title: Platelet apoptosis by cold-induced glycoprotein Ibα clustering.
abstract: BACKGROUND
  Cold-storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Ibα-distribution indicative of receptor clustering and initiates thromboxane A(2) -formation. GPIbα is associated with 14-3-3 proteins, which contribute to GPIbα-signaling and in nucleated cells take part in apoptosis regulation.
  
  
  OBJECTIVE
  We investigated whether GPIbα-clustering induces platelet apoptosis through 14-3-3 proteins during cold (4 h 0 °C)-rewarming (1 h 37 °C).
  
  
  RESULTS
  During cold-rewarming, 14-3-3 proteins associate with GPIbα and dissociate from Bad inducing Bad-dephosphorylation and activation. This initiates pro-apoptosis changes in Bax/Bcl-x(L) and Bax-translocation to the mitochondria, inducing cytochrome c release. The result is activation of caspase-9, which triggers phosphatidylserine exposure and platelet phagocytosis by macrophages. Responses are prevented by N-acetyl-D-glucosamine (GN), which blocks GPIbα-clustering, and by O-sialoglycoprotein endopeptidase, which removes extracellular GPIbα.
  
  
  CONCLUSIONS
  Cold-rewarming triggers apoptosis through a GN-sensitive GPIbα-change indicative of receptor clustering. Attempts to improve platelet transfusion by cold-storage should focus on prevention of the GPIbα-change.
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: D E
authors.initials: DE
authors.lastname: van der Wal
authors.forename: V X
authors.initials: VX
authors.lastname: DU
authors.forename: K S L
authors.initials: KS
authors.lastname: Lo
authors.forename: J T
authors.initials: JT
authors.lastname: Rasmussen
authors.forename: S
authors.initials: S
authors.lastname: Verhoef
authors.forename: J W N
authors.initials: JW
authors.lastname: Akkerman
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000117:Acetylglucosamine / Q000378:metabolism; D017209:Apoptosis; D001665:Binding Sites; D001792:Blood Platelets / Q000166:cytology*; D053453:Caspase 9 / Q000378:metabolism; D016000:Cluster Analysis; D003080:Cold Temperature; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D010766:Phosphorylation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D013928:Thromboxane A2 / Q000378:metabolism; 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; D013928:Thromboxane A2; D053453:Caspase 9; D000117:Acetylglucosamine