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NF‐κB activation but not PI3K/Akt is required for dexamethasone dependent protection against TNF‐α cytotoxicity in L929 cells
Author(s) -
Mendoza-Milla Criselda,
Rodríguez Catalina Machuca,
Alarcón Emilio Córdova,
Bernal Adriana Estrada,
Toledo-Cuevas E. Mayra,
Martínez Eduardo Martínez,
Dehesa Alejandro Zentella
Publication year - 2005
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.2005.05.081
Subject(s) - xiap , pi3k/akt/mtor pathway , tumor necrosis factor alpha , dexamethasone , programmed cell death , cytotoxicity , protein kinase b , nf κb , chemistry , apoptosis , microbiology and biotechnology , nfkb1 , cancer research , biology , biochemistry , immunology , in vitro , caspase , endocrinology , transcription factor , gene
Tumor necrosis factor alpha (TNF‐α) is one of the best‐described cell death promoters. In murine L929 fibroblasts, dexamethasone inhibits TNF‐α‐induced cytotoxicity. Since phosphatidyl inositol 3 kinase (PI3K) and nuclear factor kappa B (NF‐κB) proteins regulate several survival pathways, we evaluated their participation in dexamethasone protection against TNF‐α cell death. We interfered with these pathways by overexpressing a negative dominant mutant of PI3K or a non‐degradable mutant of inhibitor of NF‐κB alpha (IκBα) (the cytoplasmic inhibitor of NF‐κB) in L929 cells. The mutant IκB, but not the mutant PI3K, abrogated dexamethasone‐mediated protection. The loss of dexamethasone protection was associated with a diminished accumulation in XIAP and c‐IAP proteins.