中国药理学通报2013，Vol.29Issue(7)：985-990,6.DOI:10.3969/j.issn.1001-1978.2013.07.022
活性氧激活的ERK1/2通路在化学性缺氧损伤PC12细胞中的作用
Role of ROS-activated ERK1/2 pathway in chemical hypoxia-induced injury in PC12 cells
摘要
Abstract
Aim To explore the role of extracellular signal-regulated kinase l/2( ERK1/2 ) in the chemical hypoxia-induced injury in PC12 cells. Methods PC12 cells were treated with cobalt chloride( CoCl2 ), a well-known chemical hypoxia mimetic agent, to establish a chemical hypoxia-induced cellular injury model. Cell viability was detected by cell counter kit ( CCK-8 ). Apoptotic cells were analysed by Flow cy-tometry ( FCM ). Mitochondrial membrane potential ( MMP ) was examined by rhodamine 123 ( RH123 ) staining and photoflutograph. The expression levels of caspase-3 , ERK1/2 and p38 mitogen-activated protein kinase( MAPK ) were tested by Western blot assay. Results Exposure of PC 12 cells to 600 μmol · L-1 CoCl2 for 60 min markedly enhanced the expression of phosphorylated( p ) ERK1/2. Pretreatment of PC12 cells with 500 μmol · L-1 N-acetyl-L-cystein( NAC ), a reactive oxygen species ( ROS ) scavenger, for 1h before exposure to CoCl2 inhibited the upregulation of p-ERK1/2 expression induced by CoCl2 treatment. Pretreatment of PC 12 cells with 10 μmol · L-1 U0126( an inhibitor of ERK1/2 ) for 2h prior to exposure to 600 μmol · L-1 CoCl2 protected against the CoCl2-induced injuries , leading to decreases in the number of apoptotic cells, expression of cleaved caspase-3 as well as MMP loss. Pretreatment with 10 μmol · L-1 U0126 also attenuated the CoCl2-induced upregulation of p-p38MAPK expression. Furthermore, preteatment with 20 μmol· L-1 SB203580, an inhibitor of p38MAPK, blocked the CoCl2 -induced upregulation of p-ERK1/2 expression. Conclusions ROS-activated ERK1/2 pathway mediates the CoCl2 -induced injury and there is a synergetic interaction between ERK1/2 pathway and p38MAPK in CoCl2 treated PC12 cells.关键词
ERK1/2/活性氧/氯化钴/凋亡/线粒体膜电位/p38MAPKKey words
ERK1/2/ reactive oxygen species/ cobalt chloride/ apoptosis/ mitochondrial membrane potential/p38MAPK分类
医药卫生引用本文复制引用
徐文明,兰爱平,林建聪,郭润民,沈宁,陈培熹,冯鉴强..活性氧激活的ERK1/2通路在化学性缺氧损伤PC12细胞中的作用[J].中国药理学通报,2013,29(7):985-990,6.基金项目
广东省科技计划基金资助项目(No 2012B031800358,2010B080701035) （No 2012B031800358,2010B080701035）
