Paradoxical Fate and Biological Action of Peroxynitrite on Human Platelets
Peroxynitrite (ONOO-), which is formed from the reaction of nitric oxide (NO) and superoxide (O- 2), 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...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1994-07, Vol.91 (14), p.6702-6706 |
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| creator | Moro, Maria Angeles Darley-Usmar, Victor M. Goodwin, David A. Read, Nicholas G. Zamora-Pino, Ruben Feelisch, Martin Radomski, Marek W. Moncada, Salvador |
| description | Peroxynitrite (ONOO-), which is formed from the reaction of nitric oxide (NO) and superoxide (O-
2), 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. |
| doi_str_mv | 10.1073/pnas.91.14.6702 |
| format | Article |
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2), 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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.91.14.6702</identifier><identifier>PMID: 7517561</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Aggregation ; Antigens, CD - blood ; Blood plasma ; Blood Platelets - drug effects ; Blood Platelets - physiology ; Blood Platelets - ultrastructure ; Cell Adhesion Molecules - blood ; Cellular biology ; Collagen - pharmacology ; Collagens ; Epoprostenol - pharmacology ; Glutathione - analogs & derivatives ; Glutathione - pharmacology ; Health savings accounts ; Hemoglobins ; Hemoglobins - pharmacology ; Humans ; In Vitro Techniques ; Indomethacin - pharmacology ; Kinetics ; Nitrates - blood ; Nitrates - pharmacology ; Nitroso Compounds - pharmacology ; Oxidation ; P-Selectin ; Penicillamine - analogs & derivatives ; Penicillamine - pharmacology ; Pharmacology ; Phosphates ; Platelet aggregation ; Platelet Aggregation - drug effects ; Platelet Aggregation - physiology ; Platelet Membrane Glycoproteins - blood ; Platelets ; S-Nitroso-N-Acetylpenicillamine ; S-Nitrosoglutathione ; Serum Albumin - pharmacology ; Sodium ; Thiols ; Time Factors ; Vasodilator Agents - pharmacology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1994-07, Vol.91 (14), p.6702-6706</ispartof><rights>Copyright 1994 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jul 5, 1994</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c586t-1ea5950fa1f6fd7287f3b5ad9856825a84cfcd5b7a7c53adbc92f400b80798e93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/91/14.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2365042$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2365042$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7517561$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moro, Maria Angeles</creatorcontrib><creatorcontrib>Darley-Usmar, Victor M.</creatorcontrib><creatorcontrib>Goodwin, David A.</creatorcontrib><creatorcontrib>Read, Nicholas G.</creatorcontrib><creatorcontrib>Zamora-Pino, Ruben</creatorcontrib><creatorcontrib>Feelisch, Martin</creatorcontrib><creatorcontrib>Radomski, Marek W.</creatorcontrib><creatorcontrib>Moncada, Salvador</creatorcontrib><title>Paradoxical Fate and Biological Action of Peroxynitrite on Human Platelets</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Peroxynitrite (ONOO-), which is formed from the reaction of nitric oxide (NO) and superoxide (O-
2), 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.</description><subject>Aggregation</subject><subject>Antigens, CD - blood</subject><subject>Blood plasma</subject><subject>Blood Platelets - drug effects</subject><subject>Blood Platelets - physiology</subject><subject>Blood Platelets - ultrastructure</subject><subject>Cell Adhesion Molecules - blood</subject><subject>Cellular biology</subject><subject>Collagen - pharmacology</subject><subject>Collagens</subject><subject>Epoprostenol - pharmacology</subject><subject>Glutathione - analogs & derivatives</subject><subject>Glutathione - pharmacology</subject><subject>Health savings accounts</subject><subject>Hemoglobins</subject><subject>Hemoglobins - pharmacology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Indomethacin - pharmacology</subject><subject>Kinetics</subject><subject>Nitrates - blood</subject><subject>Nitrates - pharmacology</subject><subject>Nitroso Compounds - pharmacology</subject><subject>Oxidation</subject><subject>P-Selectin</subject><subject>Penicillamine - analogs & derivatives</subject><subject>Penicillamine - pharmacology</subject><subject>Pharmacology</subject><subject>Phosphates</subject><subject>Platelet aggregation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation - physiology</subject><subject>Platelet Membrane Glycoproteins - blood</subject><subject>Platelets</subject><subject>S-Nitroso-N-Acetylpenicillamine</subject><subject>S-Nitrosoglutathione</subject><subject>Serum Albumin - pharmacology</subject><subject>Sodium</subject><subject>Thiols</subject><subject>Time Factors</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1vEzEQxS0EKqFw5gJoxQFOScdef0pcSkUpqBI5wNnyeu2ykbNObS9K_3scEiLKAU4jzfu90cw8hJ5jWGAQ7dlmNHmh8ALTBRdAHqAZBoXnnCp4iGYARMwlJfQxepLzCgAUk3CCTgTDgnE8Q5-XJpk-bgdrQnNpimvM2Dfvhxjiza_euS1DHJvom6VLcXs3DiUNFau9q2ltxmYZqiu4kp-iR96E7J4d6in6dvnh68XV_PrLx08X59dzyyQvc-wMUwy8wZ77XhApfNsx0yvJuCTMSGq97VknjLCsNX1nFfEUoJMglHSqPUXv9nM3U7d2vXVjSSboTRrWJt3paAZ9XxmH7_om_tCUEoGr_c3BnuLt5HLR6yFbF4IZXZyyFpwJSTj7L4g5bzkwXsHXf4GrOKWx_kATwG09C0OFzvaQTTHn5PxxYQx6F6XeRakV1pjqXZTV8fLPO4_8IbuqvzroO-Nv9d6At_8EtJ9CKG5bKvliT65yiemIkpYzoKT9CT87vDE</recordid><startdate>19940705</startdate><enddate>19940705</enddate><creator>Moro, Maria Angeles</creator><creator>Darley-Usmar, Victor M.</creator><creator>Goodwin, David A.</creator><creator>Read, Nicholas G.</creator><creator>Zamora-Pino, Ruben</creator><creator>Feelisch, Martin</creator><creator>Radomski, Marek W.</creator><creator>Moncada, Salvador</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7U7</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19940705</creationdate><title>Paradoxical Fate and Biological Action of Peroxynitrite on Human Platelets</title><author>Moro, Maria Angeles ; 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2), 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.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>7517561</pmid><doi>10.1073/pnas.91.14.6702</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1994-07, Vol.91 (14), p.6702-6706 |
| issn | 0027-8424 1091-6490 |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Aggregation Antigens, CD - blood Blood plasma Blood Platelets - drug effects Blood Platelets - physiology Blood Platelets - ultrastructure Cell Adhesion Molecules - blood Cellular biology Collagen - pharmacology Collagens Epoprostenol - pharmacology Glutathione - analogs & derivatives Glutathione - pharmacology Health savings accounts Hemoglobins Hemoglobins - pharmacology Humans In Vitro Techniques Indomethacin - pharmacology Kinetics Nitrates - blood Nitrates - pharmacology Nitroso Compounds - pharmacology Oxidation P-Selectin Penicillamine - analogs & derivatives Penicillamine - pharmacology Pharmacology Phosphates Platelet aggregation Platelet Aggregation - drug effects Platelet Aggregation - physiology Platelet Membrane Glycoproteins - blood Platelets S-Nitroso-N-Acetylpenicillamine S-Nitrosoglutathione Serum Albumin - pharmacology Sodium Thiols Time Factors Vasodilator Agents - pharmacology |
| title | Paradoxical Fate and Biological Action of Peroxynitrite on Human Platelets |
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