title: [Activation of cellular defense mechanism by organic-inorganic hybrid molecules].
abstract: Organic-inorganic hybrid molecules can exhibit biological activities by controlling the activities of their individual components. These molecules can be applied as seed/lead compounds in drug development, and can be used as molecular probes in chemical biology for the elucidation of the molecular mechanisms of biological systems. In this review, we introduce copper diethyldithiocarbamate (Cu10), a copper complex, as a compound that activates nuclear factor erythroid 2-related factor 2 (Nrf2) and induces metallothionein, which are the key cellular defense factors against toxic metals and oxidative stress in vascular endothelial cells. It was found that neither the complexes with the same ligand and other metal ions (including zinc and iron) nor the ligand alone was inactive. Therefore, both copper ion and the ligand of Cu10 are essential components for the biological functioning of the complex. In addition, Cu10 may be useful in clarifying the molecular mechanism underlying metallothionein induction in vascular endothelial cells.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Fujie
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naka
authors.forename: Chika
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shinkai
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaji
mesh_terms: D000818:Animals; D003300:Copper / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008668:Metallothionein / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
chemical_list: D051267:NF-E2-Related Factor 2; D009942:Organometallic Compounds; D003300:Copper; D008668:Metallothionein