title: Keratinocytes cultured from patients with Hailey-Hailey disease and Darier disease display distinct patterns of calcium regulation.
abstract: BACKGROUND
  Hailey-Hailey disease (HHD) (OMIM 16960) and Darier disease (DD) (OMIM 124200) are dominantly inherited acantholytic skin diseases, respectively, caused by mutations in the genes encoding the Golgi secretory pathway Ca2+-ATPase (SPCA1, ATP2C1) and the sarco/endoplasmic reticulum Ca2+-ATPase type 2 (SERCA2, ATP2A2) genes.
  
  
  OBJECTIVE
  To investigate calcium regulation in keratinocytes cultured from patients with HHD and DD by measuring intracellular calcium resting levels and the cellular responses to ATP and thapsigargin.
  
  
  METHODS
  The study was carried out using keratinocyte cultures established from four patients with HHD and four with DD. Calcium concentrations were measured with fluorescence ratio imaging using fura-2 loading.
  
  
  RESULTS
  Control and HHD keratinocytes displayed approximately the same Ca2+ levels in resting phase, while DD keratinocytes showed elevated Ca2+ levels. Application of ATP caused less pronounced elevation of intracellular calcium concentration ([Ca2+]i) in both HHD and DD keratinocytes than in control cells. HHD keratinocytes did not lower their [Ca2+]i as efficiently as control keratinocytes after treatment with thapsigargin. In addition, DD keratinocytes were practically incapable of lowering their [Ca2+]i after treatment with thapsigargin.
  
  
  CONCLUSIONS
  The results demonstrate that the defects in SPCA1 and SERCA2 calcium ATPases result in distinct patterns of calcium metabolism. This is also supported by the different clinical features of the diseases.
authors: Department of Anatomy and Cell Biology, University of Oulu, PB 5000, 90014 Oulu, Finland.
authors: P T
authors: PT
authors: Leinonen
authors: R M
authors: RM
authors: Myllylä
authors: P M
authors: PM
authors: Hägg
authors: J
authors: J
authors: Tuukkanen
authors: J
authors: J
authors: Koivunen
authors: S
authors: S
authors: Peltonen
authors: A
authors: A
authors: Oikarinen
authors: T
authors: T
authors: Korkiamäki
authors: J
authors: J
authors: Peltonen
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000328:Adult; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D007644:Darier Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D016506:Pemphigus, Benign Familial / Q000378:metabolism* / Q000473:pathology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D019284:Thapsigargin; D000255:Adenosine Triphosphate; D002118:Calcium