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Title: Stimulation of proliferation in the colorectal mucosa by gastrin precursors is blocked by desferrioxamine.
Austin Authors: Ferrand, Audrey;Lachal, Shamilah;Bramante, Gianni;Kovac, Suzana;Shulkes, Arthur;Baldwin, Graham S
Affiliation: University of Melbourne Department of Surgery, Austin Health, Heidelberg 3084, Victoria, Australia
Issue Date: 15-Apr-2010
Publication information: American Journal of Physiology. Gastrointestinal and Liver Physiology 2010; 299(1): G220-7
Abstract: Precursors of the peptide hormone gastrin stimulate proliferation in the colorectal mucosa and promote the development of colorectal carcinoma. Gastrins bind two ferric ions selectively and with high affinity, and the biological activity of glycine-extended gastrin (Ggly) in vitro is dependent on the presence of ferric ions. The aim of the present study was to determine whether or not iron is required for biological activity of progastrin and Ggly in vivo. Rats that had undergone a colostomy were infused with Ggly, and proliferation was measured in the defunctioned rectal mucosa. Proliferation was also measured in the colonic mucosa of hGAS and MTI-Ggly mice, which, by definition, overexpress progastrin and Ggly, respectively. The requirement for iron was assessed by thrice-weekly injection of the chelating agent desferrioxamine (DFO). The proliferation index in the defunctioned rectal mucosa was significantly increased in the Ggly-infused rats, and the increase was significantly reduced after treatment with DFO. Treatment with DFO significantly reduced the crypt height and proliferation index in the colonic mucosa of hGAS and MTI-Ggly mice but had no effect on the same variables in wild-type mice. These observations are consistent with the hypothesis that the biological activity of progastrin and Ggly in vivo is dependent on the presence of ferric ions and further suggest that chelating agents may block the stimulatory effects of gastrin precursors in the development of colorectal carcinoma.
Gov't Doc #: 20395538
DOI: 10.1152/ajpgi.00046.2010
Type: Journal Article
Subjects: Animals
Cell Proliferation
Colon.drug effects.metabolism.pathology
Deferoxamine.administration & dosage.pharmacology
Gastrins.administration & dosage.blood.genetics.metabolism
Infusion Pumps, Implantable
Injections, Intraperitoneal
Intestinal Mucosa.drug effects.metabolism.pathology
Mice, Transgenic
Protein Precursors.administration & dosage.blood.genetics.metabolism
Rats, Sprague-Dawley
Rectum.drug effects.metabolism.pathology
Siderophores.administration & dosage.pharmacology
Time Factors
Appears in Collections:Journal articles

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