The excitatory neurotransmitter glutamate stimulates DNA repair to increase neuronal resiliency.
The excitatory neurotransmitter glutamate stimulates DNA repair to increase neuronal resiliency.
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DOI：
10.1016/j.mad.2011.06.005
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发表时间：
2011-08
影响因子：
5.3
通讯作者：
Bohr, Vilhelm A.
中科院分区：
文献类型：
--
作者：
Yang, Jenq-Lin;Sykora, Peter;Wilson, David M., III;Mattson, Mark P.;Bohr, Vilhelm A.
谷氨酸是脊椎动物中枢神经系统中最丰富的兴奋性神经递质，在学习和记忆所需的突触可塑性中起重要作用。谷氨酸嗜离子受体的激活迅速触发膜去极化和Ca2+内流，导致几种不同的蛋白激酶和转录因子的激活。例如，谷氨酸介导的Ca2+内流激活Ca2+/钙调素依赖性激酶、蛋白激酶C和丝裂原活化的蛋白激酶，从而激活转录因子，如环AMP反应元件结合蛋白（CREB）。异常长时间暴露于谷氨酸会导致神经元损伤，这种“兴奋性毒性”与许多急慢性疾病有关，包括缺血性中风、低血糖症、癫痫、肌萎缩侧索硬化症、阿尔茨海默氏症、亨廷顿氏症和帕金森病。有趣的是，尽管谷氨酸诱导的Ca2+内流可以通过线粒体活性氧介导的机制引起DNA损伤，但Ca2+同时激活CREB，导致DNA修复和氧化还原蛋白apurinic/ ap嘧啶内切酶1的上调。在这里，我们回顾了生理或异常谷氨酸受体激活、Ca2+介导的信号、氧化DNA损伤和修复效率以及神经元易感性之间的联系。我们得出的结论是，谷氨酸信号涉及一个适应性细胞应激反应途径，增强DNA修复能力，从而保护神经元免受损伤和疾病。
Glutamate is the most abundant excitatory neurotransmitter in the vertebrate central nerve system and plays an important role in synaptic plasticity required for learning and memory. Activation of glutamate ionotropic receptors promptly triggers membrane depolarization and Ca2+ influx, resulting in the activation of several different protein kinases and transcription factors. For example, glutamate-mediated Ca2+ influx activates Ca2+/calmodulin-dependent kinase, protein kinase C, and mitogen activated protein kinases resulting in activation of transcription factors such as cyclic AMP response element binding protein (CREB). Abnormally prolonged exposure to glutamate causes neuronal injury, and such “excitotoxicity” has been implicated in many acute and chronic diseases including ischemic stroke, hypoglycemia, epilepsy, amyotrophic lateral sclerosis, Alzheimer’s, Huntington’s and Parkinson’s diseases. Interestingly, although glutamate-induced Ca2+ influx can cause DNA damage by a mitochondrial reactive oxygen species-mediated mechanism, the Ca2+ simultaneously activates CREB, resulting in up-regulation of the DNA repair and redox protein apurinic/apyrimidinic endonuclease 1. Here, we review connections between physiological or aberrant glutamate receptor activation, Ca2+-mediated signaling, oxidative DNA damage and repair efficiency, and neuronal vulnerability. We conclude that glutamate signaling involves an adaptive cellular stress response pathway that enhances DNA repair capability, thereby protecting neurons against injury and disease.
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影响因子：
25
作者：
Choi, S;Klingauf, J;Tsien, RW
通讯作者：
Tsien, RW
DOI：
10.1016/j.bbrc.2004.08.035
发表时间：
2004-10-01
影响因子：
3.1
作者：
Bezprozvanny, I;Hayden, MR
通讯作者：
Hayden, MR
影响因子：
4.7
作者：
Alam, ZI;Jenner, A;Halliwell, B
通讯作者：
Halliwell, B
影响因子：
15.9
作者：
Endres, M;Biniszkiewicz, D;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
4.7
作者：
Bogdanov, MB;Andreassen, OA;Beal, MF
通讯作者：
Beal, MF