Different modes of NF-kappaB/Rel activation in pancreatic lobules.
The eukaryotic transcription factor nuclear factor-kappaB (NF-kappaB)/Rel is activated by a large variety of stimuli. It has been demonstrated that NF-kappaB/Rel is induced during the course of cerulein pancreatitis. Here, we show that NF-kappaB/Rel is differentially activated in pancreatic lobules. Cerulein induces NF-kappaB/Rel via activation of IkappaB kinase (IKK), which causes degradation of IkappaBalpha but not IkappaBbeta. Tumor necrosis factor-alpha-mediated IKK activation leads to IkappaBalpha and IkappaBbeta degradation. In contrast, oxidative stress induced by H(2)O(2) activates NF-kappaB/Rel independent of IKK activation and IkappaBalpha degradation; instead IkappaBalpha is phosphorylated on tyrosine. H(2)O(2) but not cerulein-mediated NF-kappaB/Rel activation can be blocked by stabilizing microtubules with Taxol. Inhibition of tubulin polymerization with nocodazole causes NF-kappaB/Rel activation in pancreatic lobules. These results propose three different pathways of NF-kappaB/Rel activation in pancreatic acinar cells. Furthermore, these data demonstrate that microtubules play a key role in IKK-independent NF-kappaB/Rel activation following oxidative stress.
Department of Internal Medicine I, University of Ulm, Germany.
Hana
H
Algül
Yusuke
Y
Tando
Michael
M
Beil
Christoph K
CK
Weber
Claus
C
Von Weyhern
Günter
G
Schneider
Guido
G
Adler
Roland M
RM
Schmid
D000818:Animals; D002108:Ceruletide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D015739:Nocodazole / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011108:Polymers / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D016877:Oxidants; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D002108:Ceruletide; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; D017239:Paclitaxel; D015739:Nocodazole