Unexpected role of ceruloplasmin in intestinal iron absorption

• Published in: Cell metabolism Vol. 2; no. 5; pp. 309 - 319
• Main Authors: Cherukuri, Srujana, Potla, Ramesh, Sarkar, Joydeep, Nurko, Saul, Harris, Z. Leah, Fox, Paul L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2005
• Subjects: Animals; Cation Transport Proteins - metabolism; Ceruloplasmin - genetics; Ceruloplasmin - metabolism; Duodenum - cytology; Duodenum - metabolism; Enterocytes - metabolism; Homeostasis; Humans; Intestinal Absorption; Iron - blood; Iron - metabolism; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucous Membrane - metabolism; RNA, Messenger - metabolism; Spleen - metabolism; Stress, Physiological - metabolism; Time Factors; Transferrin - metabolism
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2005.10.003

Ferroxidases are essential for normal iron homeostasis in most organisms. The paralogous vertebrate ferroxidases ceruloplasmin (Cp) and hephaestin (Heph) are considered to have nonidentical functions in iron transport: plasma Cp drives iron transport from tissue stores while intestinal Heph facilitates iron absorption from the intestinal lumen. To clarify the function of Cp, we acutely bled Cp −/− mice to stress iron homeostasis pathways. Red cell hemoglobin recovery was defective in stressed Cp −/− mice, consistent with low iron availability. Contrary to expectations, iron was freely released from spleen and liver stores in Cp −/− mice, but intestinal iron absorption was markedly impaired. Phlebotomy of wild-type mice caused a striking shift of Cp from the duodenal epithelium to the underlying lamina propria, suggesting a critical function of Cp in basolateral iron transport. Regulated relocalization of intestinal Cp may represent a fail-safe mechanism in which Cp shares with Heph responsibility for iron absorption under stress.