Fujie Tomoya, Okino Shiori, Yoshida Eiko, Yamamoto Chika, Naka Hiroshi, Kaji Toshiyuki
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho University.
J Toxicol Sci. 2017;42(5):553-558. doi: 10.2131/jts.42.553.
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 (Cu10) - 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 Cu10 ligand, and zinc/iron complexes with the same Cu10 ligand, did not exhibit such biological activity. These results indicate that Cu10 has the potential to provide a useful tool for finding alternative pathways that downregulate endothelial t-PA synthesis.
最近的研究进展表明，有机-无机杂化分子有潜力为分析生物系统提供有用的工具。以纤维蛋白溶解为例，纤维蛋白溶解是一种纤维蛋白被纤溶酶降解的现象，纤溶酶是由血管内皮细胞分泌的组织纤溶酶原激活物（t-PA）将纤溶酶原转化而来的。我们推测，可能存在可用于分析内皮细胞纤维蛋白溶解调节机制的有机-无机杂化分子。在我们目前的研究中，我们发现一种铜络合物——二乙基二硫代氨基甲酸铜（Cu10）——通过抑制t-PA的合成来降低培养的人冠状动脉内皮细胞条件培养基中的t-PA活性，而不改变1型纤溶酶原激活物抑制剂（一种t-PA抑制剂）的合成。硫酸铜、Cu10配体以及具有相同Cu10配体的锌/铁络合物均未表现出这种生物活性。这些结果表明，Cu10有潜力为寻找下调内皮细胞t-PA合成的替代途径提供有用的工具。
