Back to Search
Start Over
Effect of Lysosomotropic Polyamineoxidase Inhibitor MDL-72527 on Platelet Activation.
- Source :
-
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2016; Vol. 38 (5), pp. 1695-702. Date of Electronic Publication: 2016 May 03. - Publication Year :
- 2016
-
Abstract
- 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).<br />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.<br />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.<br />Conclusions: MDL-72527 is a powerful inhibitor of platelet activation, apoptosis and aggregation.<br /> (© 2016 The Author(s) Published by S. Karger AG, Basel.)
- Subjects :
- Aniline Compounds chemistry
Animals
Apoptosis drug effects
Blood Platelets cytology
Blood Platelets metabolism
Calcium chemistry
Calcium metabolism
Carrier Proteins pharmacology
Cell Membrane metabolism
Female
Flow Cytometry
Male
Mice
Oxidoreductases Acting on CH-NH Group Donors antagonists & inhibitors
Oxidoreductases Acting on CH-NH Group Donors metabolism
P-Selectin metabolism
Peptides pharmacology
Phosphatidylserines
Platelet Glycoprotein GPIIb-IIIa Complex metabolism
Putrescine pharmacology
Reactive Oxygen Species metabolism
Xanthenes chemistry
Polyamine Oxidase
Platelet Activation drug effects
Putrescine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1421-9778
- Volume :
- 38
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 27160671
- Full Text :
- https://doi.org/10.1159/000443108