Calcium-dependent mitochondrial superoxide modulates nuclear CREB phosphorylation in hippocampal neurons.

摘要: We report evidence that mitochondrially produced superoxide (O(2)(-)) is involved in signaling hippocampal neurons by examining the relationship between strong but physiological increases cytosolic free Ca(2+), mitochondrial calcium accumulation, O(2)(-) production, and CREB phosphorylation. Strong depolarization-induced Ca(2+) entry through NMDA or L-type channels evoked large transients, a sustained increase O(2)(-), rise nuclear CaM pCREB. Under these conditions, inhibition of uptake consequent production suppressed entry-induced pCREB elevation, indicating mitochondria supports Similarly, inhibiting respiration blocked also depressed elevation Blocking calcineurin reversed this depression. conclude promotes accumulation subsequent enhancement which turn prolongs lifetime suppressing calcineurin-dependent dephosphorylation.