Arachidonic acid depletion extends survival of cold-stored platelets by interfering with the [glycoprotein Ibα--14-3-3ζ] association.
Haematologica
; 97(10): 1514-22, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22371179
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. DESIGN ANDMETHODS:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Preservação de Sangue
/
Ácido Araquidônico
/
Complexo Glicoproteico GPIb-IX de Plaquetas
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Proteínas 14-3-3
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article