HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/G1150    most recent 00157.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Uc, A. Articles by Britigan, B. E. Search for Related Content PubMed PubMed Citation Articles by Uc, A. Articles by Britigan, B. E.

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

This article has been cited by other articles:

				A. Uc, K. J. Reszka, G. R. Buettner, and J. B. Stokes Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1906 - C1914. [Abstract] [Full Text] [PDF]

				M. Basireddy, J. T. Lindsay, A. Agarwal, and D. F. Balkovetz Epithelial cell polarity and hypoxia influence heme oxygenase-1 expression by heme in renal epithelial cells Am J Physiol Renal Physiol, October 1, 2006; 291(4): F790 - F795. [Abstract] [Full Text] [PDF]

				C. Chicault, B. Toutain, A. Monnier, M. Aubry, P. Fergelot, A. L. Treut, M.-D. Galibert, and J. Mosser Iron-related transcriptomic variations in CaCo-2 cells, an in vitro model of intestinal absorptive cells Physiol Genomics, September 14, 2006; 26(1): 55 - 67. [Abstract] [Full Text] [PDF]

				A. Uc, R. F. Husted, R. L. Giriyappa, B. E. Britigan, and J. B. Stokes Hemin induces active chloride secretion in Caco-2 cells Am J Physiol Gastrointest Liver Physiol, August 1, 2005; 289(2): G202 - G208. [Abstract] [Full Text] [PDF]