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Am J Physiol Gastrointest Liver Physiol 278: G855-G865, 2000;
0193-1857/00 $5.00
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Vol. 278, Issue 6, G855-G865, June 2000

Induction of transcriptional activity of AP-1 and NF-kappa B in the gastric mucosa during aging

Zhi-Qiang Xiao1 and Adhip P. N. Majumdar2,3,4

2 Veterans Affairs Medical Center, Departments of 1 Internal Medicine and 3 Biochemistry and Molecular Biology, and 4 Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201

Although aging enhances expression and tyrosine kinase activity of epidermal growth factor receptor (EGFR) in the gastric mucosa, there is no information about EGFR signaling cascades. We examined the age-related changes in mitogen-activated protein kinases (MAPKs) [extracellular signal-related kinases (ERKs), c-Jun NH2-terminal kinases (JNKs), and p38], an EGFR-induced signaling cascade, and activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B) transcriptional activity in the gastric mucosa of 4- to 6-, 12- to 14-, and 22- to 24-mo-old Fischer 344 rats. AP-1 and NF-kappa B transcriptional activity in the gastric mucosa rose steadily with advancing age. This can be further induced by transforming growth factor-alpha . The age-related activation of AP-1 and NF-kappa B in the gastric mucosa was associated with increased levels of c-Jun, c-Fos, and p52, but not p50 or p65. Total and phosphorylated Ikappa Balpha levels in the gastric mucosa were unaffected by aging. Aging was also associated with marked activation of ERKs (p42/p44) and JNK1. In contrast, aging decreased p38 MAPK activity in the gastric mucosa. Our observation of increased activation of ERKs and JNK1 in the gastric mucosa of aged rats suggests a role for these MAPKs in regulating AP-1 and NF-kappa B transcriptional activity. These events may be responsible for the age-related rise in gastric mucosal proliferative activity.

activator protein-1; nuclear factor-kappa B; mitogen-activated protein kinases; extracellular signal-related kinases; c-Jun NH2-terminal kinases; p38; transforming growth factor-alpha


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