the cells to interferon-gamma and bacterial lipopolysaccharide. Nitrogen oxide synthetase activity was characterized further ... More
Effects of NG-methyl-L-arginine, NG-nitro-L-arginine, and aminoguanidine on constitutive and inducible nitric oxide synthase in rat aorta.
AuthorsJoly GA, Ayres M, Chelly F, Kilbourn RG
JournalBiochem Biophys Res Commun
PubMed ID7510104
A new selective inhibitor of the inducible nitric oxide synthase in the treatment of pathogenesis characterized by overproduction of nitric oxide may be useful. Therefore, we have examined the effects of two L-arginine analogues, NG-methyl-L-arginine (L-NMA) and NG-nitro-L-arginine (L-NNA), and aminoguanidine (AG) on the constitutive and inducible nitric oxide synthase ... More
Effects of selective inhibitors of neuronal nitric oxide synthase on carrageenan-induced mechanical and thermal hyperalgesia.
AuthorsHandy RL, Moore PK
JournalNeuropharmacology
PubMed ID9680257
The effect of inhibition of nitric oxide synthase (NOS) on hindpaw hyperalgesia (assessed using mechanical and thermal noxious stimuli) and oedema formation following intraplantar injection of carrageenan (150 microl, 2% w v(-1)) in the rat was determined. For this purpose, NOS inhibitors including L-N(G) nitro-arginine methyl ester (L-NAME; isoform non-selective ... More
Detection of nitric oxide production from a perfused organ by a luminol-H2O2 system.
AuthorsKikuchi K, Nagano T, Hayakawa H, Hirata Y, Hirobe M
JournalAnal Chem
PubMed ID8368532
Nitric oxide, thought to be the endothelium-derived relaxing factor (EDRF), is involved in intra- and intercellular signalling in various tissues. A system for the continuous detection of NO in the picomolar range from a perfused organ is described. The detection is based upon the chemiluminescence reaction between NO and the ... More
Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B.
AuthorsPeng HB, Libby P, Liao JK
JournalJ Biol Chem
PubMed ID7775482
To determine the mechanism(s) by which the endogenous mediator nitric oxide (NO) inhibits the activation of transcription factor NF-kappa B, we stimulated human vascular endothelial cells with tumor necrosis factor-alpha in the presence of two NO donors, sodium nitroprusside and S-nitrosoglutathione. Electrophoretic mobility shift assays demonstrated that both NO donors ... More
Involvement of reactive oxygen species in cytokine and growth factor induction of c-fos expression in chondrocytes.
AuthorsLo YY, Cruz TF
JournalJ Biol Chem
PubMed ID7744816
The cytokine tumor necrosis factor alpha (TNF alpha) and the growth factor basic fibroblast growth factor (bFGF) are known to induce early response genes such as c-fos and c-jun in various cell types. Activation of AP-1, a heterodimeric complex of Fos and Jun proteins, is required for matrix metalloproteinase production ... More
Superantigen-induced CD4 T cell tolerance mediated by myeloid cells and IFN-gamma.
AuthorsCauley LS, Miller EE, Yen M, Swain SL
JournalJ Immunol
PubMed ID11086037
We have previously shown that systemic staphylococcal enterotoxin A (SEA) injections cause CD4 T cells in TCR-transgenic mice to become tolerant to subsequent ex vivo restimulation. An active IFN-gamma-dependent mechanism of suppression was responsible for the apparent unresponsiveness of the CD4 T cells. In this study, we analyze the response ... More
A gastric housekeeping Cl- channel activated via prostaglandin EP3 receptor-mediated Ca2+/nitric oxide/cGMP pathway.
AuthorsSakai H, Kumano E, Ikari S, Takeguchi N
JournalJ Biol Chem
PubMed ID7642528
Prostaglandin E2 (PGE2) has a cytoprotective role in the gastric parietal cell. PGE2 opened a housekeeping basolateral Cl- channel of rabbit gastric parietal cells, the single channel conductance of which was about 0.3 picosiemens. In the present patch-clamp and Fura 2 fluorescence studies, we found that PGE2 increased the intracellular ... More
The HIV-1 Nef protein and phagocyte NADPH oxidase activation.
