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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

A biphasic role of nuclear transcription factor (NF)-kappaB in the islet beta-cell apoptosis induced by interleukin (IL)-1beta.

IL-1beta is an important mediator in the pathogenesis of type 1 diabetes both in vivo and in vitro and it has been shown to induce islet beta-cell apoptosis. Most of the IL-1beta effects seem to be mediated by NF-kappaB transcription factor activation, but its role in the induction of islet beta-cell apoptosis has not yet been clarified. Taking advantage of the protease inhibitor TPCK (N-tosyl-L-phenylalanine chloromethyl ketone), which specifically inhibits the nuclear transcription factor NF-kappaB activation, we studied the role of NF-kappaB in the rIL-1beta treated rat pancreatic islets. Our results show that TPCK blocked rIL-1beta-mediated early increase of MnSOD activity and beta-cell defence/repair protein expression, suggesting a protective role for NF-kappaB at the beginning of IL-1beta treatment; but, in a second phase, NF-kappaB induces a sustained decrease of specific beta-cell proteins like insulin, GLUT-2 and PDX-1 with a concomitant increase of aspecific proteins and iNOS transcription. The appearance of iNOS expression correlates with increased levels of nitrite + nitrate levels and appearance of mitochondrial damage detected either at morphological and biochemical level. After 36 h of IL-1beta treatment islet beta-cells begin to undergo apoptosis. Since IL-1beta induction of apoptosis is completely prevented by TCPK treatment, this finding underscores the central role of NF-kappaB in this process. Thus, our results clearly indicate that NF-kappaB regulates MnSOD genes expression and MnSOD activity, which protects islet beta-cells by IL-1beta damage. Furthermore, when the IL-1beta stress impairs islet beta-cell function, NF-kappaB activation regulates the entrance of islet beta-cell into the cell death program.[1]

References

  1. A biphasic role of nuclear transcription factor (NF)-kappaB in the islet beta-cell apoptosis induced by interleukin (IL)-1beta. Papaccio, G., Graziano, A., D'Aquino, R., Valiante, S., Naro, F. J. Cell. Physiol. (2005) [Pubmed]
 
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