NF-kappaB activation prevents apoptotic oxidative stress via an increase of both thioredoxin and MnSOD levels in TNFalpha-treated Ewing sarcoma cells

Repression of activation of c-Jun N-terminal kinase (JNK) participates in the anti-apoptotic effect of nuclear factor-kappaB (NF-kappaB) in TNFalpha-treated Ewing sarcoma cells. As oxidative stress is one of the most prominent activators of JNK, we investigated the relationship between TNFalpha-indu...

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Bibliographic Details
Published in:FEBS letters 2004-12, Vol.578 (1-2), p.111-115
Main Authors: Djavaheri-Mergny, Mojgan, Javelaud, Delphine, Wietzerbin, Juana, Besançon, Françoise
Format: Article
Language:English
Subjects:
Adolescent
Antioxidants - metabolism
Apoptosis - physiology
Caspase 3
Caspases - metabolism
Child
Enzyme Activation
Humans
JNK Mitogen-Activated Protein Kinases - metabolism
Lipid Peroxidation
NF-kappa B - metabolism
Oxidative Stress
Reactive Oxygen Species - metabolism
Sarcoma, Ewing - metabolism
Superoxide Dismutase - metabolism
Thioredoxins - metabolism
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - metabolism
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Summary:Repression of activation of c-Jun N-terminal kinase (JNK) participates in the anti-apoptotic effect of nuclear factor-kappaB (NF-kappaB) in TNFalpha-treated Ewing sarcoma cells. As oxidative stress is one of the most prominent activators of JNK, we investigated the relationship between TNFalpha-induced NF-kappaB activation and the control of oxidative stress. Inhibition of NF-kappaB activation resulted in an increase in TNFalpha-induced ROS production, lipid peroxidation and protein oxidation. Those ROS and lipid peroxides were both involved in TNFalpha-induced apoptosis, whereas only ROS elevation triggered sustained JNK activation. TNFalpha increased the level of two antioxidant enzymes, thioredoxin and manganese superoxide dismutase by an NF-kappaB-dependent mechanism. Inhibition of expression or activity of these enzymes sensitized cells to TNFalpha-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.
ISSN:0014-5793