Nitric Oxide Plays a Crucial Role in the Development/Progression of Nonalcoholic Steatohepatitis in the Choline-Deficient, l-Amino Acid-Defined Diet-Fed Rat Model

2010 ◽  
Vol 34 ◽  
pp. S18-S24 ◽  
Author(s):  
Koji Fujita ◽  
Yuichi Nozaki ◽  
Masato Yoneda ◽  
Koichiro Wada ◽  
Hirokazu Takahashi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Amino Acid ◽  
Rat Model ◽  
Nonalcoholic Steatohepatitis ◽  
Crucial Role

Search for Potential Inducible Nitric Oxide Synthase Inhibitors with Favorable ADMET Profiles for the Therapy of Helicobacter pylori Infections

2020 ◽  
Vol 19 (30) ◽  
pp. 2795-2804 ◽  
Author(s):  
Ricardo Pereira Rodrigues ◽  
Juliana Santa Ardisson ◽  
Rita de Cássia Ribeiro Gonçalves ◽  
Tiago Branquinho Oliveira ◽  
Vinicius Barreto da Silva ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Helicobacter Pylori ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Crucial Role ◽  
Chemical Space ◽  
Target Selection ◽  
Oxide Synthase ◽  
Inos Inhibition ◽  
Inducible Nitric Oxide

Background: Helicobacter pylori is a gram-negative bacterium related to chronic gastritis, peptic ulcer and gastric carcinoma. During its infection process, promotes excessive inflammatory response, increasing the release of reactive species and inducing the production of pro-inflammatory mediators. Inducible Nitric Oxide Synthase (iNOS) plays a crucial role in the gastric carcinogenesis process and a key mediator of inflammation and host defense systems, which is expressed in macrophages induced by inflammatory stimuli. In chronic diseases such as Helicobacter pylori infections, the overproduction of NO due to the prolonged induction of iNOS is of major concern. Objective: In this sense, the search for potential iNOS inhibitors is a valuable strategy in the overall process of Helicobacter pylori pathogeny. Method: In silico techniques were applied in the search of interesting compounds against Inducible Nitric Oxide Synthase enzyme in a chemical space of natural products and derivatives from the Analyticon Discovery databases. Results: The five compounds with the best iNOS inhibition profile were selected for activity and toxicity predictions. Compound 9 (CAS 88198-99-6) displayed significant potential for iNOS inhibition, forming hydrogen bonds with residues from the active site and an ionic interaction with heme. This compound also displayed good bioavailability and absence of toxicity/or from its probable metabolites. Conclusion: The top-ranked compounds from the virtual screening workflow show promising results regarding the iNOS inhibition profile. The results evidenced the importance of the ionic bonding during docking selection, playing a crucial role in binding and positioning during ligand-target selection for iNOS.

scholarly journals The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erna Davydova ◽  
Tadahiro Shimazu ◽  
Maren Kirstin Schuhmacher ◽  
Magnus E. Jakobsson ◽  
Hanneke L. D. M. Willemen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Crucial Role ◽  
Complex I ◽  
Protein Modification ◽  
Zinc Binding ◽  
Functional Studies ◽  
Mitochondrial Respiratory Complex ◽  
Respiratory Complex I ◽  
Broad Specificity

AbstractPost-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where “x” is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.

Lung microvascular permeability and neutrophil recruitment are differently regulated by nitric oxide in a rat model of intestinal ischemia–reperfusion

2004 ◽  
Vol 494 (2-3) ◽  
pp. 241-249 ◽  
Author(s):  
Gabriela Cavriani ◽  
Ricardo Martins Oliveira-Filho ◽  
Aryene Góes Trezena ◽  
Zilma Lúcia da Silva ◽  
Helori Vanni Domingos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Rat Model ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Microvascular Permeability ◽  
Neutrophil Recruitment ◽  
Intestinal Ischemia Reperfusion

Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide

2002 ◽  
Vol 92 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Daniel Nyhan ◽  
Soonyul Kim ◽  
Stacey Dunbar ◽  
Dechun Li ◽  
Artin Shoukas ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Pulmonary Artery ◽  
Lung Tissue ◽  
Rat Model ◽  
Orthostatic Intolerance ◽  
Volume Distribution ◽  
Contractile Responses ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Vascular contractile hyporesponsiveness is an important mechanism underlying orthostatic intolerance after microgravity. Baroreceptor reflexes can modulate both pulmonary resistance and capacitance function and thus cardiac output. We hypothesized, therefore, that pulmonary vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model of microgravity. Pulmonary artery (PA) contractile responses to phenylephrine (PE) and U-46619 (U4) were significantly decreased in the PAs from HLU vs. control (C) animals. N G-nitro-l-arginine methyl ester (10−5 M) enhanced the contractile responses in the PA rings from both C and HLU animals and completely abolished the differential responses to PE and U4 in HLU vs. C animals. Vasorelaxant responses to ACh were significantly enhanced in PA rings from HLU rats compared with C. Moreover, vasorelaxant responses to sodium nitroprusside were also significantly enhanced. Endothelial nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression were significantly enhanced in PA and lung tissue from HLU rats. In marked contrast, the expression of inducible nitric oxide synthase was unchanged in lung tissue. These data support the hypothesis that vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.

Inhibition of Inducible Nitric Oxide Synthase Reduces Bacterial Translocation in a Rat Model of Acute Pancreatitis

Pancreas ◽  
2001 ◽  
Vol 23 (3) ◽  
pp. 296-301 ◽  
Author(s):  
Ismail Simsek ◽  
Mehmet Refik ◽  
Mehmet Yasar ◽  
Mustafa Ozyurt ◽  
Ugur Saglamkaya ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Pancreatitis ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Bacterial Translocation ◽  
Rat Model ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Exercise-Induced Oxidative Stress, Nitric Oxide and Plasma Amino Acid Profile in Recreational Runners with Vegetarian and Non-Vegetarian Dietary Patterns

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1875 ◽  
Author(s):  
Josefine Nebl ◽  
Kathrin Drabert ◽  
Sven Haufe ◽  
Paulina Wasserfurth ◽  
Julian Eigendorf ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Amino Acid ◽  
Acute Exercise ◽  
Amino Acid Profile ◽  
Post Exercise ◽  
Stable Isotope Dilution ◽  
Amino Acid Profiles ◽  
Recreational Runners ◽  
Exercise Induced

This study investigated the exercise-induced changes in oxidative stress, nitric oxide (NO) metabolism and amino acid profile in plasma of omnivorous (OMN, n = 25), lacto-ovo-vegetarian (LOV, n = 25) and vegan (VEG, n = 23) recreational runners. Oxidative stress was measured as malondialdehyde (MDA), NO as nitrite and nitrate, and various amino acids, including homoarginine and guanidinoacetate, the precursor of creatine. All analytes were measured by validated stable-isotope dilution gas chromatographic-mass spectrometric methods. Pre-exercise, VEG had the highest MDA and nitrate concentrations, whereas nitrite concentration was highest in LOV. Amino acid profiles differed between the groups, with guanidinoacetate being highest in OMN. Upon acute exercise, MDA increased in the LOV and VEG group, whereas nitrate, nitrite and creatinine did not change. Amino acid profiles changed post-exercise in all groups, with the greatest changes being observed for alanine (+28% in OMN, +21% in LOV and +28% in VEG). Pre-exercise, OMN, LOV and VEG recreational runners differ with respect to oxidative stress, NO metabolism and amino acid profiles, in part due to their different dietary pattern. Exercise elicited different changes in oxidative stress with no changes in NO metabolism and closely comparable elevations in alanine. Guanidinoacetate seems to be differently utilized in OMN, LOV and VEG, pre- and post-exercise.

Sign in / Sign up

Export Citation Format

Share Document