Calmodulin Activities Are Significantly Increased in Both Uninvolved and Involved Epidermis in Psoriasis

Abstract

In order to elucidate a part of calmodulin actions in the hyperproliferative state in human epidermis, calmodulin activities in the psoriatic and in the normal human epidermis were determined using calmodulin-deficient phosphodiesterase from bovine heart and purified pig skin epidermal calmodulin as a standard. Skin samples were obtained from 11 normal healthy controls and from both the uninvolved and involved regions of 8 nonconsanguineous psoriatic patients. Pure epidermal samples, prepared by the microdissection method, were used for calmodulin assays. Normal human epidermis contained 270 +/- 13 ng/mg dry weight, whereas calmodulin activities were significantly increased in psoriatic epidermis, 412 +/- 29 ng/mg dry weight for the uninvolved epidermis and 747 +/- 46 ng/mg dry weight for the involved epidermis, respectively. These results suggest that calmodulin may play an important role in cell proliferation in human epidermis.

Identification and Cloning of a New Calmodulin-like Protein from Human Epidermis

“…B, the alignment was used to establish a phylogenetic relationship between EF-hand proteins, calculated with the puzzle 3. (1) and from human tissues, spleen (2), testis (3), small intestine (4), placenta (5), heart (6), liver (7), skeletal muscle (8), pancreas (9), kidney (10), and lung (11). Panel B, expression of markers of epidermal differentiation, CaM, GAPDH, and CLSP in proliferating keratinocytes (K) and differentiating keratinocyte of reconstructed human epidermis at days 3, 6, and 13.…”

“…In highly proliferating in vitro cultures of keratinocytes, and in psoriasis, a hyperproliferative, epidermal skin disease, CaM levels are particularly elevated (7)(8)(9). Besides the identification of a CaMbinding protein in epidermal desmosomes, named desmocalmin (10), and the CaM regulation of human platelet transglutaminase (factor XIII), no specific information is available on the mediation of calcium signals in the epidermis to control keratinocyte proliferation and differentiation.…”

Calcium-activated adenosine triphosphatase and gap junctions in rat epidermis.

“…In the previous study of the plasmalemmal Ca++-ATPase in chick growth-plate cartilage (1) a similar result was demonstrated, i.e., strong enzyme activity in the proliferative and hypertrophic zones, and decreasing reaction products with the calcifying process. Moreover, the intense activity on the basal cell may have some connection with the report that the level of calmodulin increases in the hyperproliferative state (8,15). That appears to be convenient, because it was reported that Ca++ affinity to the Ca++-transporting part of ATPase increased with existence of Ca+ + -calmodulin complex (7).…”

“…Rat skin calcium binding protein has been speculated to involve the control of the basal cell proliferation from the immunohistochemical observation (4,20). The level of calmodulin, which is highly conserved throughout animal and plant species, increased in the in vivo hyperproliferative state (15), psoriasis, and in the in vitro low calcium-induced hyperproliferative state (8). The plasmalemmal Ca++-ATPase is accepted to be an intrinsic protein that serves for the control of intracellular calcium level as a calcium extrusion pump .…”

“…Therefore, it requires cautiousness to discuss this sequence of calcium-induced differentiation of keratinocytes in vitro with relation to the intracellular event that calcium and calciumrelated agents regulate. There have been several studies which focussed on calciumbinding proteins, such as calmodulin (8,15) and on the other calcium-related agents (4,14,20). Ca++-ATPase activity, an energy dependent calcium extrusion pump, is well accepted to reflect intracellular calcium level.…”