Asiatic acid protects primary neurons against C2-ceramide-induced apoptosis
Asiatic acid protects primary neurons against C2-ceramide-induced apoptosis
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DOI：
10.1016/j.ejphar.2012.01.006
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发表时间：
2012-03-15
影响因子：
5
通讯作者：
Lou, Yijia
中科院分区：
文献类型：
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作者：
Zhang, Xiangnan;Wu, Jiaying;Lou, Yijia
鞘氨醇衍生的神经酰胺参与包括阿尔茨海默病在内的神经退行性疾病的神经元细胞凋亡过程。本研究探讨了从积雪草中提取的三萜亚洲酸对原代培养的大鼠皮质神经元细胞c -2神经酰胺诱导的细胞死亡的潜在神经保护作用。在原代神经元中，亚细亚酸（0.01 ~ 1.0 μ mol/l）以浓度依赖的方式降低c -2神经酰胺诱导的细胞死亡和线粒体膜电位损失。此外，亚细亚酸减少了c -2神经酰胺处理后的细胞活性氧的产生。在最大浓度为1.0 μ mol/l时，亚硝酸通过降低细胞内HtrA2/Omi的释放，上调Bax和caspase 3，以及ERK1/2的去磷酸化，部分抵消了c -2神经酰胺的促凋亡作用。综上所述，这些数据表明，亚细亚酸通过拮抗线粒体依赖性细胞凋亡，保护神经元免受c -2神经酰胺诱导的细胞死亡。(C) 2012 Elsevier B.V.版权所有
Ceramides derived from sphingosine contribute to the apoptotic processes of neuronal cells in neurodegenerative disorders including Alzheimer's disease. This study investigates the potential neuroprotective effects of Asiatic acid, a triterpenoid derived from Centella asiatica, against C-2-ceramides-induced cell death in primary cultured rat cortical neuronal cells. In primary neurons, Asiatic acid (0.01 to 1.0 mu mol/l) reduced C-2-ceramide-induced cell death and mitochondria membrane potential loss in a concentration-dependent manner. Furthermore, Asiatic acid decreased cellular production of reactive oxygen species following C-2-ceramide treatment. At a maximal concentration of 1.0 mu mol/l, Asiatic acid partly counteracted the pro-apoptotic effects of the C-2-ceramide by reducing the cytosolic release of HtrA2/Omi, the upregulation of Bax and caspase 3, as well as the dephosphorlyation of ERK1/2. Taken together, these data suggest that Asiatic acid protects neurons from C-2-ceramide-induced cell death by antagonizing mitochondria-dependent apoptosis. (C) 2012 Elsevier B.V. All rights reserved.