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MUCOSAL BIOLOGY

Heme transport exhibits polarity in Caco-2 cells: evidence for an active and membrane protein-mediated process

Departments of ¹Pediatrics and ²Internal Medicine, Veterans Administration Medical Center, The University of Iowa, and the Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242

Submitted 8 April 2004 ; accepted in final form 6 August 2004

Heme prosthetic groups are vital for all living organisms, but they can also promote cellular injury by generating reactive oxygen species. Therefore, intestinal heme absorption and distribution should be carefully regulated. Although a human intestine brush-border heme receptor/transporter has been suggested, the mechanism by which heme crosses the apical membrane is unknown. After it enters the cell, heme is degraded by heme oxygenase-1 (HO-1), and iron is released. We hypothesized that heme transport is actively regulated in Caco-2 cells. Cells exposed to hemin from the basolateral side demonstrated a higher HO-1 induction than cells exposed to hemin from the apical surface. Hemin secretion was more rapid than absorption, and net secretion occurred against a concentration gradient. Treatment of the apical membrane with trypsin increased hemin absorption by threefold, but basolateral treatment with trypsin had no effect on hemin secretion. Neither apical nor basolateral trypsin changed the paracellular pathway. We conclude that heme is acquired and transported in both absorptive and secretory directions in polarized Caco-2 cells. Secretion is via an active metabolic/transport process. Trypsin applied to the apical surface increased hemin absorption, suggesting that protease activity can uncover a process for heme uptake that is otherwise quiescent. These processes may be involved in preventing iron overload in humans.

heme oxygenase; alveolar epithelial cells; small intestine; enterocyte; tin protoporphyrin

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