Temporal relationship of autophagy and apoptosis in neurons challenged by low molecular weight β-amyloid peptide
| Autor: | Kwok-Fai So, Man-Shan Yu, Cora Sau Wan Lai, Natalie Qishan Zhang, YT Cheung, Raymond Chuen-Chung Chang, Clara Hiu-Ling Hung |
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| Rok vydání: | 2011 |
| Předmět: |
death associated protein kinase
autophagy Programmed cell death Poly ADP ribose polymerase Caspase 3 Biology ATG12 Alzheimer Disease Animals Phosphorylation Cells Cultured Neurons Amyloid beta-Peptides β-amyloid Kinase Adenine Autophagy apoptosis Articles Cell Biology Alzheimer's disease Rats Cell biology Death-Associated Protein Kinases Apoptosis Calcium-Calmodulin-Dependent Protein Kinases Molecular Medicine Poly(ADP-ribose) Polymerases Signal transduction Apoptosis Regulatory Proteins Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-1838 |
| DOI: | 10.1111/j.1582-4934.2009.00990.x |
| Popis: | Alzheimer's disease (AD) is an aging-related progressive neurodegenerative disorder. Previous studies suggested that various soluble Aβ species are neurotoxic and able to activate apoptosis and autophagy, the type I and type II programmed cell death, respectively. However, the sequential and functional relationships between these two cellular events remain elusive. Here we report that low molecular weight Aβ triggered cleavage of caspase 3 and poly (ADP-ribose) polymerase to cause neuronal apoptosis in rat cortical neurons. On the other hand, Aβ activated autophagy by inducing autophagic vesicle formation and autophagy related gene 12 (ATG12), and up-regulated the lysoso-mal machinery for the degradation of autophagosomes. Moreover, we demonstrated that activation of autophagy by Aβ preceded that of apoptosis, with death associated protein kinase phosphorylation as the potential molecular link. More importantly, under Aβ toxicity, neurons exhibiting high level of autophagosome formation were absent of apoptotic features, and inhibition of autophagy by 3-methylade-nine advanced neuronal apoptosis, suggesting that autophagy can protect neurons from Aβ-induced apoptosis. |
| Databáze: | OpenAIRE |
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