{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T01:22:56Z","timestamp":1770513776917,"version":"3.49.0"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"01","license":[{"start":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T00:00:00Z","timestamp":1546214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>\n            Background\u2003Zinc (Zn2+) is an essential trace element that regulates intracellular processes in multiple cell types. While the role of Zn2+ as a platelet agonist is known, its secondary messenger activity in platelets has not been demonstrated.<\/jats:p><jats:p>\n            Objectives\u2003This article determines whether cytosolic Zn2+ concentrations ([Zn2+]i) change in platelets in response to agonist stimulation, in a manner consistent with a secondary messenger, and correlates the effects of [Zn2+]i changes on activation markers.<\/jats:p><jats:p>\n            Methods\u2003Changes in [Zn2+]i were quantified in Fluozin-3 (Fz-3)-loaded washed, human platelets using fluorometry. Increases in [Zn2+]i were modelled using Zn2+-specific chelators and ionophores. The influence of [Zn2+]i on platelet function was assessed using platelet aggregometry, flow cytometry and Western blotting.<\/jats:p><jats:p>\n            Results\u2003Increases of intra-platelet Fluozin-3 (Fz-3) fluorescence occurred in response to stimulation by cross-linked collagen-related peptide (CRP-XL) or U46619, consistent with a rise of [Zn2+]i. Fluoresence increases were blocked by Zn2+ chelators and modulators of the platelet redox state, and were distinct from agonist-evoked [Ca2+]i signals. Stimulation of platelets with the Zn2+ ionophores clioquinol (Cq) or pyrithione (Py) caused sustained increases of [Zn2+]i, resulting in myosin light chain phosphorylation, and cytoskeletal re-arrangements which were sensitive to cytochalasin-D treatment. Cq stimulation resulted in integrin \u03b1IIb\u03b23 activation and release of dense, but not \u03b1, granules. Furthermore, Zn2+-ionophores induced externalization of phosphatidylserine.<\/jats:p><jats:p>\n            Conclusion\u2003These data suggest that agonist-evoked fluctuations in intra-platelet Zn2+ couple to functional responses, in a manner that is consistent with a role as a secondary messenger. Increased intra-platelet Zn2+ regulates signalling processes, including shape change, \u03b1IIb\u03b23 up-regulation and dense granule release, in a redox-sensitive manner.<\/jats:p>","DOI":"10.1055\/s-0038-1676589","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T23:31:15Z","timestamp":1546299075000},"page":"128-139","source":"Crossref","is-referenced-by-count":12,"title":["Agonist-Evoked Increases in Intra-Platelet Zinc Couple to Functional Responses"],"prefix":"10.1055","volume":"119","author":[{"given":"Niaz","family":"Ahmed","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Anglia Ruskin University, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Lopes Pires","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Anglia Ruskin University, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirk","family":"Taylor","sequence":"additional","affiliation":[{"name":"Cardio-Respiratory Interface Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Pugh","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Anglia Ruskin University, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2018,12,31]]},"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0038-1676589.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T21:13:31Z","timestamp":1557177211000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0038-1676589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,31]]},"references-count":0,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2018,12,31]]},"published-print":{"date-parts":[[2019,1]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0038-1676589","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,31]]}}}