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A critical facet of the balance that facilitates platelet clearance from the circulation is apoptosis (programmed cell death). The precise cellular mechanisms that underpin platelet apoptosis are not defined. In nucleated cells, reorganization of the actin cytoskeleton is known to regulate platelet apoptosis. However, the role of the actin cytoskeleton in regulating apoptosis in platelets has not been extensively studied as they are anucleate and exhibit a distinctive physiology. Here, apoptosis was induced in washed human platelets using ABT-737, a BH3-mimetic drug. Mitochondrial depolarization was measured using the ratiometric dye JC-1; surface phosphatidylserine (PS) exposure was measured by annexin V binding; caspase-3 activation was measured by Western blotting. All three apoptotic markers were unaffected by the presence of either the actin depolymerizing drug cytochalasin D or the actin polymerizing drug jasplakinolide. Moreover, platelets were isolated from wild-type (<jats:italic>WT<\/jats:italic>) mice and mice deficient in gelsolin (<jats:italic>Gsn<\/jats:italic>), an actin-binding protein that is essential for normal cytoskeletal remodeling. In response to ABT-737, gelsolin-null (<jats:italic>Gsn<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup>) platelets initially showed accelerated PS exposure relative to <jats:italic>WT<\/jats:italic> platelets, however, both <jats:italic>WT<\/jats:italic> and <jats:italic>Gsn<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> platelets exhibited similar levels of mitochondrial depolarization and caspase-3 activation in response to ABT-737. We conclude that ABT-737 induces established markers of platelet apoptosis in an actin-independent manner.<\/jats:p>","DOI":"10.1371\/journal.pone.0276584","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T18:28:11Z","timestamp":1668536891000},"page":"e0276584","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Apoptosis in platelets is independent of the actin cytoskeleton"],"prefix":"10.1371","volume":"17","author":[{"given":"Enoli","family":"De Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1543-6726","authenticated-orcid":true,"given":"Hugh","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"issue":"2","key":"pone.0276584.ref001","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.blre.2011.10.002","article-title":"Apoptosis in the anucleate platelet","volume":"26","author":"V. 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