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2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷对星形孢菌素诱导的培养大鼠海马神经元毒性的潜在保护作用。

Potential protection of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside against staurosporine-induced toxicity on cultured rat hippocampus neurons.

作者信息

Yang Xiao-Ping, Liu Tao-Yan, Qin Xiao-Yan, Yu Long-Chuan

机构信息

Laboratory of Biotechnology and State Key Laboratory of Chinese Ethnic Minority Traditional Medicine, College of Life & Environmental Science, Minzu University of China, Beijing 100081, China.

Laboratory of Biotechnology and State Key Laboratory of Chinese Ethnic Minority Traditional Medicine, College of Life & Environmental Science, Minzu University of China, Beijing 100081, China.

出版信息

Neurosci Lett. 2014 Jul 25;576:79-83. doi: 10.1016/j.neulet.2014.05.045. Epub 2014 Jun 2.

Abstract

The present study explored the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG) on the staurosporine (STS)-induced toxicity in cultured rat hippocampal neurons. The results showed that administration of 200μM of THSG significantly protected against 0.3μM of STS-induced apoptosis in cultured rat hippocampal neurons tested by methyl thiazolyl tetrazolium (MTT) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays. Furthermore, when the Akt signaling pathway was blocked by LY294002, an inhibitor of Phosphatidyl Inositol 3-kinase (PI3K), the protective effects of THSG against STS-induced neurotoxicity were abrogated. We further examined the involvement of PI3K/Akt signaling pathway in THSG protection against STS-induced cytotoxicity on cultured neurons and found that administration of THSG significantly inhibited the STS-induced decreases in the content of phosphorylated AKt (p-Akt). Moreover, we found that THSG rescued the down-regulation of B cell lymphoma/lewkmia-2 (Bcl2) and pro-caspase-3 (pro-Csp3) caused by STS in the neurons. These results indicate that THSG protect the cultured rat hippocampal neurons against STS-induced cytotoxicity and the PI3K/Akt signaling and mitochondrial apoptotic pathways are involved in the THSG-induced protective effects.

摘要

本研究探讨了2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷(THSG)对星形孢菌素(STS)诱导的原代培养大鼠海马神经元毒性的影响。结果显示,通过噻唑蓝(MTT)和脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)检测发现,给予200μM的THSG可显著保护原代培养大鼠海马神经元免受0.3μM的STS诱导的细胞凋亡。此外,当磷脂酰肌醇3激酶(PI3K)抑制剂LY294002阻断Akt信号通路时,THSG对STS诱导的神经毒性的保护作用被消除。我们进一步研究了PI3K/Akt信号通路在THSG保护原代培养神经元免受STS诱导的细胞毒性中的作用,发现给予THSG可显著抑制STS诱导的磷酸化Akt(p-Akt)含量降低。此外,我们发现THSG可挽救神经元中由STS引起的B细胞淋巴瘤/白血病-2(Bcl2)和前半胱天冬酶-3(pro-Csp3)的下调。这些结果表明,THSG可保护原代培养大鼠海马神经元免受STS诱导的细胞毒性,且PI3K/Akt信号通路和线粒体凋亡途径参与了THSG诱导的保护作用。

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