UNIGE document Scientific Article
previous document  unige:90664  next document
add to browser collection
Title

Insulin-induced vascular endothelial growth factor expression is mediated by the NADPH oxidase NOX3

Authors
Szanto, Ildiko
Published in Experimental Cell Research. 2006, vol. 312, no. 17, p. 3413-24
Abstract Vascular endothelial growth factor (VEGF) is the most potent stimulatory factor of angiogenesis. Its expression is induced by reactive oxygen species (ROS) in hypoxic conditions and by insulin in normoxic cells. Both ROS and insulin can activate mitogen-activated protein kinases (MAPKs) and induce the transcriptional factor Sp1, components that are essential for VEGF gene expression. The aim of this study was to investigate the role of ROS producing NADPH oxidase enzymes (NOX-es) in insulin-regulated VEGF gene activation. To achieve this goal we chose HepG2 cells as our model system as these cells express the NADPH oxidase isoform NOX3 and respond to insulin stimulation with enhanced ROS production and mRNA transcription and production of VEGF. We demonstrate that in control cells insulin stimulation leads to H2O2 generation, a biphasic activation of p42/44 MAPK and the induction of both Sp1 and HIF-1alpha. Transfection of NOX3-specific siRNA abrogates H2O2 production and inhibits exclusively the second phase of p42/44 MAPK phosphorylation and Sp1 DNA binding and thus prevents upregulation of VEGF-A mRNA expression. In conclusion, our results demonstrate that NOX3, a ROS generating NADPH oxidase, plays an integral role in insulin-induced p42/44 MAPK signal transmission and VEGF-A production.
Keywords Acetophenones/pharmacologyCell LineTumorEnzyme Inhibitors/pharmacokineticsHumansHydrogen Peroxide/metabolismInsulin/metabolismMembrane Proteins/genetics/metabolismMitogen-Activated Protein Kinases/metabolismNADPH Oxidase/genetics/metabolismPhosphorylationProto-Oncogene Proteins c-akt/metabolismRNASmall Interfering/geneticsSignal TransductionTranscriptionGeneticTransfectionUp-Regulation/drug effectsVascular Endothelial Growth Factor A/biosynthesis/genetics
Identifiers
PMID: 16949073
Full text
Article (Published version) (631 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Obésité et syndrome métabolique (803)
Citation
(ISO format)
CARNESECCHI, Stéphanie et al. Insulin-induced vascular endothelial growth factor expression is mediated by the NADPH oxidase NOX3. In: Experimental Cell Research, 2006, vol. 312, n° 17, p. 3413-24. https://archive-ouverte.unige.ch/unige:90664

33 hits

1 download

Update

Deposited on : 2016-12-21

Export document
Format :
Citation style :