Different modes of NF-κB/Rel activation in pancreatic lobules

被引：21

作者：

Algül, H ^{[1
]}

Tando, Y ^{[1
]}

Beil, M ^{[1
]}

Weber, CK ^{[1
]}

Von Weyhern, C ^{[1
]}

Schneider, G ^{[1
]}

Adler, G ^{[1
]}

Schmid, RM ^{[1
]}

机构：

[1] Univ Ulm, Dept Internal Med 1, D-89081 Ulm, Germany

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2002年 / 283卷 / 02期

关键词：

acute pancreatitis; inhibitor protein I kappa B; I kappa B kinase; inflammation; hydrogen peroxide; tyrosine phosphorylation; cytokines; cerulein;

D O I：

10.1152/ajpgi.00407.2001

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 H2O2 activates NF-kappaB/Rel independent of IKK activation and IkappaBalpha degradation; instead IkappaBalpha is phosphorylated on tyrosine. H2O2 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.

引用

页码：G270 / G281

页数：12

共 52 条

[1] c-Src is required for oxidative stress-mediated activation of big mitogen-activated protein kinase 1 (BMK1) [J].