Copper diethyldithiocarbamate as an inhibitor of tissue plasminogen activator synthesis in cultured human coronary endothelial cells
Copper diethyldithiocarbamate as an inhibitor of tissue plasminogen activator synthesis in cultured human coronary endothelial cells
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DOI：
10.2131/jts.42.553
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发表时间：
2017-10-01
影响因子：
2
通讯作者：
Kaji, Toshiyuki
中科院分区：
文献类型：
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作者：
Fujie, Tomoya;Okino, Shiori;Kaji, Toshiyuki
最近的发展表明，有机-无机杂化分子有可能为分析生物系统提供有用的工具。在纤维蛋白溶解的情况下，这是纤维蛋白被纤维蛋白溶酶降解的现象，纤维蛋白溶酶已从纤溶酶原通过组织纤溶酶原激活剂（t-PA）从血管内皮细胞分泌的转换，我们假设，可能有有机-无机杂合分子，可用于分析内皮纤维蛋白溶解的调节机制。在我们目前的研究中，我们发现，铜络合物二乙基二硫代氨基甲酸铜（Cu 10）降低t-PA活性的条件培养基中培养的人冠状动脉内皮细胞通过抑制t-PA的合成，而不改变合成的纤溶酶原激活物抑制剂1型，这是一种t-PA抑制剂。硫酸铜、CulO配体和具有相同CulO配体的锌/铁络合物没有表现出这样的生物活性。这些结果表明，CulO有可能提供一个有用的工具，找到替代途径，下调内皮t-PA的合成。
Recent developments have shown that organic-inorganic hybrid molecules have the potential to provide useful tools for analyzing biological systems. In the case of fibrinolysis, which is the phenomenon whereby fibrin is degraded by plasmin that has been converted from plasminogen via tissue plasminogen activator (t-PA) secreted from vascular endothelial cells, we hypothesized that there may be organic-inorganic hybrid molecules that could be used to analyze the mechanisms by which endothelial fibrinolysis is regulated. In our present study, we found that a copper complex copper diethyldithiocarbamate (Cu 10) reduces t-PA activity in a conditioned medium of cultured human coronary endothelial cells by inhibiting the t-PA synthesis without changing the synthesis of plasminogen activator inhibitor type 1, which is a t-PA inhibitor. Copper sulfate, the CulO ligand, and zinc/iron complexes with the same CulO ligand, did not exhibit such biological activity. These results indicate that CulO has the potential to provide a useful tool for finding alternative pathways that downregulate endothelial t-PA synthesis.