Changes in calcium responsiveness and handling during keratinocyte differentiation - Potential role of the calcium receptor
Changes in calcium responsiveness and handling during keratinocyte differentiation - Potential role of the calcium receptor
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DOI：
10.1172/jci118501
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发表时间：
1996-02-15
影响因子：
15.9
通讯作者：
Pillai, S
中科院分区：
文献类型：
--
作者：
Bikle, DD;Ratnam, A;Pillai, S
细胞外钙浓度（Cao）> 0.1 mM是培养物中正常人角质形成细胞分化所需的。Cao的增加导致细胞内钙水平（Cai）的急性和持续增加，推测涉及钙从细胞内储存中释放和随后通过非特异性阳离子通道的钙内流增加。Cai的持续上升似乎是角质形成细胞分化所必需的。为了了解角质形成细胞对Cao反应的机制，我们测量了Cao对不同分化阶段角质形成细胞中Cai和钙内流的急性影响。然后，我们证明了角质形成细胞中钙受体（CaR）的存在，并确定钙诱导分化对其mRNA水平的影响。最后，我们研究了Cai在调节Cai转换为更高Cao后的初始上升和钙内流发生的非特异性阳离子通道活性中的作用。我们的数据表明，随着细胞分化和增加其基础Cai，对CaO的急性Cai反应丧失。这些数据与在低钙条件下生长的细胞中CaR mRNA水平的降低相关。然而，钙内流作为测量的Ca-45的摄取增加与分化在1.2 mM的钙，在这些细胞中的CaR mRNA的增加，以及钙诱导的非特异性阳离子通道的开放一致。我们的结论是，角质形成细胞包含一个钙调素受体，调节初始释放的蔡从细胞内存储和随后的增加，通过非特异性钙通道的钙流量。Cai水平的升高可能会关闭细胞内储存的钙的释放，同时增强通过非特异性阳离子通道的流入。角质形成细胞的分化似乎增加了CaR，这可能有助于维持分化所需的高Cai。
Extracellular calcium concentrations (Cao) > 0.1 mM are required for the differentiation of normal human keratinocytes in culture. Increments in Cao result in acute and sustained increases in the intracellular calcium level (Cai), postulated to involve both a release of calcium from intracellular stores and a subsequent increase in calcium influx through nonspecific cation channels. The sustained rise in Cai appears to be necessary for keratinocyte differentiation. To understand the mechanism by which keratinocytes respond to Cao, we measured the acute effects of Cao on Cai and calcium influx in keratinocytes at various stages of differentiation. We then demonstrated the existence of the calcium receptor (CaR) in keratinocytes and determined the effect of calcium-induced differentiation on its mRNA levels. Finally, we examined the role of Cai in regulating both the initial rise in Cai after the switch to higher Cao and the activity of the nonspecific cation channel through which calcium influx occurs. Our data indicate that the acute Cai response to Cao is lost as the cells differentiate and increase their basal Cai. These data correlated with the decrease in CaR mRNA levels in cells grown in low calcium. However, calcium influx as measured by Ca-45 uptake increased with differentiation in 1.2 mM calcium, consistent with the increase in CaR mRNA in these cells as well as the calcium-induced opening of the nonspecific cation channels. We conclude that the keratinocyte contains a CaR that regulates both the initial release of Cai from intracellular stores and the subsequent increase in calcium flux through nonspecific calcium channels. A rising level of Cai may turn off the release of calcium from intracellular stores while potentiating the influx through the nonspecific cation channels. Differentiation of keratinocytes appears to increase the CaR, which may facilitate the maintenance of the high Cai required for differentiation.