Glucocorticoids Inhibit Plasminogen Activator Production by Endothelial Cells

Glucocorticoids Inhibit Plasminogen Activator Production by Endothelial Cells
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糖皮质激素抑制内皮细胞产生纤溶酶原激活剂

DOI:
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发表时间:
1983
影响因子:
6.7
通讯作者:
W. Laug
W. Laug
中科院分区:
医学2区
文献类型:
--
作者:
W. Laug

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发现牛主动脉内皮细胞(BEC)的汇合培养物分泌组织型纤溶酶原激活物(t-PA)和尿激酶型纤溶酶原激活物(u-PA)。暴露的文化,以增加浓度的地塞米松导致在时间和浓度依赖性抑制细胞和分泌u-PA。在10-8摩尔或更高的地塞米松浓度下发现u-PA的产生和分泌的完全抑制。在未经处理的BEC培养物的条件培养基中发现了分子量范围为10,000 - 20,000至> 200,000的几种不同的PA形式。在培养基中加入地塞米松(10-7摩尔)后,分子量为117,000、58,000、47,000的PA不存在,表明它们是u-PA,而分子量> 200,000和75,000的PA保持不变,表明它们是t-PA来源。具有35,000、28,000和10,000至20,000的较低分子量的PA最有可能通过有限的蛋白水解从较高分子量形式产生,因为当在蛋白酶抑制剂Trasylol存在下调节培养基时,它们不存在。因此,这两种PA类型可以在BEC中独立调节。
Summary Confluent cultures of bovine aortic endothelial cells (BEC) were found to secrete both tissue type plasminogen activator (t- PA) and urokinase type plasminogen activator (u-PA). Exposure of the cultures to increasing concentrations of dexamethasone resulted in a time and concentration dependent inhibition of cellular and secreted u-PA. Complete inhibition of u-PA production and secretion was found at dexamethasone concentrations of 10-8 molar or higher. Several distinct PA forms with molecular weights ranging from 10,000-20,000 to >200,000 were found in the conditioned medium of untreated BEC cultures. After addition of dexamethasone (10-7 molar) to the culture medium the PAs with molecular weights of 117,000, 58,000,47,000, were absent suggesting that they were u-PAs, whereas the PAs with molecular weights of >200,000 and 75,000 remained unchanged suggesting their t-PA origins. The PAs with lower molecular weights of 35,000, 28,000 and 10,000 to 20,000 were most likely generated from the higher molecular weight forms by limited proteolysis since they were absent when the medium was conditioned in the presence of the protease inhibitor Trasylol. The two PA types may therefore be independently regulated in BEC.