Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) as an O2•- generator induces apoptosis via the depletion of intracellular GSH contents in Calu-6 cells
Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) as an O2•- generator induces apoptosis via the depletion of intracellular GSH contents in Calu-6 cells
复制标题
DOI：
10.1016/j.lungcan.2008.05.005
复制
发表时间：
2009-02-01
期刊：
影响因子：
5.3
通讯作者：
Park, Woo Hyun
中科院分区：
文献类型：
--
作者：
Han, Yong Hwan;Kim, Suhn Hee;Park, Woo Hyun
羰基氰对三氟甲氧基苯腙（FCCP）是真核细胞线粒体氧化磷酸化的解偶联剂。在这里，我们研究了O-2（中心点-）和GSH在FCCP诱导的Calu-6细胞死亡的参与，并检查ROS清除剂是否从FCCP诱导的细胞死亡中拯救细胞。细胞内O-2（中心点-）的水平显着增加，这取决于FCCP的浓度（5-100 μ M）。在将细胞暴露于FCCP稳定SOD模拟物后，也观察到细胞内GSH含量的耗尽，Tempol和Tiron不改变细胞内O-2（中心点-）、凋亡和线粒体膜电位（DIP m）的损失的水平。巯基抗氧化剂，NAC和DTT的治疗，表现出恢复的GSH消耗和减少的O-2（中心点-）水平在FCCP处理的细胞，这是伴随着细胞凋亡的抑制。与此相反，BSO，一个众所周知的GSH合成抑制剂，加重GSH消耗，O-2（中心点-）的氧化应激和FCCP处理的细胞中的细胞死亡。综上所述，我们的数据表明，FCCP作为一个O-2（中心点-）发生器，诱导细胞凋亡，通过细胞内GSH含量的耗尽在Calu-6细胞。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) is an uncoupler of mitochondrial oxidative phosphorylation in eukaryotic cells. Here, we investigated an involvement of O-2(center dot-) and GSH in FCCP-induced Calu-6 cell death and examined whether ROS scavengers rescue cells from FCCP-induced cell death. Levels of intracellular O-2(center dot-) were markedly increased depending on the concentrations (5-100 mu M) of FCCP. A depletion of intracellular GSH content was also observed after exposing cells to FCCP Stable SOD mimetics, Tempol and Tiron did not change the levels of intracellular O-2(center dot-), apoptosis and the loss of mitochondrial membrane potential (DIP m). Treatment with thiol antioxidants, NAC and DTT, showed the recovery of GSH depletion and the reduction of O-2(center dot-) levels in FCCP-treated cells, which were accompanied by the inhibition of apoptosis. In contrast, BSO, a well-known inhibitor of GSH synthesis, aggravated GSH depletion, oxidative stress of O-2(center dot-) and cell death in FCCP-treated cells. Taken together, our data suggested that FCCP as an O-2(center dot-) generator, induces apoptosis via the depletion of intracellular GSH contents in Calu-6 cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.