scholarly journals Nitric oxide and platelet energy metabolism.

2004 ◽  
Vol 51 (3) ◽  
pp. 789-803 ◽  
Author(s):  
Marian Tomasiak ◽  
Halina Stelmach ◽  
Tomasz Rusak ◽  
Jolanta Wysocka
Keyword(s):  
Nitric Oxide ◽  
Cytochrome Oxidase ◽  
Respiratory Chain ◽  
Energy Production ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Antimycin A ◽  
No Donors ◽  
Mitochondrial Energy Production ◽  
Induced Aggregation ◽  
Platelet Secretion

This study was undertaken to determine whether nitric oxide (NO) can affect platelet responses through the inhibition of energy production. It was found that NO donors: S-nitroso-N-acetylpenicyllamine, SNAP, (5-50 microM) and sodium nitroprusside, SNP, (5-100 microM) inhibited collagen- and ADP-induced aggregation of porcine platelets. The corresponding IC50 values for SNAP and SNP varied from 5 to 30 microM and from 9 to 75 microM, respectively. Collagen- and thrombin-induced platelet secretion was inhibited by SNAP (IC50 = 50 microM) and by SNP (IC50 = 100 microM). SNAP (20-100 microM), SNP (10-200 microM) and collagen (20 microg/ml) stimulated glycolysis in intact platelets. The degree of glycolysis stimulation exerted by NO donors was similar to that produced by respiratory chain inhibitors (cyanide and antimycin A) or uncouplers (2,4-dinitrophenol). Neither the NO donors nor the respiratory chain blockers affected glycolysis in platelet homogenate. SNAP (20-100 microM) and SNP (50-200 microM) inhibited oxygen consumption by platelets. The effect of SNP and SNAP on glycolysis and respiration was not reduced by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, a selective inhibitor of NO-stimulated guanylate cyclase. SNAP (5-100 microM) and SNP (10-300 microM) inhibited the activity of platelet cytochrome oxidase and had no effect on NADH:ubiquinone oxidoreductase and succinate dehydrogenase. Blocking of the mitochondrial energy production by antimycin A slightly affected collagen-evoked aggregation and strongly inhibited platelet secretion. The results indicate that: 1) in porcine platelets NO is able to diminish mitochondrial energy production through the inhibition of cytochrome oxidase, 2) the inhibitory effect of NO on platelet secretion (but not aggregation) can be attributed to the reduction of mitochondrial energy production.

scholarly journals Elevated neuronal nitric oxide synthase expression during ageing and mitochondrial energy production

2009 ◽  
Vol 43 (5) ◽  
pp. 431-439 ◽  
Author(s):  
Philip Y. Lam ◽  
Fei Yin ◽  
Ryan T. Hamilton ◽  
Alberto Boveris ◽  
Enrique Cadenas
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Energy Production ◽  
Neuronal Nitric Oxide Synthase ◽  
Mitochondrial Energy Production ◽  
Oxide Synthase

scholarly journals Peroxynitrite can affect platelet responses by inhibiting energy production.

2006 ◽  
Vol 53 (4) ◽  
pp. 769-776 ◽  
Author(s):  
Tomasz Rusak ◽  
Marian Tomasiak ◽  
Michal Ciborowski
Keyword(s):  
Oxygen Consumption ◽  
Energy Production ◽  
Dense Granule ◽  
Resting Cells ◽  
Antimycin A ◽  
Dependent Manner ◽  
Atp Content ◽  
Dense Granule Secretion ◽  
Granule Secretion ◽  
Induced Aggregation

