scholarly journals A computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide

2021 ◽  
Vol 22 (S1) ◽  
Author(s):  
Akila Surendran ◽  
C. Forbes Dewey ◽  
Boon Chuan Low ◽  
Lisa Tucker-Kellogg
Keyword(s):  
Nitric Oxide ◽  
Cross Talk ◽  
Experimental Testing ◽  
Concentration Gradients ◽  
Master Regulator ◽  
Mutual Antagonism ◽  
Common Motif ◽  
Bistable Switching ◽  
Sharp Concentration

Abstract Background RhoA is a master regulator of cytoskeletal contractility, while nitric oxide (NO) is a master regulator of relaxation, e.g., vasodilation. There are multiple forms of cross-talk between the RhoA/ROCK pathway and the eNOS/NO/cGMP pathway, but previous work has not studied their interplay at a systems level. Literature review suggests that the majority of their cross-talk interactions are antagonistic, which motivates us to ask whether the RhoA and NO pathways exhibit mutual antagonism in vitro, and if so, to seek the theoretical implications of their mutual antagonism. Results Experiments found mutual antagonism between RhoA and NO in epithelial cells. Since mutual antagonism is a common motif for bistability, we sought to explore through theoretical simulations whether the RhoA-NO network is capable of bistability. Qualitative modeling showed that there are parameters that can cause bistable switching in the RhoA-NO network, and that the robustness of the bistability would be increased by positive feedback between RhoA and mechanical tension. Conclusions We conclude that the RhoA-NO bistability is robust enough in silico to warrant the investment of further experimental testing. Tension-dependent bistability has the potential to create sharp concentration gradients, which could contribute to the localization and self-organization of signaling domains during cytoskeletal remodeling and cell migration.

502: Pressure Induces Nitric Oxide Production by Human Ureteral Cells in Vitro

2005 ◽  
Vol 173 (4S) ◽  
pp. 137-137
Author(s):  
Michael M. Ohebshalom ◽  
Stella K. Maeng ◽  
Jie Chen ◽  
Dix P. Poppas ◽  
Diane Felsen
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Production ◽  
Oxide Production

Effects of sodium nitroprusside(a donor of nitric oxide) on development of porcine preantral follicle cultured in vitro

2011 ◽  
Vol 37 (1) ◽  
pp. 55-59
Author(s):  
Qing QUAN ◽  
Yong TAO ◽  
Xiao-rong ZHANG ◽  
Gui-dong YAO ◽  
Jin-ju WANG
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Preantral Follicle

Appraisal of Immunological Impacts of Melaleuca leucadendra Extract over Macrophage Performance in Vitro

2020 ◽  
Keyword(s):  
Nitric Oxide ◽  
Interleukin 2 ◽  
Dependent Manner ◽  
Reduced Pressure ◽  
Medical Plant ◽  
Dose Dependent ◽  
Level Production ◽  
Melaleuca Leucadendra ◽  
Phagocytic Killing

This trial research was performed to discuss the immune-influence of Melaleuca leucadendra ‘paper-bark tree’ dried leaves which is an important medical plant known in many regions in the world. The leaves were dissolved in a mixture of (ethanol + water) (3:1) mixture, then filtered, evaporated and dried under reduced pressure to obtain leaves extract. The macrophages of blood derived origin were provided from rats and mixed with three different leaves extracts doses in tissue culture plates and incubated then stained with fluorescent acridine orange and examined under fluorescent microscope to assess the phagocytic and killing potency. The wells contents were aspirated and assayed for nitric oxide and interleukin-2 levels. The results displayed an obvious increase in phagocytic, killing performance as well as nitric oxide and IL-2 level production than control in a dose dependent manner. The obtained results suggested the immune-stimulant impact of the paper-bark tree leaves.

Investigation of Oral Subacute Toxicity and In-Vitro Antioxidant Activity of Standardized Methanolic Extract of Quercus serrata Leaves

2020 ◽  
Vol 16 ◽  
Author(s):  
Maibam Beebina Chanu ◽  
Biseshwori Thongam ◽  
Khumukcham Nongalleima ◽  
Hans Raj Bhat ◽  
Surajit Kumar Ghosh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Antioxidant Activity ◽  
Biochemical Parameters ◽  
Methanolic Extract ◽  
Reducing Power ◽  
Quercus Serrata ◽  
Control Group ◽  
Blood Cell Count ◽  
Toxicological Profile

