A novel pathway of NADPH oxidase/vascular peroxidase 1 in mediating oxidative injury following ischemia–reperfusion

• DOI: 10.1007/s00395-012-0266-4
• Publication Date: 2012-04-02T13:35:42Z
• 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
• Keywords: Hemeproteins; Male; 0301 basic medicine; Membrane Glycoproteins; Caspase 3; Myocardium; JNK Mitogen-Activated Protein Kinases; Myocardial Infarction; NADPH Oxidases; Apoptosis; Myocardial Reperfusion Injury; Hydrogen Peroxide; Cell Line; Hypochlorous Acid; Disease Models, Animal; Oxidative Stress; 03 medical and health sciences; NADPH Oxidase 4; NADPH Oxidase 2; Animals; Enzyme Inhibitors; Creatine Kinase

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 H(2)O(2) 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 H(2)O(2) production accompanied by a decrease in VPO1 expression and HOCl production. However, silencing of VPO1 expression did not affect NOX2 expression and H(2)O(2) production. H(2)O(2)-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.