دورية أكاديمية
Influence of γ-Secretase Inhibitor 24-Diamino-5-Phenylthiazole DAPT on Platelet Activation
| العنوان: | Influence of γ-Secretase Inhibitor 24-Diamino-5-Phenylthiazole DAPT on Platelet Activation |
|---|---|
| المؤلفون: | Guoxing Liu, Guilai Liu, Madhumita Chatterjee, Anja T. Umbach, Hong Chen, Meinrad Gawaz, Florian Lang |
| المصدر: | Cellular Physiology and Biochemistry, Vol 38, Iss 2, Pp 726-736 (2016) |
| بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Physiology LCC:Biochemistry |
| مصطلحات موضوعية: | Integrin activation, Reactive oxygen species, Phosphatidylserine translocation, Cytosolic Ca2+ concentration, Platelet activation, Platelet degranulation, Collagen related peptide, Physiology, QP1-981, Biochemistry, QD415-436 |
| الوصف: | Background/Aims: DAPT (24-diamino-5-phenylthiazole) inhibits γ-secretase, which cleaves the signaling molecule CD44, a negative regulator of platelet activation and apoptosis. CD44 is a co-receptor for macrophage migration inhibitory factor (MIF) an anti-apoptotic pro-inflammatory cytokine expressed and released from blood platelets. Whether DAPT influences platelet function, remained, however, elusive. Activators of platelets include collagen related peptide (CRP). The present study thus explored whether DAPT modifies the stimulating effect of CRP on platelet function. Methods: Platelets isolated from wild-type mice were exposed for 30 minutes to DAPT (10 µM). Flow cytometry was employed to estimate Orai1 abundance with specific antibodies, cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, platelet degranulation from P-selectin abundance, integrin activation from αIIbβ3 integrin abundance, generation of reactive oxygen species (ROS) from DCFDA fluorescence, mitochondrial transmembrane potential from TMRE fluorescence, phospholipid scrambling of the cell membrane from annexin-V-binding, relative platelet volume from forward scatter and aggregation utilizing staining with CD9-APC and CD9-PE. Results: Exposure of platelets to 2-5 µg/ml CRP was followed by significant increase of Orai1 abundance, [Ca2+]i, and P-selectin abundance, as well as by αIIbβ3 integrin activation, ROS generation, mitochondrial depolarization, enhanced annexin-V-binding, decreased cell volume, and aggregation. All CRP induced effects were significantly blunted in the presence of DAPT. Conclusions: The γ-secretase inhibitor DAPT counteracts agonist induced platelet activation, apoptosis and aggregation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1015-8987 1421-9778 |
| العلاقة: | http://www.karger.com/Article/FullText/443029Test; https://doaj.org/toc/1015-8987Test; https://doaj.org/toc/1421-9778Test |
| DOI: | 10.1159/000443029 |
| الوصول الحر: | https://doaj.org/article/b23072ceb6f0498f95e7e7639a996df3Test |
| رقم الانضمام: | edsdoj.b23072ceb6f0498f95e7e7639a996df3 |
| قاعدة البيانات: | Directory of Open Access Journals |
| تدمد: | 10158987 14219778 |
|---|---|
| DOI: | 10.1159/000443029 |