Does heme oxygenase-1 have a role in Caco-2 cell cycle progression?

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Intestinal epithelium undergoes a rapid self-renewal process characterized by the proliferation of the crypt cells, their differentiation into mature enterocytes as they migrate up to the villi, followed by their shedding as they become senescent villus enterocytes. The exact mechanism that regulates the intestinal epithelium renewal process is not well understood, but the differential expression of regulatory genes along the crypt-villus axis may have a role. Heme oxygenase-1 (HO-1) is involved in endothelial cell cycle progression, but its role in the intestinal epithelial cell turnover has not been explored. With its effects on cell proliferation and its differential expression along the crypt-villus axis, HO-1 may play a role in the intestinal epithelial cell renewal process. In this study, we examined the role of HO-1 in the proliferation and differentiation of Caco-2 cells, a well-established in vitro model for human enterocytes. After confluence, Caco-2 cells undergo spontaneous differentiation and mimic the crypt to villus maturation observed in vivo. In preconfluent and confluent Caco-2 cells, HO-1 protein expression was determined with the immunoblot. HO-1 activity was determined by the ability of the enzyme to generate bilirubin from hemin. The effect of a HO-1 enzyme activity inhibitor, tin protoporphyrin (SnPP), on Caco-2 cell proliferation and differentiation was examined. In preconfluent cells, cell number was determined periodically as a marker of proliferation. Cell viability was measured with MTT assay. Cell differentiation was assessed by the expression of a brush border enzyme, alkaline phophatase (ALP). HO-1 was expressed in subconfluent Caco-2 cells and remained detectable until 2 days postconfluency. This timing was consistent with cells starting their differentiation and taking the features of normal intestinal epithelial cells. HO-1 was inducible in confluent Caco-2 cells by the enzyme substrate, hemin in a dose- and time-dependent manner. SnPP decreased the cell number and viability of preconfluent cells and delayed the ALP enzyme activity of confluent cells. HO-1 may be involved in intestinal cell cycle progression.

Original languageEnglish (US)
Pages (from-to)590-595
Number of pages6
JournalExperimental Biology and Medicine
Volume228
Issue number5
DOIs
StatePublished - May 2003

Fingerprint

Heme Oxygenase-1
Caco-2 Cells
Cell Cycle
Enterocytes
Cells
Cell Differentiation
Hemin
Epithelial Cells
Cell proliferation
Enzyme activity
Enzymes
Intestinal Mucosa
Cell Survival
Cell Count
Cell Proliferation
Endothelial cells
Enzyme Inhibitors
Brushes
Regulator Genes
Microvilli

Keywords

  • Apoptosis
  • Cell cycle
  • Cell proliferation
  • Differentiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Does heme oxygenase-1 have a role in Caco-2 cell cycle progression? / Uc, Aliye; Britigan, Bradley E.

In: Experimental Biology and Medicine, Vol. 228, No. 5, 05.2003, p. 590-595.

Research output: Contribution to journalArticle

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