RESUMO
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.
Assuntos
Epigênese Genética/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Antígeno Ki-67/genética , Oligopeptídeos/farmacologia , Transativadores/genética , Proteína Supressora de Tumor p53/genética , Motivos de Aminoácidos , Apoptose/efeitos dos fármacos , Apoptose/genética , Sítios de Ligação , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células HeLa , Proteínas de Homeodomínio/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Simulação de Acoplamento Molecular , Motivos de Nucleotídeos , Oligopeptídeos/síntese química , Regiões Promotoras Genéticas , Ligação Proteica , Eletricidade Estática , Termodinâmica , Transativadores/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
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.
Assuntos
Fibronectinas/metabolismo , Telômero/genética , Animais , Epigênese Genética/genética , Fibronectinas/genética , Humanos , Camundongos , Peptídeos/genética , Peptídeos/metabolismoRESUMO
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.
Assuntos
DNA/metabolismo , Dipeptídeos/metabolismo , Modelos Moleculares , Animais , Proliferação de Células/efeitos dos fármacos , Dipeptídeos/química , Dipeptídeos/farmacologia , Masculino , Simulação de Acoplamento Molecular , Ligação Proteica , Ratos , Ratos Wistar , Baço/citologiaRESUMO
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.
Assuntos
Envelhecimento , Moléculas de Adesão Celular , Receptores de Superfície Celular , Envelhecimento/genética , Envelhecimento/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Epigênese Genética , Expressão Gênica , Humanos , Oligopeptídeos/metabolismo , Fatores de Proteção , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismoRESUMO
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.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Oligopeptídeos/farmacologia , Serotoninérgicos/farmacologia , Serotonina/biossíntese , Animais , Sequência de Bases , Sítios de Ligação , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Simulação de Acoplamento Molecular , Dados de Sequência Molecular , Cultura Primária de Células , Ligação Proteica , Ratos , Ratos Wistar , Serotonina/genética , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismoRESUMO
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.
Assuntos
DNA/química , Simulação de Acoplamento Molecular , Oligopeptídeos/química , Sequência de Aminoácidos , Sequência de BasesRESUMO
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.
Assuntos
DNA/química , Dipeptídeos/química , Metaloproteinase 2 da Matriz/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Oligopeptídeos/química , Regiões Promotoras Genéticas , Sequência de Bases , Sítios de Ligação , Antígenos CD5/genética , Peptídeos Penetradores de Células/metabolismo , DNA/metabolismo , Proteínas de Ligação a DNA/análise , Dipeptídeos/metabolismo , Interleucina-2/genética , Dados de Sequência Molecular , Oligopeptídeos/metabolismo , Fragmentos de Peptídeos , Eletricidade EstáticaRESUMO
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.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Oligopeptídeos/farmacologia , Pâncreas/citologia , Linhagem Celular , Senescência Celular/efeitos dos fármacos , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio , Humanos , Proteínas Nucleares , Fatores de TranscriçãoRESUMO
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.
