Self-evolving oxidative stress with identifiable pre- and postmitochondrial phases in PC12 cells.

Abstract

During the neurodegenerative process in several brain diseases, oxidative stress is known to play important roles in disease severity and evolution. Although early events of stress, such as increased lipid peroxidation and decreased superoxide dismutase, are known to characterize early onsets of these diseases, little is known about the events that participate in maintaining the chronic evolving phase influencing the disease progression in neurons. Here, we used differentiated PC12 cells to identify premitochondrial and postmitochondrial events occurring during the oxidative stress cascade leading to apoptosis. Our data indicate that an acute and strong oxidative impulse (500 μM H(2)O(2), 30 min) can induce, in this model, a 24-hr self-evolving stress, which advances from a premitochondrial phase characterized by lysosomes and cathepsin B and D translocations to cytosol and early mitochondrial membrane hyperpolarization. This phase lasts for about 5 hr and is followed by a postmitochondrial phase distinguished by mitochondrial membrane depolarization, reactive oxygen species increase, caspase-9 and caspase-3 activations, and apoptosis. Inhibition of cathepsins B and D suggests that cells can be protected at the premitochondrial phase of stress evolution and that new cathepsins regulators, such as glycosaminoglycans mimetics, can be considered as new therapeutic prototypes for neurodegeneration. Insofar as early oxidative stress markers have been related to the early onset of neurodegeneration, strategies protecting cells at the premitochondrial phase of oxidative stress may have important therapeutic applications.

• Authors: Ganlin Zhang, Christophe Morin, Xiaoxin Zhu, Minh Bao Huynh, Mohand Ouidir Ouidja, Julia Elisa Sepulveda-Diaz, Rita Raisman-Vozari, Ping Li, Dulce Papy-Garcia
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 91 Issue 2 Pg. 273-84 (Feb 2013) ISSN: 1097-4547 [Electronic] United States
• PMID: 23161662 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Enzyme Inhibitors
• Reactive Oxygen Species
• Malondialdehyde
• Hydrogen Peroxide
• Superoxide Dismutase
• Caspase 3
• Caspase 9
• Cathepsin E
• Cathepsin D
• Aconitate Hydratase

Topics

• Aconitate Hydratase (metabolism)
• Animals
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Cathepsin D (metabolism)
• Cathepsin E (metabolism)
• Cell Survival (drug effects)
• Enzyme Inhibitors (pharmacology)
• Hydrogen Peroxide (pharmacology)
• Lipid Peroxidation (drug effects)
• Lysosomes (drug effects, metabolism)
• Malondialdehyde (metabolism)
• Mitochondria (drug effects, metabolism)
• Oxidation-Reduction (drug effects)
• Oxidative Stress (drug effects, physiology)
• PC12 Cells (drug effects, enzymology)
• Rats
• Reactive Oxygen Species (metabolism)
• Superoxide Dismutase (metabolism)
• Time Factors