 |
 Previous Article | Next Article 
The Journal of Neuroscience, March 15, 2000, 20(6):2094-2103
Exacerbated Responses to Oxidative Stress by an Na+
Load in Isolated Nerve Terminals: the Role of ATP Depletion and
Rise of [Ca2+]i
Christos
Chinopoulos,
Laszlo
Tretter,
Adrienn
Rozsa, and
Vera
Adam-Vizi
Department of Medical Biochemistry, Neurochemical Group, Semmelweis
University of Medicine, Budapest H-1444, Hungary
We have explored the consequences of a
[Na+]i load and oxidative stress in
isolated nerve terminals. The Na+ load was achieved
by veratridine (5-40 µM), which allows
Na+ entry via a voltage-operated
Na+ channel, and oxidative stress was induced by
hydrogen peroxide (0.1-0.5 mM). Remarkably, neither the
[Na+]i load nor exposure to
H2O2 had any major effect on
[Ca2+]i, mitochondrial membrane
potential (  m), or ATP level. However, the combination of an
Na+ load and oxidative stress caused ATP depletion,
a collapse of m, and a progressive deregulation of
[Ca2+]i and
[Na+]i homeostasis. The decrease in
the ATP level was unrelated to an increase in
[Ca2+]i and paralleled the rise in
[Na+]i. The loss of m was
prevented in the absence of Ca2+ but unaltered in
the presence of cyclosporin A. We conclude that the increased ATP
consumption by the Na,K-ATPase that results from a modest
[Na+]i load places an additional
demand on mitochondria metabolically compromised by an oxidative
stress, which are unable to produce a sufficient amount of ATP to fuel
the ATP-driven ion pumps. This results in a deregulation of
[Na+]i and
[Ca2+]i, and as a result of the
latter, collapse of m. The vicious cycle generated in the
combined presence of Na+ load and oxidative stress
could be an important factor in the neuronal injury produced by
ischemia or excitotoxicity, in which the oxidative insult is
superimposed on a disturbed Na+ homeostasis.
Key words:
oxidative stress; Na+ load; mitochondrial membrane potential; ATP depletion; Na+
deregulation; Ca2+ deregulation
Copyright © 2000 Society for Neuroscience 0270-6474/00/2062094-10$05.00/0
This article has been cited by other articles:
|
|
|
|
 
R. I. Stanika, N. B. Pivovarova, C. A. Brantner, C. A. Watts, C. A. Winters, and S. B. Andrews
Coupling diverse routes of calcium entry to mitochondrial dysfunction and glutamate excitotoxicity
PNAS,
June 16, 2009;
106(24):
9854 - 9859.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Vander Jagt, J. A. Connor, and C. W. Shuttleworth
Localized Loss of Ca2+ Homeostasis in Neuronal Dendrites Is a Downstream Consequence of Metabolic Compromise during Extended NMDA Exposures
J. Neurosci.,
May 7, 2008;
28(19):
5029 - 5039.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Greenwood, S. M. Mizielinska, B. G. Frenguelli, J. Harvey, and C. N. Connolly
Mitochondrial Dysfunction and Dendritic Beading during Neuronal Toxicity
J. Biol. Chem.,
September 7, 2007;
282(36):
26235 - 26244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Tretter and V. Adam-Vizi
Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress
Phil Trans R Soc B,
December 29, 2005;
360(1464):
2335 - 2345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Sheldon, A. Diarra, Y. M. Cheng, and J. Church
Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons
J. Neurosci.,
December 8, 2004;
24(49):
11057 - 11069.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Tretter and V. Adam-Vizi
Generation of Reactive Oxygen Species in the Reaction Catalyzed by {alpha}-Ketoglutarate Dehydrogenase
J. Neurosci.,
September 8, 2004;
24(36):
7771 - 7778.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Mehta and C. Shaha
Apoptotic Death in Leishmania donovani Promastigotes in Response to Respiratory Chain Inhibition: COMPLEX II INHIBITION RESULTS IN INCREASED PENTAMIDINE CYTOTOXICITY
J. Biol. Chem.,
March 19, 2004;
279(12):
11798 - 11813.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. Mukherjee, M. Das, G. Sudhandiran, and C. Shaha
Increase in Cytosolic Ca2+ Levels through the Activation of Non-selective Cation Channels Induced by Oxidative Stress Causes Mitochondrial Depolarization Leading to Apoptosis-like Death in Leishmania donovani Promastigotes
J. Biol. Chem.,
June 28, 2002;
277(27):
24717 - 24727.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Sheldon and J. Church
Intracellular pH Response to Anoxia in Acutely Dissociated Adult Rat Hippocampal CA1 Neurons
J Neurophysiol,
May 1, 2002;
87(5):
2209 - 2224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Diarra, C. Sheldon, and J. Church
In situ calibration and [H+] sensitivity of the fluorescent Na+ indicator SBFI
Am J Physiol Cell Physiol,
June 1, 2001;
280(6):
C1623 - C1633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Tretter and V. Adam-Vizi
Inhibition of Krebs Cycle Enzymes by Hydrogen Peroxide: A Key Role of {alpha}-Ketoglutarate Dehydrogenase in Limiting NADH Production under Oxidative Stress
J. Neurosci.,
December 15, 2000;
20(24):
8972 - 8979.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
