caa a22 4500 378858874 CHVBK 20180305123341.0 cr unu---uuuuu 161128e20031107xx s 000 0 eng 10.1515/BC.2003.166 doi (NATIONALLICENCE)gruyter-10.1515/BC.2003.166 Suboptimal Action of NF-κB in Fanconi Anemia Cells Results from Low Levels of Thioredoxin [Elektronische Daten] [M. Kontou, C. Adelfalk, M. Hirsch-Kauffmann, M. Schweiger] Electrophoretic mobility shift assays (EMSA) revealed that under standard cell culture conditions NF-κB was induced in Fanconi anemia fibroblasts in contrast to control cells. Dithiothreitol, a potent synthetic redox potential-delivering compound, when added to growing cells, prevented this induction of NF-κB and, simultaneously, chromosomal instability was reduced. Fanconi anemia cells possess low endogenous levels of the naturally occurring antioxidant thioredoxin. Transfection of Fanconi anemia cells with thioredoxin cDNA containing a nuclear localization signal prevented both spontaneous as well as mitomycin Cinduced chromosomal instability. A promotor construct with two NF-κB binding sites in front of the CAT gene induced little CAT expression in cells with low thioredoxin content in spite of induced NF-κB. In cells with higher thioredoxin content CAT expression was increased. Cotransfection of the NF-κB-dependent CAT plasmid with the Trx/nuc-plasmid into FA fibroblasts increased the CAT expression to almost that of control cells, indicating that in this model system with diminished thioredoxin content NF-κB requires thioredoxin for binding to its specific promotor. Since Fanconi anemia cells have low thioredoxin contents, NF-κB-dependent genes are expressed insufficiently. This explains part of the pathophysiological processes observed in Fanconi anemia. Copyright © 2003 by Walter de Gruyter GmbH & Co. KG Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence Kontou M. aut Adelfalk C. aut Hirsch-Kauffmann M. aut Schweiger M. aut Biological Chemistry Walter de Gruyter 384/10-11(2003-11-07), 1501-1507 1431-6730 384:10-11<1501 2003 384 bchm https://doi.org/10.1515/BC.2003.166 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2003.166 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kontou M. aut NATIONALLICENCE 700 1- Adelfalk C. aut NATIONALLICENCE 700 1- Hirsch-Kauffmann M. aut NATIONALLICENCE 700 1- Schweiger M. aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 384/10-11(2003-11-07), 1501-1507 1431-6730 384:10-11<1501 2003 384 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter