 |
 Previous Article | Next Article 
The Journal of Neuroscience, May 1, 2001, 21(9):2929-2938
How Protein Kinase C Activation Protects Nerve Cells from
Oxidative Stress-Induced Cell Death
Pamela
Maher
Department of Cell Biology, The Scripps Research Institute, La
Jolla, California 92037
Oxidative stress is implicated in the nerve cell death that occurs
in a variety of neurological disorders, and the loss of protein kinase
C (PKC) activity has been coupled to the severity of the damage. The
functional relationship between stress, PKC, and cell death is,
however, unknown. Using an immortalized hippocampal cell line that is
particularly sensitive to oxidative stress, I show that activation of
PKC by the phorbol ester tetradecanoylphorbol acetate (TPA) inhibits
cell death via the stimulation of a complex protein phosphorylation
pathway. TPA treatment leads to the rapid activation of extracellular
signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), the
inactivation of p38 mitogen-activated protein kinase (MAPK), and the
downregulation of PKC . Inhibition of either ERK or JNK activation
blocks TPA-mediated protection, whereas p38 MAPK and PKC inhibitors
block stress-induced nerve cell death. Both p38 MAPK inactivation and
JNK activation appear to be downstream of ERK because an agent that
blocks ERK activation also blocks the modulation of these other MAP
kinase family members by TPA treatment. Thus, the protection from
oxidative stress afforded nerve cells by PKC activity requires the
combined modulation of multiple enzyme pathways and suggests why the
loss of PKC activity contributes to nerve cell death.
Key words:
oxidative stress; programmed cell death; MAP kinases; protein kinase C; oxidative glutamate toxicity; reactive oxygen
species
Copyright © 2001 Society for Neuroscience 0270-6474/01/2192929-10$05.00/0
This article has been cited by other articles:
|
|
|
|
 
S. K. Venugopal, J. Chen, Y. Zhang, D. Clemens, A. Follenzi, and M. A. Zern
Role of MAPK Phosphatase-1 in Sustained Activation of JNK during Ethanol-induced Apoptosis in Hepatocyte-like VL-17A Cells
J. Biol. Chem.,
November 2, 2007;
282(44):
31900 - 31908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Zhang, A. Kanthasamy, Y. Yang, V. Anantharam, and A. Kanthasamy
Protein Kinase C{delta} Negatively Regulates Tyrosine Hydroxylase Activity and Dopamine Synthesis by Enhancing Protein Phosphatase-2A Activity in Dopaminergic Neurons
J. Neurosci.,
May 16, 2007;
27(20):
5349 - 5362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Luo and D. B. DeFranco
Opposing Roles for ERK1/2 in Neuronal Oxidative Toxicity: DISTINCT MECHANISMS OF ERK1/2 ACTION AT EARLY VERSUS LATE PHASES OF OXIDATIVE STRESS
J. Biol. Chem.,
June 16, 2006;
281(24):
16436 - 16442.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B.-H. Choi, E.-M. Hur, J.-H. Lee, D.-J. Jun, and K.-T. Kim
Protein kinase C{delta}-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death
J. Cell Sci.,
April 1, 2006;
119(7):
1329 - 1340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-Y. Choi, M.-J. Kim, C.-M. Kang, S. Bae, C.-K. Cho, J.-W. Soh, J.-H. Kim, S. Kang, H. Y. Chung, Y.-S. Lee, et al.
Activation of Bak and Bax through c-Abl-Protein Kinase C{delta}-p38 MAPK Signaling in Response to Ionizing Radiation in Human Non-small Cell Lung Cancer Cells
J. Biol. Chem.,
March 17, 2006;
281(11):
7049 - 7059.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Hui, A. L. Bauer, J. B. Striet, P. O. Schnell, and M. F. Czyzyk-Krzeska
Calcium signaling stimulates translation of HIF-{alpha} during hypoxia
FASEB J,
March 1, 2006;
20(3):
466 - 475.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Lallemend, S. Hadjab, G. Hans, G. Moonen, P. P. Lefebvre, and B. Malgrange
Activation of protein kinase C{beta}I constitutes a new neurotrophic pathway for deafferented spiral ganglion neurons
J. Cell Sci.,
October 1, 2005;
118(19):
4511 - 4525.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Minutoli, P. Antonuccio, C. Romeo, P. A. Nicotina, A. Bitto, S. Arena, F. Polito, D. Altavilla, N. Turiaco, A. Cutrupi, et al.
Evidence for a Role of Mitogen-Activated Protein Kinase 3/Mitogen-Activated Protein Kinase in the Development of Testicular Ischemia-Reperfusion Injury
Biol Reprod,
October 1, 2005;
73(4):
730 - 736.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pandolfo and B. P.C. van de Warrenburg
Spinocerebellar ataxia type 14: Opening a new door in dominant ataxia research?
Neurology,
April 12, 2005;
64(7):
1113 - 1114.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Jung, M. B. Gatch, and J. W. Simpkins
Estrogen Neuroprotection Against the Neurotoxic Effects of Ethanol Withdrawal: Potential Mechanisms
Experimental Biology and Medicine,
January 1, 2005;
230(1):
8 - 22.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R. Elliott-Hunt, B. Marsh, A. Bacon, R. Pope, P. Vanderplank, and D. Wynick
Galanin acts as a neuroprotective factor to the hippocampus
PNAS,
April 6, 2004;
101(14):
5105 - 5110.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Sagara, K. Ishige, C. Tsai, and P. Maher
Tyrphostins Protect Neuronal Cells from Oxidative Stress
J. Biol. Chem.,
September 20, 2002;
277(39):
36204 - 36215.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Levites, T. Amit, M. B. H. Youdim, and S. Mandel
Involvement of Protein Kinase C Activation and Cell Survival/ Cell Cycle Genes in Green Tea Polyphenol (-)-Epigallocatechin 3-Gallate Neuroprotective Action
J. Biol. Chem.,
August 16, 2002;
277(34):
30574 - 30580.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
