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

Chul Hoon Kim, Joo Hee Kim, Jinu Lee, Young Soo Ahn

Research output: Contribution to journalReview articlepeer-review

53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)189-196
Number of pages8
JournalToxicology and Applied Pharmacology
Volume190
Issue number2
DOIs
Publication statusPublished - 2003 Jul 15

Bibliographical note

Funding Information:
This study was supported by a research grant for research instructor of Yonsei University College of Medicine (1998-02).

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

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