Increase in cytosolic calcium upregulates the synthesis of type 1 plasminogen activator inhibitor in the human histiocytic cell line U937.
Increase in cytosolic calcium upregulates the synthesis of type 1 plasminogen activator inhibitor in the human histiocytic cell line U937.
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细胞质钙的增加上调人组织细胞系 U937 中 1 型纤溶酶原激活剂抑制剂的合成。
DOI：
10.1182/blood.v87.1.162.162
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发表时间：
1996
期刊：
影响因子：
20.3
通讯作者：
G. Nalbone
中科院分区：
文献类型：
--
作者：
F. Peiretti;C. Fossat;F. Anfosso;M. Alessi;M. Henry;I. Juhan;G. Nalbone
在U937组织细胞系中，我们研究了含或不含肿瘤坏死因子α (TNF)的钙动员剂对纤溶酶原激活物抑制剂1型（PAI-1）合成的调节作用。用离子载体A23187和thapsigarin刺激培养的U937细胞，加或不加TNF。从细胞内钙动员、培养基中PAI-1的积累和PAI-1 mRNA的表达等方面分析了这种反应。研究扩展到尿激酶（uPA）的分泌及其受体（uPAR）的表面表达。使用Fluo-3作为钙指示染料来测量胞质钙动员，我们通过流式细胞术显示两种药物都以剂量依赖的方式动员钙。TNF引起轻微的钙动员，这也是通过数字成像显微镜观察到的。TNF与钙动员剂的关联增强了钙的动员。两种钙动员剂均在18小时诱导培养基中PAI-1的剂量依赖性积累，而uPA不受影响。TNF单独诱导PAI-1的积累比uPA更明显。TNF与这些药物的关联诱导了PAI-1反应，这种反应超过了两者的相加，而uPA的分泌没有增强。流式细胞术检测uPAR的膜表达，仅钙动员剂有轻微增强的趋势。所有处理均导致刺激后3小时PAI-1 mRNA水平显著升高，当钙动员剂存在时，这一现象非常明显。U937细胞在无钙培养基中孵育，完全阻止了钙动员剂诱导的PAI-1 mRNA的表达和积累，在较小程度上阻止了TNF诱导的PAI-1的表达和积累。PAI-1 mRNA表达的增加不需要从头合成蛋白质，因为环己亚胺不抑制钙动员剂诱导的PAI-1 mRNA的增加。综上所述，在U937细胞中，钙触发一条上调PAI-1合成的通路，并与tnf诱导的刺激PAI-1合成的通路正相互作用。由于uPA和uPAR受到不同程度的影响，这表明细胞质钙的增加导致细胞周蛋白水解减少。
In the U937 histiocytic cell line, we investigated the effect of calcium-mobilizing agents with or without tumor necrosis factor-alpha (TNF) on the regulation of the synthesis of plasminogen activator inhibitor-type 1 (PAI-1). Cultured U937 cells were stimulated with ionophore A23187 and thapsigargin with or without TNF. The response was analyzed in terms of cytosolic calcium mobilization, PAI-1 accumulation in the medium, and PAI-1 mRNA expression. The study was extended to urokinase (uPA) secretion and surface expression of its receptor (uPAR). Using Fluo-3 as a calcium-indicator dye to measure cytosolic calcium mobilization, we showed by flow cytometry that both agents mobilized calcium in a dose-dependent manner. TNF provoked a slight calcium mobilization that was also observed by digital imaging microscopy. Association of TNF with the calcium-mobilizing agents potentiated the calcium mobilization. Both calcium-mobilizing agents induced at 18 hours a dose-dependent accumulation of PAI-1 in culture medium, whereas uPA was not affected. TNF alone induced a more marked accumulation of PAI-1 than of uPA. Association of TNF with the agents induced a PAI-1 response that was more than additive of the two, whereas the secretion of uPA was not enhanced. Membrane expression of uPAR, measured by flow cytometry, tended to be slightly augmented by the calcium-mobilizing agents only. All the treatments resulted in a significant increase in PAI-1 mRNA level at 3 hours after the stimulation, which was very marked when calcium-mobilizing agents were present. Incubation of U937 cells in a calcium-free medium totally prevented both the mRNA expression and accumulation of PAI-1 induced by calcium-mobilizing agents and, to lesser extent, that induced by TNF. The increase in PAI-1 mRNA expression did not require de novo protein synthesis, as cycloheximide did not suppress the increase in PAI-1 mRNA induced by calcium-mobilizing agents. It is concluded that, in U937 cells, calcium triggers a pathway that upregulates PAI-1 synthesis and positively interacts with the TNF-induced pathway that stimulates PAI-1 synthesis. As uPA and uPAR were differently affected, it is suggested that an increase in cytosolic calcium leads to a reduced pericellular proteolysis.
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DOI：
--
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期刊：
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DOI：
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发表时间：
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作者：
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DOI：
10.1210/mend.6.1.1738371
发表时间：
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期刊：
Molecular endocrinology (Baltimore, Md.)
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10.1073/pnas.92.5.1614
发表时间：
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