MADP, a salidroside analog, protects hippocampal neurons from glutamate induced apoptosis.
MADP, a salidroside analog, protects hippocampal neurons from glutamate induced apoptosis.
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DOI：
10.1016/j.lfs.2014.02.040
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发表时间：
2014-05
期刊：
影响因子：
6.1
通讯作者：
H. Xian;Jing Zhao-;Yuan Zheng;Meihong Wang;Jun Huang;Bingxin Wu;Cheng Sun;Yumin Yang
中科院分区：
文献类型：
--
作者：
H. Xian;Jing Zhao-;Yuan Zheng;Meihong Wang;Jun Huang;Bingxin Wu;Cheng Sun;Yumin Yang
目的探讨红景天苷类似物MADP对谷氨酸诱导的大鼠海马神经元凋亡的抑制作用。Hoechst 33342染色、TUNEL法和流式细胞术检测细胞凋亡。Western blotting检测细胞信号分子的蛋白水平。关键发现我们的研究结果表明，谷氨酸暴露显着诱导细胞凋亡，而红景天苷或MADP的预处理显着提高细胞活力。最重要的是，MADP对谷氨酸损伤的抗凋亡作用上级红景天苷。为了探讨其机制，我们检测了一些促凋亡和抗凋亡蛋白的水平，并分析了几种细胞存活信号通路。MADP或红景天苷对Bcl-2和Bax蛋白水平无明显影响。在谷氨酸处理的神经元中，MADP强烈刺激Akt和JNK磷酸化。红景天苷处理后Akt略有激活，而JNK活性无明显变化，MADP对谷氨酸诱导的海马神经元凋亡有较强的抑制作用，提示MADP可能是一种比红景天苷更好的治疗神经元丢失相关疾病的药物。
AimsTo investigate the anti-apoptotic effect of MADP, an analog of salidroside, against glutamate induced apoptosis in the cultured rat hippocampal neurons.Main methodsCytotoxicity was determined by the MTT method and lactate dehydrogenase release to the medium. Cell apoptosis was evaluated by Hoechst 33342 staining, TUNEL assay and flow cytometric analysis. Western blotting was applied for detecting protein levels of cellular signaling molecules.Key findingsOur results showed that glutamate exposure significantly induces cell apoptosis, whereas the pretreatment of salidroside or MADP remarkably improves cell viability. Most importantly, the anti-apoptotic effect of MADP against glutamate insult is superior to salidroside. To explore the involved mechanisms, we measured some pro-apoptotic and anti-apoptotic protein levels, and several cell survival signaling pathways were analyzed as well. No visible alterations in Bcl-2 and Bax protein levels were observed by MADP or salidroside. Akt and JNK phosphorylation was robustly stimulated by MADP in the glutamate-treated neurons. Salidroside treatment results in a slight activation in Akt, while no significant alteration in JNK activity was observed.SignificanceMADP exhibits higher capacity to attenuate glutamate induced cell apoptosis in the cultured rat hippocampal neurons, suggesting that MADP might be a better candidate than salidroside for developing novel drugs treating neuron loss associated disorders.