Taurine attenuates methamphetamine-induced autophagy and apoptosis in PC12 cells through mTOR signaling pathway
Taurine attenuates methamphetamine-induced autophagy and apoptosis in PC12 cells through mTOR signaling pathway
复制标题
牛磺酸通过 mTOR 信号通路减弱甲基苯丙胺诱导的 PC12 细胞自噬和凋亡。
DOI：
10.1016/j.toxlet.2012.09.019
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发表时间：
2012-11-23
影响因子：
3.5
通讯作者：
Cen, Xiaobo
中科院分区：
文献类型：
--
作者：
Li, Yan;Hu, Zhengtao;Cen, Xiaobo
甲基苯丙胺（METH）是一种常见的滥用精神兴奋剂，已证实其可通过产生活性氧（ROS）、诱导细胞凋亡和自噬来造成神经元损伤。牛磺酸（2 - 氨基乙磺酸）参与大脑中的多种生理活动，包括神经保护、渗透调节和神经传递。在本研究中，我们探究了牛磺酸对METH诱导的PC12细胞神经毒性的保护作用及其潜在机制。结果显示，牛磺酸显著提高了被METH抑制的细胞活力。METH处理可使LC3 - II表达升高，而牛磺酸能明显减弱这种升高。牛磺酸与METH共同处理可强烈逆转由METH诱导的抗氧化酶活性下降。此外，METH显著抑制雷帕霉素的磷酸化哺乳动物靶点（p - mTOR），而补充牛磺酸则显著增加PC12细胞中p - mTOR的表达，但对磷酸化细胞外调节蛋白激酶（p - Erk）无此作用。有趣的是，牛磺酸诱导的LC3 - II表达下降可部分被mTOR抑制剂RAD001预处理所阻断。这些结果表明，牛磺酸通过激活mTOR而非Erk信号通路来抑制METH诱导的自噬过程。总体而言，我们的研究表明，牛磺酸至少部分地通过mTOR信号通路，通过减少ROS生成、细胞凋亡和自噬来保护PC12细胞免受METH诱导的损伤。（C）2012爱思唯尔爱尔兰有限公司。保留所有权利。
Methamphetamine (METH), a commonly abused psychostimulant, has been shown to induce neuronal damage by causing reactive oxygen species (ROS) formation, apoptosis and autophagy. Taurine (2-aminoethanesulfonic acid) is involved in several physiological actions in the brain, including neuroprotection, osmoregulation and neurotransmission. In this study, we investigate the protective effect of taurine against METH-induced neurotoxicity in PC12 cells and the underlying mechanism. The results showed that taurine significantly increased the cell viability inhibited by METH. LC3-II expression was elevated by METH treatment, whereas such increase was obviously attenuated by taurine. Co-treatment of taurine strongly reversed the decline of antioxidase activities induced by METH. Moreover, phosphorylated mammalian target of rapamycin (p-mTOR) was significantly inhibited by METH, whereas complementation of taurine markedly increased the expression of p-mTOR in PC12 cells, rather than phosphorylated Erk. Interestingly, taurine-induced decreasing expression of LC3-II was partially blocked by pretreatment of RAD001, an mTOR inhibitor. These results indicated that taurine inhibits METH-induced autophagic process through activating mTOR rather than Erk signaling. Collectively, our study shows that taurine protects METH-induced PC12 cells damage by attenuating ROS production, apoptosis and autophagy, at least in part, via mTOR signaling pathway. (C) 2012 Elsevier Ireland Ltd. All rights reserved.