التفاصيل البيبلوغرافية
| العنوان: |
The Antioxidant N-Acetylcysteine Prevents the Mitochondrial Fragmentation Induced by Soluble Amyloid-β Peptide Oligomers. |
| المؤلفون: |
SanMartin, C.D., Adasme, T., Hidalgo, C., Paula-Lima, A.C. |
| المصدر: |
Neurodegenerative Diseases; Apr2012, Vol. 10 Issue 1-4, p34-37, 4p, 1 Graph |
| مصطلحات موضوعية: |
AMYLOID beta-protein, ACETYLCYSTEINE, ALZHEIMER'S disease, METHYL aspartate receptors, RYANODINE, OLIGOMERS |
| مستخلص: |
Background: Soluble amyloid-β peptide oligomers (AβOs), which are centrally involved in the pathogenesis of Alzheimer's disease, trigger Ca2+ influx through N-methyl-D-aspartate receptors and stimulate reactive oxygen species generation in primary hippocampal neurons. We have previously reported that AβOs promote Ca2+ release mediated by ryanodine receptors (RyR), which in turn triggers mitochondrial fragmentation. We have also reported that the antioxidant N-acetylcysteine (NAC) prevents AβOs-induced Ca2+ signal generation. Objectives: To determine if RyR-mediated Ca2+ release activated by the specific agonist 4-chloro-m-cresol (4-CMC) induces fragmentation of the mitochondrial network, and to ascertain if NAC prevents the mitochondrial fragmentation induced by AβOs and/or 4-CMC. Methods: Mature primary rat hippocampal neurons were incubated for 24 h with sublethal concentrations of AβOs (500 nM) or for 1-3 h with 4-CMC (0.5-1 mM), ±10 mM NAC. Mitochondrial morphology was assessed by confocal microscopy of fixed neurons stained with anti-mHsp70. Intracellular Ca2+ levels were determined by time series microscopy of neurons preloaded with Fluo-4 AM. Results: Preincubation of neurons for 30 min with NAC prevented the mitochondrial fragmentation induced by AβOs or 4-CMC. In addition, we confirmed that preincubation with NAC abolished the stimulation of RyR-mediated Ca2+ release induced by AβOs or 4-CMC. Conclusion: The present results strongly suggest that the general antioxidant NAC prevents AβO-induced mitochondrial fragmentation by preventing RyR-mediated Ca2+-induced Ca2+ release. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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