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

ABSTRACT: BACKGROUND: Cold storage of platelets reduces bacterial growth and preserves their hemostatic properties better than current procedures do. However, storage at 0°C induces [14-3-3?-glycoprotein Ib?] association, 14-3-3? release from phospho-Bad, Bad activation and apoptosis. DESIGN AND METHODS: We investigated whether arachidonic acid, which also binds 14-3-3?, 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 14-3-3? 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-14-3-3?-glycoprotein Ib?] complex. Indomethacin promoted complex formation by accumulating arachidonic acid and released 14-3-3? 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-14-3-3?-glycoprotein Ib?] complex, which released 14-3-3? from Bad in an arachidonic acid-dependent manner. Although arachidonic acid depletion reduced agonist-induced thromboxane A(2) formation and aggregation, arachidonic acid repletion restored these functions, opening ways to reduce apoptosis during storage without compromising hemostatic functions post-transfusion.

SUBMITTER: van der Wal DE 

PROVIDER: S-EPMC3487552 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature