A novel pathway of NADPH oxidase/vascular peroxidase 1 in mediating oxidative injury following ischemia-reperfusion
A novel pathway of NADPH oxidase/vascular peroxidase 1 in mediating oxidative injury following ischemia-reperfusion
复制标题
NADPH氧化酶/血管过氧化物酶1介导缺血再灌注后氧化损伤的新途径
DOI：
10.1007/s00395-012-0266-4
复制
发表时间：
2012-05-01
影响因子：
9.5
通讯作者：
Peng, Jun
中科院分区：
文献类型：
--
作者：
Zhang, Yi-Shuai;He, Lan;Peng, Jun
血管过氧化物酶1（VPO 1）可利用NADPH氧化酶（NOX）产生的活性氧（ROS）催化过氧化反应。本研究旨在探讨NOX/VPO 1介导心肌缺血再灌注（IR）后氧化损伤的新途径。在大鼠心肌缺血再灌注模型上，检测心肌梗死面积、血清肌酸激酶（CK）活性、细胞凋亡、一氧化氮（NOX）活性、NOX 2和VPO 1表达。在缺氧/复氧（HR）的细胞（大鼠心脏来源的H9 c2细胞）模型中，检测细胞凋亡、NOX活性、NOX 2和VPO 1表达以及H2 O2和HOCl水平。在体内，IR导致心肌梗死面积为54.8 +/-1.7%，伴有CK、caspase-3和NOX活性升高，VPO 1表达上调和大量心肌凋亡细胞;用NOX抑制剂预处理可减弱这些效应。在体外，抑制NOX或沉默NOX 2或VPO 1的表达显着抑制HR诱导的细胞凋亡伴随着HOCl生产减少。抑制NOX或沉默NOX 2导致H2 O2产生减少，伴随着VPO 1表达和HOCl产生减少。然而，VPO 1表达的沉默并不影响NOX 2的表达和H2 O2的产生。JNK或p38 MAPK抑制剂可部分逆转H2 O2诱导的VPO 1表达。我们的研究结果证明了心肌中NOX 2/VPO 1的新途径，其中VPO 1与NOX 2协调并放大了IR后氧化损伤中NOx衍生的ROS的作用。
Vascular peroxidase 1 (VPO1) can utilize reactive oxygen species (ROS) generated from NADPH oxidase (NOX) to catalyze peroxidative reactions. This study was performed to identify a novel pathway of NOX/VPO1 in mediating the oxidative injury following myocardial ischemia reperfusion (IR). In a rat model of myocardial IR, the infarct size, serum creatine kinase (CK) activity, apoptosis, NOX activity, NOX2 and VPO1 expression were measured. In a cell (rat heart-derived H9c2 cells) model of hypoxia/reoxygenation (HR), the apoptosis, NOX activity, NOX2 and VPO1 expression, and H2O2 and HOCl levels were examined. In vivo, IR caused 54.8 +/- 1.7 % infarct size in myocardium accompanied by elevated activities of CK, caspase-3 and NOX, up-regulated VPO1 expression and high numbers of myocardial apoptotic cells; these effects were attenuated by pretreatment with the inhibitor of NOX. In vitro, inhibition of NOX or silencing of NOX2 or VPO1 expression significantly suppressed HR-induced cellular apoptosis concomitantly with decreased HOCl production. Inhibition of NOX or silencing of NOX2 led to a decrease in H2O2 production accompanied by a decrease in VPO1 expression and HOCl production. However, silencing of VPO1 expression did not affect NOX2 expression and H2O2 production. H2O2-induced VPO1 expression was partially reversed by JNK or p38 MAPK inhibitor. Our results demonstrate a novel pathway of NOX2/VPO1 in myocardium, where VPO1 coordinates with NOX2 and amplifies the role of NOX-derived ROS in oxidative injury following IR.