scholarly journals Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts

2013 ◽  
Vol 304 (7) ◽  
pp. G673-G679
Author(s):  
Yishi Chen ◽  
Taned Chitapanarux ◽  
Jianfeng Wu ◽  
Russell K. Soon ◽  
Andrew C. Melton ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylyl Cyclase ◽  
No Production ◽  
No Signaling ◽  
Inflammatory Bowel ◽  
Relaxation Responses ◽  
Oxide Synthase ◽  
Human And Mouse ◽  
Inducible Nitric Oxide

Contraction of intestinal myofibroblasts (IMF) contributes to the development of strictures and fistulas seen in inflammatory bowel disease, but the mechanisms that regulate tension within these cells are poorly understood. In this study we investigated the role of nitric oxide (NO) signaling in C-type natriuretic peptide (CNP)-induced relaxation of IMF. We found that treatment with ODQ, a soluble guanylyl cyclase (sGC) inhibitor, or NG-nitro-l-arginine (l-NNA) or NG-monomethyl-l-arginine (l-NMMA), inhibitors of NO production, all impaired the relaxation of human and mouse IMF in response to CNP. ODQ, l-NNA, and l-NMMA also prevented CNP-induced elevations in cGMP concentrations, and l-NNA or l-NMMA blocked CNP-induced decreases in myosin light phosphorylation. IMF isolated from transgenic mice deficient in inducible nitric oxide synthase (iNOS) had reduced relaxation responses to CNP compared with IMF from control mice and were insensitive to the effects of ODQ, l-NNA, and l-NMMA on CNP treatment. Together these data indicate that stimulation of sGC though NO produced by iNOS activation is required for maximal CNP-induced relaxation in IMF.

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

Parasite killing in murine malaria does not require nitric oxide production

Parasitology ◽  
1999 ◽  
Vol 118 (2) ◽  
pp. 139-143 ◽  
Author(s):  
N. FAVRE ◽  
B. RYFFEL ◽  
W. RUDIN
Keyword(s):  
Nitric Oxide ◽  
Blood Stage ◽  
No Production ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Stage Parasite ◽  
Blood Stage Malaria ◽  
Inducible Nitric Oxide

Nitric oxide (NO) production has been suggested to play a role as effector molecule in the control of the malarial infections. However, the roles of this molecule are debated. To assess whether blood-stage parasite killing is NO dependent, we investigated the course of blood-stage Plasmodium chabaudi chabaudi (Pcc) infections in inducible nitric oxide synthase (iNOS)-deficient mice. Parasitaemia, haematological alterations, and survival were not affected by the lack of iNOS. To exclude a role of NO produced by other NOS, controls included NO suppression by oral administration of aminoguanidine (AG), a NOS inhibitor. As in iNOS-deficient mice, no difference in the parasitaemia course, survival and haematological values was observed after AG treatment. Our results indicate that NO production is not required for protection against malaria in our murine experimental model. However, C57BL/6 mice treated with AG lost their resistance to Pcc infections, suggesting that the requirement for NO production for parasite killing in murine blood-stage malaria might be strain dependent.

scholarly journals Novel role of the nitrite transporter NirC in Salmonella pathogenesis: SPI2-dependent suppression of inducible nitric oxide synthase in activated macrophages

