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1 Department of Surgery, University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
2 Department of Pathology, University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
3 Department of Surgery, University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA; Department of Pathology, University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
* To whom correspondence should be addressed. E-mail: jwang{at}smail.umaryland.edu.
Occludin is an integral membrane protein that forms the sealing element of tight
junctions and is critical for epithelial barrier function. Polyamines are implicated in multiple
signaling pathways driving different biological functions of intestinal epithelial cells (IEC). The
current study determined whether polyamines are involved in expression of occludin and play a
role in intestinal epithelial barrier function. Studies were conducted in stable Cdx2-transfected
IEC-6 cells (IEC-Cdx2L1), which were associated with a highly differentiated phenotype.
Polyamine depletion by 
-difluoromethylornithine (DFMO) decreased levels of occludin protein
but failed to affect expression of its mRNA. Other tight junction proteins, ZO-1, ZO-2, claudin-
2, and claudin-3, were also decreased in polyamine-deficient cells. Decreased levels of tight
junction proteins in DFMO-treated cells were associated with dysfunction of the epithelial
barrier, which was overcome by exogenous polyamine spermidine. Decreased levels of occludin
in polyamine-deficient cells was not due to the reduction of intracellular free Ca2+ ([Ca2+]cyt),
because either increased or decreased [Ca2+]cyt did not alter levels of occludin in the presence or
absence of polyamines. Level of newly synthesized occludin protein was decreased by ~70%
following polyamine depletion, while its protein half-life was reduced from ~120 min in control
cells to ~75 min in polyamine-deficient cells. These findings indicate that polyamines are
necessary for the synthesis and stability of occludin protein and that polyamine depletion
disrupts the epithelial barrier function, at least partially, by decreasing occludin.
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