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

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Query: EC:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription factor NF-kappaB is essential for the induction of nitric oxide synthase (NOS) II (iNOS) by bacterial lipopolysaccharide in murine macrophages (Xie, Q. W., Kashiwabara, Y., and Nathan, C. (1994) J. Biol. Chem. 269, 4705-4708). In 3T3 fibroblasts, agents other than cytokines are efficacious inducers of NOS II expression. In addition to cytokines such as interferon-gamma or tumor necrosis factor-alpha, protein kinase C-stimulating agents such as tetradecanoylphorbol-13-acetate, or cyclic AMP-elevating agents such as forskolin and 8-bromo-cAMP markedly increased NOS II mRNA (measured by Sl nuclease and RNase protection analyses), NOS II protein (determined by Western blotting), and NOS activity (measured by chemiluminescence detection of NO2-). Transforming growth factor-beta1 (which is an inhibitor of NOS II induction in other cell types) potentiated NOS II mRNA expression produced by all inducing agents listed, whereas dexamethasone, pyrrolidine dithiocarbamate and 3,4-dichloroisocoumarin (inhibitors of NF-kappaB activation) suppressed NOS II mRNA induction in response to all stimulants. In electrophoretic mobility shift assays, nuclear protein extracts from 3T3 cells stimulated with any of the inducing agents significantly slowed the migration of an NF-kappaB-binding oligonucleotide, whereas nuclear extracts from untreated control cells did not. These experiments indicate that NF-kappaB is the key control element for the induction of NOS II in response to at least three different second messenger pathways in 3T3 cells.
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PMID:In murine 3T3 fibroblasts, different second messenger pathways resulting in the induction of NO synthase II (iNOS) converge in the activation of transcription factor NF-kappaB. 862 88

Nitric oxide is reportedly involved in the regulation of several ovarian processes, yet the isoforms of nitric oxide synthase (NOS) expressed in the ovary are unknown. Our purpose was to identify and localize NOS isoenzymes in the rat ovary and to examine++ if mRNA expression of NOS isoenzymes change after gonadotropin stimulation. Using reverse transcriptase-PCR, we demonstrated that inducible (iNOS) and endothelial (eNOS), but not neuronal, NOS mRNAs are expressed in the ovary. In a gonadotropin-stimulated rat model, unstimulated ovaries had the highest levels of iNOS mRNA as quantified by ribonuclease protection assay. After gonadotropin injection, iNOS mRNA declined to undetectable levels in ovaries containing ovulatory follicles before increasing slighty in ovaries containing copora lutea. In situ hybridization studies localized iNOS to granulosa cells of secondary follicles and small antral follicles. Western blots of unstimulated ovaries demonstrated iNOS protein. In contrast to iNOS, eNOS mRNA levels, determined by quantitative PCR, increased after gonadotropin stimulation and peaked in ovaries containing ovulatory follicles before declining in the luteal phase. eNOS protein was localized to blood vessels in the ovary by immunohistochemistry. We conclude that two isoforms of NOS are expressed in the ovary and the mRNA levels for these isozymes are differentially regulated.
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PMID:Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo. 867 39

