Induction of transcriptional activity of AP-1 and NF-kappaB in the gastric mucosa during aging.
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 NH(2)-terminal kinases (JNKs), and p38], an EGFR-induced signaling cascade, and activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) 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-kappaB 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-kappaB in the gastric mucosa was associated with increased levels of c-Jun, c-Fos, and p52, but not p50 or p65. Total and phosphorylated IkappaBalpha 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-kappaB transcriptional activity. These events may be responsible for the age-related rise in gastric mucosal proliferative activity.
Xiao
Z Q
ZQ
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Majumdar
A P
AP
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism / Q000502:physiology*; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D016211:Transforming Growth Factor alpha; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases