Dithiocarbamates are well-known antioxidants and nuclear factor-κB (NF-κB) inhibitors. Recently, they have been characterized as zinc ionophores. Concentration-dependent biphasic effects of dithiocarbamates on NF-κB activity have been widely reported. We studied the mechanism of this phenomenon in relation to Zn2+ influx. Two dithiocarbamates, pyrrolidine dithiocarbamate and diethyldithiocarbamate, showed concentration-dependent biphasic effects in inhibiting NF-κB activation in cerebral endothelial cells. These unique effects of dithiocarbamates on NF-κB were tightly linked to their ability to elevate intracellular Zn2+ levels. At high concentrations (>500 μM), dithiocarbamates started to lose their ability to promote Zn2+ influx and to inhibit NF-κB activation. These results might provide insight into the appropriate use of dithiocarbamates in various disorders. Copyright (C) 2000 Elsevier Science B.V.
Bibliographical noteFunding Information:
This study was supported by a grant (#HMP-98-M-5-0057) of the 1998 Good Health R&D Project, Ministry of Health and Welfare, Korea and an NIH grant, NS 28895.
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