The calcium-activated neutral protease calpain I is present in normal foetal skin and is decreased in neonatal harlequin ichthyosis

Calcium concentration is a critical factor for epidermal differentiation an d is implicated in the expression and post-translational modification of nu merous proteins in suprabasal cells of the epidermis. Calpains (calcium-act ivated neutral proteases) are believed to participate in signal transductio n via highly regulated cytoplasmic protease activity, Here we investigate t he expression of calpain I in normal human skin development and in neonatal harlequin ichthyosis (HI), a disorder of altered epidermal differentiation , especially the transition from the granular to the fully differentiated c ornified layer. Calpain I was detected in developing foetal epidermis at 54 days estimated gestational age in the basal layer and the periderm of the de developing foetal epidermis, By 125 days, calpain I was also detected in the granular layer. This pattern was maintained in newborn skin, but expre ssion was significantly weaker in HI biopsies (n = 7), Reduced expression o f calpain was specific to HI and was not observed in other skin diseases, C alpain was also normally expressed in the outer root sheath of hair follicl es, in sebaceous glands and in sweat ducts and glands. Immunoblots of epide rmal and keratinocyte extracts showed that the 78-kDa and 76-kDa active for ms were generated via limited proteolysis of the 80-kDa inactive subunit; h owever, all forms were diminished in HI, consistent with findings in tissue sections. Our results show that calpain is present throughout the epidermi s and is expressed from the early stages of development, These findings imp licate calcium-mediated signalling events in the alteration of differentiat ion that occurs in HI.