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Keratinocytes cultured from patients with Hailey–Hailey disease and Darier disease display distinct patterns of calcium regulation
Author(s) -
Lein P.T.,
Myllylä R.M.,
Hägg P.M.,
Tuukkanen J.,
Koivunen J.,
Peltonen S.,
Oikarinen A.,
Korkiamäki T.,
Peltonen J.
Publication year - 2005
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2005.06623.x
Subject(s) - thapsigargin , darier disease , darier's disease , keratinocyte , calcium , endoplasmic reticulum , calcium in biology , calcium metabolism , biology , microbiology and biotechnology , calcium signaling , golgi apparatus , medicine , endocrinology , chemistry , disease , genetics , cell culture
Summary 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 Ca 2+ ‐ATPase (SPCA1, ATP2C1 ) and the sarco/endoplasmic reticulum Ca 2+ ‐ATPase type 2 (SERCA2, ATP2A2 ) genes. Objectives 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 Ca 2+ levels in resting phase, while DD keratinocytes showed elevated Ca 2+ levels. Application of ATP caused less pronounced elevation of intracellular calcium concentration ([Ca 2+ ] i ) in both HHD and DD keratinocytes than in control cells. HHD keratinocytes did not lower their [Ca 2+ ] i as efficiently as control keratinocytes after treatment with thapsigargin. In addition, DD keratinocytes were practically incapable of lowering their [Ca 2+ ] 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.