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Regulatory role of metallothionein in NF‐κB activation
Author(s) -
Sakurai Atsuko,
Hara Shuntaro,
Okano Noriko,
Kondo Yukihiro,
Inoue Jun-ichiro,
Imura Nobumasa
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00839-x
Subject(s) - transfection , metallothionein , cytoprotection , microbiology and biotechnology , nf κb , transcription factor , chemistry , tumor necrosis factor alpha , gene expression , intracellular , nfkb1 , gene , electrophoretic mobility shift assay , cell culture , regulation of gene expression , biology , signal transduction , biochemistry , oxidative stress , immunology , genetics
Metallothionein (MT), a low molecular weight, cysteine‐rich metal binding protein, has been associated with cytoprotection from heavy metals and cellular oxidants. As MT has the ability to scavenge hydroxyl radicals, MT may control intracellular redox status. In the present study, we examined whether MT regulates the activity of nuclear factor‐κB (NF‐κB), which is one of the redox‐regulated transcription factors, using the MT null embryonic cell lines established from MT null mice. We first found that tumor necrosis factor (TNF)‐induced activation of the binding of NF‐κB protein to DNA in wild type MT+/+ cells was lower than that in MT−/− cells. The NF‐κB activation in MT‐expressing cells established from MT−/− cells by the transfection of mouse MT‐I gene was also significantly lower than that in MT−/− cells. In addition, transfection of the MT gene inhibited TNF‐induced IκB degradation and suppressed NF‐κB‐dependent gene expression induced by TNF. These results demonstrate that MT may function as a negative regulator of NF‐κB activity.