Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12475
Title: Increased gastrin gene expression provides a physiological advantage to mice under hypoxic conditions.
Austin Authors: Laval, Marie;Baldwin, Graham S;Shulkes, Arthur;Marshall, Kathryn M
Affiliation: Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 13-Nov-2014
Publication information: American Journal of Physiology. Gastrointestinal and Liver Physiology 2014; 308(2): G76-84
Abstract: Hypoxia, or a low concentration of O2, is encountered in humans undertaking activities such as mountain climbing and scuba diving and is important pathophysiologically as a limiting factor in tumor growth. Although data on the interplay between hypoxia and gastrins are limited, gastrin expression is upregulated by hypoxia in gastrointestinal cancer cell lines, and gastrins counterbalance hypoxia by stimulating angiogenesis in vitro and in vivo. The aim of this study was to determine if higher concentrations of the gastrin precursor progastrin are protective against hypoxia in vivo. hGAS mice, which overexpress progastrin in the liver, and mice of the corresponding wild-type FVB/N strain were exposed to normoxia or hypoxia. Iron status was assessed by measurement of serum iron parameters, real-time PCR for mRNAs encoding critical iron regulatory proteins, and Perls' stain and atomic absorption spectrometry for tissue iron concentrations. FVB/N mice lost weight at a faster rate and had higher sickness scores than hGAS mice exposed to hypoxia. Serum iron levels were lower in hGAS than FVB/N mice and decreased further when the animals were exposed to hypoxia. The concentration of iron in the liver was strikingly lower in hGAS than FVB/N mice. We conclude that increased circulating concentrations of progastrin provide a physiological advantage against systemic hypoxia in mice, possibly by increasing the availability of iron stores. This is the first report of an association between progastrin overexpression, hypoxia, and iron homeostasis.
Gov't Doc #: 25394662
URI: http://ahro.austin.org.au/austinjspui/handle/1/12475
DOI: 10.1152/ajpgi.00344.2014
URL: https://pubmed.ncbi.nlm.nih.gov/25394662
Type: Journal Article
Subjects: gastrin
hypoxia
iron
Animals
Anoxia.genetics.metabolism
Colon.metabolism
Erythropoietin.blood
Female
Gastrins.metabolism
Gene Expression.physiology
Iron.metabolism
Liver.metabolism
Male
Mice
RNA, Messenger.metabolism
Real-Time Polymerase Chain Reaction.methods
Appears in Collections:Journal articles

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