Effect of Neuropeptide Cyclo-L-Prolylglycine on Cell Proliferative Activity

Endogenous neuropeptide cyclo-L-prolylglycine possesses mnemotropic and neuroprotective properties, which can result from its positive effect on the level of brain-derived neurotrophic factor and modulation of activity of insulin-like growth factor-1 and AMPA receptors. For detection of possible mitogenic action of cyclo-L-prolylglycine, we analyzed its effect on proliferative activity of HEK293 and SH-SY5Y cells assessed by expression of Ki-67 proliferation marker, cell cycle examination, and incorporation of modified nucleotide analog EdU into DNA. Cyclo-L-prolylglycine did not affect the level of Ki-67 in examined cell lines and distribution of the cells over G1 and G2 phases of the cell cycle, although it insignificantly reduced the percentage of S phase cells, which attested to the absence of intrinsic mitogenic activity of the peptide. At the same time, cyclo-L-prolylglycine reduced the number of the early apoptotic cells, which can be a mechanisms of its protective action.