Peroxynitrite (ONOO-) strongly inhibits agonist-induced platelet responses. However, the mechanisms involved are not completely defined. Using porcine platelets, we tested the hypothesis that ONOO- reduces platelet aggregation and dense granule secretion by inhibiting energy production. It was found that ONOO- (25-300 microM) inhibited collagen-induced dense granule secretion (IC50 = 55 +/- 7 microM) more strongly than aggregation (IC(50) = 124 +/- 16 microM). The antiaggregatory and antisecretory effects of ONOO- were only slightly (5-10%) reduced by 1H-[1,2,4]-oxadiazolo-[4,3-alpha]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase. In resting platelets ONOO- (50-300 microM) enhanced glycolysis rate and reduced oxygen consumption, in a dose dependent manner. The ONOO- effects on glycolysis rate and oxygen consumption were not abolished by ODQ. The extent of glycolysis stimulation exerted by ONOO- was similar to that produced by respiratory chain inhibitors (cyanide and antimycin A) or an uncoupler (2,4-dinitrophenol). Stimulation of platelets by collagen was associated with a rise in mitochondrial oxygen consumption, accelerated lactate production, and unchanged intracellular ATP content. In contrast to resting cells, in collagen-stimulated platelets, ONOO- (200 microM) distinctly decreased the cellular ATP content. The glycolytic activity and oxygen consumption of resting platelets were not affected by 8-bromoguanosine 3',5'-cyclic monophosphate. Blocking of the mitochondrial ATP production by antimycin A slightly reduced collagen-induced aggregation and strongly inhibited dense granule secretion. Treatment of platelets with ONOO- (50-300 microM) resulted in decreased activities of NADH : ubiquinone oxidoreductase, succinate dehydrogenase and cytochrome oxidase. It is concluded that the inhibitory effect of ONOO- on platelet secretion and to a lesser extent on aggregation may be mediated, at least in part, by the reduction of mitochondrial energy production.

Succinate, glycerophosphate and ascorbate as sources of cellular energy and as antiteratogens

Development ◽  
1970 ◽  
Vol 24 (1) ◽  
pp. 187-202
Author(s):  
Walter Landauer ◽  
Dinah Sopher
Keyword(s):  
Respiratory Chain ◽  
Energy Production ◽  
High Energy ◽  
Teratogenic Effects ◽  
Cellular Energy ◽  
Specific Affinity ◽  
Mitochondrial Energy Production ◽  
Experimental Findings ◽  
Induced Defects

Our experimental findings show that succinate and ascorbate greatly reduce the teratogenic effects of 3-acetylpyridine, 6-aminonicotinamide and sulfanilamide. Glycerophosphate led to similar alleviating results when used in combination with 3-acetylpyridine and 6-aminonicotinamide, but not with sulfanilamide. With certain other teratogens the high-energy intermediates failed to alleviate; in some instances (acetazolamide, insulin) they even led to potentiation of teratogen-induced defects. The results of our experiments demonstrate clearly that high-energy intermediates, by being fed into the respiratory chain of the mitochondria, can alleviate incidence and degree of expression of malformations produced by specific teratogens. In concert with earlier evidence on the nature of antiteratogenic compounds it can further be concluded that the particular teratogens in question exert their effects by interference with mitochondrial energy production in the tissues for which they have specific affinity.

Deficiency of (33P)2MeS-ADP Binding Sites on Platelets with Secretion Defect, Normal Granule Stores and Normal Thromboxane A2 Production

1997 ◽  
Vol 77 (05) ◽  
pp. 0986-0990 ◽  
Author(s):  
Marco Cattaneo ◽  
Rossana Lombardi ◽  
Maddalena L Zighetti ◽  
Christian Gachet ◽  
Philippe Ohlmann ◽  
...  
Keyword(s):  
Binding Sites ◽  
Specific Binding ◽  
Thromboxane A2 ◽  
Normal Subjects ◽  
Congenital Defects ◽  
Normal Production ◽  
Adp Receptor ◽  
Partial Deficiency ◽  
Induced Aggregation ◽  
Platelet Secretion

