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A novel pathway of NADPH oxidase/vascular peroxidase 1 in mediating oxidative injury following ischemia-reperfusion.
- Source :
-
Basic Research in Cardiology . May2012, Vol. 107 Issue 3, p1-19. 19p. - Publication Year :
- 2012
-
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 HO 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 HO production accompanied by a decrease in VPO1 expression and HOCl production. However, silencing of VPO1 expression did not affect NOX2 expression and HO production. HO-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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03008428
- Volume :
- 107
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Basic Research in Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 75163999
- Full Text :
- https://doi.org/10.1007/s00395-012-0266-4