Differential Effects of Nitric Oxide on Cyclooxygenase 1 and 2 Activities in Cultured Cells

Author(s):  
Sei-itsu Murota ◽  
Mitsue Onodera ◽  
Ikuo Morita
Genetics ◽  
1996 ◽  
Vol 142 (3) ◽  
pp. 893-906 ◽  
Author(s):  
Elizabeth Gustavson ◽  
Andrew S Goldsborough ◽  
Zehra Ali ◽  
Thomas B Kornberg

Abstract We isolated and characterized numerous engrailed and invected alleles. Among the deficiencies we isolated, a mutant lacking invected sequences was viable and phenotypically normal, a mutant lacking engrailed was an embryo lethal and had slight segmentation defects, and a mutant lacking both engrailed and invected was most severely affected. In seven engrailed alleles, mutations caused translation to terminate prematurely in the central or C-terminal portion of the coding sequence, resulting in embryonic lethality and segmentation defects. Both engrailed and invected expression declined prematurely in these mutant embryos. In wild-type embryos, engrailed and invected are juxtaposed and are expressed in essentially identical patterns. A breakpoint mutant that separates the mgrailed and invected transcription units parceled different aspects of the expression pattern to engrailed or invected. We also found that both genes cause similar defects when expressed ectopically and that the protein products of both genes act to repress transcription in cultured cells. We propose that the varied phenotypes of the engrailed alleles can be explained by the differential effects these mutants have on the combination of engrailed and invected activities, that engrailed and invected share a regulatory region, and that they encode redundant functions.


1996 ◽  
Vol 183 (4) ◽  
pp. 1447-1459 ◽  
Author(s):  
F P Huang ◽  
G J Feng ◽  
G Lindop ◽  
D I Stott ◽  
F Y Liew

MRL/MP-lpr/lpr (MRL/lpr) mice develop a spontaneous autoimmune disease. Serum from these mice contained significantly higher concentrations of nitrite/nitrate than serum from age-matched control MRL/MP-+/+ (MRL/+), BALB/c or CBA/6J mice. Spleen and peritoneal cells from MRL/lpr mice also produced significantly more nitric oxide (NO) than those from the control mice when cultured with interferon (IFN) gamma and lipopolysaccharide (LPS) in vitro. It is interesting to note that peritoneal cells from MRL/lpr mice also produced markedly higher concentrations of interleukin (IL) 12 than those from MRL/+ or BALB/c mice when cultured with same stimuli. It is striking that cells from MRL/lpr mice produced high concentrations of NO when cultured cells from MRL/+ or BALB/c mice. The enhanced NO synthesis induced by IFN-gamma/LPS was substantially inhibited by anti-IL-12 antibody. In addition, IL-12-induced NO production can also be markedly inhibited by anti-IFN-gamma antibody, but only weakly inhibited by anti-tumor necrosis factor alpha antibody. The effect of IL-12 on NO production was dependent on the presence of natural killer and possibly T cells. Serum from MRL/lpr mice contained significantly higher concentrations of IL-12 compared with those of MRL/+ or BALB/c control mice. Daily injection of recombinant IL-12 led to increased serum levels of IFN-gamma and NO metabolites, and accelerated glomerulonephritis in the young MRL/lpr mice (but not in the MRL/+ mice) compared with controls injected with phosphate-buffered saline alone. These data, together with previous finding that NO synthase inhibitors can ameliorate autoimmune disease in MRL/lpr mice, suggest that high capacity of such mice to produce IL-12 and their greater responsiveness to IL-12, leading to the production of high concentrations of NO, are important factors in this spontaneous model of autoimmune disease.


2005 ◽  
Vol 21 (6) ◽  
pp. 917-922 ◽  
Author(s):  
Seung-Cheol Chang ◽  
Nazaré Pereira-Rodrigues ◽  
James R. Henderson ◽  
Anthony Cole ◽  
Fethi Bedioui ◽  
...  

2014 ◽  
Vol 34 (14) ◽  
pp. 5023-5028 ◽  
Author(s):  
Elena Molokanova ◽  
Mohd Waseem Akhtar ◽  
Sara Sanz-Blasco ◽  
Shichun Tu ◽  
Juan C. Piña-Crespo ◽  
...  

