Molecular mechanisms of TNFalpha cytotoxicity: activation of NF-kappaB and nuclear translocation

Experimental Cell Research
E ClaudioP S Lazo

Abstract

The murine fibrosarcoma cell line WEHI 164 is well known for its susceptibility to tumor necrosis factor (TNFalpha). We have studied the activation of the transcription factor NF-kappaB when WEHI 164 cells are challenged with TNFalpha. NF-kappaB is retained in the cytoplasm of unchallenged cells by its inhibitor IkappaB-alpha. Upon cellular stimulation, IkappaB-alpha is functionally inactivated and NF-kappaB translocated to the nucleus. The extent of the cytotoxic effect and that of nuclear translocation of NF-kappaB show the same TNFalpha dependence. TNFalpha induces a rapid and transient activation of NF-kappaB in WEHI 164 cells which is followed by a second, long lasting phase in which the amount of NF-kappaB complex in the nucleus remains at about 50% of maximum. Upon TNFalpha treatment, IkappaB-alpha is rapidly degraded. However, newly synthesized IkappaB-alpha can be demonstrated later in the cell cytosol. A persistent nuclear localization of NF-kappaB is an obligatory step for the cytotoxic effect to take place. Thus, WEHI 164 cells treated with TNFalpha for up to 6 h can be rescued as long as NF-kappa relocalizes to the cytoplasm in its inactive form. On the other hand, TNFalpha treatments as short as 15 min cause the c...Continue Reading

Citations

Jul 2, 2002·American Journal of Respiratory Cell and Molecular Biology·Evelyne GozalMitchell Friedman
Mar 22, 2005·European Journal of Haematology·N Sae-UngK Muta
Oct 23, 2003·The Journal of Biological Chemistry·Federica GambelliLuis A Ortiz
Dec 17, 1997·Nature Genetics·S R KleebergerK J Holroyd
Jun 20, 2018·Scandinavian Journal of Pain·Elisabeth Hansson
Apr 8, 2010·Free Radical Research·Geou-Yarh Liou, Peter Storz
Sep 22, 2001·The Journal of Biological Chemistry·J F KurlandR E Meyn
Apr 25, 2006·The Journal of Biological Chemistry·Yinfei TanPeter A Greer
Jul 18, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Bruno NeuChristian Prinz
Jul 12, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jun YinMin Won Lee
May 24, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S TomekM Krainer

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