Microbiology ◽  
2009 ◽  
Vol 155 (8) ◽  
pp. 2476-2489 ◽  
Author(s):  
Priyanka Das ◽  
Amit Lahiri ◽  
Ayan Lahiri ◽  
Dipshikha Chakravortty
Keyword(s):  
Nitric Oxide ◽  
Type Strain ◽  
Wild Type Strain ◽  
No Production ◽  
Activated Macrophages ◽  
Wild Type ◽  
Raw264.7 Macrophages ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Activation of macrophages by interferon gamma (IFN-γ) and the subsequent production of nitric oxide (NO) are critical for the host defence against Salmonella enterica serovar Typhimurium infection. We report here the inhibition of IFN-γ-induced NO production in RAW264.7 macrophages infected with wild-type Salmonella. This phenomenon was shown to be dependent on the nirC gene, which encodes a potential nitrite transporter. We observed a higher NO output from IFN-γ-treated macrophages infected with a nirC mutant of Salmonella. The nirC mutant also showed significantly decreased intracellular proliferation in a NO-dependent manner in activated RAW264.7 macrophages and in liver, spleen and secondary lymph nodes of mice, which was restored by complementing the gene in trans. Under acidified nitrite stress, a twofold more pronounced NO-mediated repression of SPI2 was observed in the nirC knockout strain compared to the wild-type. This enhanced SPI2 repression in the nirC knockout led to a higher level of STAT-1 phosphorylation and inducible nitric oxide synthase (iNOS) expression than seen with the wild-type strain. In iNOS knockout mice, the organ load of the nirC knockout strain was similar to that of the wild-type strain, indicating that the mutant is exclusively sensitive to the host nitrosative stress. Taken together, these results reveal that intracellular Salmonella evade killing in activated macrophages by downregulating IFN-γ-induced NO production, and they highlight the critical role of nirC as a virulence gene.

The development of murine cerebral malaria does not require nitric oxide production

Parasitology ◽  
1999 ◽  
Vol 118 (2) ◽  
pp. 135-138 ◽  
Author(s):  
N. FAVRE ◽  
B. RYFFEL ◽  
W. RUDIN
Keyword(s):  
Nitric Oxide ◽  
Cerebral Malaria ◽  
Plasmodium Berghei ◽  
No Production ◽  
Survival And Development ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Inducible Nitric Oxide

Nitric oxide (NO) production has been suggested to be required for the development of cerebral malaria. However, the importance of this molecule for the appearance of this pathology is debated. To assess whether murine cerebral malaria is NO dependent, we investigated the course of blood-stage Plasmodium berghei ANKA (PbA) infections in inducible nitric oxide synthase (iNOS)-deficient mice. Parasitaemia, haematological alterations, survival and development of cerebral malaria were not affected by the lack of iNOS. To exclude a role of NO produced by other NOS, controls included NO suppression by oral administration of aminoguanidine (AG), a NOS inhibitor. As in iNOS-deficient mice, no difference in the parasitaemia course, survival and haematological values was observed after AG treatment. Our results indicate that NO production is not a crucial factor for the development of murine cerebral malaria.

Vasculoprotective Role of Inducible Nitric Oxide Synthase at Inflammatory Coronary Lesions Induced by Chronic Treatment With Interleukin-1β in Pigs in Vivo

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3104-3111 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa ◽  
Toshiyuki Kozai ◽  
Toshiaki Kadokami ◽  
Kouichi Kuwata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Chronic Treatment ◽  
Interleukin 1Β ◽  
Coronary Lesions ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Effects of chitosan on nitric oxide production and inducible nitric oxide synthase activity and mRNA expression in weaned piglets

2018 ◽  
Vol 60 (No. 8) ◽  
pp. 359-366
Author(s):  
J. Li ◽  
B. Shi ◽  
S. Yan ◽  
L. Jin ◽  
Y. Guo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Inducible Nitric Oxide Synthase ◽  
No Production ◽  
Weaned Piglets ◽  
Inos Activity ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The effects of chitosan on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity and gene expression in vivo or vitro were investigated in weaned piglets. In vivo, 180 weaned piglets were assigned to five dietary treatments with six replicates. The piglets were fed on a basal diet supplemented with 0 (control), 100, 500, 1000, and 2000 mg chitosan/kg feed, respectively. In vitro, the peripheral blood mononuclear cells (PBMCs) from a weaned piglet were cultured respectively with 0 (control), 40, 80, 160, and 320 &micro;g chitosan/ml medium. Results showed that serum NO concentrations on days 14 and 28 and iNOS activity on day 28 were quadratically improved with increasing chitosan dose (P &lt; 0.05). The iNOS mRNA expressions were linearly or quadratically enhanced in the duodenum on day 28, and were improved quadratically in the jejunum on days 14 and 28 and in the ileum on day 28 (P &lt; 0.01). In vitro, the NO concentrations, iNOS activity, and mRNA expression in unstimulated PBMCs were quadratically enhanced by chitosan, but the improvement of NO concentrations and iNOS activity by chitosan were markedly inhibited by N-(3-[aminomethyl] benzyl) acetamidine (1400w) (P&nbsp;&lt; 0.05). Moreover, the increase of NO concentrations, iNOS activity, and mRNA expression in PBMCs induced by lipopolysaccharide (LPS) were suppressed significantly by chitosan (P &lt; 0.05). The results indicated that the NO concentrations, iNOS activity, and mRNA expression in piglets were increased by feeding chitosan in a dose-dependent manner. In addition, chitosan improved the NO production in unstimulated PBMCs but inhibited its production in LPS-induced cells, which exerted bidirectional regulatory effects on the NO production via modulated iNOS activity and mRNA expression.

