scholarly journals Hydrogen peroxide at low concentrations strongly enhances the inhibitory effect of nitric oxide on platelets

1995 ◽  
Vol 310 (1) ◽  
pp. 149-153 ◽  
Author(s):  
K M Naseem ◽  
K R Bruckdorfer
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Physiological Role ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Radical Scavengers ◽  
Simultaneous Application ◽  
Inhibition Of Platelet Aggregation ◽  
Enhanced Sensitivity ◽  
Low Concentrations

Simultaneous application of NO and H2O2 to human platelets at physiologically relevant concentrations increased inhibition of platelet aggregation by NO almost 100-fold. If NO and H2O2 were mixed before the addition to platelets, the inhibitory effect remained but still depended on the presence of NO. This suggested an enhanced sensitivity of the platelets to residual NO in the presence of H2O2. The inhibition by the NO/H2O2 mixture was not due to peroxynitrite and was only partly reversed by radical scavengers. The mechanism includes enhanced formation of cyclic GMP in response to NO in the presence of H2O2. H2O2 may play a positive physiological role by amplification and/or prolongation of the action of NO.

scholarly journals Hormetic Concentrations of Hydrogen Peroxide but Not Ethanol Induce Cross-Adaptation to Different Stresses in Budding Yeast

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Halyna M. Semchyshyn
Keyword(s):  
Hydrogen Peroxide ◽  
Dose Response ◽  
Budding Yeast ◽  
Regulatory Protein ◽  
Colony Growth ◽  
Inhibitory Effect ◽  
Cross Resistance ◽  
Mild Stress ◽  
Low Concentrations ◽  
Cross Adaptation

The biphasic-dose response of microorganisms to hydrogen peroxide is a phenomenon of particular interest in hormesis research. In different animal models, the dose-response curve for ethanol is also nonlinear showing an inhibitory effect at high doses but a stimulatory effect at low doses. In this study, we observed the hormetic-dose response to ethanol in budding yeastS. cerevisiae. Cross-protection is a phenomenon in which exposure to mild stress results in the acquisition of cellular resistance to lethal stress induced by different factors. Since both hydrogen peroxide and ethanol at low concentrations were found to stimulate yeast colony growth, we evaluated the role of one substance in cell cross-adaptation to the other substance as well as some weak organic acid preservatives. This study demonstrates that, unlike ethanol, hydrogen peroxide at hormetic concentrations causes cross-resistance ofS. cerevisiaeto different stresses. The regulatory protein Yap1 plays an important role in the hormetic effects by low concentrations of either hydrogen peroxide or ethanol, and it is involved in the yeast cross-adaptation by low sublethal doses of hydrogen peroxide.

Abstract 489: Mechanisms of Carbon Monoxide Attenuation of Tubuloglomerular Feedback

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
YiLin Ren ◽  
Martin A D'Ambrosio ◽  
Hong Wang ◽  
Jeffrey L Garvin ◽  
Oscar A Carretero
Keyword(s):  
Carbon Monoxide ◽  
Physiological Role ◽  
Inhibitory Effect ◽  
Tubuloglomerular Feedback ◽  
Renal Microcirculation ◽  
Low Concentrations ◽  
Cgmp Analog ◽  
Cell Depolarization ◽  
Toxic Concentrations