SummaryBy the term “Primary Secretion Defect” (PSD), we mean a common heterogeneous group of congenital defects of platelet secretion, characterized by a normal primary wave of platelet aggregation induced by ADP and other agonists, a normal concentration of platelet granule contents, and normal production of thromboxane A2. The biochemical abnormalities responsible for PSD are not well known. Since a secretion defect similar to PSD is found in platelets that are severely deficient of binding sites for the ADP analogue 2MeS-ADP and do not aggregate in response to ADP, we tested the hypothesis that PSD platelets have moderately decreased 2MeS-ADP binding sites, which may be sufficient for normal ADP-induced aggregation but not for potentiating platelet secretion. The specific binding of [33P]2MeS-ADP to platelets from 3 PSD patients (347,443 and 490 sites/platelet; KD 2.8-3.9 nM) was lower than to platelets from 24 normal subjects (647 [530-1102]; KD = 3.8 [2.3-7.3]) (median [range]). Normal values were found in a fourth PSD patient (710; KD 3.7). The degree of inhibition of PGE1- induced cAMP increase by 0.1 |μM ADP was lower in patients than in controls. The secretion induced by the endoperoxide analogue U46619 from normal, acetylsalicylic acid-treated platelets under conditions that prevented the formation of large aggregates was potentiated by 1 fimol/1 ADP and inhibited by apyrase. These findings indicate that a partial deficiency of the platelet ADP receptor(s) might be responsible for the defect of platelet secretion in some PSD patients and that ADP potentiates platelet secretion independently of the formation of large aggregates and thromboxane A2 production.

Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury

1997 ◽  
Vol 273 (3) ◽  
pp. L504-L512 ◽  
Author(s):  
Y. C. Huang ◽  
P. W. Fisher ◽  
E. Nozik-Grayck ◽  
C. A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Lung Injury ◽  
Average Rate ◽  
Ischemia Reperfusion ◽  
Oxidant Stress ◽  
No Production ◽  
Protective Effects ◽  
Lung Weight ◽  
Edema Formation ◽  
No Donors

Because both the biosynthesis of nitric oxide (NO.) and its metabolic fate are related to molecular O2, we hypothesized that hypoxia would alter the effects of NO. during ischemia-reperfusion (IR) in the lung. In this study, buffer-perfused lungs from rabbits underwent either normoxic IR (AI), in which lungs were ventilated with 21% O2 during ischemia and reperfusion, or hypoxic IR (NI), in which lungs were ventilated with 95% N2 during ischemia followed by reoxygenation with 21% O2. Lung weight gain (WG) and pulmonary artery pressure (Ppa) were monitored continuously, and microvascular pressure (Pmv) was measured after reperfusion to calculate pulmonary vascular resistance. We found that both AI and NI produced acute lung injury, as shown by increased WG and Ppa during reperfusion. In AI, where perfusate PO2 was > 100 mmHg, the administration of the NO. synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) before ischemia worsened WG and Ppa. Pmv also increased, suggesting a hydrostatic mechanism involved in edema formation. The effects of L-NAME could be attenuated by giving L-arginine and exogenous NO. donors before ischemia or before reperfusion. Partial protection was also provided by superoxide dismutase. In contrast, lung injury in NI at perfusate PO2 of 25-30 mmHg was attenuated by L-NAME; this effect could be reversed by L-arginine. Exogenous NO. donors given either before ischemia or before reperfusion, however, did not increase lung injury. NO. production was measured by quantifying the total nitrogen oxides (NOx) accumulating in the perfusate. The average rate of NOx accumulation was greater in AI than in NI. We conclude that hypoxia prevented the protective effects of NO on AI lung injury. The effects of hypoxia may be related to lower NO. production relative to oxidant stress during IR and/or altered metabolic fates of NO.-mediated production of peroxynitrite by hypoxic ischemia.

Inhibition of endotoxemia-induced nitric oxide synthase expression by cyclosporin A enhances hepatocyte injury in rats: amelioration by NO donors

2002 ◽  
Vol 2 (1) ◽  
pp. 117-127 ◽  
Author(s):  
Hassan Farghali ◽  
Nikolina Canová ◽  
Norbert Gaier ◽  
Dagmar Lincová ◽  
Eva Kmonı́čková ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cyclosporin A ◽  
No Donors ◽  
Hepatocyte Injury ◽  
Oxide Synthase
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