scholarly journals Differential Regulation of Nitric Oxide Synthase-2 and Arginase-1 by Type 1/Type 2 Cytokines In Vivo: Granulomatous Pathology Is Shaped by the Pattern of l-Arginine Metabolism

2001 ◽  
Vol 167 (11) ◽  
pp. 6533-6544 ◽  
Author(s):  
Matthias Hesse ◽  
Manuel Modolell ◽  
Anne C. La Flamme ◽  
Marco Schito ◽  
José Manuel Fuentes ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Differential Regulation ◽  
Arginine Metabolism ◽  
Arginase 1 ◽  
Type 2 Cytokines ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase

scholarly journals Differential Regulation of L-Arginine Metabolism through Arginase 1 during Infection with Leishmania mexicana Isolates Obtained from Patients with Localized and Diffuse Cutaneous Leishmaniasis

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Arturo A. Wilkins-Rodríguez ◽  
Armando Pérez-Torres ◽  
Alma R. Escalona-Montaño ◽  
Laila Gutiérrez-Kobeh
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Clinical Manifestations ◽  
Differential Regulation ◽  
Leishmania Mexicana ◽  
Arginine Metabolism ◽  
Content Type ◽  
Arginase 1 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT l-Arginine metabolism through arginase 1 (Arg-1) and inducible nitric oxide synthase (NOS2) constitutes a fundamental axis for the resolution or progression of leishmaniasis. Infection with Leishmania mexicana can cause two distinct clinical manifestations: localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL). In this work, we analyzed in an in vivo model the capacity of two L. mexicana isolates, one obtained from a patient with LCL and the other from a patient with DCL, to regulate the metabolism of l-arginine through Arg-1 and NOS2. Susceptible BALB/c mice were infected with L. mexicana isolates from both clinical manifestations, and the evolution of the infection as well as protein presence and activity of Arg-1 and NOS2 were evaluated. The lesions of mice infected with the DCL isolate were bigger, had higher parasite loads, and showed greater protein presence and enzymatic activity of Arg-1 than the lesions of mice infected with the LCL isolate. In contrast, NOS2 protein synthesis was poorly or not induced in the lesions of mice infected with the LCL or DCL isolate. The immunochemistry analysis of the lesions allowed the identification of highly parasitized macrophages positive for Arg-1, while no staining for NOS2 was found. In addition, we observed in lesions of patients with DCL macrophages with higher parasite loads and stronger Arg-1 staining than those in lesions of patients with LCL. Our results suggest that L. mexicana isolates obtained from patients with LCL or DCL exhibit different virulence or pathogenicity degrees and differentially regulate l-arginine metabolism through Arg-1.

Molecular targets of nitric-oxide-donating aspirin in cancer

2005 ◽  
Vol 33 (4) ◽  
pp. 701-704 ◽  
Author(s):  
K. Kashfi ◽  
B. Rigas
Keyword(s):  
Nitric Oxide ◽  
Cell Signalling ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Inhibition Of Proliferation ◽  
Mitogen Activated Protein ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase

Nitric-oxide-donating aspirin (NO-ASA), consisting of ASA (aspirin) plus an -ONO2 moiety linked to it via a molecular spacer, is a new drug for cancer prevention. NO-ASA seems to overcome the low potency and toxicity of traditional ASA. The -ONO2 moiety is responsible for releasing NO, and it appears to be required for biological activity. In studies in vitro, NO-ASA inhibits the growth of colon, pancreatic, prostate, lung, skin, leukaemia and breast cancer cells, and is up to 6000-fold more potent than traditional ASA. This effect is owing to cell kinetics [inhibition of proliferation, induction of apoptosis (multiple criteria) and blocking the G1 to S cell-cycle transition] and cell signalling [inhibition of Wnt signalling (IC50=0.2 μM), inhibition of NF-κB (nuclear factor κB) activation (IC50=7.5 μM), inhibition of nitric oxide synthase-2 expression (IC50=48 μM), inhibition of MAPK (mitogen-activated protein kinase) signalling (IC50=10 μM) and induction of cyclo-oxygenase-2 at approx. 10 μM]. In studies in vivo, NO-ASA inhibits intestinal carcinogenesis in Min mice (tumour multiplicity was reduced by 59% after 3 weeks, with no effect in control animals and no side effects) and in the N-nitrosobis(2-oxopropyl)amine model of pancreatic cancer, where there was an 89% reduction in NO-ASA (3000 p.p.m. in the diet)-treated animals (P<0.001). There was no statistically significant effect by traditional ASA at equimolar doses. Our data indicate that NO-ASA is a highly promising agent for the prevention and/or treatment of cancer.

