Published in:
01-05-2012 | Original Contribution
A novel pathway of NADPH oxidase/vascular peroxidase 1 in mediating oxidative injury following ischemia–reperfusion
Authors:
Yi-Shuai Zhang, Lan He, Bin Liu, Nian-Sheng Li, Xiu-Ju Luo, Chang-Ping Hu, Qi-Lin Ma, Guo-Gang Zhang, Yuan-Jian Li, Jun Peng
Published in:
Basic Research in Cardiology
|
Issue 3/2012
Login to get access
Abstract
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.