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

Marchbank, T.; Boulton, R.; Hansen, H.; Playford, R.J.
December 2002
Gut;Dec2002, Vol. 51 Issue 6, p787
Academic Journal
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 patients 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-α[sub 1-50] is cleaved to TGF-α[sub 1-43] 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-α[sub 1-50]. TGF-α[sub 1-43] had only half of the ability to maximally stimulate [³H]thymidine incorporation into primary rat hepatocytes (28 177 (1 130) DPM/well for 2.16 nM TGF-α[sub 1-43] v 63 1 84 (3536) DPM/well for TGF-α[sub 1-50]; p<0.001 ). A similar reduced potency was seen when used in an indomethacin induced rat gastric damage model (0.1 8 μmol/kg/h of TGF-α[sub 1-43] reduced ulcer area by 19% whereas TGF-α[sub 1-50] reduced area by 62%; p<0.001). Conclusions: TGF-α[sub 1-50] is cleaved to the TGF-α[sub 1-43] 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.


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