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NF‐κB activation prevents apoptotic oxidative stress via an increase of both thioredoxin and MnSOD levels in TNFα‐treated Ewing sarcoma cells
Author(s) -
Djavaheri-Mergny Mojgan,
Javelaud Delphine,
Wietzerbin Juana,
Besançon Françoise
Publication year - 2004
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/j.febslet.2004.10.082
Subject(s) - oxidative stress , apoptosis , thioredoxin , tumor necrosis factor alpha , chemistry , superoxide dismutase , reactive oxygen species , lipid peroxidation , nf κb , kinase , signal transduction , antioxidant , microbiology and biotechnology , cancer research , biochemistry , biology , endocrinology
Repression of activation of c‐Jun N‐terminal kinase (JNK) participates in the anti‐apoptotic effect of nuclear factor‐κB (NF‐κB) in TNFα‐treated Ewing sarcoma cells. As oxidative stress is one of the most prominent activators of JNK, we investigated the relationship between TNFα‐induced NF‐κB activation and the control of oxidative stress. Inhibition of NF‐κB activation resulted in an increase in TNFα‐induced ROS production, lipid peroxidation and protein oxidation. Those ROS and lipid peroxides were both involved in TNFα‐induced apoptosis, whereas only ROS elevation triggered sustained JNK activation. TNFα increased the level of two antioxidant enzymes, thioredoxin and manganese superoxide dismutase by an NF‐κB‐dependent mechanism. Inhibition of expression or activity of these enzymes sensitized cells to TNFα‐induced apoptosis, indicating their functional role in protection from cell death. Thus, agents that inhibit activities of these enzymes may prove helpful in the treatment of Ewing tumors.