School of Medicine, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China.
Brain Res Bull. 2011 Feb 1;84(2):183-8. doi: 10.1016/j.brainresbull.2010.12.008. Epub 2010 Dec 21.
This study investigated effects of trifluoperazine (TFP) against the cytotoxicity induced by H₂O₂ in PC12 cells and the mechanisms thereof. Different concentrations of H₂O₂ (100-500 μM) induced a significant decrease in cell viability accompanied by increased oxidative stress and cell apoptosis. Pretreatment with TFP inhibited H₂O₂-induced cell viability loss. The flow cytometric assay showed that TFP can inhibit intracellular reactive oxygen species (ROS) generation and reduce the cell apoptosis. The electrophysiological recordings indicated that when treated with H₂O₂, the calcium current was significantly increased. Pretreatment with TFP increased mitochondrial membrane potential (MMP) in cells of oxidative injury. These results suggested that TFP can reduce apoptosis by inhibiting ROS generation and preventing loss of MMP in cells. Meanwhile, the protective effect of TFP on the cell apoptosis may be related to the calcium overload. TFP may inhibit the calcium overload process to achieve the protection against apoptosis.
本研究探讨了三氟拉嗪(TFP)对 H₂O₂诱导的 PC12 细胞毒性的作用及其机制。不同浓度的 H₂O₂(100-500μM)可显著降低细胞活力,同时增加氧化应激和细胞凋亡。TFP 预处理可抑制 H₂O₂诱导的细胞活力丧失。流式细胞术检测显示,TFP 可抑制细胞内活性氧(ROS)的产生,并减少细胞凋亡。电生理记录表明,用 H₂O₂处理后,钙电流显著增加。TFP 预处理可增加氧化损伤细胞的线粒体膜电位(MMP)。这些结果表明,TFP 可通过抑制 ROS 生成和防止 MMP 丧失来减少细胞凋亡。同时,TFP 对细胞凋亡的保护作用可能与钙超载有关。TFP 可能通过抑制钙超载过程来实现对凋亡的保护。