Mitochondrial involvement in nitric oxide-induced cellular death in cortical neurons in culture
Mitochondrial involvement in nitric oxide-induced cellular death in cortical neurons in culture
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DOI：
10.1002/jnr.20739
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发表时间：
2006-02-15
影响因子：
4.2
通讯作者：
González, MP
中科院分区：
文献类型：
--
作者：
Figueroa, S;Oset-Gasque, MJ;González, MP
一氧化氮（NO）是一种不稳定的分子，具有生理和病理特性。在大脑中，NO作为神经传递的调节剂以及防止多种死亡刺激引起的神经元死亡的保护剂。然而，除了这种保护作用之外，高NO浓度通过涉及半胱天冬酶途径的机制产生神经元死亡。在这项工作中，我们证明，在皮层神经元的NO毒性介导的线粒体功能障碍。SNAP，一种NO供体，诱导这些细胞的凋亡，因为它1）增加p53和2）诱导细胞色素c释放和半胱天冬酶-9和半胱天冬酶-3的活化。SNAP还通过1）线粒体膜电位的破坏，2）ATP减少，3）ROS形成，和4）LDH和ATP释放诱导坏死，指示氧化应激和坏死引起的死亡。总之，在皮质神经元中，高浓度的NO通过线粒体参与的凋亡和坏死机制产生细胞死亡。(c)2006 Wiley-Liss，Inc.
Nitric oxide (NO) is an unstable molecule with physiological and pathological properties. In brain, NO acts as a modulator of neurotransmission as well as a protector against neuronal death from several death stimuli. However, beside this protector effect, high NO concentrations produce neuronal death by a mechanism in which the caspase pathway is implicated. In this work, we demonstrate that in cortical neurons the NO toxicity is mediated by mitochondrial dysfunction. SNAP, an NO donor, induces apoptosis in these cells because it 1) increases the p53 and 2) induces cytochrome c release and activation of caspase-9 and caspase-3. SNAP also induces necrosis, through 1) breakdown of the mitochondrial membrane potential, 2) ATP decrease, 3) ROS formation, and 4) LDH and ATP release, indicative of oxidative stress and death by necrosis. To sum up, in cortical neurons, high NO concentrations produced cellular death by both an apoptotic and a necrotic mechanism in which the mitochondria are implicated. (c) 2006 Wiley-Liss, Inc.