Yada Y, Ozeki T, Meguro S, Mori S, Nozawa Y
Department of Biochemistry, Gifu University School of Medicine, Japan.
Biochem Biophys Res Commun. 1989 Sep 29;163(3):1517-22. doi: 10.1016/0006-291x(89)91152-2.
We have investigated the possible involvement of phosphoinositide turnover in the keratinocyte differentiation induced by 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3]. The mass contents of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol and intracellular calcium level were measured in murine keratinocytes stimulated with 1 alpha,25(OH)2D3 or its derivatives. Although production of these second messengers was enhanced, there were no significant differences in time- and dose-dependences between 1 alpha,25(OH)2D3 and its derivatives. These vitamin D3 compounds promoted the translocation from the cytosol to membrane of protein kinase C (PKC). Despite such common profiles in the early signal transduction parameters, only 1 alpha,25(OH)2D3 induced formation of a cornified envelope characteristic of keratinocyte differentiation. Down-regulation of PKC by prolonged pretreatment with PDBu or inhibition of the enzyme with H-7 caused marked suppression of 1 alpha,25(OH)2D3-induced formation of cornified envelopes. These findings imply that PKC is necessary but not sufficient for the onset of terminal differentiation by 1 alpha,25(OH)2D3, and also that another as yet unspecified signal generated specifically by the active vitamin D3 is required for keratinocyte differentiation.
我们研究了磷酸肌醇代谢周转在1α,25 - 二羟基维生素D3 [1α,25(OH)2D3]诱导的角质形成细胞分化过程中可能发挥的作用。我们测定了用1α,25(OH)2D3或其衍生物刺激的小鼠角质形成细胞中肌醇1,4,5 - 三磷酸和1,2 - 二酰基甘油的质量含量以及细胞内钙水平。尽管这些第二信使的产生有所增强，但1α,25(OH)2D3与其衍生物在时间和剂量依赖性方面并无显著差异。这些维生素D3化合物促进了蛋白激酶C（PKC）从胞质溶胶向细胞膜的转位。尽管在早期信号转导参数方面有这些共同特征，但只有1α,25(OH)2D3诱导了角质形成细胞分化所特有的角质包膜的形成。用佛波醇 - 12,13 - 二丁酸酯（PDBu）进行长时间预处理或用H - 7抑制该酶导致PKC下调，从而显著抑制了1α,25(OH)2D3诱导的角质包膜形成。这些发现表明，PKC对于1α,25(OH)2D3诱导的终末分化的起始是必要的，但并不充分，而且角质形成细胞分化还需要活性维生素D3特异性产生的另一种尚未明确的信号。
