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Paradoxical fate and biological action of peroxynitrite on human platelets

Paradoxical fate and biological action of peroxynitrite on human platelets
Paradoxical fate and biological action of peroxynitrite on human platelets
Peroxynitrite (ONOO-), which is formed from the reaction of nitric oxide (NO) and superoxide (O2-), has been suggested to be responsible for some of the cytotoxic effects of these molecules. When protonated, ONOO- gives rise to hydroxyl (OH.) and nitrogen dioxide (NO2) radicals, which are capable of inducing tissue damage. We have investigated the effects of ONOO- on human platelets in vitro in order to explore the potential of this oxidant to contribute to tissue damage. ONOO- caused aggregation of washed platelets and reversed the inhibition of aggregation induced by S-nitroso-N-acetyl-DL-penicillamine (SNAP), prostacyclin, and indomethacin. However, in platelet-rich plasma, ONOO- not only did not possess proaggregatory properties but acted as an inhibitor of platelet aggregation. This reversal of the aggregatory effect of ONOO- could also be achieved in washed platelets by adding low concentrations of plasma, human serum albumin, or glutathione and was inhibited by hemoglobin. An analysis of the reaction products of ONOO- and glutathione revealed the presence of both NO and S-nitrosoglutathione in quantities sufficient to account for the antiaggregatory effects observed. Thus the fate and therefore the actions of ONOO- in biological systems are critically dependent on the biological environment in which this oxidant is present.
0027-8424
6702-6706
Moro, María Ángeles
9cd6e6f4-e04c-463c-96fc-b2cf54640393
Darley-Usmar, Victor M.
5ec7caf9-551d-4920-b896-44e84fea9b9d
Goodwin, David A.
3d9841c2-96d4-45a7-910c-161d514e65bd
Read, Nicholas G.
143a4216-4d8d-4250-b347-e35eb864a539
Zamora-Pino, Rubén
df392cf3-7511-412b-9c15-ab7904071a42
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Radomski, Marek W.
711a9214-799f-4e98-932b-68ee39b08da3
Moncada, Salvador
0f661842-cd67-46e6-b82d-47f2c5e0e750
Moro, María Ángeles
9cd6e6f4-e04c-463c-96fc-b2cf54640393
Darley-Usmar, Victor M.
5ec7caf9-551d-4920-b896-44e84fea9b9d
Goodwin, David A.
3d9841c2-96d4-45a7-910c-161d514e65bd
Read, Nicholas G.
143a4216-4d8d-4250-b347-e35eb864a539
Zamora-Pino, Rubén
df392cf3-7511-412b-9c15-ab7904071a42
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Radomski, Marek W.
711a9214-799f-4e98-932b-68ee39b08da3
Moncada, Salvador
0f661842-cd67-46e6-b82d-47f2c5e0e750

Moro, María Ángeles, Darley-Usmar, Victor M., Goodwin, David A., Read, Nicholas G., Zamora-Pino, Rubén, Feelisch, Martin, Radomski, Marek W. and Moncada, Salvador (1994) Paradoxical fate and biological action of peroxynitrite on human platelets. Proceedings of the National Academy of Sciences, 91 (14), 6702-6706. (PMID:1346070)

Record type: Article

Abstract

Peroxynitrite (ONOO-), which is formed from the reaction of nitric oxide (NO) and superoxide (O2-), has been suggested to be responsible for some of the cytotoxic effects of these molecules. When protonated, ONOO- gives rise to hydroxyl (OH.) and nitrogen dioxide (NO2) radicals, which are capable of inducing tissue damage. We have investigated the effects of ONOO- on human platelets in vitro in order to explore the potential of this oxidant to contribute to tissue damage. ONOO- caused aggregation of washed platelets and reversed the inhibition of aggregation induced by S-nitroso-N-acetyl-DL-penicillamine (SNAP), prostacyclin, and indomethacin. However, in platelet-rich plasma, ONOO- not only did not possess proaggregatory properties but acted as an inhibitor of platelet aggregation. This reversal of the aggregatory effect of ONOO- could also be achieved in washed platelets by adding low concentrations of plasma, human serum albumin, or glutathione and was inhibited by hemoglobin. An analysis of the reaction products of ONOO- and glutathione revealed the presence of both NO and S-nitrosoglutathione in quantities sufficient to account for the antiaggregatory effects observed. Thus the fate and therefore the actions of ONOO- in biological systems are critically dependent on the biological environment in which this oxidant is present.

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Published date: 5 July 1994
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337903
URI: http://eprints.soton.ac.uk/id/eprint/337903
ISSN: 0027-8424
PURE UUID: 8e2a23b5-e70e-4142-99e1-411160520d16
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 15 Jun 2012 09:27
Last modified: 15 Mar 2024 03:41

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Contributors

Author: María Ángeles Moro
Author: Victor M. Darley-Usmar
Author: David A. Goodwin
Author: Nicholas G. Read
Author: Rubén Zamora-Pino
Author: Martin Feelisch ORCID iD
Author: Marek W. Radomski
Author: Salvador Moncada

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