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绒毛野靛堿诱导 C6 神经胶质瘤细胞凋亡需要线粒体来源的活性氧的释放和 p38、JNK 的激活。

Mimosine-induced apoptosis in C6 glioma cells requires the release of mitochondria-derived reactive oxygen species and p38, JNK activation.

机构信息

Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi, 487-8501, Japan.

出版信息

Neurochem Res. 2012 Feb;37(2):417-27. doi: 10.1007/s11064-011-0628-6. Epub 2011 Oct 11.

Abstract

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 cytochrome c from 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.

摘要

分析了植物氨基酸——含羞草氨酸对大鼠 C6 神经胶质瘤细胞的生长抑制作用。含羞草氨酸呈剂量和时间依赖性显著抑制 C6 神经胶质瘤细胞的增殖并诱导其凋亡。含羞草氨酸介导的细胞凋亡伴随着线粒体中活性氧(ROS)生成的增加,以及线粒体膜电位(Δψ)的降低和细胞色素 c 从线粒体中的释放,随后激活半胱天冬酶 3。此外,含羞草氨酸增加了 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。含羞草氨酸通过 ROS 调节的线粒体途径证实对 C6 神经胶质瘤细胞的凋亡有显著影响,这些结果支持了含羞草氨酸作为治疗恶性神经胶质瘤的有前途的药物的假设。

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