title: Peripheral benzodiazepine binding sites in platelets of patients affected by mitochondrial diseases and large scale mitochondrial DNA rearrangements.
abstract: BACKGROUND
  The peripheral-type benzodiazepine receptors (PBR) are localized on the outer mitochondrial membrane, as a constituent of mitochondrial permeability transition (MPT)-pore. Among its hypothesized functions, the regulation of the mitochondrial respiratory chain and apoptosis have been suggested; in addition alterations of PBR site density have been shown in some neuropathologic conditions with putative mitochondrial involvement. The aim of this work has been to evaluate PBR kinetic binding parameters in platelets from patients affected by mitochondrial disorders (MD) with large-scale mitochondrial DNA deletions and reduced cytochrome c oxidase activity.
  
  
  METHODS
  Using the specific PBR radioligand [(3) H] PK 11195, the kinetic binding parameters of PBR sites were determined in platelet membrane of 15 healthy subjects and 11 patients affected by different form of MD.
  
  
  RESULTS
  Significant changes of dissociation constant (K(d)) and maximal number of binding sites (B(max)) values were evidenced in platelets of patients versus controls. In all patients the B(max) values were decreased (2,387.0 +/- 305.6 fmol/ mg proteins versus 4889.0 +/- 357.8 fmol/mg proteins, p< 0.05), whereas the K(d) values were higher in patients than controls (13.18 +/- 2.06 nM versus 5.63 +/- 0.46 nM, p< 0.05).
  
  
  CONCLUSIONS
  These data suggest that the kinetic binding parameters of PBR are altered in MD and that the observed changes might be related to the mitochondrial dysfunction associated with MD.
authors.affiliation: Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
authors.forename: Beatrice
authors.initials: B
authors.lastname: Chelli
authors.forename: Laura
authors.initials: L
authors.lastname: Betti
authors.forename: Marina
authors.initials: M
authors.lastname: Montali
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Anna
authors.initials: A
authors.lastname: Rocchi
authors.forename: Luigi
authors.initials: L
authors.lastname: Murri
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
mesh_terms: D000328:Adult; D000368:Aged; D001569:Benzodiazepines / Q000378:metabolism*; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D015321:Gene Rearrangement / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D001569:Benzodiazepines