Resistance to the Nitric Oxide/Cyclic Guanosine 5′-Monophosphate/Protein Kinase G Pathway in Vascular Smooth Muscle Cells from the Obese Zucker Rat, a Classical Animal Model of Insulin Resistance: Role of Oxidative Stress

Some in vivo and ex vivo studies demonstrated a resistance to the vasodilating effects of nitric oxide (NO) in insulin-resistant states and, in particular, obese Zucker rats (OZR). To evaluate the biochemical basis of this phenomenon, we aimed to identify defects of the NO/cGMP/cGMP-dependent protein kinase (PKG) pathway in cultured vascular smooth muscle cells (VSMCs) from OZR and lean Zucker rats (LZR) by measuring: 1) NO donor ability to increase cGMP in the absence and presence of inhibitors of soluble guanylate cyclase (sGC) and phosphodiesterases (PDEs); 2) NO and cGMP ability to induce, via PKG, vasodilator-stimulated phosphoprotein (VASP) phosphorylation at serine 239 and PDE5 activity; 3) protein expression of sGC, PKG, total VASP, and PDE5; 4) superoxide anion concentrations and ability of antioxidants (superoxide dismutase+catalase and amifostine) to influence the NO/cGMP/PKG pathway activation; and 5) hydrogen peroxide influence on PDE5 activity and VASP phosphorylation. VSMCs from OZR vs. LZR showed: 1) baseline cGMP concentrations higher, at least in part owing to reduced catabolism by PDEs; 2) impairment of NO donor ability to increase cGMP, even in the presence of PDE inhibitors, suggesting a defect in the NO-induced sGC activation; 3) reduction of NO and cGMP ability to activate PKG, indicated by the impaired ability to phosphorylate VASP at serine 239 and to increase PDE5 activity via PKG; 4) similar baseline protein expression of sGC, PKG, total VASP, and PDE5; and 5) higher levels of superoxide anion. Antioxidants partially prevented the defects of the NO/cGMP/PKG pathway observed in VSMCs from OZR, which were reproduced by hydrogen peroxide in VSMCs from LZR, suggesting the pivotal role of oxidative stress.

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Abscisic Acid-Induced Chilling Tolerance in Maize Seedlings Is Mediated by Nitric Oxide and Associated with Antioxidant System

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.378-379.423 ◽

2011 ◽

Vol 378-379 ◽

pp. 423-427 ◽

Cited By ~ 1

Author(s):

Hai Yan Li ◽

Wan Zhong Zhang

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Hydrogen Peroxide ◽

Lipid Peroxidation ◽

Abscisic Acid ◽

Chilling Stress ◽

Chilling Tolerance ◽

Maize Seedlings ◽

No Donor ◽

Contrary Effect

Abscisic acid (ABA) and sodium nitroprusside (SNP) treatment significantly increased chilling tolerance in maize seedlings. ABA in combination with nitric oxide (NO) donor SNP further enhanced the ABA-induced chilling tolerance. But the addition of NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) nullified the increasing effect of SNP on chilling tolerance. In addition, the combination of ABA and PTIO decreased the ABA-induced chilling tolerance. Measurement of activities of superoxide dismutase (SOD) and catalase (CAT), hydrogen peroxide (H2O2) content and the level of lipid peroxidation (in terms of malondialdehyde) indicated that chilling stress induced an oxidative stress in maize seedlings. ABA treatment enabled maize seedlings to maintain higher SOD and CAT activities and lower level of H2O2 and lipid peroxidation under chilling stress. ABA in combination with SNP further enhanced the ABA-induced increase in SOD and CAT activities and lowered the chilling stress-induced lipid peroxidation in the ABA-treated seedlings. But the addition of PTIO scavenged the increasing effect of SNP. In addition, the combination of ABA and PTIO had a contrary effect with that of ABA and SNP. These results suggest that the ABA-induced chilling tolerance is mediated by NO, NO is involved in ABA-induced chilling tolerance by increasing activities of antioxidant enzymes and reduced endogenous H2O2 accumulation.

