Lithium Suppresses Epidermal SERCA2 and PMR1 Levels in the Rat

Norbert SÜLE1, Alexandra TÉSZÁS2, Endre KÁLMÁN1, Réka SZIGETI3, Attila MISETA4, Richard KELLERMAYER2

1Department of Pathology, University of Pécs, Pécs, Hungary
2Department of Medical Genetics and Child Development, University of Pécs, Pécs, Hungary
3Department of Dermatology, University of Pécs, Pécs, Hungary
4Department of Laboratory Medicine, University of Pécs, Pécs, Hungary


Autosomal dominant mutations in the genes encoding the calcium ATPases SERCA2 and PMRI/SPCA1 cause the genodermatoses Darier disease (DD) and Hailey-Hailey disease (HHD), respectively. Recent observations indicated that the level of the pathogenic proteins greatly decreases in the affected areas of the epidermis in these disorders. Here we addressed how lithium, a recognized exacerbating factor in Darier disease, affects the epidermal expression of SERCA2 and PMR1/SPCA1 in the rat as a model. Standard histologic and immunohistochemical methods were utilized in 3 lithium-treated and 3 control animals. A significant suppression of epidermal SERCA2 and PMR1 levels were observed as a result of lithium therapy in addition to marked qualitative and quantitative changes in the stratum corneum and the granular layer of the epidermis in the treated animals. Our findings suggest that exacerbating factors in calcium ATPase disorders of the skin suppress epidermal SERCA2 and PMR1 levels, further decreasing the already haploinsufficient protein expression to a potentially critical level in Darier disease and Hailey-Hailey disease, respectively. Lithium therapy should specifically be avoided not only in Darier disease, but Hailey-Hailey disease as well. Pathology & Oncology Research, Vol 12, Nr 4, 234-236, 2006

Key words: Hailey-Hailey disease; Darier disease; lithium; rat; SERCA2; PMR1

Received: Jun 19, 2006; accepted: Oct 21, 2006
Correspondence: , Department of Medical Genetics and Child Development, University of Pécs, József A. u. 7. Pécs H-7623, Hungary; Tel: +36 72 535-977/-972, Fax: +36 72 535-977/-972; E-mail:

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