Turnover of inositol phospholipids in cultured murine keratinocytes: possible involvement of inositol triphosphate in cellular differentiation.

Turnover of inositol phospholipids in cultured murine keratinocytes: possible involvement of inositol triphosphate in cellular differentiation.
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培养的鼠角质形成细胞中肌醇磷脂的周转:肌醇三磷酸可能参与细胞分化。

DOI:
10.1111/1523-1747.ep12462536
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发表时间:
1988
期刊:
The Journal of investigative dermatology
影响因子:
--
通讯作者:
Martinez,D
Martinez,D
中科院分区:
--
文献类型:
--
作者:
Tang,W;Ziboh,VA;Isseroff,R;Martinez,D

文献摘要

被引文献

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研究了肌醇磷脂(PtdIns)周转与培养的正常小鼠角质形成细胞生长分化的关系。在新培养的细胞中加入Myo-[U-14C]肌醇,在培养的最初36h内,放射性标记物线性地掺入到增殖的基底细胞的肌醇磷脂中,此后放射性标记物掺入细胞的速率下降。放射性标记掺入PtdIns的减少,尤其是高度磷酸化的PtdIns-4P和PtdIns4,5P2,与这些多磷脂的显著水解和肌醇磷酸盐(InsP和InsP3)的快速水解性释放有关。Insps的瞬时积聚与这些细胞的分化开始有关。为了确定在培养过程中处于正常增殖和分化阶段的角质形成细胞的上述观察结果是否与更同步的增殖和分化细胞群一致,我们研究了在0.09 mM Ca~(2+)和1.8 mM Ca~(2+)中PtdIns在钙调节系统中的周转情况。我们来自系统的数据显示,在从低钙到正常的细胞外钙介质切换后,预先标记的低钙增殖细胞中的PtdIns迅速降解。与这种水解相关的是INSP的快速和瞬时积累(最长60秒)。当预先标记的增殖细胞从低钙到正常细胞外钙时,没有观察到PtdIns的降解和InsP3的积聚。与这种水解相关的是INSP的快速和瞬时积累(最长60秒)。当预先标记的增殖细胞从低钙到低细胞外钙时,没有观察到PtdIns的降解和InsP3的聚集。这些结果表明,PtdIns,尤其是PtdIns4,5P2的快速水解伴随着InsP3的水解性释放,可能是启动增殖的角质形成细胞分化的信号。
The relationship between the turnover of inositol phospholipids (PtdIns) and the growth and differentiation of normal murine keratinocytes in culture was studied. Addition of myo-[U-14C] inositol to freshly plated cells resulted ma linear incorporation of radiolabel into the inositol phospholipids of the proliferating basal cells in culture during the initial 36 h, after which time the rate of radiolabel incorporation into the cells declined. The decrease in the incorporation of the radiolabel into the PtdIns, particularly the more highly phosphorylated PtdIns-4P and PtdIns4,5P2, correlated with the marked hydrolysis of these polyphosphoinositides and the rapid hydrolytic release of the inositol phosphates (InsP2and InsP3). The transient accumulation of the InsPs correlated with the onset of differentiation of these cells. To ascertain whether the above observations of keratinocytes that were undergoing normal proliferative and differentiating phases in culture are consistent with the more synchronized populations of proliferative and differentiating cells, we investigated the turnover of PtdIns in a Ca2+-regulated system of homogenous populations of proliferating mouse keratinocytes in 0.09 mM Ca2+and a differentiating population in 1.8 mM Ca2+. Our data from system revealed rapid hydrolysis of the PtdIns in the prelabeled low-Ca2+proliferating cells immediately after a switch from the low to normal extracellular Ca2+medium. Associated with this hydrolysis was the rapid and transient accumulation of the InsPs (maximum of 60 sec). The hydrolysis of the PtdIns and the accumulation of the InsP3were not observed when the prelabeled proliferating cells were switched from a low to normal extracellular Ca2+medium. Associated with this hydrolysis was the rapid and transient accumulation of the InsPs (maximum of 60 sec). The hydrolysis of the PtdIns and the acumulation of the InsP3were not observed when the prelabeled proliferating cells were switched from a low to a low extracellular Ca2+medium. These results suggest that the rapid hydrolysis of the PtdIns, particurarly PtdINs4,5P2, which was accompanied by the hydrolytic release of InsP3, could be the initiating signal to program proliferating keratinocytes into differentiation.