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A Short-Term Incubation with High Glucose Impairs VASP Phosphorylation at Serine 239 in response to the Nitric Oxide/cGMP Pathway in Vascular Smooth Muscle Cells: Role of Oxidative Stress

BioMed Research International ◽

10.1155/2014/328959 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Isabella Russo ◽

Michela Viretto ◽

Gabriella Doronzo ◽

Cristina Barale ◽

Luigi Mattiello ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Smooth Muscle ◽

Nadph Oxidase ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

High Glucose ◽

Short Term ◽

Vasp Phosphorylation ◽

Cgmp Pathway

A reduction of the nitric oxide (NO) action in vascular smooth muscle cells (VSMC) could play a role in the vascular damage induced by the glycaemic excursions occurring in diabetic patients; in this study, we aimed to clarify whether a short-term incubation of cultured VSMC with high glucose reduces the NO ability to increase cGMP and the cGMP ability to phosphorylate VASP at Ser-239. We observed that a 180 min incubation of rat VSMC with 25 mmol/L glucose does not impair the NO-induced cGMP increase but reduces VASP phosphorylation in response to both NO and cGMP with a mechanism blunted by antioxidants. We further demonstrated that high glucose increases radical oxygen species (ROS) production and that this phenomenon is prevented by the PKC inhibitor chelerythrine and the NADPH oxidase inhibitor apocynin. The following sequence of events is supported by these results: (i) in VSMC high glucose activates PKC; (ii) PKC activates NADPH oxidase; (iii) NADPH oxidase induces oxidative stress; (iv) ROS impair the signalling of cGMP, which is involved in the antiatherogenic actions of NO. Thus, high glucose, via oxidative stress, can reduce the cardiovascular protection conferred by the NO/cGMP pathway via phosphorylation of the cytoskeleton protein VASP in VSMC.

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The homeostatic role of hydrogen peroxide, superoxide anion and nitric oxide in the vasculature

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2020.11.021 ◽

2020 ◽

Author(s):

Tiago J. Costa ◽

Paula Rodrigues Barros ◽

Cristina Arce ◽

Jeimison Duarte Santos ◽

Júlio da Silva-Neto ◽

...

Keyword(s):

Nitric Oxide ◽

Hydrogen Peroxide ◽

Superoxide Anion

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Protective role of nitric oxide during hydrogen peroxide-induced oxidative stress in tobacco plants

Russian Journal of Plant Physiology ◽

10.1134/s1021443707060064 ◽

2007 ◽

Vol 54 (6) ◽

pp. 755-762 ◽

Cited By ~ 22

Author(s):

L. V. Dubovskaya ◽

E. V. Kolesneva ◽

D. M. Knyazev ◽

I. D. Volotovskii

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Hydrogen Peroxide ◽

Protective Role ◽

Tobacco Plants

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Florigen governs shoot regeneration

Scientific Reports ◽

10.1038/s41598-021-93180-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yaarit Kutsher ◽

Michal Fisler ◽

Adi Faigenboim ◽

Moshe Reuveni

Keyword(s):

Nitric Oxide ◽

Shoot Regeneration ◽

Ectopic Expression ◽

Flowering Plants ◽

Regeneration Capacity ◽

No Donor ◽

Tobacco Leaves ◽

Age Related ◽

Delayed Flowering

AbstractIt is widely known that during the reproductive stage (flowering), plants do not root well. Most protocols of shoot regeneration in plants utilize juvenile tissue. Adding these two realities together encouraged us to study the role of florigen in shoot regeneration. Mature tobacco tissue that expresses the endogenous tobacco florigen mRNA regenerates poorly, while juvenile tissue that does not express the florigen regenerates shoots well. Inhibition of Nitric Oxide (NO) synthesis reduced shoot regeneration as well as promoted flowering and increased tobacco florigen level. In contrast, the addition of NO (by way of NO donor) to the tissue increased regeneration, delayed flowering, reduced tobacco florigen mRNA. Ectopic expression of florigen genes in tobacco or tomato decreased regeneration capacity significantly. Overexpression pear PcFT2 gene increased regeneration capacity. During regeneration, florigen mRNA was not changed. We conclude that florigen presence in mature tobacco leaves reduces roots and shoots regeneration and is the possible reason for the age-related decrease in regeneration capacity.

