Biphasic effects of dithiocarbamates on the activity of nuclear factor-κB

Chul Hoon Kim; Joo Hee Kim; Seok Jun Moon; Chung Y. Hsu; Jeong Taeg Seo; Young Soo Ahn

doi:10.1016/S0014-2999(00)00109-6

Biphasic effects of dithiocarbamates on the activity of nuclear factor-κB

Chul Hoon Kim, Joo Hee Kim, Seok Jun Moon, Chung Y. Hsu, Jeong Taeg Seo, Young Soo Ahn

Department of Oral Biology

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	133-136
Number of pages	4
Journal	European Journal of Pharmacology
Volume	392
Issue number	3
DOIs	https://doi.org/10.1016/S0014-2999(00)00109-6
Publication status	Published - 2000 Mar 31

Bibliographical note

Funding 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.

All Science Journal Classification (ASJC) codes

Pharmacology

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10.1016/S0014-2999(00)00109-6

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title = "Biphasic effects of dithiocarbamates on the activity of nuclear factor-κB",

abstract = "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.",

keywords = "(Bovine), Cerebral endothelial cell, Dithiocarbamate, NF-κB (nuclear factor-κB), Zn",

author = "Kim, {Chul Hoon} and Kim, {Joo Hee} and Moon, {Seok Jun} and Hsu, {Chung Y.} and Seo, {Jeong Taeg} and Ahn, {Young Soo}",

note = "Funding 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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AU - Hsu, Chung Y.

AU - Seo, Jeong Taeg

AU - Ahn, Young Soo

N1 - Funding 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.

PY - 2000/3/31

Y1 - 2000/3/31

N2 - 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.

AB - 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.

KW - (Bovine)

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KW - NF-κB (nuclear factor-κB)

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Biphasic effects of dithiocarbamates on the activity of nuclear factor-κB

Abstract

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