 |
 Previous Article | Next Article 
Volume 17, Number 24,
Issue of December 15, 1997
pp. 9656-9666
Analysis of the Mechanism of Loss of Trophic Factor Dependence
Associated with Neuronal Maturation: A Phenotype Indistinguishable from
Bax Deletion
Received Aug. 7, 1997; revised Sept. 24, 1997; accepted Oct. 6, 1997.
Rachael M. Easton1, 2,
Thomas L. Deckwerth1, 2,
Alexander Sh. Parsadanian1, and
Eugene M. Johnson Jr1, 2
Departments of 1 Neurology and 2 Molecular
Biology and Pharmacology, Washington University School of Medicine, Saint Louis, Missouri 63110
During development, sympathetic neurons are critically dependent on
nerve growth factor (NGF) for survival. Neurons isolated from the
superior cervical ganglia (SCG) of embryonic rodents and maintained for
1 week in vitro undergo programmed cell death in
response to NGF deprivation. As the cells mature in
vitro and in vivo, however, these neurons
develop a resistance to NGF deprivation and become much less acutely
dependent on NGF for survival. Using an in vitro model
of neuronal maturation, we confirmed that SCG neurons maintained in
culture for 3-4 weeks did not experience a dramatic loss in viability
after NGF removal, yet they did undergo the initial biochemical and
genetic changes elicited by NGF deprivation of young neurons. NGF
deprivation of mature neurons produced rapid decreases in glucose
uptake and protein and RNA synthesis rates, increased phosphorylation
of c-Jun, and an increase in c-jun mRNA. Mature neurons,
however, experienced a block in the cell death program before the final
stages of the pathway activated in young neurons, which includes the
induction of c-fos mRNA and characteristic apoptotic
nuclear changes. This maturation-induced block was indistinguishable by
these criteria from the block produced by Bax
deficiency. Expression of Bax in mature neurons restored
the apoptotic pathway, such that after NGF removal,
Bax-overexpressing mature neurons resumed the apoptotic
program, including the induction of c-Fos and passage through a
caspase checkpoint. Thus, a block in the apoptotic program at or near
the BAX checkpoint accounts for the decreased dependence of mature
neurons on neurotrophic factor to maintain survival.
Key words:
neuronal maturation;
trophic factor dependence;
neuronal
cell death;
BAX;
gene expression;
neuronal metabolism
This article has been cited by other articles:
|
|
|
|
 
K. M. Wright, M. I. Smith, L. Farrag, and M. Deshmukh
Chromatin modification of Apaf-1 restricts the apoptotic pathway in mature neurons
J. Cell Biol.,
December 3, 2007;
179(5):
825 - 832.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Samuel, H. Wang, V. Siddharthan, J. D. Morrey, and M. S. Diamond
Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis
PNAS,
October 23, 2007;
104(43):
17140 - 17145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Samuel, K. Whitby, B. C. Keller, A. Marri, W. Barchet, B. R. G. Williams, R. H. Silverman, M. Gale Jr., and M. S. Diamond
PKR and RNase L Contribute to Protection against Lethal West Nile Virus Infection by Controlling Early Viral Spread in the Periphery and Replication in Neurons
J. Virol.,
July 15, 2006;
80(14):
7009 - 7019.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Pierchala, J. Milbrandt, and E. M. Johnson Jr
Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation.
J. Neurosci.,
March 8, 2006;
26(10):
2777 - 2787.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Samuel and M. S. Diamond
Alpha/Beta Interferon Protects against Lethal West Nile Virus Infection by Restricting Cellular Tropism and Enhancing Neuronal Survival
J. Virol.,
November 1, 2005;
79(21):
13350 - 13361.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Sun, T. W. Gould, J. Newbern, C. Milligan, S. Y. Choi, H. Kim, and R. W. Oppenheim
Phosphorylation of c-Jun in Avian and Mammalian Motoneurons In Vivo during Programmed Cell Death: An Early Reversible Event in the Apoptotic Cascade
J. Neurosci.,
June 8, 2005;
25(23):
5595 - 5603.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. S. Walsh, N. Orike, D. R. Kaplan, and F. D. Miller
The Invulnerability of Adult Neurons: A Critical Role for p73
J. Neurosci.,
October 27, 2004;
24(43):
9638 - 9647.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T.-J. Huang, S. A. Price, L. Chilton, N. A. Calcutt, D. R. Tomlinson, A. Verkhratsky, and P. Fernyhough
Insulin Prevents Depolarization of the Mitochondrial Inner Membrane in Sensory Neurons of Type 1 Diabetic Rats in the Presence of Sustained Hyperglycemia
Diabetes,
August 1, 2003;
52(8):
2129 - 2136.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Kirkland, J. A. Windelborn, J. M. Kasprzak, and J. L. Franklin
