Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells
| Autor: | Jean-Claude Irminger, Dominique G. Rouiller, Philippe A. Halban, Géraldine Parnaud, Domenico Bosco, Katharina Rickenbach, Pascale Ribaux, Eva Hammar |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Male
Time Factors Islets of Langerhans/ metabolism Biochemistry Extracellular matrix chemistry.chemical_compound NF-KappaB Inhibitor alpha Insulin Sulfones Enzyme Inhibitors Phosphorylation Cytoskeleton Cells Cultured ddc:616 Enzyme Inhibitors/pharmacology 0303 health sciences Insulin/ metabolism biology Reverse Transcriptase Polymerase Chain Reaction Integrin beta1 030302 biochemistry & molecular biology NF-kappa B Antigens CD29/metabolism Extracellular Matrix Cell biology medicine.anatomical_structure Nitriles/pharmacology I-kappa B Proteins Beta cell NF-kappa B/ metabolism Cell Adhesion Molecules/metabolism Protein Binding medicine.medical_specialty I-kappa B Proteins/metabolism Cell Survival Integrin Blotting Western Active Transport Cell Nucleus Alpha (ethology) Actins/chemistry/metabolism Actin cytoskeleton organization Adenoviridae Islets of Langerhans 03 medical and health sciences Internal medicine Nitriles medicine In Situ Nick-End Labeling Animals Adenoviridae/genetics Rats Wistar Molecular Biology DNA/chemistry 030304 developmental biology NF-κB DNA Cell Biology Glucose/ metabolism Actins Rats Sulfones/pharmacology Cell nucleus Kinetics Glucose Endocrinology chemistry Extracellular Matrix/ metabolism Cytoskeleton/metabolism biology.protein Cell Adhesion Molecules |
| Zdroj: | Journal of Biological Chemistry, Vol. 280, No 34 (2005) pp. 30630-30637 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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