Differential regulation of X-chromosome-linked inhibitor of apoptosis protein (XIAP) and caspase-3 by NMDA in developing hippocampal neurons; involvement of the mitochondrial pathway in NMDA-mediated neuronal survival
| Autor: | Ulla Näpänkangas, Håkan Steen, Rodrigo Martinez, Laura Korhonen, Dan Lindholm, Yuming Chen |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
N-Methylaspartate
X Chromosome Cell Survival Caspase 3 Apoptosis X-Linked Inhibitor of Apoptosis Protein Biology Inhibitor of apoptosis Neuroprotection Hippocampus Models Biological Receptors N-Methyl-D-Aspartate Inhibitor of Apoptosis Proteins medicine Excitatory Amino Acid Agonists Staurosporine Animals RNA Messenger Rats Wistar Long-term depression Cells Cultured Neurons Glutamate receptor Cytochromes c Gene Expression Regulation Developmental Proteins Cell Biology XIAP Cell biology Mitochondria Rats Enzyme Activation nervous system Caspases NMDA receptor Protein Processing Post-Translational medicine.drug |
| Zdroj: | Experimental cell research. 295(2) |
| ISSN: | 0014-4827 |
| Popis: | N-methyl-d-aspartate (NMDA) subtype of glutamate receptors plays an important role during brain development and receptor activation has been shown to promote neuronal survival. The mechanisms by which NMDA increases neuronal survival are not fully understood. Here, we show that treatment with low concentrations of NMDA upregulates the neuroprotective molecule, X-chromosome-linked inhibitor of apoptosis protein (XIAP) in cultured hippocampal neurons at the post-transcriptional level. In contrast, NMDA treatment decreased mRNA and protein levels of caspase-3 in these neurons. The activation of the caspase-3 was also inhibited by NMDA, and the neurons were more resistant towards death caused by high concentrations of glutamate and staurosporine. Data on cytochrome c release in hippocampal neurons showed that NMDA pretreatment inhibits the mitochondrial pathway of cell death. The results demonstrate that the activation of NMDA receptors induces an anti-apoptotic program in hippocampal neurons that involves mitochondria and alterations of the levels of caspase-3 and XIAP. These findings are of importance for understanding the function of NMDA receptors in the control of neuronal survival during development and in other conditions. |
| Databáze: | OpenAIRE |
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