A Bax-Induced Pro-Oxidant State Is Critical for Cytochrome c Release during Programmed Neuronal Death
J. Neurosci.,
August 1, 2002;
22(15):
6480 - 6490.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Windebank and E. Mcdonald
Book Review: Cell Death in the Peripheral Nervous System: Potential Rescue Strategies
Neuroscientist,
February 1, 2002;
8(1):
62 - 72.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. A. Harris, M. Deshmukh, B. Tsui-Pierchala, A. C. Maroney, and E. M. Johnson Jr
Inhibition of the c-Jun N-Terminal Kinase Signaling Pathway by the Mixed Lineage Kinase Inhibitor CEP-1347 (KT7515) Preserves Metabolism and Growth of Trophic Factor-Deprived Neurons
J. Neurosci.,
January 1, 2002;
22(1):
103 - 113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Xia, P. A. Lampe, M. Deshmukh, A. Yang, B. S. Brown, S. M. Rothman, E. M. Johnson Jr, and S. P. Yu
Multiple Channel Interactions Explain the Protection of Sympathetic Neurons from Apoptosis Induced by Nerve Growth Factor Deprivation
J. Neurosci.,
January 1, 2002;
22(1):
114 - 122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Kirkland and J. L. Franklin
Evidence for Redox Regulation of Cytochrome c Release during Programmed Neuronal Death: Antioxidant Effects of Protein Synthesis and Caspase Inhibition
J. Neurosci.,
March 15, 2001;
21(6):
1949 - 1963.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. C. Fletcher, L. Xue, S. K. Passingham, and A. M. Tolkovsky
Death Commitment Point Is Advanced by Axotomy in Sympathetic Neurons
J. Cell Biol.,
August 21, 2000;
150(4):
741 - 754.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. H. Han and D. M. Holtzman
BDNF Protects the Neonatal Brain from Hypoxic-Ischemic Injury In Vivo via the ERK Pathway
J. Neurosci.,
August 1, 2000;
20(15):
5775 - 5781.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. I. Savitz and J. A. Kessler
Leukemia Inhibitory Factor Requires Concurrent p75LNTR Signaling to Induce Apoptosis of Cultured Sympathetic Neurons
J. Neurosci.,
June 1, 2000;
20(11):
4198 - 4205.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. V. Putcha, M. Deshmukh, and E. M. Johnson Jr.
Inhibition of Apoptotic Signaling Cascades Causes Loss of Trophic Factor Dependence during Neuronal Maturation
J. Cell Biol.,
May 29, 2000;
149(5):
1011 - 1018.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Hicks and J. Sahel
The Implications of Rod-Dependent Cone Survival for Basic and Clinical Research
Invest. Ophthalmol. Vis. Sci.,
December 1, 1999;
40(13):
3071 - 3074.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Katai and N. Yoshimura
Apoptotic Retinal Neuronal Death by Ischemia-Reperfusion Is Executed by Two Distinct Caspase Family Proteases
Invest. Ophthalmol. Vis. Sci.,
October 1, 1999;
40(11):
2697 - 2705.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Tsui-Pierchala and D. D. Ginty
Characterization of an NGF-P-TrkA Retrograde-Signaling Complex and Age-Dependent Regulation of TrkA Phosphorylation in Sympathetic Neurons
J. Neurosci.,
October 1, 1999;
19(19):
8207 - 8218.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. V. Putcha, M. Deshmukh, and E. M. Johnson Jr
BAX Translocation Is a Critical Event in Neuronal Apoptosis: Regulation by Neuroprotectants, BCL-2, and Caspases
J. Neurosci.,
September 1, 1999;
19(17):
7476 - 7485.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Canete-Soler, D. G. Silberg, M. D. Gershon, and W. W. Schlaepfer
Mutation in Neurofilament Transgene Implicates RNA Processing in the Pathogenesis of Neurodegenerative Disease
J. Neurosci.,
February 15, 1999;
19(4):
1273 - 1283.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Aloyz, S. X. Bamji, C. D. Pozniak, J. G. Toma, J. Atwal, D. R. Kaplan, and F. D. Miller
P53 Is Essential for Developmental Neuron Death as Regulated by the TrkA and p75 Neurotrophin Receptors
J. Cell Biol.,
December 14, 1998;
143(6):
1691 - 1703.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Vogelbaum, J. X. Tong, and K. M. Rich
Developmental Regulation of Apoptosis in Dorsal Root Ganglion Neurons
J. Neurosci.,
November 1, 1998;
18(21):
8928 - 8935.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sh. Parsadanian, Y. Cheng, C. R. Keller-Peck, D. M. Holtzman, and W. D. Snider
Bcl-xL is an Antiapoptotic Regulator for Postnatal CNS Neurons
J. Neurosci.,
February 1, 1998;
18(3):
1009 - 1019.
[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]
|
|
|
|
|
|
|
N. Orike, G. Middleton, E. Borthwick, V. Buchman, T. Cowen, and A. M. Davies
Role of PI 3-kinase, Akt and Bcl-2-related proteins in sustaining the survival of neurotrophic factor-independent adult sympathetic neurons
J. Cell Biol.,
September 3, 2001;
154(5):
995 - 1006.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
