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Zinc-induced NF-κB inhibition can be modulated by changes in the intracellular metallothionein level

Authors
 Chul Hoon Kim  ;  Joo Hee Kim  ;  Young Soo Ahn  ;  Jinu Lee 
Citation
 TOXICOLOGY AND APPLIED PHARMACOLOGY, Vol.190(2) : 189-196, 2003 
Journal Title
 TOXICOLOGY AND APPLIED PHARMACOLOGY 
ISSN
 0041-008X 
Issue Date
2003
MeSH
Dose-Response Relationship, Drug ; Feedback, Physiological/physiology* ; HeLa Cells ; Humans ; Metallothionein/genetics ; Metallothionein/metabolism* ; NF-kappa B/antagonists & inhibitors* ; Transfection ; Zinc/pharmacology*
Keywords
Zinc homeostasis ; Metallothionein ; NF-κB ; Pyrrolidine dithiocarbanate
Abstract
Metallothionein (MT), a small metal-binding protein, is involved in the regulation of cellular metal homeostasis. Sequestration and the release of metals to and from MT plays an important role in the attenuation or amplification of signal transduction. Zinc has been suggested to be an important regulator of nuclear factor κB (NF-κB). In this study, the effect of MT expression on the zinc-induced inhibition of NF-κB activity was examined. In HeLa cells, pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, and zinc itself inhibited NF-κB activity. When the cells were pretreated with MT-inducers, cadmium, or dexamethasone, PDTC did not inhibit NF-κB activity. We transfected HeLa cells with a DNA construct in which expression of MT-IIA is controlled by tet operator protein. Treatment of HeLa cells with doxycycline, a tetracycline analogue, induced the expression of MT-IIA, which attenuated the effect of PDTC on NF-κB activity. These results implicate MT in the zinc regulation of NF-κB and identify MT as one of the potential intracellular modulators of NF-κB activation.
Full Text
http://www.sciencedirect.com/science/article/pii/S0041008X03001674
DOI
10.1016/S0041-008X(03)00167-4
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Ahn, Young Soo(안영수)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114566
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