Tubuloglomerular feedback (TGF) is an autoregulatory mechanism of the renal microcirculation in which the macula densa (MD) senses NaCl concentration in the lumen of the nephron and sends a signal that controls glomerular filtration rate by constricting the afferent arteriole (Af-Art). We have shown that MD depolarization is sufficient for inducing TGF. Carbon monoxide (CO), either endogenous or exogenous, is known to inhibit TGF, at least in part via cGMP. However, whether cGMP-independent mechanisms are involved, and where in the TGF cascade CO exerts its inhibitory effect, remain unknown. Thus we hypothesize that CO, acting via both cGMP-dependent and -independent mechanisms, attenuates TGF by acting downstream from MD cell depolarization. In vitro , microdissected rabbit Af-Arts and their attached MD were simultaneously perfused and TGF was measured as the decrease in Af-Art diameter. Depolarization of the MD was induced by switching luminal KCl from 4 to 50 mM in the presence of the potassium ionophore valinomycin, while adding the CO-releasing molecule CORM-3 to the MD perfusate at non-toxic concentrations. CORM-3 blunted depolarization-induced TGF at a concentration of 50 μM, from 3.6±0.4 to 2.5±0.4 μm (P<0.01), and completely abolished it at a concentration of 100 μM, to 0.1±0.1 μm (P<0.001, n=6). Similar results were found with 100 μM CORM-3 when depolarization was induced by nystatin (3.0±0.2 vs. 0.4±0.2 μm, P <0.001, n=6). This indicates that CO inhibits TGF acting downstream from depolarization. When cGMP generation was blocked with the guanylate cyclase inhibitor LY-83583 (1 μM) added to the MD, CORM-3 no longer had an effect on depolarization-induced TGF at 50 μM (2.9±0.4 vs. 3.0±0.4 μm), but retained partial inhibitory effect on TGF at 100 μM (1.3±0.2 μm, P =0.02, n=9). This suggests that CO acts via cGMP at low concentrations, but additional mechanisms of action may be involved at higher concentrations. Finally, we confirmed that cGMP inhibits TGF downstream from MD depolarization by adding the degradation-resistant cGMP analog dibutyryl-cGMP (500 μM), which attenuated depolarization-induced TGF (from 3.9±0.5 to 0.6±0.2 μm, P <0.01, n=6). Our results could help explain the physiological role of CO in controlling the renal microcirculation.

scholarly journals THE RELATIONSHIP OF HYDROGEN PEROXIDE TO THE INHIBITION OF THE GLYOXALASE ACTIVITY OF INTACT ERYTHROCYTES BY X-RADIATION

1958 ◽  
Vol 41 (4) ◽  
pp. 737-753 ◽  
Author(s):  
S. J. Klebanoff
Keyword(s):  
Hydrogen Peroxide ◽  
Plasma Glucose ◽  
Physiological Saline ◽  
Inhibitory Effect ◽  
Enzyme Systems ◽  
Low Concentrations ◽  
X Irradiation ◽  
Ionizing Radiations ◽  
Relationship Of

The x-irradiation of a dilute suspension of erythrocytes results in a decrease in the glyoxalase activity of the cells as a result of a fall in the reduced glutathione level. The present paper deals with the possible role of H2O2 in this reaction. The addition of intact erythrocytes to physiological saline previously irradiated with 150,000 r or 225,000 r results in a fall in the glyoxalase activity of the cells. The inhibition is prevented by the preincubation of the irradiated saline with catalase and is reversed by the addition of plasma, glucose, adenosine, and inosine to the cell suspension. An inhibition of the glyoxalase activity is also produced by the addition of H2O2 to the suspension of erythrocytes. The inhibitory effect of H2O2 can be prevented and largely reversed by plasma, glucose, adenosine, and inosine. Methylglyoxal is also protective under these conditions. Hydrogen peroxide formed continuously and in low concentrations by enzyme systems appears to be more effective than added H2O2 in inhibiting the glyoxalase system. The inhibition by H2O2-producing enzyme systems is minimized by the addition of catalase, plasma, glucose, methylglyoxal, and to a lesser extent, by adenosine and inosine, and is accentuated by the addition of sodium azide. The results are discussed in relation to the role of H2O2 and catalase in the toxicity of ionizing radiations.

Accumulation of Unphosphorylated Calponin in the Submembranous Cytoskeletons of Arachidonic Acid-stimulated Human Platelets

1996 ◽  
Vol 75 (04) ◽  
pp. 617-622 ◽  
Author(s):  
Thomas Meyer ◽  
Christina Unterberg ◽  
Heinrich Kreuzer ◽  
Arnd B Buchwald
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase ◽  
Muscle Protein ◽  
Physiological Role ◽  
Protein Band ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Calpain Inhibitor ◽  
Dependent Protein

