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Title

Insulin-induced vascular endothelial growth factor expression is mediated by the NADPH oxidase NOX3
Authors
Carnesecchi, Stéphanie
Carpentier, Jean-Louis
Foti, Michelangelo
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/pharmacology — Cell Line — Tumor — Enzyme Inhibitors/pharmacokinetics — Humans — Hydrogen Peroxide/metabolism — Insulin/metabolism — Membrane Proteins/genetics/metabolism — Mitogen-Activated Protein Kinases/metabolism — NADPH Oxidase/genetics/metabolism — Phosphorylation — Proto-Oncogene Proteins c-akt/metabolism — RNA — Small Interfering/genetics — Signal Transduction — Transcription — Genetic — Transfection — Up-Regulation/drug effects — Vascular Endothelial Growth Factor A/biosynthesis/genetics
Identifiers
PMID: 16949073
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Structures
Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
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

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Deposited on : 2016-12-21

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