中国药理学通报2012，Vol.28Issue(7)：961-966,6.DOI:10.3969/j.issn.1001-1978.2012.07.018
胞外信号调节激酶1/2通路在阿霉素引起的心肌细胞损伤中的作用
Role of ERK1/2 pathway in doxorubicin-induced cardiomyocyte injury
摘要
Abstract
Aim To investigate the role of extracellular signal-regulated kinases 1/2 (ERK1/2) pathway in doxorubicin ( DOX) -induced injury in H9c2 cardiac cells (H9c2 cells). Methods H9c2 cells were treated with DOX to establish a model of cellular injury. PD-98059 was applied before exposure to DOX to inhibit ERK1/2 pathway. Cell viability, activation of ERK1/ 2, intracellular reactive oxygen species ( ROS) , mito-chondrial membrane potential ( MMP) and cystathi-onine-γ4yase ( CSE, a synthase of endogenous hydro-gen sulfide ) expression were tested. Results Exposure of H9c2 ceUs to 5 μmol· I-1 DOX for 1 to 6 h time-dependently induced the activation of ERK1/2. DOX at 5 μmol ·L-1 had a damage effect on H9c2 cells, evidenced by decreases in cell viability , MMP and expression of CSE , and an increase in intracellular ROS level. Pretreatment with PD-98059 at 10 μmol· L-1 for 30 min before exposure of H9c2 cells to DOX significantly blocked DOX -induced cell injury , leadingto increases in cell viability, MMP and CSE expression, and a decrease in ROS level. Conclusion ERK1/2 pathway is involved in H9c2 cell injury induced by DOX.关键词
阿霉素/心肌毒性/H9c2心肌细胞/氧自由基/线粒体膜电位/胞外信号调节激酶1/2Key words
doxorubicin/ cardiac toxicity/ H9c2 cardiac cells/ reactive oxygen species/ mitochondrial membrane potential/ extracellular signal regulated kinase 1/2分类
医药卫生引用本文复制引用
张莉莉,赖东平,王秀玉,郑东诞,郭润民,沈宁,陈培熹,冯鉴强..胞外信号调节激酶1/2通路在阿霉素引起的心肌细胞损伤中的作用[J].中国药理学通报,2012,28(7):961-966,6.基金项目
广东省科技计划项目(No 2011B080701051,2010B080701105,2010B080701035,2010B080701015) （No 2011B080701051,2010B080701105,2010B080701035,2010B080701015）
