دورية أكاديمية
Effect of Lysosomotropic Polyamineoxidase Inhibitor MDL-72527 on Platelet Activation
| العنوان: | Effect of Lysosomotropic Polyamineoxidase Inhibitor MDL-72527 on Platelet Activation |
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| المؤلفون: | Guoxing Liu, Hang Cao, Guilai Liu, David Heinzmann, Hong Chen, Anja T. Umbach, Meinrad Gawaz, Florian Lang |
| المصدر: | Cellular Physiology and Biochemistry, Vol 38, Iss 5, Pp 1695-1702 (2016) |
| بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Physiology LCC:Biochemistry |
| مصطلحات موضوعية: | Collagen related peptide, platelet activation, Platelet degranulation, integrin activation, cytosolic Ca2+ concentration, Reactive oxygen species, Phosphatidylserine translocation, Physiology, QP1-981, Biochemistry, QD415-436 |
| الوصف: | Background/Aims: The polyamine oxidase inhibitor MDL-72527 (N1,N4-bis(2,3-butadienyl)-1,4-butanediamine) were expected to increase the abundance of spermine, a powerful inhibitor of platelet activation. Nothing is known, however, on the sensitivity of platelet function and survival to MDL-72527 exposure. The present study thus explored whether MDL-72527 modifies function and survival of platelets without and with platelet activation by collagen related peptide (CRP). Methods: Platelets isolated from wild-type mice were exposed for 30 minutes to MDL-72527 (100 µM) with or without subsequent activation with CRP (2-5 µg/ml). Flow cytometry was employed to estimate 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, phospholipid scrambling of the cell membrane from annexin-V-binding, platelet volume from forward scatter and aggregation utilizing staining with CD9-APC and CD9-PE. Results: In the absence of CRP, exposure of platelets to MDL-72527 did not significantly modify [Ca2+]i, P-selectin abundance, αIIbβ3 integrin abundance, ROS, annexin-V-binding, and forward scatter. The addition of 2-5 µg/ml CRP was followed by significant increase of [Ca2+]i, P-selectin abundance, αIIbβ3 integrin activation, ROS abundance, annexin-V-binding, and aggregation as well as a significant decrease of forward scatter, all effects significantly blunted or virtually abolished in the presence of MDL-72527. Conclusions: MDL-72527 is a powerful inhibitor of 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/443108Test; https://doaj.org/toc/1015-8987Test; https://doaj.org/toc/1421-9778Test |
| DOI: | 10.1159/000443108 |
| الوصول الحر: | https://doaj.org/article/fa1d482c144c44e79d548e322f7b03a2Test |
| رقم الانضمام: | edsdoj.fa1d482c144c44e79d548e322f7b03a2 |
| قاعدة البيانات: | Directory of Open Access Journals |
| تدمد: | 10158987 14219778 |
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| DOI: | 10.1159/000443108 |