title: Reduced expression of the antiapoptotic proteins of Bcl-2 gene family in the lesional epidermis of patients with Darier's disease.
abstract: BACKGROUND
  Dyskeratotic cells in Darier's disease (DD) are thought to represent apoptotic keratinocytes. Bcl-2 gene family proteins play a major role in the regulation of apoptosis of epidermal keratinocytes and reveal pleiotropic interactions with intracellular Ca2+ homeostasis. The latter is impaired in DD because of mutations of ATP2A2 gene that encodes the type 2 isoforms of the sarcoplasmic/endoplasmic reticulum (ER) Ca++ ATPase 2 (SERCA2) pump.
  
  
  METHODS
  The expression of Bcl-2, Bax, and Bcl-x(L) proteins was investigated in the epidermis of 11 patients with DD and of 11 sex- and age-matched healthy controls by immunohistochemistry.
  
  
  RESULTS
  The expression of Bcl-2 and Bcl-xL was clearly reduced in the lesional epidermis of the patients, as compared with the normal epidermis of healthy controls, whereas the expression of Bax remained unaltered.
  
  
  CONCLUSIONS
  The alterations in the expression of Bcl-2 gene family proteins could be a crucial event for the activation of the apoptotic process in the lesional epidermis of DD patients and for the occurrence of the characteristic dyskeratotic keratinocytes. The question as to whether these alterations are associated with the ER Ca2+ depletion in DD or represent secondary phenomena unrelated to the genetic defect of this genodermatosis remains to be elucidated.
authors.affiliation: Department of Dermatology, University of Patras, Patras, Greece. pasmatzi@med.upatras.gr
authors.forename: Efi
authors.initials: E
authors.lastname: Pasmatzi
authors.forename: George
authors.initials: G
authors.lastname: Badavanis
authors.forename: Alexandra
authors.initials: A
authors.lastname: Monastirli
authors.forename: Dionysios
authors.initials: D
authors.lastname: Tsambaos
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D007644:Darier Disease / Q000378:metabolism* / Q000473:pathology; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019254:Genes, bcl-2; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein