Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1

Abstract

The results suggest that modulation of ATP2A2 and ATP2C1 mRNA expression by UV or cytokines might contribute to the clinical presentations unique to DD and HHD, and that the controlled expression of these genes plays an important role in keratinocyte homeostasis, function and differentiation.

ATP2C1 is specifically localized in the basal layer of normal epidermis and its depletion triggers keratinocyte differentiation

“…5, we observed no change in the ATP2C1 expression level upon the treatment of keratinocytes by extracellularly applied calcium at 1 mM, whereas the recently published data showed its marked induction of ATP2C1 with 1.8 mM calcium [1] or with 1.2 mM calcium [36], and by contrast, its reduction with 1.2 mM calcium [37]. These apparently contradictory results from the four studies likely indicate that the changes in the ATP2C1 expression level may not be directly regulated with the extracellular concentration of calcium applied, but may be related to the cytoplasmic calcium level, which, of course, depends on extracellularly applied calcium, but also probably depends on the ability and living-conditions of cells to handle the increased cytoplasmic calcium ATP2C1 depletion triggers keratinocyte differentiation 31 Fig.…”

“…ATP2C1 is a calcium/manganese-ATPase localized in the Golgi apparatus and is highly expressed in cultured human keratinocytes [1][2][3][4]. It has been known that calcium uptake into the Golgi apparatus is performed by both ATP2C1 ($70% contribution) and ATP2A2 ($30% contribution) with its concentration to submillimolar order [5][6][7][8].…”

Darier disease

“…15 Based on these results, anti-IL-6 antibodies are expected to be developed for the prevention of DD exacerbations, particularly during the summer.…”

Hailey Hailey disease-a rare case report

“…[16][17][18] Treatment may up-regulate SPCA1 expression either indirectly through an effect on cytokine production or by a direct effect on keratinocytes. 19,20 The role of antiseptics, antibiotics and/or topical antifungal agents as steroid-sparing agents is unproven, but long-term antimicrobial treatment appears to be helpful. 14,16,21 Topical tetracyclines, aminoglycosides, fusidic acid or imidazoles may be added to a topical corticosteroid.…”