title: Acquired cytochrome C oxidase impairment in apheresis platelets during storage: a possible mechanism for depletion of metabolic adenosine triphosphate.
abstract: BACKGROUND
  Intracellular adenosine triphosphate (ATP) levels decline significantly during storage of platelet (PLT) products, in part due to PLT degranulation. However, metabolic ATP stores also become depleted during storage through an unclear mechanism. Since both anaerobic glycolysis and oxidative phosphorylation are important for PLT ATP production, it is possible that the reduction in metabolic ATP reflects impaired oxidative phosphorylation. To assess this, we evaluated the kinetic activity and protein expression of cytochrome C oxidase (CcOX) in stored apheresis PLTs.
  
  
  METHODS
  Apheresis PLTs were collected and stored with agitation at 22 ± 2°C for 7 days. In vitro measurements of PLT metabolic state, function, and activation were performed on Days 0, 2, 4, and 7 of storage. Total PLT ATP content, steady-state CcOX kinetic activity, and protein immunoblotting for CcOX Subunits I and IV were also performed using isolated PLT mitochondria from simultaneously collected samples.
  
  
  RESULTS
  Intra-PLT ATP and steady-state PLT CcOX activity declined significantly and in a progressive manner throughout storage while steady-state levels of CcOX I and IV protein remained unchanged. Time-dependent decline in CcOX activity correlated with progressive ATP depletion over time.
  
  
  CONCLUSIONS
  During storage of apheresis PLTs for 7 days, the parallel decline in CcOX function and intra-PLT ATP suggests development of an acquired impairment in PLT oxidative phosphorylation associated with perturbed ATP homeostasis in stored PLTs.
authors.affiliation: Division of Hematology, Center for Cancer and Blood Disorders, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA.
authors.forename: Yaser A
authors.initials: YA
authors.lastname: Diab
authors.forename: Adia
authors.initials: A
authors.lastname: Thomas
authors.forename: Naomi L C
authors.initials: NL
authors.lastname: Luban
authors.forename: Edward C C
authors.initials: EC
authors.lastname: Wong
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wagner
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Levy
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D001793:Blood Preservation; D003576:Electron Transport Complex IV / Q000097:blood* / Q000502:physiology; D006801:Humans; D010983:Plateletpheresis
chemical_list: D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV