Researching glutamate - induced cytotoxicity in different cell lines: a comparative/collective analysis/study.
Researching glutamate - induced cytotoxicity in different cell lines: a comparative/collective analysis/study.
复制标题
DOI：
10.3389/fncel.2015.00091
复制
发表时间：
2015
影响因子：
5.3
通讯作者：
Vavilis TD
中科院分区：
文献类型：
--
作者：
Kritis AA;Stamoula EG;Paniskaki KA;Vavilis TD
尽管谷氨酸是中枢神经系统最重要的兴奋性神经递质之一，但其细胞外浓度过高会导致神经元不受控制的持续去极化，这种毒性过程称为兴奋性毒性。在兴奋性毒性中，谷氨酸引发细胞内 Ca2+ 水平升高，随后 nNOS 上调、线粒体功能障碍、ROS 产生、内质网应激和溶酶体酶释放。钙浓度过高是通过过度激活离子型和代谢型受体而导致谷氨酸毒性的关键介质。此外，谷氨酸积累还可以通过逆转 CySS/谷氨酸逆向转运蛋白的作用来抑制胱氨酸 (CySS) 的摄取。反向转运蛋白作用的逆转通过耗尽神经元的半胱氨酸并最终耗尽谷胱甘肽的还原潜力来强化上述事件。为了了解兴奋性毒性影响细胞并最终导致细胞死亡的机制，已采用各种细胞系。在一些细胞系中，谷氨酸毒性主要通过 NMDA、AMPA 或红藻氨酸受体的过度激活而发挥，而在缺乏此类受体的其他细胞系中，毒性是由于谷氨酸诱导的氧化应激所致。然而，在大多数细胞系中存在离子型谷氨酸受体，与CySS/谷氨酸逆向转运蛋白和代谢型谷氨酸受体共存，支持了这些细胞中兴奋性毒性作用是累积的假设。不同的细胞系在接触谷氨酸时的反应不同。在这篇综述文章中，系统地收集和分析了 PC12、SH-SY5Y、HT-22、NT-2、OLC、C6、原代大鼠皮质神经元、RGC-5 和 SCN2.2 细胞系统的反应。
Although glutamate is one of the most important excitatory neurotransmitters of the central nervous system, its excessive extracellular concentration leads to uncontrolled continuous depolarization of neurons, a toxic process called, excitotoxicity. In excitotoxicity glutamate triggers the rise of intracellular Ca2+ levels, followed by up regulation of nNOS, dysfunction of mitochondria, ROS production, ER stress, and release of lysosomal enzymes. Excessive calcium concentration is the key mediator of glutamate toxicity through over activation of ionotropic and metabotropic receptors. In addition, glutamate accumulation can also inhibit cystine (CySS) uptake by reversing the action of the CySS/glutamate antiporter. Reversal of the antiporter action reinforces the aforementioned events by depleting neurons of cysteine and eventually glutathione’s reducing potential. Various cell lines have been employed in the pursuit to understand the mechanism(s) by which excitotoxicity affects the cells leading them ultimately to their demise. In some cell lines glutamate toxicity is exerted mainly through over activation of NMDA, AMPA, or kainate receptors whereas in other cell lines lacking such receptors, the toxicity is due to glutamate induced oxidative stress. However, in the greatest majority of the cell lines ionotropic glutamate receptors are present, co-existing to CySS/glutamate antiporters and metabotropic glutamate receptors, supporting the assumption that excitotoxicity effect in these cells is accumulative. Different cell lines differ in their responses when exposed to glutamate. In this review article the responses of PC12, SH-SY5Y, HT-22, NT-2, OLCs, C6, primary rat cortical neurons, RGC-5, and SCN2.2 cell systems are systematically collected and analyzed.
登录
查看更多内容
DOI：
10.1073/pnas.92.16.7162
发表时间：
1995-08-01
影响因子：
11.1
作者：
BONFOCO, E;KRAINC, D;LIPTON, SA
通讯作者：
LIPTON, SA
影响因子：
16.2
作者：
ANKARCRONA, M;DYPBUKT, JM;NICOTERA, P
通讯作者：
NICOTERA, P
影响因子：
4.8
作者：
Anrather, J;Racchumi, G;Iadecola, C
通讯作者：
Iadecola, C
DOI：
10.1196/annals.1299.053
发表时间：
2003-01-01
期刊：
APOPTOSIS: FROM SIGNALING PATHWAYS TO THERAPEUTIC TOOLS
影响因子：
--
作者：
Akundi, RS;Hüll, M;Fiebich, BL
通讯作者：
Fiebich, BL
DOI：
10.1016/j.nurt.2008.10.038
发表时间：
2009-01
期刊：
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Byrnes KR;Loane DJ;Faden AI
通讯作者：
Faden AI