Copper diethyldithiocarbamate as an activator of Nrf2 in cultured vascular endothelial cells

• DOI: 10.1007/s00775-016-1337-z
• Publication Date: 2016-01-29T06:56:48Z
• Authors: Tomoya Fujie; Masaki Murakami; Eiko Yoshida; Tadashi Tachinami; Yasuhiro Shinkai; Yasuyuki Fujiwara; Chika Yamamoto; Yoshito Kumagai; Hiroshi Naka; Toshiyuki Kaji
• Keywords: 0301 basic medicine; Original Paper; NF-E2-Related Factor 2; Ligands; Biochemistry; Inorganic Chemistry; 03 medical and health sciences; Animals; Cattle; Endothelium, Vascular; Ditiocarb; Cells, Cultured; Copper

The interest in organic–inorganic hybrid molecules as molecular probes for biological systems has been growing rapidly. Such exhibit unique activities. Herein, copper(II) bis(diethyldithiocarbamate) (Cu10) was found to activate the transcription factor NF-E2-related 2 (Nrf2), which is responsible regulating antioxidant and phase II xenobiotic enzymes, vascular endothelial cells. copper complex rapidly accumulated within cells induced nuclear translocation of Nrf2, leading upregulation expression downstream proteins without cytotoxic effects. However, while bis(2-hydroxyethyl)dithiocarbamate activated ion, diethyldithiocarbamate ligand with or zinc iron failed this activity. Intracellular accumulation Cu10 higher than that Cu(II) Cu(I). While bis(dimethyldithiocarbamate) reduced by small interfering RNA (siRNA)-mediated knockdown transporter CTR1, did not affect accumulation, indicating enters via CTR1-independent mechanisms. In addition, complexes other ligands tested could suggesting intramolecular interaction between dithiocarbamate important activation factor. heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, γ-glutamylcysteine synthetase, Nrf2. It suggested Cu10-induced Nrf2 due proteasome inhibition well binding Kelch-like ECH-associated protein 1. Since effects on are diverse, may be a good probe analyze functions