Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10738856 | Free Radical Biology and Medicine | 2005 | 9 Pages |
Abstract
The role of reactive oxygen species (ROS) in regulating the expression of the inducible nitric oxide synthase (iNOS) was studied in rat aortic vascular smooth muscle cells (VSMC). We hypothesized that ROS regulate iNOS expression through the mitogen-activated protein kinases ERK and p38MAPK. We found that interleukin-1β (IL-1β) stimulated the production of hydrogen peroxide (H2O2) which could be inhibited by loading the cells with the H2O2-scavenging enzyme catalase. Inhibition of the upstream ERK1,2 activator MEK1,2 with U0126 prevented IL-1β-stimulated iNOS expression, while the p38MAPK inhibitor SB03580 potentiated iNOS expression. Loading the cells with catalase enhanced ERK activation and iNOS expression but had no effect on p38MAPK activation or PDGF-induced ERK activation. These data indicated that H2O2 negatively regulates iNOS expression through ERK inhibition independently of p38MAPK. The present results outline a novel role for H2O2 in suppressing signaling pathways leading to gene expression such as iNOS in VSMC in response to cytokines.
Keywords
NF-κBH2DCF-DADCIDMEMVSMCSDSPDGFFBSdichlorofluoresceinIL-1βiNOSERKDcfDTTMAPKDulbecco's modified Eagle's mediumROSHydrogen peroxideInterleukin-1βdithiothreitolsodium dodecyl sulfatefetal bovine serumVascular smooth muscle cellsinducible nitric oxide synthasesmooth muscle platelet-derived growth factorNuclear factor–κBNitric oxidemitogen-activated protein kinaseCatalaseextracellular signal-regulated kinasesmitogen-activated protein kinasesReactive oxygen species
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Authors
Benjamin J. Guikema, Roman Ginnan, Harold A. Singer, David Jourd'heuil,