Calcium-dependent mitochondrial superoxide modulates nuclear CREB phosphorylation in hippocampal neurons
| Autor: | Christine A. Winters, S. Brian Andrews, Jarin Hongpaisan |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
chemistry.chemical_element Calcium Hippocampal formation Biology Mitochondrion Hippocampus Rats Sprague-Dawley Dephosphorylation Cellular and Molecular Neuroscience chemistry.chemical_compound Superoxides Internal medicine medicine Animals Phosphorylation Cyclic AMP Response Element-Binding Protein Molecular Biology Cells Cultured Neurons Superoxide Cell Biology Mitochondria Rats Cell biology Cytosol Endocrinology chemistry NMDA receptor |
| Zdroj: | Molecular and Cellular Neuroscience. 24:1103-1115 |
| ISSN: | 1044-7431 |
| DOI: | 10.1016/j.mcn.2003.09.003 |
| Popis: | We report evidence that mitochondrially produced superoxide (O(2)(-)) is involved in signaling in hippocampal neurons by examining the relationship between strong but physiological increases in cytosolic free Ca(2+), mitochondrial calcium accumulation, O(2)(-) production, and CREB phosphorylation. Strong depolarization-induced Ca(2+) entry through NMDA or L-type Ca(2+) channels evoked large Ca(2+) transients, a sustained increase in O(2)(-), and a large rise in nuclear CaM and pCREB. Under these conditions, inhibition of mitochondrial Ca(2+) uptake and consequent O(2)(-) production suppressed Ca(2+) entry-induced pCREB elevation, indicating that O(2)(-) produced by mitochondria supports CREB phosphorylation. Similarly, inhibiting mitochondrial respiration blocked O(2)(-) production and also depressed the elevation of pCREB. Blocking calcineurin reversed this depression. We conclude that strong Ca(2+) entry promotes mitochondrial calcium accumulation and the subsequent enhancement of mitochondrial O(2)(-) production, which in turn prolongs the lifetime of pCREB by suppressing calcineurin-dependent pCREB dephosphorylation. |
| Databáze: | OpenAIRE |
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