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-xL 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.