Protective effect of casuarinin against glutamate-induced apoptosis in HT22 cells through inhibition of oxidative stress-mediated MAPK phosphorylation
Protective effect of casuarinin against glutamate-induced apoptosis in HT22 cells through inhibition of oxidative stress-mediated MAPK phosphorylation
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DOI：
10.1016/j.bmcl.2017.10.075
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发表时间：
2017-12-01
影响因子：
2.7
通讯作者：
Choi, You-Kyung
中科院分区：
文献类型：
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作者：
Song, Ji Hoon;Kang, Ki Sung;Choi, You-Kyung
谷氨酸是中枢神经系统中主要的兴奋性神经递质，在神经退行性变过程中参与氧化应激。在本研究中，木麻黄素通过抑制细胞内活性氧(ROS)的产生来阻止谷氨酸诱导的HT22小鼠海马神经细胞死亡。此外，木麻黄素可减少谷氨酸诱导的染色质凝集和膜联蛋白V阳性细胞的产生。我们还证实了木麻黄素对谷氨酸诱导的神经毒性的潜在保护机制。谷氨酸显著增加细胞外信号调节激酶(ERK)-1/2和p38的磷酸化，这两个蛋白在氧化应激介导的神经细胞死亡中起关键作用。相反，用木麻黄素处理后，ERK1/2和P38的磷酸化程度降低。综上所述，本研究结果表明，从天然产物中获得的木麻黄素通过抑制ROS的产生和激活丝裂原活化蛋白激酶(MAPK)途径来抑制谷氨酸介导的细胞凋亡，从而起到有效的神经保护作用。因此，木麻黄素有可能成为治疗神经退行性疾病的潜在药物。(C)2017爱思唯尔有限公司。保留所有权利。
Glutamate is the major excitatory neurotransmitter in the central nervous system and is involved in oxidative stress during neurodegeneration. In the present study, casuarinin prevented glutamate-induced HT22 murine hippocampal neuronal cell death by inhibiting intracellular reactive oxygen species (ROS) production. Moreover, casuarinin reduced chromatin condensation and annexin-V-positive cell production induced by glutamate. We also confirmed the underlying protective mechanism of casuarinin against glutamate-induced neurotoxicity. Glutamate markedly increased the phosphorylation of extracellular signal regulated kinase (ERK)-1/2 and p38, which are crucial in oxidative stress-mediated neuronal cell death. Conversely, treatment with casuarinin diminished the phosphorylation of ERK1/2 and P38. In conclusion, the results of this study suggest that casuarinin, obtained from natural products, acts as potent neuroprotective agent by suppressing glutamate-mediated apoptosis through the inhibition of ROS production and activation of the mitogen activated protein kinase (MAPK) pathway. Thus, casuarinin can be a potential therapeutic agent in the treatment of neurodegenerative diseases. (C) 2017 Elsevier Ltd. All rights reserved.