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Cited by 93Polyamine Metabolism and ApplicationsBarrier Structure and Function StudiesGastrointestinal motility and disorders

Polyamines are necessary for synthesis and stability of occludin protein in intestinal epithelial cells

Guo, Xin, Rao, Jaladanki N., Liu, Lan, Zou, Tongtong, Keledjian, Kaspar M., Boneva, Dessy, Marasa, Bernard S., Wang, Jian-Ying·2005·American Journal of Physiology-Gastrointestinal and Liver Physiology
DOI 10.1152/ajpgi.00407.2004
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Abstract

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 present 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) associated with a highly differentiated phenotype. Polyamine depletion by alpha-difluoromethylornithine (DFMO) decreased levels of occludin protein but failed to affect expression of its mRNA. Other tight junction proteins, zonula occludens (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 Ca(2+) concentration ([Ca(2+)](cyt)), because either increased or decreased [Ca(2+)](cyt) did not alter levels of occludin in the presence or absence of polyamines. The level of newly synthesized occludin protein was decreased by approximately 70% following polyamine depletion, whereas its protein half-life was reduced from approximately 120 min in control cells to approximately 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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Crossref · 10.1152/ajpgi.00407.2004

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  • Blocking endogenous polyamine production with an ornithine decarboxylase inhibitor negatively affects maintenance, repair, and function of the intestinal epithelium.

    “blocking endogenous production of polyamines with a chemical inhibitor of ornithine decarboxylase negatively affects maintenance, repair and function of the intestinal epithelium”

    From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as X. Guo et al., 2005

  • Exogenous supplementation of spermidine reversed the effects of α-difluoromethylornithine on intracellular Ca2+ and E-cadherin expression and restored paracellular permeability to near normal levels.

    “However, exogenous supplementation of the spermidine reversed the effects of α-difluoromethylornithine on intracellular Ca2+ and E-cadherin expression and restored paracellular permeability to near normal levels.128”

    From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [128]

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Related

Authors
Guo, X., Rao, J. N., Liu, L., Zou, T., Keledjian, K. M., Boneva, D., Marasa, B. S., & Wang, J.-Y.
Affiliations
  • Baltimore VA Medical Center (US)
  • University of Maryland, Baltimore (US)
ORCID
Venue
American Journal of Physiology-Gastrointestinal and Liver Physiology
Publisher
American Physiological Society
Published
2005-06
Volume
288
Issue
6
Pages
G1159-G1169
ISSN
  • 0193-1857 (ISSN-L)
  • 1522-1547
DOI
10.1152/ajpgi.00407.2004
OpenAlex
W2162157128
Cited by
93
References
66
Citations by year
2026: 8 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 7 · 2013: 3 · 2012: 2
FWCI
1.63
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061972, (DK-57819, R01DK068491, DK-61972, R01DK057819, DK-68491)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
polyamines, occludin, tight junctions, intestinal epithelial barrier function, polyamine depletion, difluoromethylornithine, protein stability, protein synthesis, ZO-1, ZO-2, claudin-2, claudin-3, spermidine, IEC-6 cells, CDX2, intracellular calcium
MeSH terms
CDX2 Transcription Factor, Eflornithine, Enzyme Inhibitors, Gene Expression Regulation, Humans, Intestinal Mucosa, Membrane Proteins, Phenotype, Polyamines, RNA, Messenger, Transfection, Homeodomain Proteins, Cell Culture Techniques, Occludin

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