Synergistic effects of hydrogen peroxide and ethanol on cell viability loss in PC12 cells by increase in mitochondrial permeability transition
Synergistic effects of hydrogen peroxide and ethanol on cell viability loss in PC12 cells by increase in mitochondrial permeability transition
复制标题
DOI：
10.1016/j.bcp.2005.04.029
复制
发表时间：
2005-07-15
影响因子：
5.8
通讯作者：
Han, ES
中科院分区：
文献类型：
--
作者：
Lee, CS;Kim, YJ;Han, ES
通过测量对线粒体膜通透性的影响来评估乙醇对过氧化氢（H2 O2）在分化的PC 12细胞中的细胞毒性的促进作用。H_2O_2处理PC 12细胞后，细胞核损伤，线粒体跨膜电位降低，细胞色素c积聚，caspase-3激活，活性氧（ROS）生成增加，GSH耗竭。在PC 12细胞和多巴胺能神经母细胞瘤SH-SY 5 Y细胞中，乙醇对H2 O2诱导的细胞死亡的促进作用随着暴露时间的增加而增加。乙醇可引起PC 12细胞核损伤、线粒体膜通透性改变、ROS生成及GSH含量下降。过氧化氢酶、羧基PTIO、Mn-TBAP、N-乙酰半胱氨酸、环孢素A和三氟拉嗪可抑制H2 O2和乙醇诱导的线粒体功能障碍和细胞损伤。结果表明，乙醇处理可促进H2 O2对PC 12细胞的毒性作用。乙醇可能通过促进线粒体膜通透性的改变、细胞色素c的释放以及随后的caspase-3的激活而增强H2 O2诱导的PC 12细胞活力丧失，这与ROS的形成增加和GSH的耗竭有关。结果提示乙醇作为线粒体通透性转换的促进剂，可能会增强氧化剂对神经细胞的损伤。(c)2005年爱思唯尔公司All rights reserved.
The promoting effect of ethanol against the cytotoxicity of hydrogen peroxide (H2O2) in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. Treatment of PC12 cells with H2O2 resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species (ROS) and depletion of GSH. In PC12 cells and dopaminergic neuroblastoma SH-SY5Y cells, the promoting effect of ethanol on the H2O2-induced cell death was increased with exposure time. Ethanol promoted the nuclear damage, change in the mitochondrial membrane permeability, ROS formation and decrease in GSH contents due to H2O2, in PC12 cells. Catalase, carboxy-PTIO, Mn-TBAP, N-acetylcysteine, cyclosporin A and trifluoperazine inhibited the H2O2 and ethanol-induced mitochondrial dysfunction and cell injury. The results show that the ethanol treatment promotes the cytotoxicity of H2O2 against PC12 cells. Ethanol may enhance the H2O2-induced viability loss in PC12 cells by promoting the mitochondrial membrane permeability change, release of cytochrome c and subsequent activation of caspase-3, which is associated with the increased formation of ROS and depletion of GSH. The findings suggest that ethanol as a promoting agent for the formation of mitochondrial permeability transition may enhance the neuronal cell injury caused by oxidants. (c) 2005 Elsevier Inc. All rights reserved.