Reduction of calcium release from the endoplasmic reticulum could only provide partial neuroprotection against beta-amyloid peptide toxicity
| Autor: | Suen, K. -C, Lin, K. -F, Elyaman, W., So, K. -F, Raymond Chuen-Chung Chang, Hugon, J. |
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| Rok vydání: | 2004 |
| Předmět: |
Boron Compounds
Indoles Macrocyclic Compounds Time Factors Blotting Western Intracellular Space Endoplasmic Reticulum Biochemistry Tacrolimus Rats Sprague-Dawley Cellular and Molecular Neuroscience Animals Drug Interactions Enzyme Inhibitors Endoplasmic Reticulum Chaperone BiP Oxazoles Cells Cultured Heat-Shock Proteins Cerebral Cortex Neurons Analysis of Variance Amyloid beta-Peptides Cell Death Dose-Response Relationship Drug L-Lactate Dehydrogenase Caspase 3 Embryo Mammalian Peptide Fragments Rats Caspases Calcium Carrier Proteins Immunosuppressive Agents Molecular Chaperones |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0022-3042 |
| Popis: | Beta-amyloid (Abeta) peptide has been suggested to play important roles in the pathogenesis of Alzheimer's disease (AD). Abeta peptide neurotoxicity was shown to induce disturbance of cellular calcium homeostasis. However, whether modulation of calcium release from the endoplasmic reticulum (ER) can protect neurons from Abeta toxicity is not clearly defined. In the present study, Abeta peptide-triggered ER calcium release in primary cortical neurons in culture is modulated by Xestospongin C, 2-aminoethoxydiphenyl borate or FK506. Our results showed that reduction of ER calcium release can partially attenuate Abeta peptide neurotoxicity evaluated by LDH release, caspase-3 activity and quantification of apoptotic cells. While stress signals associated with perturbations of ER functions such as up-regulation of GRP78 was significantly attenuated, other signaling machinery such as activation of caspase-7 transmitting death signals from ER to other organelles could not be altered. We further provide evidence that molecular signaling in mitochondria play also a significant role in determining neuronal apoptosis because Abeta peptide-triggered activation of caspase-9 was not significantly reduced by attenuating ER calcium release. Our results suggest that neuroprotective strategies aiming at reducing Abeta toxicity should include molecular targets linked to ER perturbations associated with ER calcium release as well as mitochondrial stress. |
| Databáze: | OpenAIRE |
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