1 The role of nitric oxide (NO) derived from constitutive and inducible nitric oxide synthase (cNOS and iNOS) and its relationship to oxygen-derived free radicals and prostaglandins (PG) was investigated in a carrageenan-induced model of acute hindpaw inflammation. 2 The intraplantar injection of carrageenan elicited an inflammatory response that was characterized by a time-dependent increase in paw oedema, neutrophil infiltration, and increased levels of nitrite/nitrate (NO2-/NO3-) and prostaglandin E2(PGE2) in the paw exudate. 3 Paw oedema was maximal by 6 h and remained elevated for 10 h following carrageenan administration. The non-selective cNOS/iNOS inhibitors, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME) given intravenously (30-300 mg kg-1) 1 h before or after carrageenan administration, inhibited paw oedema at all time points. 4 The selective iNOS inhibitors, N-iminoethyl-L-lysine (L-NIL) or aminoguanidine (AG), failed to inhibit carrageenan-induced paw oedema during the first 4 h following carrageenan administration, but inhibited paw oedema at subsequent time points (from 5-10 h). iNOS mRNA was detected between 3 to 10 h following carrageenan administration using ribonuclease protection assays. iNOS protein was first detected 6 h and was maximal 10 h following carrageenan administration as shown by Western blot analysis. Administration of the iNOS inhibitors 5 h after carrageenan (a time point where iNOS was expressed) inhibited paw oedema at all subsequent time points. Infiltrating neutrophils were not the source of iNOS since pretreatment with colchicine (2 mg kg-1) suppressed neutrophil infiltration, but did not inhibit the iNOS mRNA expression or the elevated NO2-/NO3- levels in the paw exudate. 5 Inhibition of paw oedema by the NOS inhibitors was associated with attenuation of both the NO2-/NO3- and PGE2 levels in the paw exudate. These inhibitors also reduced the neutrophil infiltration at the site of inflammation. 6 Recombinant human Cu/Zn superoxide dismutase coupled to polyethyleneglycol (PEGrhSOD; 12 x 10(3) u kg-1), administered intravenously either 30 min prior to or 1 h after carrageenan injection, inhibited paw oedema and neutrophil infiltration, but had no effect on NO2-/NO3- or PGE2 production in the paw exudate. The administration of catalase (40 x 10(3) u kg-1), given intraperitoneally 30 min before carrageenan administration, had no effect on paw oedema. Treatment with desferrioxamine (300 mg kg-1), given subcutaneously 1 h before carrageenan, inhibited paw oedema during the first 2 h after carrageenan administration, but not at later times. 7 These results suggest that the NO produced by cNOS is involved in the development of inflammation at early time points following carrageenan administration and that NO produced by iNOS is involved in the maintenance of the inflammatory response at later time points. The potential interactions of NO with superoxide anion and PG is discussed.
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PMID:Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. 879 51

Arterial vasodilatation is thought to play a major role in the pathogenesis of systemic hemodynamics and renal disturbances occurring in cirrhotic patients. Recent investigations suggest that an increased vascular nitric oxide (NO) production could be implicated in this abnormality. The current study assessed whether increased expression of inducible and/or endothelial nitric oxide synthase (iNOS and eNOS, respectively) occurs in arterial vessels of cirrhotic rats. The investigation was performed in thoracic and abdominal aortas and mesenteric arteries of 10 control rats and 16 cirrhotic rats with ascites. iNOS and eNOS messenger RNA (mRNA) expression were evaluated by polymerase chain reaction and ribonuclease protection assay, respectively. Endothelial NOS protein expression was assessed by Western blot. No iNOS mRNA was detected in arterial vessels of control rats. In contrast iNOS mRNA was consistently detected in all arteries of cirrhotic rats with ascites, the weakest signal being observed in the thoracic aorta and the strongest in the mesenteric artery. Enhanced eNOS mRNA abundance was found in the aorta of cirrhotic animals as compared with controls. Higher eNOS protein expression was noted in the thoracic aorta of cirrhotic rats. These results indicate the existence of increased eNOS and iNOS expression in arterial vessels of cirrhotic rats, suggesting that transcriptional activation of vascular NOSs and the associated nitric oxide hyperproduction may be of major importance in the pathogenesis of arterial vasodilation in cirrhosis.
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PMID:Increased nitric oxide synthase expression in arterial vessels of cirrhotic rats with ascites. 893 84

