期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 280, 期 34, 页码 30630-30637出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M502493200
关键词
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Laminin-5-rich extracellular matrix derived from 804G cells ( 804G-ECM) engages beta 1 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-kappa B and the involvement of NF-kappa B 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-kappa B. 804G-ECM-induced nuclear translocation of NF-kappa B was weak as compared with that induced by interleukin-1 beta. Transient 804G-ECM-induced DNA binding activity of NF-kappa B ( peak at 2 h) and overexpression of NF-kappa B target genes I kappa B alpha and NF-kappa B1( p105) ( peak at 4 h) were observed. When NF-kappa B was inhibited by an inhibitor of I kappa B alpha phosphorylation ( Bay 11-7082) or by a recombinant adenovirus expressing the nonphosphorylatable form of I kappa B 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-kappa B activity. This study shows for the first time that ECM- induced NF-kappa B activity is necessary in maintaining GSIS, although it does not affect survival of pancreatic beta cells. The effects of ECM- induced NF-kappa B activity contrast with the deleterious effects of cytokine-induced NF-kappa B activity. It is proposed that transient and moderate NF-kappa B activity is essential for proper function of the pancreatic beta cell.
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