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

被引：55

作者：

Hongpaisan, J ^{[1
]}

Winters, CA ^{[1
]}

Andrews, SB ^{[1
]}

机构：

[1] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2003年 / 24卷 / 04期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.mcn.2003.09.003

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 Ca2+, mitochondrial calcium accumulation, O-2(-) production, and CREB phosphorylation. Strong depolarization-induced Ca2+ entry through NMDA or L-type Ca2+ channels evoked large Ca2+ transients, a sustained increase in O-2(-), and a large rise in nuclear CaM and pCREB. Under these conditions, inhibition of mitochondrial Ca2+ uptake and consequent O-2(-) production suppressed Ca2+ 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 Ca2+ 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. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：1103 / 1115

页数：13

共 54 条

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