Journal article
Priming of Platelet α IIb β 3 by Oxidants Is Associated With Tyrosine Phosphorylation of β 3
Arteriosclerosis, thrombosis, and vascular biology, Vol.18(11), pp.1698-1706
11/1998
DOI: 10.1161/01.ATV.18.11.1698
Abstract
Abstract
—Reactive oxygen species play an important role at the site of vascular injuries and arterial thromboses. We studied the mechanism mediating platelet aggregation induced by H
2
O
2
, a major cellular oxidant. Exposure to H
2
O
2
triggered platelet aggregation, but only when the platelets were stirred. Strong platelet aggregation induced by H
2
O
2
required the presence of the tyrosine phosphatase inhibitor sodium orthovanadate (NaVO
4
) and was dependent on the participation of integrin α
IIb
β
3
(glycoprotein IIb-IIIa). A specific inhibitor of α
IIb
β
3
blocked platelet aggregation induced by H
2
O
2
and NaVO
4
, thus confirming that aggregation requires this receptor. In the presence of H
2
O
2
and NaVO
4
, multiple platelet substrates were phosphorylated on tyrosine. Such tyrosine kinase response was necessary but not sufficient to activate α
IIb
β
3
, as detected by binding of soluble fibrinogen to platelets. Stirring of the platelets exposed to H
2
O
2
and NaVO
4
was also needed to allow for binding of fibrinogen to α
IIb
β
3
. The tyrosine kinase inhibitor genistein was able to block platelet aggregation induced by H
2
O
2
and NaVO
4
, thus confirming that tyrosine kinase activity was needed to trigger α
IIb
β
3
activation on stirring.
N
-Acetyl-
l
-cysteine, a cell-permeant antioxidant, blocked the tyrosine phosphorylation of platelet substrates and also the platelet aggregation induced by H
2
O
2
and NaVO
4
. We found that β
3
was phosphorylated on tyrosine in platelets exposed to H
2
O
2
and NaVO
4
, even in the absence of aggregation. Hence, tyrosine phosphorylation of β
3
might contribute to the “priming” of α
IIb
β
3
induced by H
2
O
2
and NaVO
4
, whereby the receptor can become activated on stirring of the platelets.
Details
- Title: Subtitle
- Priming of Platelet α IIb β 3 by Oxidants Is Associated With Tyrosine Phosphorylation of β 3
- Creators
- Kaikobad Irani - Johns Hopkins MedicineYoum Pham - The Ohio State UniversityLindsay D. Coleman - Johns Hopkins UniversityChristine Roos - The Ohio State UniversityGlen E. Cooke - The Ohio State UniversityAmir Miodovnik - The Ohio State UniversityNayeem Karim - Johns Hopkins UniversityCalvin C. Wilhide - Johns Hopkins UniversityPaul F. Bray - Johns Hopkins UniversityPascal J. Goldschmidt-Clermont
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.18(11), pp.1698-1706
- DOI
- 10.1161/01.ATV.18.11.1698
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Language
- English
- Date published
- 11/1998
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984312989002771
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