Peroxynitrite can affect platelet responses by inhibiting energy production

• Authors: Tomasz Rusak , Marian Tomasiak , Michal Ciborowski
• Languages of publication: EN

Abstracts

EN

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 µM) inhibited collagen-induced dense granule secretion (IC50 = 55 ± 7 µM) more strongly than aggregation (IC50 = 124 ± 16 µM). The antiaggregatory and antisecretory effects of ONOO- were only slightly (5-10%) reduced by 1H-[1,2,4]-oxadiazolo-[4,3-α]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase. In resting platelets ONOO- (50-300 µM) 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 µM) 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 µM) 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.

Keywords

EN

aggregation; porcine platelets; peroxynitrite; mitochondria; glycolysis; secretion

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2006
• Volume: 53
• Issue: 4
• Pages: 769-776

Dates

published

2006

received

2006-09-08

revised

2006-09-27

accepted

2006-10-09

(unknown)

2006-10-27

Contributors

author

Tomasz Rusak

• Department of Physical Chemistry, Medical University of Bialystok, Białystok, Poland

author

Marian Tomasiak

• Department of Physical Chemistry, Medical University of Bialystok, Białystok, Poland

author

Michal Ciborowski

• Department of Physical Chemistry, Medical University of Bialystok, Białystok, Poland

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