title: Arachidonic acid depletion extends survival of cold-stored platelets by interfering with the [glycoprotein Ibα--14-3-3ζ] 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 [14-3-3ζ-glycoprotein Ibα] association, 14-3-3ζ release from phospho-Bad, Bad activation and apoptosis.
  
  
  METHODS
  We investigated whether arachidonic acid, which also binds 14-3-3ζ, 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 14-3-3ζ 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-14-3-3ζ-glycoprotein Ibα] complex. Indomethacin promoted complex formation by accumulating arachidonic acid and released 14-3-3ζ 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-14-3-3ζ-glycoprotein Ibα] complex, which released 14-3-3ζ 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.
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Dianne E
authors.initials: DE
authors.lastname: van der Wal
authors.forename: Eelo
authors.initials: E
authors.lastname: Gitz
authors.forename: Vivian X
authors.initials: VX
authors.lastname: Du
authors.forename: Kimberly S L
authors.initials: KS
authors.lastname: Lo
authors.forename: Cornelis A
authors.initials: CA
authors.lastname: Koekman
authors.forename: Sabine
authors.initials: S
authors.lastname: Versteeg
authors.forename: Jan Willem N
authors.initials: JW
authors.lastname: Akkerman
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism; D001793:Blood Preservation; D002470:Cell Survival; D003080:Cold Temperature; D051545:Cyclooxygenase 1 / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D015539:Platelet Activation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D051025:bcl-Associated Death Protein; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1