title: Reevaluation of the normal epidermal calcium gradient, and analysis of calcium levels and ATP receptors in Hailey-Hailey and Darier epidermis.
abstract: Electron probe microanalysis was used to analyze elemental content of human epidermis. The results revealed that the calcium content of the basal keratinocyte layer was higher than that of the lowest spinous cell layer in normal epidermis. This was surprising, as it is generally accepted that the calcium level increases with cellular differentiation from the proliferative basal layer to the stratum corneum. Hailey-Hailey disease (HHD) and Darier disease (DD) are caused by mutations in Ca(2+)-ATPases with the end result of desmosomal disruption and suprabasal acantholysis. The results demonstrated three major aberrations in HHD and DD lesions. First, in HHD and DD lesions the calcium content in the basal layer was lower than in the normal skin. Second, adenosine triphosphate (ATP) receptor P2Y2 was not localized to plasma membrane in acantholytic cells, whereas P2X7 appeared in the plasma membrane, potentially mediating apoptosis. Third, transition of keratin 14 to keratin 10 was abnormal as demonstrated by the presence of keratinocytes expressing both cytokeratins, which are usually exclusive in normal epidermis. Our results provide to our knowledge previously unreported elements for understanding how the disturbed calcium gradient is linked to the alterations in ATP receptors and keratin expression, leading to the clinical findings in HHD and DD.
authors.affiliation: Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu, Finland. pekka.t.leinonen@oulu.fi
authors.forename: Pekka T
authors.initials: PT
authors.lastname: Leinonen
authors.forename: Päivi M
authors.initials: PM
authors.lastname: Hägg
authors.forename: Sirkku
authors.initials: S
authors.lastname: Peltonen
authors.forename: Eeva-Mari
authors.initials: EM
authors.lastname: Jouhilahti
authors.forename: Jukka
authors.initials: J
authors.lastname: Melkko
authors.forename: Timo
authors.initials: T
authors.lastname: Korkiamäki
authors.forename: Aarne
authors.initials: A
authors.lastname: Oikarinen
authors.forename: Juha
authors.initials: J
authors.lastname: Peltonen
mesh_terms: D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D007644:Darier Disease / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D053550:Keratin-10 / Q000378:metabolism; D053547:Keratin-14 / Q000378:metabolism; D008875:Middle Aged; D016506:Pemphigus, Benign Familial / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2; D012867:Skin / Q000473:pathology
chemical_list: D053547:Keratin-14; C546385:P2RY2 protein, human; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D053550:Keratin-10; D000252:Calcium-Transporting ATPases; D002118:Calcium