ABSTRACT
Short peptides constitute the system of signal molecules regulating the functions of the organism at the molecular, genetic, subcellular, cellular, and tissue levels. One short peptide can regulate dozens of genes, but the molecular mechanism of this process remains unclear. We suppose that short peptides penetrate through the cytoplasmic and nuclear membrane and bind to DNA. Spatial models of DNA-peptide complexes are constructed for 19 short peptides by the docking method. Some peptides have the same binding sites. Peptides KE and EDP bind agat sequence, peptides KEDW and AED to acct sequence, and peptides AEDL and EDL to ctcc sequence.
Subject(s)
Epigenesis, Genetic/drug effects , Homeodomain Proteins/genetics , Ki-67 Antigen/genetics , Oligopeptides/pharmacology , Trans-Activators/genetics , Tumor Suppressor Protein p53/genetics , Amino Acid Motifs , Apoptosis/drug effects , Apoptosis/genetics , Binding Sites , Cell Differentiation/drug effects , Cell Proliferation/drug effects , HeLa Cells , Homeodomain Proteins/metabolism , Humans , Ki-67 Antigen/metabolism , Molecular Docking Simulation , Nucleotide Motifs , Oligopeptides/chemical synthesis , Promoter Regions, Genetic , Protein Binding , Static Electricity , Thermodynamics , Trans-Activators/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
Irisin produced by muscles during exercise and promoting fat burning also exhibits geroprotective effect and induces telomere elongation in normal somatic cells. Special attention is paid to studies of the role of peptides Lys-Glu, Glu-Asp-Arg, and Ala-Glu-Asp-Gly in epigenetic regulation of irisin content. The data suggest that the immunomodulatory peptide Lys-Glu and neuroprotective peptide Glu-Asp-Arg modulate the life span by modulating irisin gene expression.
Subject(s)
Fibronectins/metabolism , Telomere/genetics , Animals , Epigenesis, Genetic/genetics , Fibronectins/genetics , Humans , Mice , Peptides/genetics , Peptides/metabolismABSTRACT
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
The article represents evidence about structures, properties and functions of adhesion molecule JAM-A/1 belonging to JAM subfamily. This protein plays an important role in epithelial tight junction formation and immune function. Current article focuses on the role of JAM-A protein in pathogenesis associated to ageing: atherosclerosis, apoplexy, thrombosis, hypertension, ophthalmological pathology. We propose short peptides Lys-Glu, Lys-Glu-Asp, and Ala-Glu-Asp-Gly could influence on F11R gene expression that leads to recovery of JAM-A synthesis in cells.
Subject(s)
Aging , Cell Adhesion Molecules , Receptors, Cell Surface , Aging/genetics , Aging/metabolism , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Epigenesis, Genetic , Gene Expression , Humans , Oligopeptides/metabolism , Protective Factors , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolismABSTRACT
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
Tetrapeptide Lys-Glu-Asp-Trp is a mimetic of insulinotropic peptides and reduces the blood glucose level. This tetrapeptide increases the content of important factors of differentiation in endocrine pancreatic cells in vitro. Molecular modeling shows that this tetrapeptide can interact with not only minor, but also major groove of DNA molecule. The interaction with the major groove is more specific, because it depends on the primary sequences of the tetrapeptide and DNA. Sequence GGCAG is the putative binding site for the tetrapeptide.
Subject(s)
DNA/chemistry , Molecular Docking Simulation , Oligopeptides/chemistry , Amino Acid Sequence , Base SequenceABSTRACT
Expression of differentiation markers was found to be reduced during ageing of pancreatic cells. Tetrapeptide pancragen stimulates the expression of differentiation factors of acinar (Pdx1, Ptfla) and islet of Langerhans (Pdx1, Pax6, Pax4, Foxa2, NKx2.2) cells in "young" and " aged" cultures. Differentiation of acinar and islet pancreatic cells induced by pancragen can be a mechanism underlying its anti-diabetic and anti-inflammatory effects. Thus, transcription factors that regulate differentiation of pancreatic cells are a pharmacological target for pancragen, which allows considering it as an effective tool in the treatment of diabetes mellitus and pancreatitis.
Subject(s)
Cell Differentiation/drug effects , Oligopeptides/pharmacology , Pancreas/cytology , Cell Line , Cellular Senescence/drug effects , Homeobox Protein Nkx-2.2 , Homeodomain Proteins , Humans , Nuclear Proteins , Transcription FactorsABSTRACT
Analysis of the main parameters of molecular mechanics (number of hydrogen bonds, hydrophobic and electrostatic interactions, DNA-peptide complex minimization energy) provided the data to validate the previously proposed qualitative models of peptide-DNA interactions and to evaluate their quantitative characteristics. Based on these estimations, a three-dimensional model of Lys-Glu and Ala-Glu-Asp-Gly peptide interactions with DNA sites (GCAG and ATTTC) located in the promoter zones of genes encoding CD5, IL-2, MMP2, and Tram1 signal molecules.
Subject(s)
DNA/chemistry , Dipeptides/chemistry , Matrix Metalloproteinase 2/genetics , Membrane Glycoproteins/genetics , Membrane Transport Proteins/genetics , Oligopeptides/chemistry , Promoter Regions, Genetic , Base Sequence , Binding Sites , CD5 Antigens/genetics , Cell-Penetrating Peptides/metabolism , DNA/metabolism , DNA-Binding Proteins/analysis , Dipeptides/metabolism , Interleukin-2/genetics , Molecular Sequence Data , Oligopeptides/metabolism , Peptide Fragments , Static ElectricityABSTRACT
We verified expression of CXCL12 and Hoxa3 transcription factors of differentiation in cultures of human embryonic pancreatic and bronchial cells and CXCL12 and WEGC1 factors in a culture of human prostatic fibroblasts. Reduced expression of these differentiation markers was detected in late-passage (aging) cultures. The expression of differentiation factors CXCL12, Hoxa3, and WEGC1 was tissue-specifically stimulated by short peptides: pancragen (Lys-Glu-Asp-Trp) in pancreatic cells, bronchogen (Ala-Glu-Asp-Leu) in bronchial epithelial cells, and vesugen (Lys-Glu-Asp) in fibroblasts. The inducing effect of peptides on the expression of differentiation factors was more pronounced in aged cultures, which can serve as a mechanism of their geroprotective effect.
