Mechanism of NF-kappaB inactivation induced by survival signal withdrawal in cerebellar granule neurons

The European Journal of Neuroscience
Attila D KovácsSanjay B Maggirwar

Abstract

Activity of the transcription factor nuclear factor-kappaB (NF-kappaB) has been shown to be necessary for maintaining neuronal viability. In cultured rat cerebellar granule neurons, trophic factor withdrawal induces NF-kappaB inactivation, resulting in cell death. The exact mechanism of this inactivation, however, has not been revealed. Here we report that trophic factor deprivation in cultured cerebellar granule neurons leads to a rapid and sustained increase in the level of IkappaBalpha and IkappaBbeta, the inhibitory proteins of NF-kappaB, causing prolonged NF-kappaB inactivation. Transient NF-kappaB activation resulting in new IkappaBalpha mRNA and protein synthesis gives rise to the rapid increase of IkappaBalpha level. The importance of elevated IkappaB level in neuronal apoptosis was confirmed in transfection experiments. Ectopic expression of a stabilized form of IkappaBalpha protein promoted neuronal death. Our findings suggest a novel mode of initiation of neuronal apoptosis wherein survival signal withdrawal induces NF-kappaB to lethally turn itself off.

References

Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·S R D'MelloP Calissano
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·B KaltschmidtC Kaltschmidt
Dec 22, 1999·Oncogene·M Barkett, T D Gilmore
Mar 25, 2000·Molecular and Cellular Biology·C ChenC Gélinas
Feb 13, 2001·The Journal of Clinical Investigation·M P Mattson, S Camandola
Dec 18, 2001·Journal of Neuroscience Research·P PiccioliG Schettini
May 2, 2002·Cell·Sankar Ghosh, Michael Karin
Jul 5, 2002·Clinical Microbiology Reviews·Jorge Caamaño, Christopher A Hunter
Nov 7, 2002·The Journal of Biological Chemistry·Rosemary KiernanMonsef Benkirane
Nov 29, 2002·The EMBO Journal·Lin-feng ChenWarner C Greene
Jan 18, 2003·Brain Research. Molecular Brain Research·Alberto Chiarugi
Apr 1, 2003·Molecular and Cellular Biology·Alain Lilienbaum, Alain Israël
Jun 25, 2003·Molecular Cell·Simona SaccaniGioacchino Natoli

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Citations

May 25, 2005·Experimental Brain Research·G PollockS Saporta
Jan 7, 2006·Cell Death and Differentiation·M P Mattson, M K Meffert
Mar 29, 2014·BioMed Research International·Valeria BortolottoMariagrazia Grilli
Apr 7, 2012·Cellular and Molecular Life Sciences : CMLS·Kai KyseniusHenri J Huttunen
Mar 8, 2016·Cerebral Cortex·Sara Anna BoniniMaurizio Memo
Aug 13, 2009·Developmental Neurobiology·Laura LossiAdalberto Merighi
Oct 13, 2006·Journal of Neurochemistry·Gerardo G MackenziePatricia I Oteiza
Apr 29, 2008·Journal of Neuroscience Research·Xiaoguang ZhangSantosh R D'Mello
Oct 11, 2016·Metabolic Brain Disease·Meredith MeyerDavid A Pearce
Sep 28, 2005·Neurochemical Research·Mark P Mattson
Nov 16, 2005·The Journal of Biological Chemistry·Li Liu, Santosh R D'Mello
Jun 28, 2005·Journal of Neuropathology and Experimental Neurology·Lisa NowoslawskiKevin A Roth
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ziye SuiSanjay B Maggirwar
May 28, 2021·Frontiers in Cellular Neuroscience·Teresa Jover-MengualR Suzanne Zukin
Jun 1, 2006·Biochemical and Biophysical Research Communications·Ziye SuiSanjay B Maggirwar

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