Mimosine-Induced Apoptosis in C6 Glioma Cells Requires the Release of Mitochondria-Derived Reactive Oxygen Species and p38, JNK Activation

Mimosine-Induced Apoptosis in C6 Glioma Cells Requires the Release of Mitochondria-Derived Reactive Oxygen Species and p38, JNK Activation
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DOI:
10.1007/s11064-011-0628-6
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发表时间:
2011-10
影响因子:
4.4
通讯作者:
Shanlou Qiao;K. Murakami;Qinghong Zhao;Bao Wang;H. Seo;H. Yamashita;Xiaotao Li;T. Iwamoto;M. Ichihara;M. Yoshino
Shanlou Qiao;K. Murakami;Qinghong Zhao;Bao Wang;H. Seo;H. Yamashita;Xiaotao Li;T. Iwamoto;M. Ichihara;M. Yoshino
中科院分区:
医学3区
文献类型:
--
作者:
Shanlou Qiao;K. Murakami;Qinghong Zhao;Bao Wang;H. Seo;H. Yamashita;Xiaotao Li;T. Iwamoto;M. Ichihara;M. Yoshino

文献摘要

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分析了植物氨基酸含羞草碱对大鼠C6胶质瘤细胞的生长抑制作用。含羞草碱可明显抑制C6胶质瘤细胞增殖并诱导其凋亡,且呈剂量和时间依赖性。含羞草素介导的细胞凋亡伴随着线粒体活性氧(ROS)的产生、线粒体膜电位(Δ E)的降低、细胞色素c的释放以及caspase 3的激活。此外,含羞草碱增加c-Jun-N-末端蛋白激酶和p38的磷酸化水平,这是ROS积累的下游效应。含羞草素通过ROS调控的线粒体途径诱导C6胶质瘤细胞凋亡,这些结果为含羞草素作为治疗恶性胶质瘤的有效药物奠定了基础。
Growth-inhibitory effects of mimosine, a plant amino acid, on rat C6 glioma cells were analyzed. Mimosine markedly inhibited proliferation and induced apoptosis of C6 glioma cells in a dose- and time-dependent manner. Mimosine-mediated apoptosis was accompanied by promoting reactive oxygen species (ROS) generation in mitochondria, and by decreased mitochondrial membrane potential (Δψ), and release of cytochromecfrom mitochondria, followed by caspase 3 activation. Furthermore, mimosine increased the phosphorylation level of c-Jun-N-terminal protein kinase and p38, which was the downstream effect of ROS accumulation. Mimosine was confirmed to show profound effects on apoptosis of C6 glioma cells by ROS-regulated mitochondria pathway, and these results bear on the hypothesized potential for mimosine as promising agents in the treatment of malignant gliomas.