title: Mitochondrial localization of vitamin D receptor in human platelets and differentiated megakaryocytes.
abstract: BACKGROUND
  Like other steroid hormones, vitamin D elicits both transcriptional events and rapid non genomic effects. Vitamin D receptor (VDR) localization and mechanisms of VDR-triggered non genomic responses are still controversial. Although anticoagulant effects of vitamin D have been reported and VDR signalling has been characterized in monocytes and vascular cells, nothing is known about VDR expression and functions in human platelets, anucleated fragments of megakaryocytes which are known targets of other steroids.
  
  
  RESULTS
  In this study we characterized the expression and cellular localization of VDR in human platelets and in a megakaryocyte lineage. Human platelets and their TPA-differentiated precursors expressed a classical 50 kDa VDR protein, which increased with megakaryocytes maturation. By biochemical fractionation studies we demonstrated the presence of the receptor in the soluble and mitochondrial compartment of human platelets, and the observation was confirmed by immunoelectron microscopy analysis. Similar localization was found in mature megakaryocytes, where besides its classical nuclear localization the receptor was evident as soluble and mitochondria resident protein.
  
  
  CONCLUSIONS
  The results reported here suggest that megakaryocytopoiesis and platelet activation, which are calcium-dependent events, might be modulated by a mitochondrial non genomic activity of VDR. These data open challenging future studies on VDR physiological role in platelets and more generally in mitochondria.
authors.affiliation: Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy. francesca.silvagno@unito.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Silvagno
authors.forename: Enrico
authors.initials: E
authors.lastname: De Vivo
authors.forename: Angelo
authors.initials: A
authors.lastname: Attanasio
authors.forename: Valentina
authors.initials: V
authors.lastname: Gallo
authors.forename: Gianna
authors.initials: G
authors.lastname: Mazzucco
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Pescarmona
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D018167:Receptors, Calcitriol; D013755:Tetradecanoylphorbol Acetate