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|Insulin-induced NADPH oxidase activation promotes proliferation and matrix metalloproteinase activation in monocytes/macrophages|
|Authors: ||San-Jose, G. (Gorka)|
Bidegain, J. (J.)
Robador, P.A. (Pablo A.)
Diez, J. (Javier)
Fortuño, A. (Ana)
Zalba, G. (Guillermo)
|Issue Date: ||2009|
|Publisher version: ||http://www.sciencedirect.com/science/article/pii/S0891584909000185|
|Citation: ||San Jose G, Bidegain J, Robador PA, Diez J, Fortuño A, Zalba G. Insulin-induced NADPH oxidase activation promotes proliferation and matrix metalloproteinase activation in monocytes/macrophages. Free Radic Biol Med 2009 Apr 15;46(8):1058-1067.|
Insulin stimulates superoxide (O(2)(-)) production in monocytes and macrophages. However, the mechanisms through which insulin induces O(2)(-) production are not completely understood. In this study, we (a) characterized the enzyme and the pathways involved in insulin-stimulated O(2)(-) production in human monocytes and murine macrophages, and (b) analyzed the consequences of insulin-stimulated O(2)(-) production on the cellular phenotype in these cells. We showed that insulin stimulated O(2)(-) production, and promoted p47(phox) translocation to the plasma membrane. Insulin-induced O(2)(-) production and p47(phox) translocation were prevented in the presence of specific inhibitors of PI3K and PKC. Insulin-mediated NADPH oxidase activation stimulated MMP-9 activation in monocytes and cell proliferation in macrophages. The effect of insulin on these phenotypic responses was mediated through NFkappaB, p38MAPK, and ERK 1/2 activation. Small-interfering RNA-specific gene silencing targeted specifically against Nox2 reduced the cognate protein expression, decreased insulin-induced O(2)(-) production, inhibited the turn on of NFkappaB, p38MAPK, and ERK 1/2, and reduced cell proliferation in macrophages. These findings suggest a pivotal role for NADPH oxidase in insulin-induced proliferation and proteolytic activation in monocytes and macrophages, respectively, and identify a pathway that may play a pathological role in hyperinsulinemic states.
|Permanent link: ||http://hdl.handle.net/10171/18011|
|Appears in Collections:||DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista|
DA - CIMA - Cardiovasculares - Enfermedad vascular - Artículos de Revista
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