 |
||||
|
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, March 15, 2001, 21(6):1949-1963
Evidence for Redox Regulation of Cytochrome c Release during Programmed Neuronal Death: Antioxidant Effects of Protein Synthesis and Caspase Inhibition
Rebecca A. Kirkland and James L. Franklin Department of Neurological Surgery, University of Wisconsin Medical School, Madison, Wisconsin 53706
Sympathetic neurons die by apoptosis when they are deprived of nerve growth factor (NGF). Activation of caspases by cytochrome c released from mitochondria is central to this death. In this report we present evidence that cellular redox state regulates cytochrome c redistribution in these neurons. An increase of mitochondrial-produced reactive oxygen species (ROS) occurred in rat sympathetic neurons in cell culture within 3 hr of NGF withdrawal. Caspase inhibitors blocked this ROS burst. By 6 hr after NGF deprivation, glutathione (GSH) levels had increased, neutralizing elevated hydrogen peroxide levels and returning cellular redox state to basal levels. By 12 hr after deprivation, ROS levels had again increased and remained elevated during the rest of the apoptotic process. The later ROS burst appeared to have both caspase-dependent and caspase-independent components and was coincident with the period of cytochrome c release. Inhibition of protein synthesis with cycloheximide (CHX) and treatment with the antioxidant compound, N-acetyl-L-cysteine (L-NAC), blocked both the early and late ROS bursts by increasing cellular GSH levels (Ratan et al., 1994; Tan et al., 1998). Both compounds, and a membrane-permeant form of GSH, also inhibited cytochrome c release and death. Treatment of NGF, CHX-, L-NAC-, and GSH-saved cells with hydrogen peroxide caused rapid cytochrome c release. These data suggest a role for cellular redox state in regulating cytochrome c release during apoptosis induced by NGF withdrawal.
Key words: reactive oxygen; mitochondria; caspase; cytochrome c; apoptosis; redox
Copyright © 2001 Society for Neuroscience 0270-6474/01/2161949-15$05.00/0
This article has been cited by other articles:
D. J. Lomb, L. A. Desouza, J. L. Franklin, and R. S. Freeman
Prolyl Hydroxylase Inhibitors Depend on Extracellular Glucose and Hypoxia-Inducible Factor (HIF)-2{alpha} to Inhibit Cell Death Caused by Nerve Growth Factor (NGF) Deprivation: Evidence that HIF-2{alpha} Has a Role in NGF-Promoted Survival of Sympathetic Neurons
Mol. Pharmacol., May 1, 2009; 75(5): 1198 - 1209.
[Abstract] [Full Text] [PDF]
V. A. Campanucci, A. Krishnaswamy, and E. Cooper
Mitochondrial Reactive Oxygen Species Inactivate Neuronal Nicotinic Acetylcholine Receptors and Induce Long-Term Depression of Fast Nicotinic Synaptic Transmission
J. Neurosci., February 13, 2008; 28(7): 1733 - 1744.
[Abstract] [Full Text] [PDF]
Y. Duan, R. A. Gross, and S.-S. Sheu
Ca2+-dependent generation of mitochondrial reactive oxygen species serves as a signal for poly(ADP-ribose) polymerase-1 activation during glutamate excitotoxicity
J. Physiol., December 15, 2007; 585(3): 741 - 758.
[Abstract] [Full Text] [PDF]
R. A. Kirkland, G. M. Saavedra, and J. L. Franklin
Rapid Activation of Antioxidant Defenses by Nerve Growth Factor Suppresses Reactive Oxygen Species during Neuronal Apoptosis: Evidence for a Role in Cytochrome c Redistribution
J. Neurosci., October 17, 2007; 27(42): 11315 - 11326.
[Abstract] [Full Text] [PDF]
H. Fukui and C. T. Moraes
Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates
Hum. Mol. Genet., April 1, 2007; 16(7): 783 - 797.
[Abstract] [Full Text] [PDF]
I. Komuro, T. Yasuda, A. Iwamoto, and K. S. Akagawa
Catalase Plays a Critical Role in the CSF-independent Survival of Human Macrophages via Regulation of the Expression of BCL-2 Family
J. Biol. Chem., December 16, 2005; 280(50): 41137 - 41145.
[Abstract] [Full Text] [PDF]
S. Vesce, M. B. Jekabsons, L. I. Johnson-Cadwell, and D. G. Nicholls
Acute Glutathione Depletion Restricts Mitochondrial ATP Export in Cerebellar Granule Neurons
J. Biol. Chem., November 18, 2005; 280(46): 38720 - 38728.
[Abstract] [Full Text] [PDF]
R. Chaturvedi, Y. Cheng, M. Asim, F. I. Bussiere, H. Xu, A. P. Gobert, A. Hacker, R. A. Casero Jr., and K. T. Wilson
Induction of Polyamine Oxidase 1 by Helicobacter pylori Causes Macrophage Apoptosis by Hydrogen Peroxide Release and Mitochondrial Membrane Depolarization
J. Biol. Chem., September 17, 2004; 279(38): 40161 - 40173.
[Abstract] [Full Text] [PDF]
S. JAYANTHI, X. DENG, P.-A. H. NOAILLES, B. LADENHEIM, and J. L. CADET
Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades
FASEB J, February 1, 2004; 18(2): 238 - 251.
[Abstract] [Full Text] [PDF]
M. V. Sanchez-Gomez, E. Alberdi, G. Ibarretxe, I. Torre, and C. Matute
Caspase-Dependent and Caspase-Independent Oligodendrocyte Death Mediated by AMPA and Kainate Receptors
J. Neurosci., October 22, 2003; 23(29): 9519 - 9528.
[Abstract] [Full Text] [PDF]
Y.-H. Ling, L. Liebes, Y. Zou, and R. Perez-Soler
Reactive Oxygen Species Generation and Mitochondrial Dysfunction in the Apoptotic Response to Bortezomib, a Novel Proteasome Inhibitor, in Human H460 Non-small Cell Lung Cancer Cells
J. Biol. Chem., September 5, 2003; 278(36): 33714 - 33723.
[Abstract] [Full Text] [PDF]
J. P. Vrabec, C. J. Lieven, and L. A. Levin
Cell-Type-Specific Opening of the Retinal Ganglion Cell Mitochondrial Permeability Transition Pore
Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2774 - 2782.
[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]
|
|
|
|
 |
|