2-Aminoethoxydiphenylborate (2-APB) inhibits release of phosphatidylserine-exposing extracellular vesicles from platelets
dc.contributor.author | Wei, Hao | |
dc.contributor.author | Davies, Jessica E. | |
dc.contributor.author | Harper, Matthew T. | |
dc.date.accessioned | 2021-02-09T16:33:40Z | |
dc.date.available | 2021-02-09T16:33:40Z | |
dc.date.issued | 2020-03-02 | |
dc.date.submitted | 2019-11-07 | |
dc.identifier.other | s41420-020-0244-9 | |
dc.identifier.other | 244 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/317399 | |
dc.description.abstract | Abstract: Activated, 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.language | en | |
dc.publisher | Nature Publishing Group UK | |
dc.rights | Attribution 4.0 International (CC BY 4.0) | en |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en |
dc.subject | Article | |
dc.subject | /631/92/609 | |
dc.subject | /692/308/153 | |
dc.subject | article | |
dc.title | 2-Aminoethoxydiphenylborate (2-APB) inhibits release of phosphatidylserine-exposing extracellular vesicles from platelets | |
dc.type | Article | |
dc.date.updated | 2021-02-09T16:33:39Z | |
prism.issueIdentifier | 1 | |
prism.publicationName | Cell Death Discovery | |
prism.volume | 6 | |
dc.identifier.doi | 10.17863/CAM.64512 | |
dcterms.dateAccepted | 2019-12-10 | |
rioxxterms.versionofrecord | 10.1038/s41420-020-0244-9 | |
rioxxterms.version | VoR | |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.identifier.eissn | 2058-7716 |
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