BACKGROUND: Genetic haemochromatosis is a common hereditary iron loading disorder in humans. The disease is associated with loss of function mutations in the HFE gene. This is thought to change iron stores via increased iron absorption. AIMS: In this study we investigated how adaptation of mucosal reductase activity is engaged in this process and how the changes compare with adaptation seen when an iron deficient diet is fed. METHODS: Duodenal mucosal surface reductase was measured with nitroblue tetrazolium in age matched groups of male Hfe knockout mice (Hfe) and wild- type mice fed a purified diet containing normal (iron adequate), high (iron rich), or low (iron deficient) iron concentrations. RESULTS: Reductase activity increased when mice were fed an iron deficient diet and decreased when they were fed an iron rich diet. Total villus activity, as measured by the average area under the activity curve along the crypt-villus axis, was increased 2.8-2.9-fold by iron deficiency in both genotypes. Approximately half of this difference was attributable to the significantly increased length of the villi in mice on an iron deficient diet (p<0.05). Hfe knockout did not affect villus length but increased mucosal reductase activity near the villus tips. Similar increases (1.3-1.6-fold) were seen on all diets but the increase was significant for iron deficient and iron loaded diets only (p<0.05). CONCLUSION: Hfe gene product and dietary iron downregulate villus reductase activity in mice.
BACKGROUND: Genetic haemochromatosis is a common hereditary iron loading disorder in humans. The disease is associated with loss of function mutations in the HFE gene. This is thought to change iron stores via increased iron absorption. AIMS: In this study we investigated how adaptation of mucosal reductase activity is engaged in this process and how the changes compare with adaptation seen when an iron deficient diet is fed. METHODS: Duodenal mucosal surface reductase was measured with nitroblue tetrazolium in age matched groups of male Hfe knockout mice (Hfe) and wild- type mice fed a purified diet containing normal (iron adequate), high (iron rich), or low (iron deficient) iron concentrations. RESULTS: Reductase activity increased when mice were fed an iron deficient diet and decreased when they were fed an iron rich diet. Total villus activity, as measured by the average area under the activity curve along the crypt-villus axis, was increased 2.8-2.9-fold by iron deficiency in both genotypes. Approximately half of this difference was attributable to the significantly increased length of the villi in mice on an iron deficient diet (p<0.05). Hfe knockout did not affect villus length but increased mucosal reductase activity near the villus tips. Similar increases (1.3-1.6-fold) were seen on all diets but the increase was significant for iron deficient and iron loaded diets only (p<0.05). CONCLUSION:Hfe gene product and dietary iron downregulate villus reductase activity in mice.
Authors: A T McKie; D Barrow; G O Latunde-Dada; A Rolfs; G Sager; E Mudaly; M Mudaly; C Richardson; D Barlow; A Bomford; T J Peters; K B Raja; S Shirali; M A Hediger; F Farzaneh; R J Simpson Journal: Science Date: 2001-02-01 Impact factor: 47.728
Authors: S Bahram; S Gilfillan; L C Kühn; R Moret; J B Schulze; A Lebeau; K Schümann Journal: Proc Natl Acad Sci U S A Date: 1999-11-09 Impact factor: 11.205
Authors: R E Fleming; C C Holden; S Tomatsu; A Waheed; E M Brunt; R S Britton; B R Bacon; D C Roopenian; W S Sly Journal: Proc Natl Acad Sci U S A Date: 2001-02-27 Impact factor: 11.205
Authors: Thomas Herrmann; Martina Muckenthaler; Frank van der Hoeven; Karen Brennan; Sven G Gehrke; Nadia Hubert; Consolato Sergi; Hermann-Josef Gröne; Iris Kaiser; Isabella Gosch; Martin Volkmann; Hans-Dieter Riedel; Matthias W Hentze; A Francis Stewart; Wolfgang Stremmel Journal: J Mol Med (Berl) Date: 2003-11-15 Impact factor: 4.599