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Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells

Published in The Journal of biological chemistry. 2005, vol. 280, no. 34, p. 30630-30637
Abstract Laminin-5-rich extracellular matrix derived from 804G cells (804G-ECM) engages beta1 integrins to induce spreading, improve glucose-stimulated insulin secretion (GSIS), and increase survival of pancreatic beta cells. The present study examines whether 804G-ECM activates the transcriptional activity of NF-kappaB and the involvement of NF-kappaB in those effects of 804G-ECM on pancreatic beta cells. 804G-ECM induces nuclear translocation and the DNA binding activity of the p65 subunit of NF-kappaB. 804G-ECM-induced nuclear translocation of NF-kappaB was weak as compared with that induced by interleukin-1beta. Transient 804G-ECM-induced DNA binding activity of NF-kappaB (peak at 2 h) and overexpression of NF-kappaB target genes IkappaB alpha and NF-kappaB1(p105) (peak at 4 h) were observed. When NF-kappaB was inhibited by an inhibitor of IkappaB alpha phosphorylation (Bay 11-7082) or by a recombinant adenovirus expressing the nonphosphorylatable form of IkappaB alpha, 804G-ECM-induced cell spreading and actin cytoskeleton organization were reduced. GSIS from cells on 804G-ECM was inhibited 5-fold, whereas cell survival was not affected. In summary, the results indicate that 804G-ECM induces a transient and moderate NF-kappaB activity. This study shows for the first time that ECM-induced NF-kappaB activity is necessary in maintaining GSIS, although it does not affect survival of pancreatic beta cells. The effects of ECM-induced NF-kappaB activity contrast with the deleterious effects of cytokine-induced NF-kappaB activity. It is proposed that transient and moderate NF-kappaB activity is essential for proper function of the pancreatic beta cell.
Keywords Actins/chemistry/metabolismActive Transport, Cell NucleusAdenoviridae/geneticsAnimalsAntigens, CD29/metabolismBlotting, WesternCell Adhesion Molecules/metabolismCell SurvivalCells, CulturedCytoskeleton/metabolismDNA/chemistryEnzyme Inhibitors/pharmacologyExtracellular Matrix/ metabolismGlucose/ metabolismI-kappa B Proteins/metabolismIn Situ Nick-End LabelingInsulin/ metabolismIslets of Langerhans/ metabolismKineticsMaleNF-kappa B/ metabolismNitriles/pharmacologyPhosphorylationProtein BindingRatsRats, WistarReverse Transcriptase Polymerase Chain ReactionSulfones/pharmacologyTime Factors
PMID: 15994334
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HAMMAR BOUVERET, Eva et al. Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells. In: The Journal of biological chemistry, 2005, vol. 280, n° 34, p. 30630-30637. doi: 10.1074/jbc.M502493200 https://archive-ouverte.unige.ch/unige:8794

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Deposited on : 2010-07-12

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