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• W2120764679 endingPage "S488" @default.
• W2120764679 startingPage "S484" @default.
• W2120764679 abstract "The purpose of the current study was to determine whether nuclear factor-kappaB (NF-kappaB) activation is a component of the depolarization/Ca(2+)-dependent signaling in beta-cells. MIN6 cells were transfected with a plasmid containing five tandem repeats of NF-kappaB binding sites linked to a luciferase reporter. The results of these experiments showed that KCl induced depolarization-activated NF-kappaB-dependent transcription (3.8-fold at 45 mmol/l, P < 0.01) in a concentration-dependent manner. Tumor necrosis factor-alpha (TNF-alpha), a known inducer of NF-kappaB signaling, activated this construct by 3.4-fold (P < 0.01). The response of NF-kappaB to depolarization was inhibited by the Ca(2+)-channel blocker verapamil and by the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 (70 and 62%, respectively). TNF-alpha, glucose, and KCl treatment resulted in inhibitory kappaBalpha degradation by Western blot analysis. TNF-alpha treatment and depolarization activation of NF-kappaB differed significantly in that TNF-alpha activation was not blocked by PD98059. Transfection with PKA, MEK, and MEK kinase induced NF-kappaB-dependent transcription by 20-, 90-, and 300-fold, respectively, suggesting that these pathways contribute to the activation in the depolarization response. These findings demonstrate that depolarization/Ca(2+) influx, as well as TNF-alpha treatment, can activate NF-kappaB-dependent transcription in pancreatic beta-cells, but by different signaling pathways. The current studies show that Ca(2+) signals in pancreatic beta-cells can activate transcription factors involved in the regulation of cell cycle and apoptosis. These findings now add NF-kappaB to the list of depolarization-induced transcription factors in pancreatic beta-cells." @default.
• W2120764679 created "2016-06-24" @default.
• W2120764679 creator A5009569763 @default.
• W2120764679 creator A5023938814 @default.
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• W2120764679 date "2002-12-01" @default.
• W2120764679 modified "2023-10-17" @default.
• W2120764679 title "Activation of Nuclear Factor-κB by Depolarization and Ca2+ Influx in MIN6 Insulinoma Cells" @default.
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• W2120764679 doi "https://doi.org/10.2337/diabetes.51.2007.s484" @default.
• W2120764679 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12475794" @default.
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