scholarly journals The Role of Nitric Oxide in Regulating Intestinal Redox Status and Intestinal Epithelial Cell Functionality

2019 ◽  
Vol 20 (7) ◽  
pp. 1755 ◽  
Author(s):  
Kaiwen Mu ◽  
Shengwu Yu ◽  
David D. Kitts
Keyword(s):  
Nitric Oxide ◽  
Current Knowledge ◽  
Redox Status ◽  
No Production ◽  
Intestinal Epithelial ◽  
Junction Protein ◽  
Optimal Function ◽  
Oxide Synthase ◽  
Free Radical Activity

Important functions of intestinal epithelial cells (IECs) include enabling nutrient absorption to occur passively and acting as a defense barrier against potential xenobiotic components and pathogens. A compromise to IEC function can result in the translocation of bacteria, toxins, and allergens that lead to the onset of disease. Thus, the maintenance and optimal function of IECs are critically important to ensure health. Endogenous biosynthesis of nitric oxide (NO) regulates IEC functionality both directly, through free radical activity, and indirectly through cell signaling mechanisms that impact tight junction protein expression. In this paper, we review the current knowledge on factors that regulate inducible nitric oxide synthase (iNOS) and the subsequent roles that NO has on maintaining IECs’ intestinal epithelial barrier structure, functions, and associated mechanisms of action. We also summarize important findings on the effects of bioactive dietary food components that interact with NO production and affect downstream intestinal epithelium integrity.

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.

scholarly journals Induction of nitric oxide synthesis in J774 cells lowers intracellular glutathione: effect of modulated glutathione redox status on nitric oxide synthase induction

1997 ◽  
Vol 322 (2) ◽  
pp. 477-481 ◽  
Author(s):  
John S. HOTHERSALL ◽  
Fernando Q. CUNHA ◽  
Guy H. NEILD ◽  
Alberto A. NOROHNA-DUTRA
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
De Novo ◽  
Redox Status ◽  
No Production ◽  
Duration Of Treatment ◽  
Intracellular Glutathione ◽  
J774 Cells ◽  
Oxide Synthase ◽  
Glutathione Redox

Under pathological conditions, the induction of nitric oxide synthase (NOS) in macrophages is responsible for NO production to a cytotoxic concentration. We have investigated changes to, and the role of, intracellular glutathione in NO production by the activated murine macrophage cell line J774. Total glutathione concentrations (reduced, GSH, plus the disulphide, GSSG) were decreased to 45% of the control 48 h after cells were activated with bacterial lipopolysaccharide plus interferon γ. This was accompanied by a decrease in the GSH/GSSG ratio from 12:1 to 2:1. The intracellular decrease was not accounted for by either GSH or GSSG efflux; on the contrary, rapid export of glutathione in control cells was abrogated during activation. The loss of intra- and extracellular glutathione indicates either a decrease in synthesis de novo, or an increase in utilization, rather than competition for available NADPH. All changes in activated cells were prevented by pretreatment with the NOS inhibitor l-N-(1-iminoethyl)ornithine. Basal glutathione levels in J774 cells were manipulated by pretreatment with (1) buthionine sulphoximine (glutathione synthase inhibitor), (2) acivicin (γ-glutamyltranspeptidase inhibitor), (3) bromo-octane (glutathione S-transferase substrate) and (4) diamide/zinc (thiol oxidant and glutathione reductase inhibitor). All treatments significantly decreased the output of NO following activation. The degree of inhibition was dependent on (i) duration of treatment prior to activation, (ii) rate of depletion or subsequent recovery and (iii) thiol end product. The level of GSH did not significantly affect the production of NO, after induction of NOS. Thus, glutathione redox status appears to plays an important role in NOS induction during macrophage activation.

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 Regulatory Role of GSK-3βon NF-κB, Nitric Oxide, and TNF-αin Group A Streptococcal Infection

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Yu-Tzu Chang ◽  
Chia-Ling Chen ◽  
Chiou-Feng Lin ◽  
Shiou-Ling Lu ◽  
Miao-Huei Cheng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mouse Model ◽  
Group A Streptococcus ◽  
Glycogen Synthase ◽  
Critical Issue ◽  
No Production ◽  
Group A ◽  
Oxide Synthase

Group A streptococcus (GAS) imposes a great burden on humans. Efforts to minimize the associated morbidity and mortality represent a critical issue. Glycogen synthase kinase-3β(GSK-3β) is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3βin GAS infection is still unknown. The present study investigates the interaction between GSK-3β, NF-κB, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF-κB, followed by an increased expression of inducible nitric oxide synthase (iNOS) and NO production in a murine macrophage cell line. Activation of GSK-3βoccurred after GAS infection, and inhibition of GSK-3βreduced iNOS expression and NO production. Furthermore, GSK-3βinhibitors reduced NF-κB activation and subsequent TNF-αproduction, which indicates that GSK-3βacts upstream of NF-κB in GAS-infected macrophages. Similar to the in vitro findings, administration of GSK-3βinhibitor in an air pouch GAS infection mouse model significantly reduced the level of serum TNF-αand improved the survival rate. The inhibition of GSK-3βto moderate the inflammatory effect might be an alternative therapeutic strategy against GAS infection.

