 |
 Previous Article | Next Article 
The Journal of Neuroscience, December 15, 1998, 18(24):10356-10365
Nerve Growth Factor-Dependent Activation of NF- B Contributes
to Survival of Sympathetic Neurons
Sanjay B.
Maggirwar1,
Patrick D.
Sarmiere2,
Stephen
Dewhurst1, 3, and
Robert S.
Freeman2
Departments of 1 Microbiology and Immunology,
2 Pharmacology and Physiology, and 3 Cancer
Center, University of Rochester Medical Center, Rochester, New York
14642
Neurotrophins activate multiple signaling pathways in neurons.
However, the precise roles of these signaling molecules in cell
survival are not well understood. In this report, we show that nerve
growth factor (NGF) activates the transcription factors NF- B and
AP-1 in cultured sympathetic neurons. Activated NF-B complexes were
shown to consist of heterodimers of p50 and Rel proteins (RelA, as well
as c-Rel), and NF-B activation was found to occur independently of
de novo protein synthesis but in a manner that required
the action of the proteasome complex. Treatment with the NF-B
inhibitory peptide SN50 in the continuous presence of NGF resulted in
dose-dependent induction of cell death. Under the conditions used, SN50
was shown to selectively inhibit NF-B activation but not the
activation of other cellular transcription factors such as AP-1 and
cAMP response element-binding protein. Cells treated with SN50
exhibited morphological and biochemical hallmarks of apoptosis, and the
kinetics of cell killing were accelerated relative to death induced by
NGF withdrawal. Finally, experiments were conducted to test directly
whether NF-B could act as a survival factor for NGF-deprived
neurons. Microinjection of cells with an expression plasmid encoding
NF-B (c-Rel) resulted in enhanced neuronal survival after withdrawal
of NGF, whereas cells that were transfected with a vector encoding a
mutated derivative of c-Rel lacking the transactivation domain
underwent cell death to the same extent as control cells. Together,
these findings suggest that the activation of NF-B/Rel transcription
factors may contribute to the survival of NGF-dependent sympathetic neurons.
Key words:
rat; neuron; apoptosis; cell death; NF-B; transcription factor
Copyright © 1998 Society for Neuroscience 0270-6474/98/182410356-10$05.00/0
This article has been cited by other articles:
|
|
|
|
 
F. Lebrun-Julien, L. Duplan, V. Pernet, I. Osswald, P. Sapieha, P. Bourgeois, K. Dickson, D. Bowie, P. A. Barker, and A. Di Polo
Excitotoxic Death of Retinal Neurons In Vivo Occurs via a Non-Cell-Autonomous Mechanism
J. Neurosci.,
April 29, 2009;
29(17):
5536 - 5545.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yao, F. Peng, N. Dhillon, S. Callen, S. Bokhari, L. Stehno-Bittel, S. O. Ahmad, J. Q. Wang, and S. Buch
Involvement of TRPC Channels in CCL2-Mediated Neuroprotection against Tat Toxicity
J. Neurosci.,
February 11, 2009;
29(6):
1657 - 1669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Niederberger and G. Geisslinger
The IKK-NF-{kappa}B pathway: a source for novel molecular drug targets in pain therapy?
FASEB J,
October 1, 2008;
22(10):
3432 - 3442.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Gallagher, H. Gutierrez, N. Gavalda, G. O'Keeffe, R. Hay, and A. M. Davies
Nuclear Factor-{kappa}B Activation via Tyrosine Phosphorylation of Inhibitor {kappa}B-{alpha} Is Crucial for Ciliary Neurotrophic Factor-Promoted Neurite Growth from Developing Neurons
J. Neurosci.,
September 5, 2007;
27(36):
9664 - 9669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. L. Chen, P.-Y. Law, and H. H. Loh
Sustained Activation of Phosphatidylinositol 3-Kinase/Akt/Nuclear Factor {kappa}B Signaling Mediates G Protein-coupled {delta}-Opioid Receptor Gene Expression
J. Biol. Chem.,
February 10, 2006;
281(6):
3067 - 3074.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Camandola, R. G. Cutler, D. S. Gary, O. Milhavet, and M. P. Mattson
Suppression of Calcium Release from Inositol 1,4,5-Trisphosphate-sensitive Stores Mediates the Anti-apoptotic Function of Nuclear Factor-{kappa}B
J. Biol. Chem.,
June 10, 2005;
280(23):
22287 - 22296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Wang, F. Gigliotti, S. Maggirwar, C. Johnston, J. N. Finkelstein, and T. W. Wright
Pneumocystis carinii Activates the NF-{kappa}B Signaling Pathway in Alveolar Epithelial Cells
Infect. Immun.,
May 1, 2005;
73(5):
2766 - 2777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Planavila, J. C. Laguna, and M. Vazquez-Carrera
Nuclear Factor-{kappa}B Activation Leads to Down-regulation of Fatty Acid Oxidation during Cardiac Hypertrophy
J. Biol. Chem.,
April 29, 2005;
280(17):
17464 - 17471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Xie, R. S. Johnson, and R. S. Freeman
Inhibition of NGF deprivation-induced death by low oxygen involves suppression of BIMEL and activation of HIF-1
J. Cell Biol.,
March 14, 2005;
168(6):
911 - 920.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Fernyhough, D. R. Smith, J. Schapansky, R. Van Der Ploeg, N. J. Gardiner, C. W. Tweed, A. Kontos, L. Freeman, T. D. Purves-Tyson, and G. W. Glazner
Activation of Nuclear Factor-{kappa}B via Endogenous Tumor Necrosis Factor {alpha} Regulates Survival of Axotomized Adult Sensory Neurons
J. Neurosci.,
February 16, 2005;
25(7):
1682 - 1690.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Rojo, M. Salinas, D. Martin, R. Perona, and A. Cuadrado
Regulation of Cu/Zn-Superoxide Dismutase Expression via the Phosphatidylinositol 3 Kinase/Akt Pathway and Nuclear Factor-{kappa}B
J. Neurosci.,
August 18, 2004;
24(33):
7324 - 7334.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Pierchala, R. C. Ahrens, A. J. Paden, and E. M. Johnson Jr.
