Gypenosides protect primary cultures of rat cortical cells against oxidative neurotoxicity
Gypenosides protect primary cultures of rat cortical cells against oxidative neurotoxicity
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DOI：
10.1016/j.brainres.2006.05.035
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发表时间：
2006-08-02
期刊：
影响因子：
2.9
通讯作者：
Xin, Hua
中科院分区：
文献类型：
--
作者：
Shang, Linshan;Liu, Jincheng;Xin, Hua
测试了绞股蓝皂苷 (GP) 保护未成熟皮质细胞原代培养物免受氧化谷氨酸毒性的能力。在未成熟的神经细胞中，已知谷氨酸细胞毒性是通过抑制胱氨酸摄取介导的，从而导致细胞内谷胱甘肽 (GSH) 的消耗。 GSH 的消耗会损害细胞的抗氧化防御，导致氧化应激和细胞死亡。我们发现，用 GP（100-400 μg/ml）预处理可显着保护细胞免受谷氨酸诱导的细胞死亡。因此，研究 GP 是否通过阻止 GSH 消耗来保护皮质细胞免受谷氨酸诱导的氧化损伤是很有意义的。结果表明，GP 显着上调编码 γ-谷氨酰半胱氨酸合成酶 (gamma-GCS) 和谷胱甘肽还原酶 (GR) 的 mRNA，并增强其 GSH 合成和循环活性。此外，GPs通过减少细胞内过氧化物的积累来降低GSH的消耗，导致细胞内GSH含量增加。还发现 GP 可以防止脂质过氧化并减少通常在谷氨酸氧化挑战后发生的 Ca2+ 流入。 GPs 治疗显着阻止谷氨酸诱导的 Bcl-2 水平下降和 Bax 水平增加，从而减少谷氨酸诱导的细胞凋亡。因此，我们得出结论，GPs 通过增强细胞内 GSH、抑制谷氨酸诱导的胞浆 Ca2+ 升高和阻止谷氨酸诱导的细胞凋亡等多种抗氧化作用来保护皮质细胞。 GP 的新作用意味着它们在治疗涉及谷氨酸和氧化应激的神经系统疾病方面具有显着的预防和治疗潜力。 (c) 2006 Elsevier B.V. 保留所有权利。
Gypenosides (GPs) were tested for their ability to protect primary cultures of immature cortical cells against oxidative glutamate toxicity. In immature neural cells, glutamate cytotoxicity is known to be mediated by the inhibition of cystine uptake, leading to depletion of intracellular glutathione (GSH). The depletion of GSH impairs cellular antioxidant defenses resulting in oxidative stress and cell death. We found that pretreatment with GPs (100-400 mu g/ml) significantly protected cells from glutamate-induced cell death. It was therefore of interest to investigate whether GPs protect cortical cells against glutamate-induced oxidative injury through preventing GSH depletion. Results show that GPs significantly up-regulated mRNAs encoding gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione reductase (GR) and enhanced their activities for GSH synthesis as well as recycle. Furthermore, GPs lowered the consumption of GSH through decreased accumulation of intracellular peroxides, leading to an increase in the intracellular GSH content. GPs.were also found to prevent lipid peroxidation and reduce the influx of Ca2+ which routinely follows glutamate oxidative challenge. GPs treatment significantly blocked glutamate-induced decrease in levels of Bcl-2 and increase in Bax, leading to a decrease in glutamate-induced apoptosis. Thus, we conclude that GPs protect cortical cells by multiple antioxidative actions via enhancing intracellular GSH, suppressing glutamate-induced cytosolic Ca2+ elevation and blocking glutamate-induced apoptosis. The novel role of GPs implies their remarkable preventative and therapeutic potential in treatment of neurological diseases involving glutamate and oxidative stress. (c) 2006 Elsevier B.V. All rights reserved.