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NAD(P)H oxidase-dependent platelet superoxide anion release increases platelet recruitment.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kroetz, Florian Sohn, Hae Young Gloe, Torsten Zahler, Stefan Riexinger, Tobias Schiele, Thomas Michael Becker, Bernhard Friedrich Theisen, Karl Klauss, Volker Pohl, Ulrich |
| Copyright Year | 2002 |
| Abstract | Platelets, although not phagocytotic, have been suggested to release O. Since O-producing reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases can be specifically activated by certain agonists and are found in several nonphagocytotic tissues, we investigated whether such an enzyme is the source of platelet-derived O. We further studied which agonists cause platelet O release and whether platelet-derived O influences thrombus formation in vitro. Collagen, but not adenosine 5'-diphosphate (ADP) or thrombin, increased O formation in washed human platelets. This was a reduced nicotinamide adenine dinucleotide (NADH)-dependent process, as shown in platelet lysates. Consistent with a role of a platelet, NAD(P)H oxidase expression of its subunits p47(phox) and p67(phox) and inhibition of platelet O formation by diphenylene-iodoniumchloride (DPI) and by the specific peptide-antagonist gp91ds-tat were observed. Whereas platelet-derived O did not influence initial aggregation, platelet recruitment to a preformed thrombus following collagen stimulation was significantly attenuated by superoxide dismutase (SOD) or DPI. It was also inhibited when ADP released during aggregation was cleaved by the ectonucleotidase apyrase. ADP in supernatants of collagen-activated platelets was decreased in the presence of SOD, resulting in lower ADP concentrations available for recruitment of further platelets. Exogenous O increased ADP- concentrations in supernatants of collagen-stimulated platelets and induced irreversible aggregation when platelets were stimulated with otherwise subthreshold concentrations of ADP. These results strongly suggest that collagen activation induces NAD(P)H oxidase-dependent O release in platelets, which in turn enhances availability of released ADP, resulting in increased platelet recruitment. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://bloodjournal.hematologylibrary.org/content/100/3/917.full.pdf |
| PubMed reference number | 12130503v1 |
| Volume Number | 100 |
| Issue Number | 3 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenosine Anions Auditory recruitment Blood Clot Blood Platelet Disorders Blood Platelets Body tissue Cleaved cell Dinucleoside Phosphates Monoamine Oxidase NADP Niacin Niacinamide Nicotinamide adenine dinucleotide (NAD) Superoxide Dismutase Superoxides diphenyleneiodonium downregulation of ferrisuperoxide dismutase activity inorganic phosphate |
| Content Type | Text |
| Resource Type | Article |