Intron 4 a/b polymorphism of the endothelial nitric oxide synthase gene is associated with both type 1 and type 2 diabetes in a genetically homogeneous population

2008 ◽  
Vol 69 (4-5) ◽  
pp. 279-283 ◽  
Author(s):  
Emmanouil Galanakis ◽  
Diamantis Kofteridis ◽  
Kalliopi Stratigi ◽  
Eleni Petraki ◽  
Vassilios Vazgiourakis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Homogeneous Population ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Intron 4

scholarly journals Nitric oxide regulates nitric oxide synthase-2 gene expression by inhibiting NF-κB binding to DNA

1997 ◽  
Vol 322 (2) ◽  
pp. 609-613 ◽  
Author(s):  
Song Kyu PARK ◽  
Hsin Lee LIN ◽  
Sean MURPHY
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Interferon Γ ◽  
No Production ◽  
No Donor ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase ◽  
Spermine Nonoate ◽  
Dna Complex

Treatment of astroglial cells with interleukin 1β and interferon γ transcriptionally activates the nitric oxide synthase (NOS)-2 gene. The duration of mRNA expression is brief because of transcript instability. In addition, NO donors reduce the expression of NOS-2 mRNA dramatically by reducing the rate of transcription. In this study we observed that the NO donor, spermine NONOate did not inhibit the activation and translocation of NF-κB, a key transcription factor in the induction of NOS-2, but inhibited formation of the NF-κB–DNA complex. This effect was reversed by methaemoglobin (acting as an NO trap) and by the reducing agent dithiothreitol. Formation of the interferon-regulatory factor–DNA complex was unaffected by NO. These results suggest that NO can modulate its own production by interfering with NF-κB interaction with the promoter region of the NOS gene, a negative feedback effect that may be important for limiting NO production in vivo.

Influence of exercise on dilatation of the basilar artery during diabetes mellitus

2004 ◽  
Vol 96 (5) ◽  
pp. 1730-1737 ◽  
Author(s):  
William G. Mayhan ◽  
Hong Sun ◽  
Jill F. Mayhan ◽  
Kaushik P. Patel
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Basilar Artery ◽  
Potential Role ◽  
Diabetic Rats ◽  
Cerebrovascular Reactivity ◽  
Oxide Synthase ◽  
Enos Protein

Our goal was to examine whether exercise training alleviates impaired nitric oxide synthase (NOS)-dependent dilatation of the basilar artery in Type 1 diabetic rats. To test this hypothesis, we measured in vivo diameter of the basilar artery in sedentary and exercised nondiabetic and diabetic rats in response to NOS-dependent (acetylcholine) and -independent (nitroglycerin) agonists. To determine the potential role for nitric oxide in vasodilatation in sedentary and exercised nondiabetic and diabetic rats, we examined responses after NG-monomethyl-l-arginine (l-NMMA). We found that acetylcholine produced dilatation of the basilar artery that was similar in sedentary and exercised nondiabetic rats. Acetylcholine produced only minimal vasodilatation in sedentary diabetic rats. However, exercise alleviated impaired acetylcholine-induced vasodilatation in diabetic rats. Nitroglycerin produced dilatation of the basilar artery that was similar in sedentary and exercised nondiabetic and diabetic rats. l-NMMA produced similar inhibition of acetylcholine-induced dilatation of the basilar artery in sedentary and exercised nondiabetic and diabetic rats. Finally, we found that endothelial NOS (eNOS) protein in the basilar artery was higher in diabetic compared with nondiabetic rats and that exercise increased eNOS protein in the basilar artery of nondiabetic and diabetic rats. We conclude that 1) exercise can alleviate impaired NOS-dependent dilatation of the basilar artery during diabetes mellitus, 2) the synthesis and release of nitric oxide accounts for dilatation of the basilar artery to acetylcholine in sedentary and exercised nondiabetic and diabetic rats, and 3) exercise may exert its affect on cerebrovascular reactivity during diabetes by altering levels of eNOS protein in the basilar artery.

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