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Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes

AJP Cell Physiology ◽

10.1152/ajpcell.1998.274.1.c245 ◽

1998 ◽

Vol 274 (1) ◽

pp. C245-C252 ◽

Cited By ~ 27

Author(s):

Junsuke Igarashi ◽

Masashi Nishida ◽

Shiro Hoshida ◽

Nobushige Yamashita ◽

Hiroaki Kosaka ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Cardiac Myocytes ◽

Myocardial Injury ◽

No Production ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

No Donor ◽

Oxide Synthase ◽

Gpx Activity

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined. Interleukin-1β induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS,l-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso- N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2(0.1 mM, 1 h). Inhibition of iNOS with Nω-nitro-l-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

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Glaucocalyxin A inhibits hydrogen peroxide‐induced oxidative stress and inflammatory response in coronary artery smooth muscle cells

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.13253 ◽

2020 ◽

Vol 47 (5) ◽

pp. 765-770

Author(s):

Shunming Zhu ◽

Junbo Zhang ◽

Ying Lv

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Smooth Muscle ◽

Coronary Artery ◽

Inflammatory Response ◽

Smooth Muscle Cells ◽

Muscle Cells

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The role of oxidative/nitrosative stress in pathogenesis of paracetamol-induced toxic hepatitis

Medicinski pregled ◽

10.2298/mpns1012827r ◽

2010 ◽

Vol 63 (11-12) ◽

pp. 827-832 ◽

Cited By ~ 7

Author(s):

Tatjana Radosavljevic ◽

Dusan Mladenovic ◽

Danijela Vucevic ◽

Rada Jesic-Vukicevic

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Reactive Oxygen Species ◽

Liver Injury ◽

Kupffer Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Severe Liver ◽

Hepatocellular Necrosis

Introduction. Paracetamol is an effective analgesic/antipyretic drug when used at therapeutic doses. However, the overdose of paracetamol can cause severe liver injury and liver necrosis. The mechanism of paracetamol-induced liver injury is still not completely understood. Reactive metabolite formation, depletion of glutathione and alkylation of proteins are the triggers of inhibition of mitochondrial respiration, adenosine triphosphate depletion and mitochondrial oxidant stress leading to hepatocellular necrosis. Role of oxidative stress in paracetamol-induced liver injury. The importance of oxidative stress in paracetamol hepatotoxicity is controversial. Paracetamol induced liver injury cause the formation of reactive oxygen species. The potent sources of reactive oxygen are mitochondria, neutrophils, Kupffer cells and the enzyme xatnine oxidase. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in paracetamol-induced oxidative stress. The production of mitochondrial reactive oxygen species is increased, and the glutathione content is decreased in paracetamol overdose. Oxidative stress in mitochondria leads to mito?chondrial dysfunction with adenosine triphosphate depletion, increase mitochondrial permeability transition, deoxyribonu?cleic acid fragmentation which contribute to the development of hepatocellular necrosis in the liver after paracetamol overdose. Role of Kupffer cells in paracetamol-induced liver injury. Paracetamol activates Kupffer cells, which then release numerous cytokines and signalling molecules, including nitric oxide and superoxide. Kupffer cells are important in peroxynitrite formation. On the other hand, the activated Kupffer cells release anti-inflammatory cytokines. Role of neutrophils in paracetamol-induced liver injury. Paracetamol-induced liver injury leads to the accumulation of neutrophils, which release lysosomal enzymes and generate superoxide anion radicals through the enzyme nicotinamide adenine dinucleotide phosphate oxidase. Hydrogen peroxide, which is influenced by the neutrophil-derived enzyme myeloperoxidase, generates hypochlorus acid as a potent oxidant. Role of peroxynitrite in paracetamol-induced oxidative stress. Superoxide can react with nitric oxide to form peroxynitrite, as a potent oxidant. Nitrotyrosine is formed by the reaction of tyrosine with peroxynitrite in paracetamol hepatotoxicity. Conclusion. Overdose of paracetamol may produce severe liver injury with hepatocellular necrosis. The most important mechanisms of cell injury are metabolic activation of paracetamol, glutathione depletion, alkylation of proteins, especially mitochondrial proteins, and formation of reactive oxygen/nitrogen species.

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