ABSTRACT
We performed a comparative analysis of biological activity of Lys-Glu peptide and its amino acid constituents. It was established that Lys-Glu stimulated proliferation of splenic cells in organotypic culture, while the mixture of glutamic acid and lysine inhibited culture growth. Using the method of molecular docking, we showed that glutamic acid, lysine, and Lys-Glu peptide can interact with different DNA sequences. The energy of interaction and the most beneficial localization of glutamic acid, lysine, and Lys-Glu peptide in DNA molecule was calculated. We demonstrated the interaction of the peptide and amino acids with DNA along the minor groove. The energy of DNA interaction with the peptide is higher than with individual amino acids. The peptide bonds increase the interaction of Lys-Glu peptide with DNA, which potentiates the biological effect on cell proliferation in organotypic culture of splenic cells.
Subject(s)
DNA/metabolism , Dipeptides/metabolism , Models, Molecular , Animals , Cell Proliferation/drug effects , Dipeptides/chemistry , Dipeptides/pharmacology , Male , Molecular Docking Simulation , Protein Binding , Rats , Rats, Wistar , Spleen/cytologyABSTRACT
Short peptides vesugen and D-7 have stimulated proliferation-associated protein Ki-67 decreased during aging in tissue-specific cell cultures received from young and old animals and in dissociated vascular endothelial cell cultures. Peptides vesugen and D-7 have interacted with promoter region of MKI67 gene coding protein Ki-67 that was obtained using methods of molecular docking. Both peptides have contacted with core promoter 5'-agcctcaaccatcaggaaaacaagagt-3' located in MKI67 gene from -14 to +12 base pairs relative to the transcriptional initiation site through sequence CATC(ENSG00000148773). Thus, vasoprotective effect of peptide vesugen revealed previously in elder people could be realized through epigenetic regulation of Ki-67 gene expression.
Subject(s)
Aging/metabolism , Endothelium, Vascular/metabolism , Ki-67 Antigen/genetics , Oligopeptides/pharmacology , Animals , Cell Proliferation/drug effects , Cells, Cultured , Epigenesis, Genetic , Gene Expression Regulation/drug effects , Peptides/pharmacology , Protective Agents/pharmacology , RatsABSTRACT
Peptides Glu-Asp-Arg and Lys-Glu-Asp stimulate serotonin expression in aging cultures of brain cortex cells. Peptide regulation of 5-tryptophan hydroxylase gene encoding the enzyme involved in serotonin synthesis was demonstrated by the molecular docking method. The CCTGCC nucleotide sequence in 5-tryptophan hydroxylase gene was found to be complementary to these peptides. Hence, Glu-Asp-Arg and Lys-Glu-Asp peptides epigenetically regulate serotonin synthesis in the brain cortex, which indicates their neuro- and geroprotective activities.
Subject(s)
Central Nervous System Stimulants/pharmacology , Gene Expression Regulation/drug effects , Oligopeptides/pharmacology , Serotonin Agents/pharmacology , Serotonin/biosynthesis , Animals , Base Sequence , Binding Sites , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Molecular Docking Simulation , Molecular Sequence Data , Primary Cell Culture , Protein Binding , Rats , Rats, Wistar , Serotonin/genetics , Tryptophan Hydroxylase/genetics , Tryptophan Hydroxylase/metabolismABSTRACT
There are the point of molecular personified medicine view the applied importance of studying the expression of a variety of genetic and epigenetic factors (miRNAs, chemokines, cytokines, adhesion molecules, proliferation and apoptosis factors of vessel endothelium) as an innovative approach to the diagnostics and treatment of atherosclerosis, coronary heart disease, myocardial infarction. The review has described the data, which is connected with development new biological active vaso- and cardioprotective substances on the peptides base. These substances can regulate the expression of signaling molecules--the molecular markers of cardiovaslular diseases.
