Regulatory role of metallothionein in NF‐κB activation

FEBS Letters

Sakurai, Atsuko²  Imura, Nobumasa²  Inoue, Jun-ichiro³  Kondo, Yukihiro¹  Okano, Noriko²  Hara, Shuntaro² 

[1] Department of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan;Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan;Department of Oncology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

关键词: Metallothionein;    Nuclear factor-κB;    Redox status;    Antioxidant;    NF-κB;    nuclear factor-κB;    TNF;    tumor necrosis factor;    ROS;    reactive oxygen species;    MT;    metallothionein;    SV40;    simian virus 40;    DMEM;    Dulbecco's modified Eagle's medium;    FCS;    fetal calf serum;    mMT-I;    mouse MT-I;   

DOI  :  10.1016/S0014-5793(99)00839-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown