α-mangostin induces Ca2+-ATPase-dependent apoptosis via mitochondrial pathway in PC12 cells
α-mangostin induces Ca2+-ATPase-dependent apoptosis via mitochondrial pathway in PC12 cells
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DOI：
10.1254/jphs.95.33
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发表时间：
2004-05-01
影响因子：
3.5
通讯作者：
Ohizumi, Y
中科院分区：
文献类型：
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作者：
Sato, A;Fujiwara, H;Ohizumi, Y
我们研究了8种氧杂蒽酮对PC 12大鼠嗜铬细胞瘤细胞的细胞死亡作用。在这些化合物中，α-倒捻子素，来自山竹果的果实船体，具有最强的作用，EC 50值为4 μ M。α-Mangostin处理的PC 12细胞表现出典型的凋亡DNA片段化和半胱天冬酶-3切割（相当于活化）。流式细胞仪分析表明，该化合物诱导细胞凋亡的时间和浓度依赖性的方式。alpha-Mangostin显示了线粒体凋亡途径的特征，如线粒体膜去极化和细胞色素c释放。此外，α-倒捻子素对肌浆网Ca ~（2+）-ATPase有明显的抑制作用。Ca ~（2+）-ATP酶抑制作用与氧杂蒽酮衍生物的细胞凋亡作用之间存在相关性。另一方面，c-Jun NH 2-末端激酶（JNK/SAPK），内质网（ER）应激的信号分子之一，被α-mangostin处理激活。这些结果表明，α-倒捻子素抑制Ca 2 +-ATP酶，通过线粒体途径引起细胞凋亡。
We investigated the cell death effects of eight xanthones on PC12 rat pheochromocytoma cells. Among these compounds, alpha-mangostin, from the fruit hull of Garcinia mangostana L., had the most potent effect with the EC50 value of 4 muM. alpha-Mangostin-treated PC12 cells demonstrated typical apoptotic DNA fragmentation and caspase-3 cleavage (equivalent to activation). The flow cytometric analysis indicated that this compound induced apoptosis in time- and concentration-dependent manners. alpha-Mangostin showed the features of the mitochondrial apoptotic pathway such as mitochondrial membrane depolarization and cytochrome c release. Furthermore, a-mangostin inhibited the sarco(endo)plasmic reticulum Ca2+-ATPase markedly. There was a correlation between the Ca2+-ATPase inhibitory effects and the apoptotic effects of the xanthone derivatives. On the other hand, c-Jun NH2-terminal kinase (JNK/SAPK), one of the signaling molecules of endoplasmic reticulum (ER) stress, was activated with alpha-mangostin treatment. These results suggest that alpha-mangostin inhibits Ca2+-ATPase to cause apoptosis through the mitochondorial pathway.