Pyrithione, a zinc ionophore, inhibits NF-κB activation

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

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60 Citations (Scopus)

Abstract

Pyrrolidine dithiocarbamate (PDTC) suppresses NF-κB activity and exhibits cytotoxic effects in bovine cerebral endothelial cells (BCECs), and we have previously reported that these PDTC effects were accompanied by an increase in intracellular zinc levels. To further explore the role of zinc in the modulation of NF-κB activation, we studied the effect of pyrithione, a zinc ionophore, on NF-κB activation in BCECs. Pyrithione inhibited NF-κB activity in a time- and dose-dependent manner. Ca-EDTA, but not Zn-EDTA, prevented pyrithione inhibition of NF-κB activity. Pyrithione increased the intracellular zinc level within 15 min. This effect was also abolished by Ca-EDTA, but not by Zn-EDTA. The potency of pyrithione on NF-κB inhibition and zinc influx was approximately one order of magnitude more potent than PDTC. These findings establish the regulatory role of intracellular zinc levels on NF-κB activity in BCECs.

Original languageEnglish
Pages (from-to)505-509
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume259
Issue number3
DOIs
Publication statusPublished - 1999 Jun 16

Bibliographical note

Funding Information:
We thank for Dr. Guy Haegeman for providing the p(IL6κB)50hu.IL6P-luc+ plasmid. This study was supported by a grant (HMP-98-M-5-0057) of the 1998 Good Health R & D Project, Ministry of Health & Welfare, Korea, and NIH Grant NS28995.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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