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Human transforming growth factor a (TGF-alpha) is digested to a smaller (1-43), less biologically active, form in acidic gastric juice

Citation

Marchbank, T and Boulton, R and Hansen, H and Playford, RJ, Human transforming growth factor a (TGF-alpha) is digested to a smaller (1-43), less biologically active, form in acidic gastric juice, Gut: An International Journal of Gastroenterology and Hepatology, 51, (6) pp. 787-792. ISSN 0017-5749 (2002) [Refereed Article]

DOI: doi:10.1136/gut.51.6.787

Abstract

Background: Transforming growth factor α (TGF-α) is a 50 amino acid peptide with potent proliferative and cytoprotective activity present in gastric mucosa and juice. Aims: To determine the forms and biological activity of natural and recombinant TGF-α following incubation with acid pepsin. Patients: Human gastric juice was obtained under basal conditions from potients taking acid suppressants and from volunteers undergoing intragastric neutralisation. Methods: Samples were analysed using mass spectroscopy and/or high pressure liquid chromatography with radioimmunoassay. Biological activity was determined using thymidine incorporation into rat hepatocytes and an indomethacin/restraint induced gastric damage rat model. Results: TGF-α1-50 is cleaved to TGF-α1-43 by acid pepsin and this is the predominant form in normal gastric juice. However, intragastric neutralisation or taking acid suppressants caused the predominant form to be TGF-α1-50. TGF-α1-43 had only half of the ability to maximally stimulate [3H]thymidine incorporation into primary rat hepatocytes (28 177 (1130) DPM/well for 2.16 nM TGF-α1-43 v 63 184 (3536) DPM/well for TGF-α1-50; p<0.001). A similar reduced potency was seen when used in an indomethacin induced rat gastric damage model (0.18 μmol/kg/h of TGF-α1-43 reduced ulcer area by 19% whereas TGF-α1-50 reduced area by 62%; p<0.001). Conclusions: TGF-α1-50 is cleaved to the TGF-α1-43 form by acid pepsin, causing 2-5-fold loss of biological activity. Such changes may have relevance to the actions of acid suppressants and the importance of this peptide in both normal and abnormal growth.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Gastroenterology and Hepatology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Digestive System Disorders
Author:Playford, RJ (Professor Ray Playford)
ID Code:72897
Year Published:2002
Web of Science® Times Cited:10
Deposited By:Research Division
Deposited On:2011-09-02
Last Modified:2011-09-05
Downloads:0

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