In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 277, No. 3 ( 1999-09-01), p. G678-G686
Abstract:
The eukaryotic transcription factor NF-κB/Rel is activated by a large variety of stimuli. We have recently shown that NF-κB/Rel is induced during the course of caerulein pancreatitis. Here, we show that activation of NF-κB/Rel by caerulein, a CCK analog, requires increasing intracellular Ca 2+ levels and protein kinase C activation. Caerulein induces a dose-dependent increase of nuclear NF-κB/Rel binding activity in pancreatic lobules, which is paralleled by degradation of IκBα. IκBβ was only slightly affected by caerulein treatment. Consistent with an involvement of Ca 2+ , the endoplasmic reticulum-resident Ca 2+ -ATPase inhibitor thapsigargin activated NF-κB/Rel in pancreatic lobules. The intracellular Ca 2+ chelator TMB-8 prevented IκBα degradation and subsequent nuclear translocation of NF-κB/Rel induced by caerulein. BAPTA-AM was less effective. Cyclosporin A, a Ca 2+ /calmodulin-dependent protein phosphatase (PP2B) inhibitor, decreased caerulein-induced NF-κB/Rel activation and IκBα degradation. The inhibitory effect of bisindolylmaleimide suggests that protein kinase C activity is also required for caerulein-induced NF-κB/Rel activation. These data suggest that Ca 2+ - as well as protein kinase C-dependent mechanisms are required for caerulein-induced NF-κB/Rel activation.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.1999.277.3.G678
Language:
English
Publisher:
American Physiological Society
Publication Date:
1999
detail.hit.zdb_id:
1477329-6
SSG:
12
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