Leishmania parasites, transmitted by phlebotomine sand flies, are obligate intracellular parasites of macrophages. The sand fly Phlebotomus papatasi is the vector of Leishmania major, a causative agent of cutaneous leishmaniasis in the Old World, and its saliva exacerbates parasite proliferation and lesion growth in experimental cutaneous leishmaniasis. Here we show that P. papatasi saliva contains a potent inhibitor of protein phosphatase 1 and protein phosphatase 2A of murine macrophages. We further demonstrate that P. papatasi saliva down regulates expression of the inducible nitric oxide synthase gene and reduces nitric oxide production in murine macrophages. Partial biochemical characterization of the protein phosphatase and nitric oxide inhibitor indicated that it is a small, ethanol-soluble molecule resistant to boiling, proteolysis, and DNase and RNase treatments. We suggest that the P. papatasi salivary protein phosphatase inhibitor interferes with the ability of activated macrophages to transmit signals to the nucleus, thereby preventing up regulation of the induced nitric oxide synthase gene and inhibiting the production of nitric oxide. Since nitric oxide is toxic to intracellular parasites, the salivary protein phosphatase inhibitor may be the mechanism by which P. papatasi saliva exacerbates cutaneous leishmaniasis.
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PMID:Phlebotomus papatasi saliva inhibits protein phosphatase activity and nitric oxide production by murine macrophages. 952 78

Nitric oxide (NO) is a ubiquitous molecule that has been associated with inflammation, arthritis, autoimmune disease, bone resorption, and other biological processes. Elucidating the role of NO at the bone-implant interface may further our understanding of the biological processes of osseointegration, loosening, and osteolysis. This study demonstrates the use of a molecular biological technique to investigate the possible role of NO in prosthetic loosening and periprosthetic bone resorption following total hip arthroplasty. Periprosthetic tissue from 12 patients undergoing revision hip arthroplasty was harvested and total ribonucleic acid (RNA) was extracted. In six of the 12 patients, multiple samples from different anatomic locations along the same interface were studied. To estimate the amount of NO present in the tissues in vivo, the level of inducible NO synthase (iNOS) messenger RNA (mRNA) was determined using a ribonuclease (RNase) protection assay. Inducible NOS mRNA was detected in every tissue sample: there was no correlation between iNOS mRNA levels and clinical loosening or osteolysis. Analysis of multiple tissue samples from the same prosthetic component revealed that the levels of iNOS mRNA vary greatly, confirming the heterogeneous nature of the interface.
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PMID:Inducible nitric oxide synthase messenger RNA levels in hip periprosthetic tissue: a preliminary study. 957 74

Previous studies suggest that inducible (i) nitric oxide synthase (NOS) expression within the pulmonary vasculature is increased in rats with chronic hypoxia (CH)-induced pulmonary hypertension. We therefore hypothesized that enhanced iNOS expression associated with CH causes attenuated pulmonary vasoconstrictor responsiveness. To test this hypothesis, we examined the effect of selective iNOS blockade with L-N6-(1-iminoethyl)lysine dihydrochloride (L-NIL) and nonselective NOS inhibition with Nomega-nitro-L-arginine (L-NNA) on vasoconstrictor responses to U-46619 in isolated saline-perfused lungs from both control and CH (4 wk at 380 mmHg) rats. We additionally measured pulmonary hemodynamic responses to L-NIL in conscious CH rats (fraction of inspired O2 = 0.12). Finally, iNOS mRNA levels were assessed in lungs from each group of rats using ribonuclease protection assays. Despite a significant increase in iNOS mRNA expression after exposure to CH, responses to U-46619 were unaltered by L-NIL but augmented by L-NNA in lungs from both control and CH rats. Pulmonary hemodynamics were similarly unaltered by L-NIL in conscious CH rats. We conclude that iNOS does not modulate pulmonary vasoconstrictor responsiveness after long-term hypoxic exposure.
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PMID:Unaltered vasoconstrictor responsiveness after iNOS inhibition in lungs from chronically hypoxic rats. 988 64