Background: Quercus serrata Murray leaves have been used traditionally in the treatment of diabetes, dysmenorrhoea, inflammation and urinary tract infection. So, far no study had been reported on the toxicological profile and antioxidant properties of the plant. Objective: The present study was aimed to investigate the in-vivo toxicological profile and in-vitro antioxidant activities of the methanolic extract of standardized Quercus serrata leaves. Methods: Per-oral sub-acute toxicity study was performed in rats using three dose levels (200, 400 and 800 mg/kg b.w.) of the extract for 28-days. Control group received gum acacia suspended in water. Bodyweight was measured weekly. Biochemical parameters were analysed using the serum, the blood-cell count was done using whole blood. Pathological changes were also checked in highly perfused tissues. Further, in-vitro reducing power assay, nitric oxide scavenging assay, DPPH free-radical scavenging assay were performed to check the antioxidant activity of the extract. Results: There were no significant alterations in the blood-cell count and biochemical parameters analysed in the treatment group when compared with the normal control. Histopathology study of liver, kidney, pancreas, heart and brain revealed normal cellular architecture in the treatment groups alike the control group animals. Quercus serrata also showed a significant reduction of DPPH with IC50 4.48±0.254 µg/mL, in-vitro reducing power activity with IC50121.65±0.320 µg/mL and nitric oxide scavenging activity IC50 106.43±0.338 µg/mL. Conclusion: The above study showed that standardized methanolic extract of Quercus serrata leaves was safe after subacute oral administration in rats and has good antioxidant potential.

scholarly journals Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa

2019 ◽  
Vol 75 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Odel Soren ◽  
Ardeshir Rineh ◽  
Diogo G Silva ◽  
Yuming Cai ◽  
Robert P Howlin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Clinical Isolates ◽  
Nitric Oxide Donor ◽  
Confocal Laser ◽  
Broth Microdilution Method

Abstract Objectives The cephalosporin nitric oxide (NO)-donor prodrug DEA-C3D (‘DiEthylAmin-Cephalosporin-3′-Diazeniumdiolate’) has been shown to initiate the dispersal of biofilms formed by the Pseudomonas aeruginosa laboratory strain PAO1. In this study, we investigated whether DEA-C3D disperses biofilms formed by clinical cystic fibrosis (CF) isolates of P. aeruginosa and its effect in combination with two antipseudomonal antibiotics, tobramycin and colistin, in vitro. Methods β-Lactamase-triggered release of NO from DEA-C3D was confirmed using a gas-phase chemiluminescence detector. MICs for P. aeruginosa clinical isolates were determined using the broth microdilution method. A crystal violet staining technique and confocal laser scanning microscopy were used to evaluate the effects of DEA-C3D on P. aeruginosa biofilms alone and in combination with tobramycin and colistin. Results DEA-C3D was confirmed to selectively release NO in response to contact with bacterial β-lactamase. Despite lacking direct, cephalosporin/β-lactam-based antibacterial activity, DEA-C3D was able to disperse biofilms formed by three P. aeruginosa clinical isolates. Confocal microscopy revealed that DEA-C3D in combination with tobramycin produces similar reductions in biofilm to DEA-C3D alone, whereas the combination with colistin causes near complete eradication of P. aeruginosa biofilms in vitro. Conclusions DEA-C3D is effective in dispersing biofilms formed by multiple clinical isolates of P. aeruginosa and could hold promise as a new adjunctive therapy to patients with CF.

scholarly journals Effect of Shuangdan Mingmu capsule, a Chinese herbal formula, on oxidative stress-induced apoptosis of pericytes through PARP/GAPDH pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fujiao Nie ◽  
Jiazhao Yan ◽  
Yanjun Ling ◽  
Zhengrong Liu ◽  
Chaojun Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Oxidative Damage ◽  
Damage Model ◽  
B Cell Lymphoma ◽  
Cell Counting ◽  
Network Pharmacology ◽  
Diabetic Patients ◽  
Induced Apoptosis

