Pyrithione, a zinc ionophore, inhibits NF-κB activation

被引:67
作者
Kim, CH
Kim, JH
Moon, SJ
Chung, KC
Hsu, CY
Seo, JT
Ahn, YS [1 ]
机构
[1] Yonsei Univ, Coll Med, Dept Pharmacol, Seoul 120752, South Korea
[2] Yonsei Univ, Coll Med, Yonsei Brain Res Inst, Seoul 120752, South Korea
[3] Yonsei Univ, Coll Dent, Dept Oral Biol, Seoul 120752, South Korea
[4] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
关键词
cerebral endothelial cells; nuclear factor kappa B; pyrrolidine dithiocarbamate; pyrithione; zinc;
D O I
10.1006/bbrc.1999.0814
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pyrrolidine dithiocarbamate (PDTC) suppresses NF-kappa B 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-kappa B activation, we studied the effect of pyrithione, a zinc ionophore, on NF-kappa B activation in BCECs. Pyrithione inhibited NF-kappa B activity in a time- and dose-dependent manner. Ca-EDTA, but not Zn-EDTA, prevented pyrithione inhibition of NF-kappa B 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-kappa B 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-kappa B activity in BCECs. (C) 1999 Academic Press.
引用
收藏
页码:505 / 509
页数:5
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