Bone marrow-culture-derived macrophages activated with interferon-gamma and lipopolysaccharide produced less nitric oxide (NO) when cultured with vesicular stomatitis virus (VSV)-infected BALB/c3T3 (3T3-VSV) than macrophages activated in an identical manner and cultured alone, with uninfected BALB/c3T3 (3T3), or with P815. However, all four groups of macrophages produced nearly the same amount of interleukin-6 (IL-6). Addition of VSV to activated macrophages did not change the amount of NO produced. The amount of NO generated by two non-macrophage sources of NO was not affected by the presence of either P815 or 3T3-VSV. Reverse transcriptase-polymerase chain reaction showed a decrease in the amount of inducible nitric oxide synthase (iNOS) but not IL-6 mRNA from macrophages cocultured with 3T3-VSV compared with macrophages cocultured with P815. The reduction in iNOS mRNA was confirmed by ribonuclease protection assay. When RAW 264.7 transfected with an iNOS regulatory construct were activated and incubated with 3T3-VSV there was a decrease in the expression of the reporter luciferase gene and NO production but not IL-6 production compared with cells incubated with either medium alone or with P815.
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PMID:Interaction with vesicular stomatitis virus-infected BALB/c3T3 cells inhibits the synthesis of nitric oxide in activated murine bone marrow culture-derived macrophages. 1033 88

Ozone (O(3)) and nitrogen dioxide (NO(2)) are highly reactive and toxic oxidant pollutants. The objective of this study is to compare chemokine, cytokine, and antioxidant changes elicited by acute exposures of O(3) and NO(2) in a genetically sensitive mouse. Eight-week-old C57Bl/6J mice were exposed to 1 or 2.5 ppm ozone or 15 or 30 ppm NO(2) for 4 or 24 h. Changes in mRNA abundance in lung were assayed by slot blot and ribonuclease protection assay (RPA). Messages encoding metallothionein (Mt), heme oxygenase I (HO-I), and inducible nitric oxide synthase (iNOS) demonstrated increased message abundance after 4 and 24 h of exposure to either O(3) or NO(2). Furthermore, increases in message abundance were of a similar magnitude for O(3) and NO(2). Messages encoding eotaxin, macrophage inflammatory protein (MIP)-1alpha, and MIP-2 were elevated after 4 and 24 h of exposure to 1 ppm ozone. Interleukin-6 was elevated after 4 h of exposure to ozone. After 4 h of 2.5 ppm ozone exposure, increased mRNAs of eotaxin, MIP-1alpha, MIP-2, Mt, HO-I, and iNOS were elevated to a higher magnitude than were detected after 1 ppm ozone. Monocyte chemoattractant protein (MCP-1) was elevated following 15 ppm NO(2) exposure. After 4 h of 30 ppm NO(2) exposure, messages encoding eotaxin, MIP-1alpha, MIP-2, and MCP-1 were elevated to levels similar to those detected after ozone exposure. Our results demonstrate a similar antioxidant and chemokine response during both O(3) and NO(2) exposure. Induction of these messages is associated with the duration and concentration of exposure. These studies suggest that these gases exert toxic action through a similar mechanism.
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PMID:Antioxidant and inflammatory response after acute nitrogen dioxide and ozone exposures in C57Bl/6 mice. 1071 24

Infection with the mosquito-transmitted Venezuelan equine encephalitis virus (VEE) causes an acute systemic febrile illness followed by meningoencephalitis. In this communication we characterize the cytokine profile induced in the central nervous system (CNS) in response to virulent or attenuated strains of VEE using RNase Protection Assays. Virulent VEE causes an upregulation of multiple pro-inflammatory genes including inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-alpha). To determine if iNOS and TNF-alpha contribute to the neuropathogenesis of VEE infection, iNOS and TNF receptor knockout mice were used in VEE mortality studies and exhibited extended survival times. Finally, CNS tissue sections labeled for VEE antigen, and adjacent sections double-labeled for an astrocyte marker and apoptosis, revealed that apoptosis of neurons occurs not only in areas of the brain positive for VEE-antigen, but also in areas of astrogliosis. These findings suggest that the inflammatory response, which is in part mediated by iNOS and TNF-alpha, may contribute to neurodegeneration following encephalitic virus infection.
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PMID:Inflammation is a component of neurodegeneration in response to Venezuelan equine encephalitis virus infection in mice. 1099 15


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