O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity
O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity
复制标题
nNOS 的 O-GlcNAc 糖基化促进谷氨酸兴奋毒性后的神经元凋亡
DOI：
10.1007/s10571-017-0477-1
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发表时间：
2017-11-01
影响因子：
4
通讯作者：
Liu, Xiaojuan
中科院分区：
文献类型：
--
作者：
Chen, Rongrong;Gong, Peipei;Liu, Xiaojuan
缺血性中风是一种主要的健康问题，具有极高的死亡率和残疾率。脑卒中后神经元损伤的主要机制是兴奋性毒性，其中神经元型一氧化氮合酶（nNOS）的激活起着至关重要的作用。然而，直接阻断N-甲基-d-天冬氨酸受体或nNOS可能导致严重的不良反应，因为它们在中枢神经系统中具有重要的生理功能。在这里，我们报告，nNOS通过与O-GlcNAc转移酶相互作用进行O-linked-beta-N-acetylglucosamine（O-GlcNAc）修饰，并且nNOS的O-GlcNAc酰化在谷氨酸诱导的兴奋性毒性期间显著增加。此外，消除nNOS的O-GlcNAc化通过减少nNOS-突触后密度蛋白95复合物的形成来保护神经元在谷氨酸刺激期间免于凋亡。总之，我们的数据表明，在谷氨酸兴奋性毒性过程中，nNOS的O-GlcNAc化在神经元凋亡中具有新的功能，这为缺血性卒中提供了一种新的治疗策略。
Ischemic stroke is a dominant health problem with extremely high rates of mortality and disability. The main mechanism of neuronal injury after stroke is excitotoxicity, during which the activation of neuronal nitric oxide synthase (nNOS) exerts a vital role. However, directly blocking N-methyl-d-aspartate receptors or nNOS can lead to severe undesirable effects since they have crucial physiological functions in the central nervous system. Here, we report that nNOS undergoes O-linked-beta-N-acetylglucosamine (O-GlcNAc) modification via interacting with O-GlcNAc transferase, and the O-GlcNAcylation of nNOS remarkably increases during glutamate-induced excitotoxicity. In addition, eliminating the O-GlcNAcylation of nNOS protects neurons from apoptosis during glutamate stimulation by decreasing the formation of nNOS-postsynaptic density protein 95 complexes. Taken together, our data suggest a novel function of the O-GlcNAcylation of nNOS in neuronal apoptosis during glutamate excitotoxicity, suggesting a novel therapy strategy for ischemic stroke.