| Research Abstract |
The purpose of the present study is to clarify the mechanism for controlling the formation and deletion of cell-cell contacts (desmosomes), and cellular pathogenesis of bullous diseases and sbnormal keratinization caused by structural and functional abnormality of cell-cell contacts.
It has been known since Henning's report (1982) that epidermal keratinocytes cultured in low calcium(0.1mM) do not form desmosome and do not differentiate, but upon raising calcium to the normal level (1 to 2 mM) desmosome formation and differentiation are initiated. However, little is known about the biochemical mechanism for this phenomenon. Besides this, it has been known that 12-0-tetra decanolylphorobol-13-acetate (TPA), which specifically binds to and activates protein kinase C (C kinase), acts as a potent modulator of differentiation in epidermal kiratinocytes.
In this respect, we studied whether inositol phospholipids (IPL) turnover and C kinase are involved in the calcium-induced formation of cell-c
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ell contacts in low-calcium grown cells. Consequently, an increase in diacylglcerol(DG), phosphatidic acid and inositol-trisphosphate were shown 30 seconds after calcium addition, and an activation of C kinase which was known to be coused by DG, was also revealed 15 min after calcium addition. These results suggest that an increase in eztracellular calcium concentration may be mediated by an activation of IPL-turnover and C kinase. This was reported at 12th Annual Meeting of Japanese Society for Investigative Dermatology and submitted to J. Invest. Dermato.
On the other hand, when TPA (10 ng/ml) was added to the low-calcium medium, the formation of desmosomal contacts and activation of C kinase in membrane fractions with a reduction of its activity in cytosol (trsnslocation of C kenase)were induced at 15 min after TPA addition. However, 24h after TPA addition, the reduction of total C kinase activity (down regulation) and a decrease in desmosomes were found. Furthermore, the addition of a C kinase inhibitor, H7, caused the reduction of the number of desmosomes in normal-calcium grown cells. These results may suggest that C kinase has some important relevance to the control systems of cell-cell contacts in keratinocytes.
Effects of pemphigus antibody on the calcium-induced formation of cell-cell contacts in keratinocytes were reported in J. Investigative Dermatology, 89; 169, 1987. Abnormal organization of keratin intermediate filaments (KIF) in epidermolysis bullosa simplex was studied and the results were submitted to J. Investigative Dermatology. These resluts prompt us to start the mollecular studies on KIF and cell-cell contacts controlling systems. Less
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