Inhibition of NF-κB binding to DNA by chromium, cadmium, mercury, zinc, and arsenite in vitro:: Evidence of a thiol mechanism

被引:109
作者
Shumilla, JA
Wetterhahn, KE
Barchowsky, A
机构
[1] Dartmouth Med Sch, Dept Pharmacol Toxicol, Hanover, NH 03755 USA
[2] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA
关键词
NF-kappa B; binding; mercury; cadmium; arsenite; chromium;
D O I
10.1006/abbi.1997.0470
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
NF-kappa B binding to DNA in the presence of thiol-reactive metals has been explored in vitro. Gel mobility shift assays using total nuclear extracts isolated from tumor necrosis factor alpha-treated A549 cells demonstrated dose-dependent inhibition of NF-kappa B binding by chromium, cadmium, mercury, zinc, and arsenite, Maximum inhibition of binding occurred when these metals were preincubated with the nuclear proteins prior to addition of radiolabeled oligonucleotide. The potency of mercury, cadmium, and zinc for inhibiting binding closely correlated to the affinity of these metals for protein thiols, Further addition of dithiothreitol competitively blocked the effects of all of the metals, except chromium(III), on NF-kappa B binding. This study demonstrates mechanisms for metals to inhibit NF-kappa B-DNA binding through interactions with critical protein sulfhydryls. (C) 1998 Academic Press.
引用
收藏
页码:356 / 362
页数:7
相关论文
共 38 条
[21]   STRUCTURE OF THE NF-KAPPA-B P50 HOMODIMER BOUND TO DNA [J].
MULLER, CW ;
REY, FA ;
SODEOKA, M ;
VERDINE, GL ;
HARRISON, SC .
NATURE, 1995, 373 (6512) :311-317
[22]   A LABILE REPRESSOR ACTS THROUGH THE NFKB-LIKE BINDING-SITES OF THE HUMAN UROKINASE GENE [J].
NOVAK, U ;
COCKS, BG ;
HAMILTON, JA .
NUCLEIC ACIDS RESEARCH, 1991, 19 (12) :3389-3393
[23]   TRANSCRIPTION FACTORS - STRUCTURAL FAMILIES AND PRINCIPLES OF DNA RECOGNITION [J].
PABO, CO ;
SAUER, RT .
ANNUAL REVIEW OF BIOCHEMISTRY, 1992, 61 :1053-1095
[24]   METAL MUTAGENS AND CARCINOGENS EFFECTIVELY DISPLACE ACRIDINE-ORANGE FROM DNA AS MEASURED BY FLUORESCENCE POLARIZATION [J].
RICHARDSON, CL ;
VERNA, J ;
SCHULMAN, GE ;
SHIPP, K ;
GRANT, AD .
ENVIRONMENTAL MUTAGENESIS, 1981, 3 (05) :545-553
[25]   ABSENCE OF ARSENITE MUTAGENICITY IN ESCHERICHIA-COLI AND CHINESE-HAMSTER CELLS [J].
ROSSMAN, TG ;
STONE, D ;
MOLINA, M ;
TROLL, W .
ENVIRONMENTAL MUTAGENESIS, 1980, 2 (03) :371-379
[26]   REACTIVE OXYGEN INTERMEDIATES AS APPARENTLY WIDELY USED MESSENGERS IN THE ACTIVATION OF THE NF-KAPPA-B TRANSCRIPTION FACTOR AND HIV-1 [J].
SCHRECK, R ;
RIEBER, P ;
BAEUERLE, PA .
EMBO JOURNAL, 1991, 10 (08) :2247-2258
[27]   INHIBITION OF GLUTATHIONE-PEROXIDASE BY CADMIUM AND OTHER METAL-IONS [J].
SPLITTGERBER, AG ;
TAPPEL, AL .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1979, 197 (02) :534-542
[28]   REDUCTION OF CHROMIUM(VI) BY ASCORBATE LEADS TO CHROMIUM DNA-BINDING AND DNA STRAND BREAKS IN-VITRO [J].
STEARNS, DM ;
KENNEDY, LJ ;
COURTNEY, KD ;
GIANGRANDE, PH ;
PHIEFFER, LS ;
WETTERHAHN, KE .
BIOCHEMISTRY, 1995, 34 (03) :910-919
[29]   OXIDATIVE MECHANISMS IN THE TOXICITY OF METAL-IONS [J].
STOHS, SJ ;
BAGCHI, D .
FREE RADICAL BIOLOGY AND MEDICINE, 1995, 18 (02) :321-336
[30]   NF-KAPPA-B - A LESSON IN FAMILY VALUES [J].
THANOS, D ;
MANIATIS, T .
CELL, 1995, 80 (04) :529-532