SummaryCalponin, a basic smooth-muscle protein capable of binding to F-actin, tropomyosin and calmodulin in vitro, was tested for its expression and subcellular localization in resting and stimulated human platelets. Using immunoblotting techniques calponin was revealed as a single protein band with a molecular weight of 34 kDa. Although calponin has been shown to be proteolytically degraded by calpain, in the presence of the calpain inhibitor E-64 and EGTA a significant hydrolysis of calponin could not be detected. Upon stimulation with 10 μM arachidonic acid calponin became increasingly incorporated into Triton X-100 insoluble cytoskeletal fractions reaching a plateau after 15 s. The accumulation of calponin in the cytoskeletons of stimulated platelets paralleled the polymerization of actin into newly formed microfilaments. Immunofluorescence microscopy revealed a sub-membranous co-localization of calponin and actin in aggregated platelets. Since isolated calponin is phosphorylated by protein kinase C and Ca2+/calmodulin-dependent protein kinase II thereby losing its inhibitory effect on the actomyosin MgATPase activity, we examined whether changes in cell shape due to platelet stimulation are accompanied by a phosphorylation of calponin. By performing immunoblotting analysis on either resting or stimulated platelets phosphorylation of calponin on tyrosine, serine or threonine residues could not be demonstrated. In line, [32P]radiolabeling experiments were unable to detect phosphate incorporation into calponin. These observations support the hypothesis that calponin plays a physiological role in regulating contraction and secretion of human platelets even in the absence of its phosphorylation.

Hydrogen peroxide downregulates IL-1-driven mesangial iNOS activity: implications for glomerulonephritis

1997 ◽  
Vol 272 (6) ◽  
pp. F721-F728 ◽  
Author(s):  
E. A. Jaimes ◽  
K. A. Nath ◽  
L. Raij
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Inos Mrna ◽  
No Production ◽  
Glomerular Injury ◽  
Inos Activity ◽  
Oxide Synthase

In glomerulonephritides, autacoids such as nitric oxide (NO), reactive oxygen species, and prostanoids are produced in increased amounts in response to cytokines such as interleukin-1 (IL-1). These autacoids influence the expression of glomerular injury by their direct as well as interactive actions. We studied the effect of hydrogen peroxide (H2O2) on NO production in rat mesangial cells. We demonstrate that transient exposure of mesangial cells to H2O2 prior to sustained exposure to IL-1 decreased extracellular accumulation of NO2/NO3 and cellular guanosine 3,'5'-cyclic monophosphate (cGMP) content. H2O2 markedly impaired inducible nitric oxide synthase (iNOS) activity induced by IL-1 directly measured by the conversion of L-[14C]arginine to L-[14C]citrulline. Such impairment in iNOS activity was accompanied by a parallel reduction in iNOS protein abundance but not by a reduced expression of iNOS mRNA. The inhibitory effect of H2O2 on NOS activity was further supported by peroxide-induced impairment in IL-1-driven, NO-dependent synthesis of prostaglandin E2. Our studies thus provide the first direct evidence of a posttranscriptional inhibitory effect of H2O2 on iNOS activity. Additionally, our studies uncover the existence of a previously unrecognized effect of H2O2 on the production of NO that may exert influence on the severity of glomerular injury during glomerular inflammation.

Targets for hydrogen-peroxide-induced damage to suspension and biofilm cells of Streptococcus mutans

2008 ◽  
Vol 54 (10) ◽  
pp. 868-875 ◽  
Author(s):  
Jeremiah D. Baldeck ◽  
Robert E. Marquis
Keyword(s):  
Hydrogen Peroxide ◽  
Protein Synthesis ◽  
Streptococcus Mutans ◽  
Inhibitory Concentration ◽  
Oral Care ◽  
Oral Bacteria ◽  
Suspension Cells ◽  
Enhanced Sensitivity ◽  
Low Concentrations ◽  
Major Target

Hydrogen peroxide (H2O2) is considered a major endogenous source of oxidative stress to oral bacteria and also is widely used in oral care products. Our study objectives were to identify specific targets for H2O2-induced damage to cells of Streptococcus mutans in suspensions and monospecies biofilms and to differentiate bacteriostatic and bactericidal actions of the peroxide. Streptococcus mutans was grown in suspension cultures and fed-batch biofilms for assessing relative sensitivities of viability, glycolysis, and protein synthesis to H2O2 damage. Biofilm cells were found to have essentially the same peroxide sensitivity as cells in suspensions. H2O2 at low concentrations of about 16.3 mmol/L was highly inhibitory for glycolysis and mainly bacteriostatic. The most sensitive target detected for glycolytic inhibition was glyceraldehyde-3-phosphate dehydrogenase with IC50 (50% inhibitory concentration) values of ca. 2.2 mmol/L for suspension cells and 2.3 mmol/L for biofilms with 15 min treatments. The phosphoenolpyruvate:glucose phosphotransferase pathway was less sensitive with an IC50 of ca. 10 mmol/L. Aldolase was not inhibited at bacteriostatic concentrations of the peroxide. For suspensions and biofilms, acidification somewhat diminished peroxide sensitivity, while increased temperature enhanced sensitivity. At concentrations above about 30 mmol/L, H2O2 became mainly bactericidal but not mutagenic for S. mutans. A major target for bactericidal damage was protein synthesis, thus rendering cells incapable of repairing or replacing oxidatively damaged proteins.

