Effects of an E-cadherin-derived peptide on the gene expression of Caco-2 cells.
OBJECTIVE
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.
Calcagno
Anna Maria
AM
Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA. calcagnoa@mail.nih.gov
Fostel
Jennifer M
JM
Reyner
Eric L
EL
Sinaga
Ernawati
E
Alston
James T
JT
Mattes
William B
WB
Siahaan
Teruna J
TJ
Ware
Joseph A
JA
D000199:Actins / Q000032:analysis / Q000096:biosynthesis; D015153:Blotting, Western; D018938:Caco-2 Cells; D015820:Cadherins / Q000494:pharmacology*; D002449:Cell Aggregation; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D012313:RNA / Q000032:analysis / Q000096:biosynthesis
D000199:Actins; D015820:Cadherins; D010455:Peptides; D012313:RNA