Arachidonic acid depletion extends survival of cold-stored platelets by interfering with the [glycoprotein ibI? - 14-3-3I?] association

Evertdina van der Wal, Eelo Gitz, Vivian X Du, Kimberly Lo, C Arnold Koekman, Sabine Versteeg, Jan-Willem N Akkerman

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29 Citations (Scopus)


Background: Cold storage of platelets reduces bacterial growth and preserves their hemostatic properties better than current procedures do. However, storage at 0A?C induces [14-3-3I?-glycoprotein IbI?] association, 14-3-3I? release from phospho-Bad, Bad activation and apoptosis. Design and Methods: We investigated whether arachidonic acid, which also binds 14-3-3I?, contributes to coldinduced apoptosis. Results: Cold storage activated P38-mitogen-activated protein kinase and released arachidonic acid, which accumulated due to cold inactivation of cyclooxygenase-1/thromboxane synthase. Accumulated arachidonic acid released 14-3-3I? from phospho-Bad and decreased the mitochondrial membrane potential, which are steps in the induction of apoptosis. Addition of arachidonic acid did the same and its depletion made platelets resistant to cold-induced apoptosis. Incubation with biotin-arachidonic acid revealed formation of an [arachidonic acid-14-3- 3I?-glycoprotein IbI?] complex. Indomethacin promoted complex formation by accumulating arachidonic acid and released 14-3-3I? from cyclo-oxygenase-1. Arachidonic acid depletion prevented the cold-induced reduction of platelet survival in mice. Conclusions: We conclude that cold storage induced apoptosis through an [arachidonic acid-14-3-3I?-glycoprotein IbI?] complex, which released 14-3-3I? from Bad in an arachidonic acid-dependent manner. Although arachidonic acid depletion reduced agonist-induced thromboxane A 2formation and aggregation, arachidonic acid repletion restored these functions, opening ways to reduce apoptosis during storage without compromising hemostatic functions post-transfusion. A?2012 Ferrata Storti Foundation.
Original languageEnglish
Pages (from-to)1501 - 1522
Number of pages22
Issue number10
Publication statusPublished - 2012

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