Abstract Background Diabetic retinopathy (DR) has become a worldwide concern because of the rising prevalence rate of diabetes mellitus (DM). Despite much energy has been committed to DR research, it remains a difficulty for diabetic patients all over the world. Since apoptosis of retinal microvascular pericytes (RMPs) is the early characteristic of DR, this study aimed to reveal the mechanism of Shuangdan Mingmu (SDMM) capsule, a Chinese patent medicine, on oxidative stress-induced apoptosis of pericytes implicated with poly (ADP-ribose) polymerase (PARP) / glyceraldehyde 3-phosphate dehydrogenase (GAPDH) pathway. Methods Network pharmacology approach was performed to predict biofunction of components of SDMM capsule dissolved in plasma on DR. Both PARP1 and GAPDH were found involved in the hub network of protein-protein interaction (PPI) of potential targets and were found to take part in many bioprocesses, including responding to the regulation of reactive oxygen species (ROS) metabolic process, apoptotic signaling pathway, and response to oxygen levels through enrichment analysis. Therefore, in vitro research was carried out to validate the prediction. Human RMPs cultured with media containing 0.5 mM hydrogen oxide (H2O2) for 4 h was performed as an oxidative-damage model. Different concentrations of SDMM capsule, PARP1 inhibitor, PARP1 activation, and GAPDH inhibitor were used to intervene the oxidative-damage model with N-Acetyl-L-cysteine (NAC) as a contrast. Flow cytometry was performed to determine the apoptosis rate of cells and the expression of ROS. Cell counting kit 8 (CCK8) was used to determine the activity of pericytes. Moreover, nitric oxide (NO) concentration of cells supernatant and expression of endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), B cell lymphoma 2 (BCL2), vascular endothelial growth factor (VEGF), endothelin 1 (ET1), PARP1, and GAPDH were tested through RT-qPCR, western blot (WB), or immunocytochemistry (ICC). Results Overproduction of ROS, high apoptotic rate, and attenuated activity of pericytes were observed after cells were incubated with media containing 0.5 mM H2O2. Moreover, downregulation of SOD, NO, BCL2, and GAPDH, and upregulation of VEGFA, ET1, and PARP1 were discovered after cells were exposed to 0.5 mM H2O2 in this study, which could be improved by PARP1 inhibitor and SDMM capsule in a dose-dependent way, whereas worsened by PARP1 activation and GAPDH inhibitor. Conclusions SDMM capsule may attenuate oxidative stress-induced apoptosis of pericytes through downregulating PARP expression and upregulating GAPDH expression.

Resveratrol and grape juice: Effects on redox status and nitric oxide production of endothelial cells in in vitro preeclampsia model

2021 ◽  
Vol 23 ◽  
pp. 205-210
Author(s):  
Mayara Caldeira-Dias ◽  
Sarah Viana-Mattioli ◽  
Jackeline de Souza Rangel Machado ◽  
Mattias Carlström ◽  
Ricardo de Carvalho Cavalli ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Grape Juice ◽  
Redox Status ◽  
Nitric Oxide Production ◽  
Oxide Production

scholarly journals Leishmanicidal Activity of Betulin Derivatives in Leishmania amazonensis; Effect on Plasma and Mitochondrial Membrane Potential, and Macrophage Nitric Oxide and Superoxide Production

2021 ◽  
Vol 9 (2) ◽  
pp. 320
Author(s):  
Wilmer Alcazar ◽  
Sami Alakurtti ◽  
Maritza Padrón-Nieves ◽  
Maija Liisa Tuononen ◽  
Noris Rodríguez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Leishmania Amazonensis ◽  
Superoxide Production ◽  
In Vitro Susceptibility ◽  
Intracellular Parasites ◽  
Betulin Derivatives

Herein, we evaluated in vitro the anti-leishmanial activity of betulin derivatives in Venezuelan isolates of Leishmania amazonensis, isolated from patients with therapeutic failure. Methods: We analyzed promastigote in vitro susceptibility as well as the cytotoxicity and selectivity of the evaluated compounds. Additionally, the activity of selected compounds was determined in intracellular amastigotes. Finally, to gain hints on their potential mechanism of action, the effect of the most promising compounds on plasma and mitochondrial membrane potential, and nitric oxide and superoxide production by infected macrophages was determined. Results: From the tested 28 compounds, those numbered 18 and 22 were chosen for additional studies. Both 18 and 22 were active (GI50 ≤ 2 µM, cytotoxic CC50 > 45 µM, SI > 20) for the reference strain LTB0016 and for patient isolates. The results suggest that 18 significantly depolarized the plasma membrane potential (p < 0.05) and the mitochondrial membrane potential (p < 0.05) when compared to untreated cells. Although neither 18 nor 22 induced nitric oxide production in infected macrophages, 18 induced superoxide production in infected macrophages. Conclusion: Our results suggest that due to their efficacy and selectivity against intracellular parasites and the potential mechanisms underlying their leishmanicidal effect, the compounds 18 and 22 could be used as tools for designing new chemotherapies against leishmaniasis.

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