The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
Letter
Copper diethyldithiocarbamate as an inhibitor of tissue plasminogen activator synthesis in cultured human coronary endothelial cells
Tomoya FujieShiori OkinoEiko YoshidaChika YamamotoHiroshi NakaToshiyuki Kaji
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2017 Volume 42 Issue 5 Pages 553-558

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Abstract

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.

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© 2017 The Japanese Society of Toxicology
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