Discovery of a cytosolic/soluble ferroxidase in rodent enterocytes.

Proceedings of the National Academy of Sciences of the United States of America
P N RanganathanJames F Collins

Abstract

Hephaestin (Heph), a membrane-bound multicopper ferroxidase (FOX) expressed in duodenal enterocytes, is required for optimal iron absorption. However, sex-linked anemia (sla) mice harboring a 194-amino acid deletion in the Heph protein are able to absorb dietary iron despite reduced expression and mislocalization of the mutant protein. Thus Heph may not be essential, and mice are able to compensate for the loss of its activity. The current studies were undertaken to search for undiscovered FOXs in rodent enterocytes. An experimental approach was developed to investigate intestinal FOXs in which separate membrane and cytosolic fractions were prepared and FOX activity was measured by a spectrophotometric transferrin-coupled assay. Unexpectedly, FOX activity was noted in membrane and cytosolic fractions of rat enterocytes. Different experimental approaches demonstrated that cytosolic FOX activity was not caused by contamination with membrane Heph or a method-induced artifact. Cytosolic FOX activity was abolished by SDS and heat (78 °C), suggesting protein-mediated iron oxidation, and was also sensitive to Triton X-100. Furthermore, cytosolic FOX activity increased ∼30% in iron-deficient rats (compared with controls) but was unchan...Continue Reading

References

Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·R J McMahon, R J Cousins
Jun 11, 2002·Annual Review of Nutrition·Nathan E Hellman, Jonathan D Gitlin
Jan 8, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·James F CollinsFayez K Ghishan
Nov 8, 2005·Cell Metabolism·Srujana CherukuriPaul L Fox
Feb 9, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·James F CollinsRichard W Browne
Dec 19, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·David M HudsonRoss T A MacGillivray
Aug 20, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Lingli JiangJames F Collins

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Citations

Jul 6, 2014·Annual Review of Nutrition·Sukru Gulec, James F Collins
Feb 22, 2012·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Perungavur N RanganathanJames F Collins
May 15, 2012·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Yan LuJames F Collins
Jul 6, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sukru GulecJames F Collins
Sep 8, 2017·PloS One·Chandrika N DeshpandeMika Jormakka
Jun 18, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jung-Heun HaJames F Collins

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