Epigenetic Regulation of “Aged” Heterochromatin by Peptide Bioregulator Cortagen

Abstract

Peptide bioregulator Cortagen (Ala-Glu-Asp-Pro) in humans demonstrated a pronounced therapeutic effect up on the structural and functional recovery of the damaged peripheral nerve tissue. The synthetic peptide Cortagen was obtained by directed synthesis based on amino acid analysis of natural brain cortex peptide preparation Cortexin. The effect of synthetic peptide bioregulator Cortagen on total, constitutive [pericentromeric, nucleolus organizer regions (NOR)] heterochromatin and facultative (transcriptionally inactive euchromatin) heterochromatin has been studied. We used a molecular-cytogenetic methods: differential scanning calorimetry; activity of ribosomal genes of acrocentric chromosome satellite stalks—NORs; polymorphism of structural pericentromeric C-heterochromatin; variability of the facultative heterochromatin (FH) in cultivated lymphocytes from individuals at the age of 80 and older. We show that peptide bioregulator Cortagen induces unrolling deheterochromatinization (decondensation) of total heterochromatin; activates synthetic processes of ribosomal genes as a result of deheterochromatinization of satellite stalks of acrocentric chromosomes; does not induce deheterochromatinization of pericentromeric structural heterochromatin; and releases repressed genes because of the condensation of euchromatic regions forming FH. Our data are important because it provides new information on the remodeling effects of FH induced by peptide bioregulator Cortagen in aging and aging pathologies, and may lead to the development of a therapeutic treatment.