Lehrstuhl für Ernährungsphysiologie der TUM, Weihenstephan, Germany (K. Schümann); European Molecular Biology Laboratory, Heidelberg, Germany (K. Brennan); Lady Davis Institute for Medical Research and McGill University, Montreal, Canada (K. Pantopoulos); Pathologisches Institut, Ludwig- Maximilians-Universität, München, Germany (M. Weiss).
Rat duodenal IRP1 activity and iron absorption in iron deficiency and after H2O2 perfusion
Article first published online: 13 APR 2004
European Journal of Clinical Investigation
Volume 34, Issue 4, pages 275–282, April 2004
How to Cite
Schümann, K., Brennan, K., Weiss, M., Pantopoulos, K. and Hentze, M. W. (2004), Rat duodenal IRP1 activity and iron absorption in iron deficiency and after H2O2 perfusion. European Journal of Clinical Investigation, 34: 275–282. doi: 10.1111/j.1365-2362.2004.01335.x
- Issue published online: 13 APR 2004
- Article first published online: 13 APR 2004
- Received 3 September 2003; accepted 26 February 2004
- oxidative stress
Background Iron regulatory protein 1 (IRP1), a post-transcriptional regulator of iron metabolism, is activated in the duodenum of iron-deficient animals, which is associated with increased iron absorption. In cell cultures IRP1 was also activated by iron-independent signals, such as H2O2. Here we investigate whether luminal perfusion of rat duodenum with H2O2 activates duodenal IRP1 and modulates duodenal iron absorption.
Methods Duodena from iron-adequate Sprague-Dawley rats were luminally perfused with H2O2. Iron regulatory protein-1 activity was determined in duodenal mucosa or in villus and crypt preparations by an electrophoretic mobility shift assay. Duodenal 59Fe absorption was measured in isolated, perfused duodenal segments ex vivo and in ligated loops in vivo. 59Fe uptake from the blood side was assessed after i.v. injection of 59Fe-nitrilotriacetic acid.
Results Similar to iron deficiency, the perfusion with 0–50 mM of H2O2 increases duodenal IRP1 activity along the entire crypt villus-axis in a dose-dependent manner. After H2O2 treatment, IRP1 remains activated for 12–24 h in the tips and for 72 h in the crypts. In iron-deficiency, IRP activation correlates with increased 59Fe absorption. However, the H2O2 treatment fails to stimulate any increase in 59Fe uptake, without promoting damage of mucosal architecture or impairing glucose and water transport.
Conclusion Duodenal 59Fe uptake is not affected by the H2O2-mediated activation of IRP1.