Nerve Growth Factor Promotes the Survival of Sympathetic Neurons through the Cooperative Function of the Protein Kinase C and Phosphatidylinositol 3-Kinase Pathways
J. Biol. Chem.,
July 2, 2004;
279(27):
27986 - 27993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Aleyasin, S. P. Cregan, G. Iyirhiaro, M. J. O'Hare, S. M. Callaghan, R. S. Slack, and D. S. Park
Nuclear Factor-{kappa}B Modulates the p53 Response in Neurons Exposed to DNA Damage
J. Neurosci.,
March 24, 2004;
24(12):
2963 - 2973.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Bhakar, L.-L. Tannis, C. Zeindler, M. P. Russo, C. Jobin, D. S. Park, S. MacPherson, and P. A. Barker
Constitutive Nuclear Factor-kappa B Activity Is Required for Central Neuron Survival
J. Neurosci.,
October 1, 2002;
22(19):
8466 - 8475.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Qin, B. Camoretti-Mercado, L. Blokh, C. G. Long, F. D. Ko, and K. J. Hamann
Fas Resistance of Leukemic Eosinophils Is Due to Activation of NF-{kappa}B by Fas Ligation
J. Immunol.,
October 1, 2002;
169(7):
3536 - 3544.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Oda, A. Ueda, N. Shimizu, H. Handa, and T. Kasahara
Suppression of Monocyte Chemoattractant Protein 1, But Not IL-8, by Alprazolam: Effect of Alprazolam on c-Rel/p65 and c-Rel/p50 Binding to the Monocyte Chemoattractant Protein 1 Promoter Region
J. Immunol.,
September 15, 2002;
169(6):
3329 - 3335.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Meng, L. Liu, P. C. Chin, and S. R. D'Mello
Akt Is a Downstream Target of NF-kappa B
J. Biol. Chem.,
August 9, 2002;
277(33):
29674 - 29680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pizzi, F. Goffi, F. Boroni, M. Benarese, S. E. Perkins, H.-C. Liou, and P. Spano
Opposing Roles for NF-kappa B/Rel Factors p65 and c-Rel in the Modulation of Neuron Survival Elicited by Glutamate and Interleukin-1beta
J. Biol. Chem.,
May 31, 2002;
277(23):
20717 - 20723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. K. Acquaah-Mensah, J. P. Kehrer, and S. W. Leslie
In Utero Ethanol Suppresses Cerebellar Activator Protein-1 and Nuclear Factor-kappa B Transcriptional Activation in a Rat Fetal Alcohol Syndrome Model
J. Pharmacol. Exp. Ther.,
April 1, 2002;
301(1):
277 - 283.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Muller, A. Morotti, and C. Ponzetto
Activation of NF-{kappa}B Is Essential for Hepatocyte Growth Factor-Mediated Proliferation and Tubulogenesis
Mol. Cell. Biol.,
February 15, 2002;
22(4):
1060 - 1072.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Fiorentini, N. Guerra, M. Facchetti, A. Finardi, L. Tiberio, L. Schiaffonati, P. Spano, and C. Missale
Nerve Growth Factor Regulates Dopamine D2 Receptor Expression in Prolactinoma Cell Lines via p75NGFR-Mediated Activation of Nuclear Factor-{kappa}B
Mol. Endocrinol.,
February 1, 2002;
16(2):
353 - 366.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yabe, D. Wilson, and J. P. Schwartz
NFkappa B Activation Is Required for the Neuroprotective Effects of Pigment Epithelium-derived Factor (PEDF) on Cerebellar Granule Neurons
J. Biol. Chem.,
November 9, 2001;
276(46):
43313 - 43319.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Tsavachidou, W. Podrzucki, J. Seykora, and S. L. Berger
Gene Array Analysis Reveals Changes in Peripheral Nervous System Gene Expression following Stimuli That Result in Reactivation of Latent Herpes Simplex Virus Type 1: Induction of Transcription Factor Bcl-3
J. Virol.,
October 15, 2001;
75(20):
9909 - 9917.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Blondeau, C. Widmann, M. Lazdunski, and C. Heurteaux
Activation of the Nuclear Factor-{kappa}B Is a Key Event in Brain Tolerance
J. Neurosci.,
July 1, 2001;
21(13):
4668 - 4677.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. T. Bui, A. Livolsi, J.-F. Peyron, and J. H.M. Prehn
Activation of Nuclear Factor {kappa}B and bcl-x Survival Gene Expression by Nerve Growth Factor Requires Tyrosine Phosphorylation of I{kappa}B{alpha}
J. Cell Biol.,
February 20, 2001;
152(4):
753 - 764.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bibel and Y.-A. Barde
Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system
Genes & Dev.,
December 1, 2000;
14(23):
2919 - 2937.