scholarly journals Role of endothelial nitric oxide synthase-derived nitric oxide in activation and dysfunction of cerebrovascular endothelial cells during early onsets of sepsis

2008 ◽  
Vol 295 (4) ◽  
pp. H1712-H1719 ◽  
Author(s):  
Osamu Handa ◽  
Jancy Stephen ◽  
Gediminas Cepinskas
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Nitric Oxide Synthase ◽  
Mass Flux ◽  
Oxidant Stress ◽  
Junction Protein ◽  
Cerebrovascular Endothelial Cells ◽  
Oxide Synthase ◽  
The Brain

Sepsis-associated encephalopathy is an early manifestation of sepsis, resulting in a diffuse dysfunction of the brain. Recently, nitric oxide (NO) has been proposed to be one of the key molecules involved in the modulation of inflammatory responses in the brain. The aim of this study was to assess the role of NO in cerebrovascular endothelial cell activation/dysfunction during the early onsets of sepsis. To this end, we employed an in vitro model of sepsis in which cultured mouse cerebrovascular endothelial cells (MCVEC) were challenged with blood plasma (20% vol/vol) obtained from sham or septic (feces-induced peritonitis, FIP; 6 h) mice. Exposing MCVEC to FIP plasma for 1 h resulted in increased production of reactive oxygen species and NO as assessed by intracellular oxidation of oxidant-sensitive fluorochrome, dihydrorhodamine 123 (DHR 123), and nitrosation of NO-specific probe, DAF-FM, respectively. The latter events were accompanied by dissociation of tight junction protein, occludin, from MCVEC cytoskeletal framework and a subsequent increase in FITC-dextran (3-kDa mol mass) flux across MCVEC grown on the permeable cell culture supports, whereas Evans blue-BSA (65-kDa mol mass) or FITC-dextran (10-kDa mol mass) flux were not affected. FIP plasma-induced oxidant stress, occludin rearrangement, and MCVEC permeability were effectively attenuated by antioxidant, 1-pyrrolidinecarbodithioic acid (PDTC; 0.5 mM), or interfering with nitric oxide synthase (NOS) activity [0.1 mM nitro-l-arginine methyl ester (l-NAME) or endothelial NOS (eNOS)-deficient MCVEC]. However, treatment of MCVEC with PDTC failed to interfere with NO production, suggesting that septic plasma-induced oxidant stress in MCVEC is primarily a NO-dependent event. Taken together, these data indicate that during early sepsis, eNOS-derived NO exhibits proinflammatory characteristics and contributes to the activation and dysfunction of cerebrovascular endothelial cells.

scholarly journals Further evidence for the role of nitric oxide in maternal aggression: effects of L-NAME on maternal aggression towards female intruders in Wistar rats

2009 ◽  
pp. 591-598
Author(s):  
S Ankarali ◽  
HC Ankarali ◽  
C Marangoz
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Aggressive Behavior ◽  
Wistar Rats ◽  
No Production ◽  
Maternal Aggression ◽  
Prairie Voles ◽  
Nos Inhibitor ◽  
Oxide Synthase

It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG -nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms.

scholarly journals Investigation of Role of Nitric Oxide in Protection from Bordetella pertussis Respiratory Challenge

2002 ◽  
Vol 70 (2) ◽  
pp. 679-684 ◽  
Author(s):  
C. Canthaboo ◽  
D. Xing ◽  
X. Q. Wei ◽  
M. J. Corbel
Keyword(s):  
Nitric Oxide ◽  
Bordetella Pertussis ◽  
Knockout Mice ◽  
No Production ◽  
Wild Type ◽  
Respiratory Challenge ◽  
Inos Knockout Mice ◽  
Oxide Synthase

ABSTRACT The mechanism whereby whole-cell pertussis vaccines (WCV) confer protection against Bordetella pertussis is still not fully understood. We have previously reported that macrophage activation produced by vaccination with WCV is associated with induction of NO synthesis by macrophages in response to in vitro stimulation with B. pertussis antigens. To determine whether NO production is an effector of protection or simply a marker of activation, the susceptibility of inducible nitric oxide synthase (type II, iNOS) knockout mice to infection with B. pertussis was examined. We showed that iNOS knockout mice were more susceptible to B. pertussis respiratory challenge than wild-type mice. iNOS-deficient mice also developed a less effective protective response than wild-type mice after the same immunization with WCV. This suggests that NO plays an important role in effecting protection against B. pertussis challenge.

