Effects of an E-cadherin-derived peptide on the gene expression of Caco-2 cells

Pharm Res. 2004 Nov;21(11):2085-94. doi: 10.1023/b:pham.0000048201.00143.72.

Abstract

Purpose: The goal of this study was to determine the effects of exposure to an HAV peptide (Ac-SHAVSS-NH2) on the protein and gene expression in Caco-2 cells, a model for the intestinal mucosa.

Methods: Caco-2 cells were incubated with either 100 or 500 microM of the hexapeptide then evaluated over a 48-h time period.

Results: Cell detachment from the monolayer was seen only after 48 h of exposure to the peptide, with the greatest effects occurring with a peptide concentration of 500 microM. Total protein expression of E-cadherin showed a decrease of nearly 20% at the 24-h time point for each concentration examined, whereas no significant changes were detected at the other time points studied. Short term exposure to a 500 microM solution of Ac-SHAVSS-NH2 caused few changes in gene expression as determined by Affymetrix GeneChip microarrays; however, longer exposure periods produced numerous changes in the treated cells. The variations in mRNA expression indicate that this HAV peptide has an effect in the E-cadherin signaling pathways. The greatest increases in mRNA expression were found in genes regulating excretion or degradation of the peptide.

Conclusions: This work suggests that this HAV peptide produces effects that reach beyond modulation of adhesion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / analysis
  • Actins / biosynthesis
  • Blotting, Western
  • Caco-2 Cells
  • Cadherins / pharmacology*
  • Cell Aggregation
  • Gene Expression / drug effects*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Peptides / chemical synthesis
  • Peptides / isolation & purification
  • Peptides / pharmacology
  • RNA / analysis
  • RNA / biosynthesis

Substances

  • Actins
  • Cadherins
  • Peptides
  • RNA