ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells
ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells
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DOI：
10.5483/bmbrep.2009.42.11.719
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发表时间：
2009-11-30
期刊：
影响因子：
3.8
通讯作者：
Oliveira, Catarina R.
中科院分区：
文献类型：
--
作者：
Arduino, Daniela M.;Esteves, A. Raquel;Oliveira, Catarina R.
最近的研究表明，内质网（ER）紊乱参与神经退行性疾病的病理生理学，有助于激活内质网应激介导的细胞凋亡途径。因此，我们在这里研究了 ER 线粒体轴的分子机制，重点关注钙作为细胞死亡信号的潜在介质。使用用布雷菲德菌素 A 或衣霉素处理的 NT2 细胞，我们观察到 ER 应激会引起线粒体功能的变化，损害线粒体膜电位并使线粒体呼吸链复合体感到痛苦。此外，ER 水平的应激刺激会引起 ER 和线粒体之间的钙通量。在这些条件下，内质网应激通过 GRP78 以及 caspase-4 和 caspase-2 的过度表达激活未折叠蛋白反应，两者都涉及 caspase-9 的上游。我们的研究结果表明，内质网和线粒体互连在特定应激环境下诱导神经元细胞死亡中发挥着重要作用。 [BMB 2009 年报告； 42（11）：719-724]
Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances. [BMB reports 2009; 42(11): 719-724]