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

Aliye Uc, John B. Stokes, Bradley E. Britigan

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)G1150-G1157
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number6 50-6
StatePublished - Dec 2004
Externally publishedYes


  • Alveolar epithelial cells
  • Enterocyte
  • Heme oxygenase
  • Small intestine
  • Tin protoporphyrin

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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