scholarly journals Platelet activation via PAR4 is involved in the initiation of thrombin generation and in clot elasticity development

2007 ◽  
Vol 97 (03) ◽  
pp. 417-424 ◽  
Author(s):  
Sofia Ramström ◽  
Maria Bjerke ◽  
Tomas Lindahl ◽  
Karin Vretenbrant
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Platelet Rich Plasma ◽  
Physiological Role ◽  
Human Platelets ◽  
Coagulation Cascade ◽  
Fluorescent Intensity ◽  
Fibrinogen Binding ◽  
Low Concentrations ◽  
Physiological Relevance

SummaryThrombin is a pivotal enzyme formed in the coagulation cascade and an important and potent platelet activator. The two pro-tease-activated thrombin receptors on human platelets are denoted PARI and PAR4. The physiological relevance of PAR4 is still unclear, as both aggregation and secretion can be accomplished by PARI activation alone. In the present study we have investigated the role of PARs in platelet activation, blood coagulation, clot elasticity and fibrinolysis. Flow cytometry, free oscillation rheometry and thrombin generation measurements were used to analyze blood or platelet-rich plasma from healthy individuals. Maximum PARI activation with the peptide SFLLRN gave fewer fibrinogen-binding platelets with lower mean fluorescent intensity than maximum PAR4 activation with AYPGKF. Inhibition of any of the receptors prolonged clotting times. However, PARI is more important for fibrinolysis; inhibition of this receptor prolonged all the steps in the fibrinolytic process. Clot elasticity decreased significantly when the PAR4 receptor was inhibited. In the thrombin generation measurements, PAR4 inhibition delayed the thrombin generation start and peak, but did not affect the total amount of thrombin generated. PAR I inhibition had no significant impact on thrombin generation. We found that PAR4 is most likely activated by low concentrations of thrombin during the initial phase of thrombin generation and is of importance to the clotting time. Furthermore, we suggest that the PAR4 receptor may have a physiological role in the stabilisation of the coagulum.

scholarly journals Thrombopoietin potentiates activation of human platelets in association with JAK2 and TYK2 phosphorylation

1996 ◽  
Vol 316 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Belén RODRÍGUEZ-LIÑARES ◽  
Steve P. WATSON
Keyword(s):  
Shape Change ◽  
Physiological Role ◽  
Human Platelets ◽  
Dense Granule ◽  
Functional Responses ◽  
Dramatic Effect ◽  
Reversible Aggregation ◽  
Low Concentrations ◽  
Dense Granule Secretion ◽  
Granule Secretion

Thrombopoietin (TPO), also known as the c-mpl ligand, stimulates rapid tyrosine phosphorylation of multiple proteins in human platelets including the Janus family kinases JAK2 and TYK2. On its own, TPO has no effect on platelet aggregation and dense-granule secretion but induces a general potentiation of these responses by other stimuli. The most dramatic effect is observed against threshold concentrations of agonists for aggregation. Shape change or weak reversible aggregation induced by low concentrations of thrombin, collagen and the thromboxane mimetic, U46619, are converted into irrreversible aggregation in the presence of TPO. A similar result is obtained in the presence of the ADP scavenger apyrase and cyclo-oxygenase inhibitor indomethacin. TPO also induces potentiation of dense-granule secretion measured through release of 5-hydroxy[3H]tryptamine. This effect is most striking against low concentrations of stimuli and is independent of aggregation as it is observed in the presence of chelation of extracellular Ca2+ with EGTA. TPO potentiates activation of phospholipase C and elevation of intracellular Ca2+, providing a molecular explanation for potentiation of functional responses. TPO may have an important physiological role in priming platelet activation in thrombocytopenia, an action that may help to compensate for the reduced platelet density.

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