scholarly journals S-Nitroso-N-Acetyl-D-Penicillamine Modified Hyperbranched Polyamidoamine for High-Capacity Nitric Oxide Storage and Release

2020 ◽  
Vol 7 (1) ◽  
pp. 9
Author(s):  
Sean P. Hopkins ◽  
Megan C. Frost
Keyword(s):  
Nitric Oxide ◽  
High Capacity ◽  
Implantable Devices ◽  
Resonance Spectroscopy ◽  
No Donor ◽  
Ionization Time ◽  
Nitric Oxide Release ◽  
Beneficial Effects ◽  
1H Nuclear Magnetic Resonance

Synthetic nitric oxide (NO)-donating materials have been shown to have many beneficial effects when incorporated into biomedical materials. When released in the correct dosage, NO has been shown to increase the biocompatibility of blood and tissue contacting materials, but materials are often limited in the amount of NO that can be administered over a period of time. To address this, hyperbranched polyamidoamine (HPAMAM) was modified with the S-nitrosothiol, S-nitroso-N-acetyl-D-penicillamine, and nitrosated to form a controlled, high-capacity NO-donating compound (SNAP-HPAMAM). This compound has the potential of modifying polymers to release NO over long periods of time by being blended into a variety of base polymers. Nitric oxide release was triggered by photoinitiation and through passive ion-mediated release seen under physiological conditions. A material that delivers the beneficial dose of NO over a long period of time would be able to greatly increase the biocompatibility of long-term implantable devices. Structural analysis of a generation 2 HPAMAM molecule was done through Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance spectroscopy (NMR), and matrix assisted laser desorption ionization, time of flight (MALDI-TOF) mass spectrometry. The NO capacity of the finalized generation 2 SNAP-HPAMAM compound was approximately 1.90 ± 0.116 µmol NO/mg. Quantification of the functional groups in the compound proved that an average of 6.40 ± 0.309 reactive primary amine sites were present compared to the 8 reactive sites on a perfectly synthesized generation 2 dendrimer. There is a substantial advantage of using the hyper-branched HPAMAM over purified dendrimers in terms of reduced labor and expense while still providing a high-capacity NO donor that can be blended into different polymer matrices.

scholarly journals Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 985
Author(s):  
Luisa Müller ◽  
Nicole Power Guerra ◽  
Jan Stenzel ◽  
Claire Rühlmann ◽  
Tobias Lindner ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Neuroprotective Effect ◽  
Resonance Spectroscopy ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Positron Emission ◽  
Pet Ct ◽  
Amyloid Aβ ◽  
Β Amyloid

Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.

scholarly journals Nitric oxide and cGMP protein kinase (cGK) regulate dendritic-cell migration toward the lymph-node–directing chemokine CCL19

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1537-1545 ◽  
Author(s):  
Daniela Giordano ◽  
Dario M. Magaletti ◽  
Edward A. Clark
Keyword(s):  
Nitric Oxide ◽  
Cell Migration ◽  
Dendritic Cell ◽  
Focal Adhesions ◽  
Protective Effects ◽  
No Donor ◽  
Vasp Phosphorylation ◽  
Dendritic Cell Migration ◽  
Chemokine Ccl19

Dendritic-cell (DC) migration to secondary lymphoid organs is crucial for the initiation of adaptive immune responses. Although LPS up-regulates CCR7 on DCs, a second signal is required to enable them to migrate toward the chemokine CCL19 (MIP-3β). We found that the nitric oxide (NO) donor NOR4 provides a signal allowing LPS-stimulated DCs to migrate toward CCL19. NO affects DC migration through both the initial activation of the cGMP/cGMP kinase (cGMP/cGK) pathway and a long-term effect that reduced cGK activity via negative feedback. Indeed, migration of DCs toward CCL19, unlike migration toward CXCL12 (SDF-1α), required inhibition of cGK. LPS increased both cGK expression and cGK activity as measured by phosphorylation of the key cGK target vasodilator-stimulated phosphoprotein (VASP). Because cGK phosphorylation of VASP can disrupt focal adhesions and inhibit cell migration, LPS-induced VASP phosphorylation may prevent DCs from migrating without a second signal. Long-term NOR4 treatment inhibited the increase in cGK-dependent VASP phosphorylation, releasing this brake so that DCs can migrate. NO has been implicated in the regulation of autoimmunity through its effect on T cells. Our results suggest that NO regulation of DC migration and cytokine production may contribute to the protective effects of NO in autoimmune disorders.

