Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats.

Abstract

BACKGROUND & AIMS:

Previous studies have shown that gastric ulceration stimulates epithelial cell proliferation and overexpression of epidermal growth factor (EGF) and EGF receptor (EGF-R) in the mucosa bordering necrosis. The aim of this study was to investigate whether extracellular signal-regulated kinase (ERK) cascade is involved in the healing of experimental gastric ulcers.

METHODS:

We studied EGF-R levels, EGF-R phosphorylation levels, and ERK1 and ERK2 activity in normal and ulcerated rat gastric mucosa. We also examined the effect of Tyrphostin A46 (potent inhibitor of EGF-R and EGF-R kinase-dependent proliferation) on the above parameters.

RESULTS:

During the initial stages of healing (3 and 7 days), ulcerated mucosa showed significant increase (vs. controls) in protein tyrosine kinase activity, EGF-R levels (510% and 550%), EGF-R phosphorylation levels, ERK1 activity (430% and 880%), and ERK2 activity (550% and 990%). Tyrphostin A46 treatment significantly inhibited ulcer healing and reduced EGF-R levels, EGF-R phosphorylation, and ERK1 and ERK2 activity.

CONCLUSIONS:

These findings indicate that experimental gastric ulcer healing involves activation of EGF-R-ERK signal transduction pathway.

• Authors: R Pai, M Ohta, R M Itani, I J Sarfeh, A S Tarnawski
• Journal: Gastroenterology (Gastroenterology) Vol. 114 Issue 4 Pg. 706-13 (Apr 1998) ISSN: 0016-5085 [Print] United States
• PMID: 9516391 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Benzylidene Compounds
• Nitriles
• Tyrphostins
• tyrphostin A46
• Tyrosine
• ErbB Receptors
• Calcium-Calmodulin-Dependent Protein Kinases
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Benzylidene Compounds (pharmacology)
• Calcium-Calmodulin-Dependent Protein Kinases (metabolism)
• ErbB Receptors (analysis)
• Male
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases
• Nitriles (pharmacology)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Signal Transduction
• Stomach Ulcer (enzymology)
• Tyrosine (metabolism)
• Tyrphostins