title: Biphasic effects of dithiocarbamates on the activity of nuclear factor-kappaB.
abstract: Dithiocarbamates are well-known antioxidants and nuclear factor-kappaB (NF-kappaB) inhibitors. Recently, they have been characterized as zinc ionophores. Concentration-dependent biphasic effects of dithiocarbamates on NF-kappaB activity have been widely reported. We studied the mechanism of this phenomenon in relation to Zn(2+) influx. Two dithiocarbamates, pyrrolidine dithiocarbamate and diethyldithiocarbamate, showed concentration-dependent biphasic effects in inhibiting NF-kappaB activation in cerebral endothelial cells. These unique effects of dithiocarbamates on NF-kappaB were tightly linked to their ability to elevate intracellular Zn(2+)500 microM), dithiocarbamates started to lose their ability to promote Zn(2+) influx and to inhibit NF-kappaB activation. These results might provide insight into the appropriate use of dithiocarbamates in various disorders.
authors.affiliation: Yonsei Brain Research Institute and Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: C H
authors.initials: CH
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: S J
authors.initials: SJ
authors.lastname: Moon
authors.forename: C Y
authors.initials: CY
authors.lastname: Hsu
authors.forename: J T
authors.initials: JT
authors.lastname: Seo
authors.forename: Y S
authors.initials: YS
authors.lastname: Ahn
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000098:blood supply; D004050:Ditiocarb / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000494:pharmacology*; D013859:Thiocarbamates / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D004050:Ditiocarb; D015032:Zinc