Nitric oxide release from a cucurbituril encapsulated NO-donor

2018 ◽  
Vol 16 (23) ◽  
pp. 4272-4278 ◽  
Author(s):  
A. Acuña ◽  
N. Basílio ◽  
M. Parajó ◽  
J. C. Mejuto ◽  
J. Pérez-Juste ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chemical Stimulus ◽  
No Donor ◽  
Nitric Oxide Release

The denitrosation of a S-nitrosothiol derivative, nitrosomercaptopyridine (SNO+), can be inhibited by incorporation into the cucurbit[7]uril cavity. Owing to the reversible character of host : guest complexation, SNO+ can be expelled from the host cavity through the application of a chemical stimulus allowing controlled nitric oxide release.

scholarly journals Effect of nitric oxide release from NOR-3 on urea synthesis, viability and oxygen consumption of rat hepatocyte cultures

2007 ◽  
pp. 427-432
Author(s):  
R Chimenti ◽  
G Martino ◽  
S Mazzulla ◽  
S Sesti
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Cell Viability ◽  
Urea Synthesis ◽  
Rat Hepatocyte ◽  
Trypan Blue Exclusion ◽  
No Donor ◽  
Nitric Oxide Release ◽  
Hepatocyte Cultures ◽  
Trypan Blue Exclusion Test

As nitric oxide is considered a mediator of liver oxidative metabolism during sepsis, we studied the effects of exogenous nitric oxide, produced by NO-donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR-3), on cell viability, urea biosynthesis and oxygen consumption in rat hepatocyte cultures. Nitric oxide release from NOR-3 was studied using 4,5-diaminofluorescein diacetate. Urea levels were measured by the spectrophotometric method. Cell viability was determined by the MTT test and trypan blue exclusion test, whereas oxygen consumption was measured by a polarographic technique. After 2 h treatment, NOR-3 induced an increase in the levels of nitric oxide. After 2 h of treatment and 24 h after the end of the treatment with NOR-3, both cell viability and urea synthesis were significantly reduced in comparison to the controls for NOR-3 concentrations equal to or greater than 50 microM. A reduction in oxygen consumption was observed in hepatocytes after 40 min treatment with 100 microM NOR-3, even if the cell viability was unchanged. Reduction of oxygen consumption is an early indicator of the metabolic alterations in hepatocytes exposed to nitric oxide. These findings suggest that nitric oxide accumulation acts on hepatocyte cultures inducing cell death and reduction of urea synthesis after 2 hours.

scholarly journals cAMP-Dependent Long-Term Potentiation of Nitric Oxide Release from Cerebellar Parallel Fibers in Rats

1998 ◽  
Vol 18 (21) ◽  
pp. 8551-8558 ◽  
Author(s):  
Shinji Kimura ◽  
Seiji Uchiyama ◽  
Hideaki E. Takahashi ◽  
Katsuei Shibuki
Keyword(s):  
Nitric Oxide ◽  
Long Term Potentiation ◽  
Parallel Fibers ◽  
Nitric Oxide Release ◽  
Term Potentiation

scholarly journals Nitric oxide accelerates germination via the regulation of respiration in chickpea

2019 ◽  
Vol 70 (17) ◽  
pp. 4539-4555 ◽  
Author(s):  
Sonika Pandey ◽  
Aprajita Kumari ◽  
Manu Shree ◽  
Vinod Kumar ◽  
Pooja Singh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pentose Phosphate ◽  
Regulation Of Respiration ◽  
Nuclear Magnetic Resonance Analysis ◽  
No Donor ◽  
Resonance Analysis ◽  
Ros Accumulation ◽  
1H Nuclear Magnetic Resonance ◽  
Plant Life Cycle

Abstract Seed germination is crucial for the plant life cycle. We investigated the role of nitric oxide (NO) in two chickpea varieties that differ in germination capacity: Kabuli, which has a low rate of germination and germinates slowly, and Desi, which shows improved germination properties. Desi produced more NO than Kabuli and had lower respiratory rates. As a result of the high respiration rates, Kabuli had higher levels of reactive oxygen species (ROS). Treatment with the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) reduced respiration in Kabuli and decreased ROS levels, resulting in accelerated germination rates. These findings suggest that NO plays a key role in the germination of Kabuli. SNAP increased the levels of transcripts encoding enzymes involved in carbohydrate metabolism and the cell cycle. Moreover, the levels of amino acids and organic acids were increased in Kabuli as a result of SNAP treatment. 1H-nuclear magnetic resonance analysis revealed that Kabuli has a higher capacity for glucose oxidation than Desi. An observed SNAP-induced increase in 13C incorporation into soluble alanine may result from enhanced oxidation of exogenous [13C]glucose via glycolysis and the pentose phosphate pathway. A homozygous hybrid that originated from a recombinant inbred line population of a cross between Desi and Kabuli germinated faster and had increased NO levels and a reduced accumulation of ROS compared with Kabuli. Taken together, these findings demonstrate the importance of NO in chickpea germination via the control of respiration and ROS accumulation.

Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis induced by long-term inhibition of nitric oxide synthesis

2004 ◽  
Vol 286 (2) ◽  
pp. H768-H774 ◽  
Author(s):  
Chu Kataoka ◽  
Kensuke Egashira ◽  
Minako Ishibashi ◽  
Shujiro Inoue ◽  
Weihua Ni ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Rat Model ◽  
Vascular Inflammation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Beneficial Effects ◽  
Pressure Lowering ◽  
Anti Inflammatory ◽  
Synthase Inhibitor

Amlodipine (a new class of calcium channel antagonist) has been shown to limit the progression of arteriosclerosis and decrease the incidence of cardiovascular events. The mechanisms underlying the beneficial effects of amlodipine, however, remain unclear. Therefore, we hypothesized that amlodipine attenuates the development of arteriosclerosis through the inhibition of inflammation in vivo. Long-term inhibition of nitric oxide (NO) by administration of a NO synthase inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME), to rats induces coronary vascular inflammation [monocyte infiltration, monocyte chemoattractant protein-1 (MCP-1) expression, increased activity of angiotensin-converting enzyme (ACE)], and arteriosclerosis. Here, we used the rat model to investigate the anti-inflammatory effects of amlodipine in vivo. Treatment with amlodipine markedly inhibited the l-NAME-induced increase in vascular inflammation, oxidative stress, and local ACE and Rho activity and prevented arteriosclerosis. Interestingly, amlodipine prevented the l-NAME-induced increase in MCP-1 receptor CCR2 expression in circulating monocytes. Amlodipine markedly attenuated the high mortality rate at 8 wk of treatment. These data suggest that amlodipine attenuated arteriosclerosis through inhibiting inflammatory disorders in the rat model of long-term inhibition of NO synthesis. The anti-inflammatory effects of amlodipine seem to be mediated not only by the inhibition of local factors such as MCP-1 but also by the decrease in CCR2 in circulating monocytes. Inhibition of the MCP-1 to CCR2 pathway may represent novel anti-inflammatory actions of amlodipine beyond blood pressure lowering.

scholarly journals Nitric Oxide Protects L-Type Calcium Channel of Cardiomyocyte during Long-Term Isoproterenol Stimulation in Tail-Suspended Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Zhi-Jie Yue ◽  
Peng-Tao Xu ◽  
Bo Jiao ◽  
Hui Chang ◽  
Zhen Song ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Calcium Channel ◽  
Calcium Current ◽  
Specific Inhibitor ◽  
Oxygen Species ◽  
Similar Extent ◽  
Initial Value ◽  
No Donor ◽  
Expression And Activity

The aim of this study was to investigate the effects of nitric oxide (NO) and reactive oxygen species (ROS) on L-type calcium channel (LTCC) gating properties of cardiomyocytes during long-term isoproterenol (ISO) stimulation. Expression and activity of nNOS as well asS-nitrosylation of LTCCα1C subunit significantly decreased in the myocardium of SUS rats. Long-term ISO stimulation increased ROS in cardiomyocytes of SUS rats. ISO-enhanced calcium current (ICa,L) in the SUS group was less than that in the CON group. The maximalICa,Ldecreased to about 80% or 60% of initial value at the 50th minute of ISO treatment in CON or SUS group, respectively. Specific inhibitor NAAN of nNOS reduced maximalICa,Lto 50% of initial value in the CON group; in contrast, NO donor SNAP maintained maximalICa,Lin SUS group to similar extent of CON group after 50 min of ISO treatment. Long-term ISO stimulation also changed steady-state activation (P<0.01), inactivation (P<0.01), and recovery (P<0.05) characteristics of LTCC in SUS group. In conclusion, NO-inducedS-nitrosylation of LTCCα1C subunit may competitively prevent oxidation from ROS at the same sites. Furthermore, LTCC can be protected by NO during long-term ISO stimulation.

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