[Full Text]
|
|
|
|
|
|
|
E. D. Foehr, X. Lin, A. O'Mahony, R. Geleziunas, R. A. Bradshaw, and W. C. Greene
NF-kappa B Signaling Promotes Both Cell Survival and Neurite Process Formation in Nerve Growth Factor-Stimulated PC12 Cells
J. Neurosci.,
October 15, 2000;
20(20):
7556 - 7563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Gentry, P. Casaccia-Bonnefil, and B. D. Carter
Nerve Growth Factor Activation of Nuclear Factor kappa B through Its p75 Receptor Is an Anti-apoptotic Signal in RN22 Schwannoma Cells
J. Biol. Chem.,
March 10, 2000;
275(11):
7558 - 7565.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Middleton, M. Hamanoue, Y. Enokido, S. Wyatt, D. Pennica, E. Jaffray, R. T. Hay, and A. M. Davies
Cytokine-induced Nuclear Factor Kappa B Activation Promotes the Survival of Developing Neurons
J. Cell Biol.,
January 24, 2000;
148(1):
325 - 332.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
P. Ernfors
Nuclear Factor-{kappa}B to the Rescue of Cytokine-induced Neuronal Survival
J. Cell Biol.,
January 24, 2000;
148(2):
223 - 226.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Middleton, M. Hamanoue, Y. Enokido, S. Wyatt, D. Pennica, E. Jaffray, R. T. Hay, and A. M. Davies
Cytokine-induced Nuclear Factor Kappa B Activation Promotes the Survival of Developing Neurons
J. Cell Biol.,
January 24, 2000;
148(2):
325 - 332.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Yu, D. Zhou, A. J. Bruce-Keller, M. S. Kindy, and M. P. Mattson
Lack of the p50 Subunit of Nuclear Factor-kappa B Increases the Vulnerability of Hippocampal Neurons to Excitotoxic Injury
J. Neurosci.,
October 15, 1999;
19(20):
8856 - 8865.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Huttunen, C. Fages, and H. Rauvala
Receptor for Advanced Glycation End Products (RAGE)-mediated Neurite Outgrowth and Activation of NF-kappa B Require the Cytoplasmic Domain of the Receptor but Different Downstream Signaling Pathways
J. Biol. Chem.,
July 9, 1999;
274(28):
19919 - 19924.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Crowder and R. S. Freeman
Glycogen Synthase Kinase-3beta Activity Is Critical for Neuronal Death Caused by Inhibiting Phosphatidylinositol 3-Kinase or Akt but Not for Death Caused by Nerve Growth Factor Withdrawal
J. Biol. Chem.,
October 27, 2000;
275(44):
34266 - 34271.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Daily, A. Vlamis-Gardikas, D. Offen, L. Mittelman, E. Melamed, A. Holmgren, and A. Barzilai
Glutaredoxin Protects Cerebellar Granule Neurons from Dopamine-induced Apoptosis by Activating NF-kappa B via Ref-1
J. Biol. Chem.,
January 5, 2001;
276(2):
1335 - 1344.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. W. Glazner, S. Camandola, J. D. Geiger, and M. P. Mattson
Endoplasmic Reticulum D-myo-Inositol 1,4,5-Trisphosphate-sensitive Stores Regulate Nuclear Factor-kappa B Binding Activity in a Calcium-independent Manner
J. Biol. Chem.,
June 15, 2001;
276(25):
22461 - 22467.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Barber, M. Nakamura, E. B. Wolpert, C. E. N. Reiter, G. M. Seigel, D. A. Antonetti, and T. W. Gardner
Insulin Rescues Retinal Neurons from Apoptosis by a Phosphatidylinositol 3-Kinase/Akt-mediated Mechanism That Reduces the Activation of Caspase-3
J. Biol. Chem.,
August 24, 2001;
276(35):
32814 - 32821.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