The role of nitric oxide synthase/nitric oxide in vascular smooth muscle control

Perfusion ◽  
2000 ◽  
Vol 15 (2) ◽  
pp. 97-104 ◽  
Author(s):  
D Bradford Sanders ◽  
Tara Kelley ◽  
Douglas Larson
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase ◽  
Vascular Smooth Muscle ◽  
Vascular Function ◽  
No Production ◽  
Amyl Nitrite ◽  
Vascular Compliance ◽  
Oxide Synthase

Vascular compliance is dependent on endogenous and exogenous sources of nitric oxide (NO). In a discussion of therapeutics and NO derived via nitric oxide synthase (NOS) enzymes, it is necessary to examine the pathways of each drug to provide the clinical perfusionist with a greater understanding of the role of NOS/NO in vascular function. Endothelial-derived NO is a contributor in the vasoregulation of vascular smooth muscle. Therapeutics seek to mimic the vasodilatory effects of the endogenous NO. The therapeutics included in this review are nitroglycerin, nitroprusside, amyl nitrite, and inhalation of NO. L-Arginine supplementation provides additional substrate for the endogenous pathway that can augment NO production. NO is a small bioactive molecule involved in various biochemical pathways. Dysregulation of NO production can impair normal physiologic control of vascular compliance. Therefore, the purpose of this review is to provide the perfusionist with an understanding of the biochemical and pharmacological aspects of NOS/NO associated with vascular function.

scholarly journals A Metronidazole-Resistant Isolate of Blastocystis spp. Is Susceptible to Nitric Oxide and Downregulates Intestinal Epithelial Inducible Nitric Oxide Synthase by a Novel Parasite Survival Mechanism

2011 ◽  
Vol 79 (12) ◽  
pp. 5019-5026 ◽  
Author(s):  
Haris Mirza ◽  
Zhaona Wu ◽  
Fahad Kidwai ◽  
Kevin S. W. Tan
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Host Defense ◽  
Resistant Isolate ◽  
No Production ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACTBlastocystis, one of the most common parasites colonizing the human intestine, is an extracellular, noninvasive, luminal protozoan with controversial pathogenesis.Blastocystisinfections can be asymptomatic or cause intestinal symptoms of vomiting, diarrhea, and abdominal pain. Although chronic infections are frequently reported,Blastocystisinfections have also been reported to be self-limiting in immunocompetent patients. Characterizing the host innate response toBlastocystiswould lead to a better understanding of the parasite's pathogenesis. Intestinal epithelial cells produce nitric oxide (NO), primarily on the apical side, in order to target luminal pathogens. In this study, we show that NO production by intestinal cells may be a host defense mechanism againstBlastocystis. Two clinically relevant isolates ofBlastocystis, ST-7 (B) and ST-4 (WR-1), were found to be susceptible to a range of NO donors. ST-7 (B), a metronidazole-resistant isolate, was found to be more sensitive to nitrosative stress. Using the Caco-2 model of human intestinal epithelium,BlastocystisST-7 (B) but not ST-4 (WR-1) exhibited dose-dependent inhibition of Caco-2 NO production, and this was associated with downregulation of inducible nitric oxide synthase (iNOS). Despite its higher susceptibility to NO,BlastocystisST-7 (B) may have evolved unique strategies to evade this potential host defense by depressing host NO production. This is the first study to highlight a strain-to-strain variation in the ability ofBlastocystisto evade the host antiparasitic NO response.

scholarly journals The fundamental role of increased production of nitric oxide in lipopolysaccharide-induced embryonic resorption in mice

Reproduction ◽  
2003 ◽  
pp. 95-110 ◽  
Author(s):  
DG Ogando ◽  
D Paz ◽  
M Cella ◽  
AM Franchi
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
No Production ◽  
Uterine Arteries ◽  
Decidual Cells ◽  
Embryonic Resorption ◽  
High Concentrations ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Nitric oxide (NO) fulfils important functions during pregnancy and has a role in implantation, decidualization, vasodilatation and myometrial relaxation. However, at high concentrations, such as those that are produced in sepsis, NO has toxic effects as it is a free radical. The aim of this study was to characterize uterine and decidual NO production in lipopolysaccharide (LPS)-induced embryonic resorption in mice and to determine which isoforms of nitric oxide synthase (NOS) take part. LPS produced 100% embryonic resorption at 24 h, with complete fetus expulsions at 48 h. Decidual and uterine NO production were increased by LPS, with maximum production at 6 h. This increase was due to the induction of expression of inducible nitric oxide synthase (iNOS) isoform in the decidua and uterus, and neuronal nitric oxide synthase (nNOS) isoform in the decidua, as detected by western blot analysis and immunohistochemistry. LPS increased iNOS expression in decidual and myometrial cells and increased nNOS expression in decidual cells. In addition, LPS caused fibrinolysis and infiltration of mesometrial decidua by macrophages positive for iNOS and CD14 (LPS receptor). Endothelial nitric oxide synthase (eNOS) was found in decidual and uterine arteries but LPS did not modify its expression. LPS induced CD14 expression in endometrial glands, and this could have amplified the inflammatory response. Aminoguanidine, an inhibitor of iNOS activity, totally reversed the LPS-induced embryonic resorption. This result could be explained by an inhibition of the increase in NO production but also by an inhibition of the cellular infiltration and fibrinolysis. These results show that NO fulfils a fundamental role in LPS-induced embryonic resorption.

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