2011 ◽  
Vol 301 (3) ◽  
pp. H1080-H1089 ◽  
Author(s):  
Vincent J. de Beer ◽  
Yannick J. Taverne ◽  
Diederik W. Kuster ◽  
Aref Najafi ◽  
Dirk J. Duncker ◽  
...  

Myocardial infarction (MI) is associated with endothelial dysfunction resulting in an imbalance in endothelium-derived vasodilators and vasoconstrictors. We have previously shown that despite increased endothelin (ET) plasma levels, the coronary vasoconstrictor effect of endogenous ET is abolished after MI. In normal swine, nitric oxide (NO) and prostanoids modulate the vasoconstrictor effect of ET. In light of the interaction among NO, prostanoids, and ET combined with endothelial dysfunction present after MI, we investigated this interaction in control of coronary vasomotor tone in the remote noninfarcted myocardium after MI. Studies were performed in chronically instrumented swine (18 normal swine; 13 swine with MI) at rest and during treadmill exercise. Furthermore, endothelial nitric oxide synthase (eNOS) and cyclooxygenase protein levels were measured in the anterior (noninfarcted) wall of six normal and six swine with MI. eNOS inhibition with Nω-nitro-l-arginine (l-NNA) and cyclooxygenase inhibition with indomethacin each resulted in coronary vasoconstriction at rest and during exercise, as evidenced by a decrease in coronary venous oxygen levels. The effect of l-NNA was slightly decreased in swine with MI, although eNOS expression was not altered. Conversely, in accordance with the unaltered expression of cyclooxygenase-1 after MI, the effect of indomethacin was similar in normal and MI swine. l-NNA enhanced the vasodilator effect of the ETA/B receptor blocker tezosentan but exclusively during exercise in both normal and MI swine. Interestingly, this effect of l-NNA was blunted in MI compared with normal swine. In contrast, whereas indomethacin increased the vasodilator effect of tezosentan only during exercise in normal swine, indomethacin unmasked a coronary vasodilator effect of tezosentan in MI swine both at rest and during exercise. In conclusion, the present study shows that endothelial control of the coronary vasculature is altered in post-MI remodeled myocardium. Thus the overall vasodilator influences of NO as well as its inhibition of the vasoconstrictor influence of ET on the coronary resistance vessels were reduced after MI. In contrast, while the overall prostanoid vasodilator influence was maintained, its inhibition of ET vasoconstrictor influences was enhanced in post-MI remote myocardium.


FEBS Letters ◽  
1996 ◽  
Vol 391 (1-2) ◽  
pp. 21-23 ◽  
Author(s):  
Igor Yu. Malyshev ◽  
Alexander V. Malugin ◽  
Lidia Yu. Golubeva ◽  
Tatiyana A. Zenina ◽  
Eugenia B. Manukhina ◽  
...  

1997 ◽  
Vol 9 (8) ◽  
pp. 789 ◽  
Author(s):  
Barbara Wiszniewska ◽  
Rafal Kurzawa ◽  
Andrzej Ciechanowicz ◽  
Boguslaw Machalinski

The expression of mRNA for inducible nitric oxide synthase (iNOS) in rat epithelial cells of epididymis was investigated with reverse transcription followed by polymerase chain reaction. Immunocytochemical reaction for iNOS was performed to confirm the enzyme’ s localization in the epididymal epithelium. Additionally, an indirect spectrophotometric method for nitric oxide (NO) determination was applied for measurement of nitrite production by cultured epididymal epithelial cells. Inducible NOS mRNA was detected in freshly isolated epithelial cells, in cultured cells without stimulation as well as in cultured cells after stimulation by lipopolysaccharide and interferon-gamma. Inducible NOS immunoreactivity was observed in the apical part of epithelial cells of epididymal sections and in the cytoplasm of cells in culture. Release of nitrite was observedin vitro in both the unstimulated and stimulated cells of caput (1·44 ± 0·94 v. 4·37 ± 2·42 µM) and cauda (0·69 ± 1·21 v. 5·21 ± 2·76 µM) epididymis (P < 0·001). To the best of our knowledge, this is the first study to demonstrate iNOS in the epididymal epithelial cells of the rat. Nitric oxide released by epididymal epithelial cells may act on cells and tissues located nearby. The results may help explain epididymal function: sperm storage, passage and maturation. Excessive epididymal NO production may also play a role in the inflammatory infertility of the male. Extra keyword: iNOS


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