Pyroglutamyl-histidyl-glycine, the endogenous colon mitosis inhibitor, regulates cyclic AMP level in non-tumorigenic colonic epithelial cells
Reichelt, W.H.; Iversen, J-Gustav.H.; Paulsen, J.Erik.; Elgjo, K.; Reichelt, K.L.
Anticancer Research 24(3a): 1465-1468
2004
ISSN/ISBN: 0250-7005 PMID: 15274311 Document Number: 583866
Background: We have proposed that the mitosis inhibiting peptide, pyroGlu-His-Gly (pEHG), a colon-specific negative feedback regulator of cell proliferation, works through a G protein-coupled receptor (GPCR), as do many other pyroglutamyl-peptides. Materials and Methods: Non-tumorigenic YAMC (colon mucosa of Immorto mice), IMCE (Immorto-Min mouse hybrid) and human hepatoma (HepG2) cell lines were exposed to pEHG. cAMP concentrations were measured with a protein binding assay, mRNA levels with real-time PCR and Ca2+ concentration with an inverted fluorescence microscope on Fura-2/AM-loaded cells. Results: pEHG (1 nM) increased the intracellular concentration of cAMP after 5-10 min in YAMC cells, but not in HepG2 cells. No effect was seen on cytosolic Ca2+, or in the expression of the proliferation and differentiation regulatory genes c-fos, egr-1 or fosB in YAMC or IMCE cells. Conclusion: pEHG stimulates the second messenger cAMP, but has no effect on intracellular Ca2+ or the gene expression of c-fos, egr-1 or fosB.