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dc.contributor.authorWei, Hao
dc.contributor.authorDavies, Jessica E
dc.contributor.authorHarper, Matthew T
dc.date.accessioned2020-04-07T00:26:46Z
dc.date.available2020-04-07T00:26:46Z
dc.date.issued2020-03-02
dc.identifier.issn2058-7716
dc.identifier.otherPMC7051957
dc.identifier.other32140260
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/304164
dc.description.abstractActivated, procoagulant platelets shed phosphatidylserine (PS)-exposing extracellular vesicles (EVs) from their surface in a Ca2+- and calpain-dependent manner. These PS-exposing EVs are prothrombotic and proinflammatory and are found at elevated levels in many cardiovascular and metabolic diseases. How PS-exposing EVs are shed is not fully understood. A clearer understanding of this process may aid the development of drugs to selectively block their release. In this study we report that 2-aminoethoxydiphenylborate (2-APB) significantly inhibits the release of PS-exposing EVs from platelets stimulated with the Ca2+ ionophore, A23187, or the pore-forming toxin, streptolysin-O. Two analogues of 2-APB, diphenylboronic anhydride (DPBA) and 3-(diphenylphosphino)-1-propylamine (DP3A), inhibited PS-exposing EV release with similar potency. Although 2-APB and DPBA weakly inhibited platelet PS exposure and calpain activity, this was not seen with DP3A despite inhibiting PS-exposing EV release. These data suggest that there is a further target of 2-APB, independent of cytosolic Ca2+ signalling, PS exposure and calpain activity, that is required for PS-exposing EV release. DP3A is likely to inhibit the same target, without these other effects. Identifying the target of 2-APB, DPBA and DP3A may provide a new way to inhibit PS-exposing EV release from activated platelets and inhibit their contribution to thrombosis and inflammation.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2058-7716
dc.sourcenlmid: 101665035
dc.subjectMechanism of action
dc.subjectDrug Development
dc.title2-Aminoethoxydiphenylborate (2-APB) inhibits release of phosphatidylserine-exposing extracellular vesicles from platelets.
dc.typeArticle
dc.date.updated2020-04-07T00:26:46Z
prism.publicationNameCell Death Discovery
prism.volume6
dc.identifier.doi10.17863/CAM.51249
rioxxterms.versionofrecord10.1038/s41420-020-0244-9
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
pubs.funder-project-idWellcome Trust (200702/Z/16/Z)
pubs.funder-project-idBritish Heart Foundation (PG/16/45/32152)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International