AuthorsVilhardt F, Plastre O, Sawada M, Suzuki K, Wiznerowicz M, Kiyokawa E, Trono D, Krause KH
JournalJ Biol Chem
PubMed ID12207012
Nef, a multifunctional HIV protein, activates the Vav/Rac/p21-activated kinase (PAK) signaling pathway. Given the potential role of this pathway in the activation of the phagocyte NADPH oxidase, we have investigated the effect of the HIV-1 Nef protein on the phagocyte respiratory burst. Microglia (cell line and primary culture) were transduced ... More
Pretreatment of astrocytes with interferon-alpha/beta impairs interferon-gamma induction of nitric oxide synthase.
AuthorsStewart VC, Giovannoni G, Land JM, McDonald WI, Clark JB, Heales SJ
JournalJ Neurochem
PubMed ID9166751
Excessive nitric oxide/peroxynitrite generation has been implicated in the pathogenesis of multiple sclerosis, and the demonstration of increased astrocytic nitric oxide synthase activity in the postmortem brain of multiple sclerosis patients supports this hypothesis. Exposure of astrocytes, in primary culture, to interferon-gamma results in stimulation of nitric oxide synthase activity ... More
Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate.
Previous studies have shown that murine macrophages immunostimulated with interferon gamma and Escherichia coli lipopolysaccharide synthesize NO2-, NO3-, and citrulline from L-arginine by oxidation of one of the two chemically equivalent guanido nitrogens. The enzymatic activity for this very unusual reaction was found in the 100,000g supernatant isolated from activated ... More
An apoptotic model for nitrosative stress.
AuthorsEu JP, Liu L, Zeng M, Stamler JS
JournalBiochemistry
PubMed ID10653649
Nitric oxide overproduction has been implicated in the pathogenesis of many disorders, including artherosclerosis, neurodegenerative diseases, inflammatory and autoimmune diseases, and cancer. The common view holds that nitric oxide-induced cellular injury is caused by oxidative stress. This theory predicts that interactions between reactive nitrogen species and reactive oxygen species produce ... More
Adenosine A3 receptors regulate serotonin transport via nitric oxide and cGMP.
AuthorsMiller KJ, Hoffman BJ
JournalJ Biol Chem
PubMed ID7525554
Many antidepressants inhibit 5-hydroxytryptamine (5HT) transport resulting in increased 5HT levels in the synapse. However, physiological regulation of neurotransmitter uptake has not been demonstrated. We have examined the effect of receptor-activated second messengers on the 5HT transporter in rat basophilic leukemia cells (RBL 2H3). Here, we show that activation of ... More
Role of endothelium-derived nitric oxide in myocardial reactive hyperemia.
AuthorsYamabe H, Okumura K, Ishizaka H, Tsuchiya T, Yasue H
JournalAm J Physiol
PubMed ID1636774
In pentobarbital sodium-anesthetized dogs we investigated the role of the endothelium-derived nitric oxide and adenosine in the regulation of the coronary blood flow during myocardial reactive hyperemia. Repayments of flow debt after 10-, 20- and 60-s occlusion of the left circumflex coronary artery (LCX) were measured before and after infusion ... More
Methylations of 70,000-Da heat shock proteins in 3T3 cells: alterations by arsenite treatment, by different stages of growth and by virus transformation.
AuthorsWang C, Lin JM, Lazarides E
JournalArch Biochem Biophys
PubMed ID1322111
We have characterized the basic amino acid methylation of three members of the 70,000-Da heat shock protein superfamily, hsp68, hsc70, and BiP, in Balb/c 3T3 cells. It appears that a lysyl residue is the only methylation site in BiP and that both lysyl and arginyl residues are methylated in hsp68 ... More