Glutamate induces mitochondrial dynamic imbalance and autophagy activation: preventive effects of selenium.
Glutamate induces mitochondrial dynamic imbalance and autophagy activation: preventive effects of selenium.
复制标题
DOI：
10.1371/journal.pone.0039382
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Li PA
中科院分区：
文献类型：
--
作者：
Kumari S;Mehta SL;Li PA
谷氨酸诱导的细胞毒性部分由增强的氧化应激介导。本研究的目的是确定谷氨酸对线粒体膜电位，耗氧量，线粒体动力学和自噬调节因子的影响，并探讨硒对谷氨酸细胞毒性的保护作用。我们的研究结果表明，谷氨酸导致细胞死亡的剂量依赖性的方式和补充100纳米亚硒酸钠防止谷氨酸对细胞存活的不利影响。谷氨酸诱导的细胞毒性与线粒体超极化、增加的ROS产生和增加的氧消耗有关。硒逆转了这些变化。此外，谷氨酸增加线粒体分裂蛋白标记pDrp 1和Fis 1的水平，并导致线粒体碎片化增加。硒纠正了谷氨酸引起的线粒体动态失衡，减少了线粒体碎片的细胞数量。最后，谷氨酸激活自噬标记Beclin 1和LC 3-II，而硒阻止激活。这些结果表明，谷氨酸靶向线粒体和生理浓度的硒补充能够防止谷氨酸对线粒体的不利影响。因此，适当的硒补充可能是一种有效的策略，以防止有害的谷氨酸毒性和进一步的研究是必要的，以确定硒在动物疾病模型和人类的治疗潜力。
Glutamate-induced cytotoxicity is partially mediated by enhanced oxidative stress. The objectives of the present study are to determine the effects of glutamate on mitochondrial membrane potential, oxygen consumption, mitochondrial dynamics and autophagy regulating factors and to explore the protective effects of selenium against glutamate cytotoxicity in murine neuronal HT22 cells. Our results demonstrated that glutamate resulted in cell death in a dose-dependent manner and supplementation of 100 nM sodium selenite prevented the detrimental effects of glutamate on cell survival. The glutamate induced cytotoxicity was associated with mitochondrial hyperpolarization, increased ROS production and enhanced oxygen consumption. Selenium reversed these alterations. Furthermore, glutamate increased the levels of mitochondrial fission protein markers pDrp1 and Fis1 and caused increase in mitochondrial fragmentation. Selenium corrected the glutamate-caused mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria. Finally, glutamate activated autophagy markers Beclin 1 and LC3-II, while selenium prevented the activation. These results suggest that glutamate targets the mitochondria and selenium supplementation within physiological concentration is capable of preventing the detrimental effects of glutamate on the mitochondria. Therefore, adequate selenium supplementation may be an efficient strategy to prevent the detrimental glutamate toxicity and further studies are warranted to define the therapeutic potentials of selenium in animal disease models and in human.
登录
查看更多内容
影响因子：
11.4
作者：
Adrain, C;Creagh, EM;Martin, SJ
通讯作者：
Martin, SJ
影响因子：
3.5
作者：
Chen H;Chan DC
通讯作者：
Chan DC
影响因子：
16.2
作者：
MURPHY, TH;MIYAMOTO, M;COYLE, JT
通讯作者：
COYLE, JT
影响因子：
8.4
作者：
Hadaszadeh, Behzad M.;Beggs, Alan H.
通讯作者：
Beggs, Alan H.
影响因子：
4.4
作者：
Mendelev, Natalia;Mehta, Suresh L.;Witherspoon, Sam;He, Qingping;Sexton, Jonathan Z.;Li, P. Andy
通讯作者：
Li, P. Andy