Ca2+ signals and neuronal death in brain ischemia
Ca2+ signals and neuronal death in brain ischemia
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DOI：
10.1161/01.str.0000256294.46009.29
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发表时间：
2007-02-01
期刊：
影响因子：
8.3
通讯作者：
Nicotera, Pierluigi
中科院分区：
文献类型：
--
作者：
Bano, Daniele;Nicotera, Pierluigi
虽然Ca 2+信号是细胞通讯和生存所必需的，但异常的细胞Ca 2+负荷可触发不同的细胞死亡程序。Ca 2+通过激活蛋白酶（即钙蛋白酶）、通过加强导致半胱天冬酶激活的信号或通过触发由脂肪酶和核酸酶介导的其他分解代谢过程来介导细胞死亡。兴奋性氨基酸的清除失败是缺血性脑中神经元损失的关键决定因素。谷氨酸激活突触和突触外位点的谷氨酸离子型受体，导致神经元去极化延长并触发细胞离子稳态（主要是细胞内钙和钠）失调。导致兴奋性毒性条件下持续钙失调的机制仅部分阐明。最近，我们已经表明，钙蛋白酶介导的抑制钙外流的主要解离神经元的兴奋毒性谷氨酸浓度的挑战。钙蛋白酶切割钠-钙交换器（NCX）并抑制其去除由于兴奋性毒性刺激而积累的钙的能力。我们的研究结果突出了兴奋性毒性损伤后钙依赖性蛋白酶、钙超载和神经元变性之间的联系。（中风。2007; 38[第2部分]：674-676。
Although Ca2+ signals are necessary for cell communication and survival, abnormal cellular Ca2+ load can trigger different cell death programs. Ca2+ mediates cell death by activating proteases (ie, calpains), by reinforcing signals leading to caspase activation or by triggering other catabolic processes mediated by lipases and nucleases. Failure in the clearance of excitatory amino acid is a critical determinant of neuronal loss in the ischemic brain. Glutamate activates glutamate-ionotropic receptors at synaptic and extra-synaptic sites, causing prolonged neuronal depolarization and triggering deregulation of cellular ion homeostasis, mainly intracellular calcium and sodium. The mechanisms leading to the sustained calcium deregulation in excitotoxic conditions are only in part elucidated. Recently, we have shown that calpains mediate the inhibition of calcium efflux in primary dissociated neurons challenged with excitotoxic glutamate concentrations. Calpains cleave the sodium-calcium exchanger (NCX) and inhibit its capability to remove calcium accumulated as a consequence of the excitotoxic stimulus. Our findings highlight the link between calcium-dependent proteases, calcium overload and neuronal degeneration after an excitotoxic insult. (Stroke. 2007; 38[part 2]:674-676.)