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

2007 ◽  
Vol 292 (4) ◽  
pp. H1995-H2003 ◽  
Author(s):  
Zuo-Hui Shao ◽  
Wei-Tien Chang ◽  
Kim Chai Chan ◽  
Kim R. Wojcik ◽  
Chin-Wang Hsu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Therapeutic Hypothermia ◽  
Optimal Timing ◽  
No Production ◽  
Early Reperfusion ◽  
No Signaling ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Pkc Activation

Optimal timing of therapeutic hypothermia for cardiac ischemia is unknown. Our prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling that confer protection against I/R injury. Thus we hypothesized that hypothermia will protect most using extended ischemia and early reperfusion cooling and is mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an established model of 1-h ischemia/3-h reperfusion, and the same field of initially contracting cells was monitored for viability and NO generation. Normothermic I/R resulted in 49.7 ± 3.4% cell death. Hypothermia induction to 25°C was most protective (14.3 ± 0.6% death, P < 0.001 vs. I/R control) when instituted during extended ischemia and early reperfusion, compared with induction after reperfusion (22.4 ± 2.9% death). Protection was completely lost if onset of cooling was delayed by 15 min of reperfusion (45.0 ± 8.2% death). Extended ischemia/early reperfusion cooling was associated with increased and sustained NO generation at reperfusion and decreased caspase-3 activation. The NOS inhibitor Nω-nitro-l-arginine methyl ester (200 μM) reversed these changes and abrogated hypothermia protection. In addition, the PKCε inhibitor myr-PKCε v1-2 (5 μM) also reversed NO production and hypothermia protection. In conclusion, therapeutic hypothermia initiated during extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R injury. Such protection appears to be mediated by increased NO generation via activation of protein kinase Cε; nitric oxide synthase.

Detection of inducible nitric oxide synthase inSchistosoma japonicumandS. mansoni

2004 ◽  
Vol 78 (1) ◽  
pp. 47-50 ◽  
Author(s):  
X.-C. Long ◽  
M. Bahgat ◽  
K. Chlichlia ◽  
A. Ruppel ◽  
Y.-L. Li
Keyword(s):  
Nitric Oxide ◽  
Molecular Weight ◽  
Inducible Nitric Oxide Synthase ◽  
Mouse Liver ◽  
Apparent Molecular Weight ◽  
Western Blots ◽  
Oxide Synthase ◽  
Host Tissues ◽  
Inducible Nitric Oxide

AbstractSchistosoma japonicumandS. mansoniwere tested for reactivity with an anti-inducible nitric oxide (iNOS) antibody and the distribution of iNOS was studied by immunofluorescent tests in different stages of the parasites. Reactivity was associated with the tegument in both larval schistosomes (sporocysts and cercariae) and eggs. With adult worms, the majority of the immunofluorescence was predominantly subtegumental inS. japonicumand parenchymal inS. mansoni. Fluorescence was also observed in host tissues (snails and mouse liver). In Western blots, the enzyme ofS. japonicumhad an apparent molecular weight of about 210 kDa. The possible role of worm and host iNOS in the parasite–host interrelation remains to be clarified.

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