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Control systems for the formation and deletion of desmosomal cell-cell contacts in response to extracellular stimuli in keratinocytes

响应角质形成细胞的细胞外刺激而形成和删除桥粒细胞-细胞接触的控制系统

基本信息

批准号：
61480229
负责人：
KITAJIMA Yasuo
金额：
$ 3.97万
依托单位：
Department of Dermatology, Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61480229/
关键词：
cell-cell contact calcium C-kinase keratinocyte desmosome pemphigus epidermolysisbullosa simplex 角化制御 C-キナーゼ

项目摘要

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 … More 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

本研究的目的是阐明控制细胞-细胞接触形成和缺失的机制自Henning（1982）的报道以来，人们已经知道，在低钙环境中培养的表皮角质形成细胞，1 mM）不形成桥粒且不分化，但在将钙升高至正常水平（1至2 mM）时，启动桥粒形成和分化。然而，人们对这种现象的生化机制知之甚少。此外，已知12-0-十四烷酚-13-乙酸酯（TPA）特异性结合并激活蛋白激酶C（C kinase），是表皮角质形成细胞分化的有效调节剂。 ...更多信息在低钙生长的细胞中的细胞接触。因此，在加入钙后30秒，二酰基甘油（DG）、磷脂酸和肌醇-三磷酸增加，并且在加入钙后15分钟，还显示了已知由DG引起的C激酶的激活。这些结果表明，细胞内钙离子浓度的增加可能是通过激活IPL-周转和C激酶介导的。这是在日本皮肤病研究学会第12届年会上报告的，并提交给J. Invest。另一方面，当TPA（10 ng/ml）加入到低钙培养基中时，在加入TPA后15分钟，诱导桥粒接触的形成和膜组分中C激酶的活化，并降低其在胞质溶胶中的活性（C激酶的转移）。然而，TPA加入后24小时，发现总C激酶活性降低（下调）和桥粒减少。此外，加入C激酶抑制剂H7，导致正常钙生长细胞中桥粒数量减少。天疱疮抗体对角质形成细胞中钙诱导的细胞-细胞接触形成的影响报道于J. Investigative Dermatology，89; 169，1987。对单纯性大疱性表皮病中角蛋白中间丝（KIF）的异常组织进行了研究，结果已提交给《皮肤病学研究杂志》。这些结果促使我们开始对KIF和细胞-细胞接触调控系统进行分子水平的研究。少