

Other version: http://www.jbc.org/content/280/34/30630.full.pdf
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Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells |
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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/metabolism — Active Transport, Cell Nucleus — Adenoviridae/genetics — Animals — Antigens, CD29/metabolism — Blotting, Western — Cell Adhesion Molecules/metabolism — Cell Survival — Cells, Cultured — Cytoskeleton/metabolism — DNA/chemistry — Enzyme Inhibitors/pharmacology — Extracellular Matrix/ metabolism — Glucose/ metabolism — I-kappa B Proteins/metabolism — In Situ Nick-End Labeling — Insulin/ metabolism — Islets of Langerhans/ metabolism — Kinetics — Male — NF-kappa B/ metabolism — Nitriles/pharmacology — Phosphorylation — Protein Binding — Rats — Rats, Wistar — Reverse Transcriptase Polymerase Chain Reaction — Sulfones/pharmacology — Time Factors | |
Identifiers | PMID: 15994334 | |
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Citation (ISO format) | 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 |