RESUMO
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.
Assuntos
Envelhecimento/metabolismo , Endotélio Vascular/metabolismo , Antígeno Ki-67/genética , Oligopeptídeos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Epigênese Genética , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos/farmacologia , Substâncias Protetoras/farmacologia , RatosRESUMO
The mechanism of geroprotective effect of peptides AED and EDL was studied in ageing renal cell culture. Peptide AED and EDL increase cell proliferation, decreasing expression of marker of aging p16, p21, p53 and increasing expression of SIRT-6 in young and aged renal cell culture. The reduction of SIRT-6 synthesis in cell is one of the causes of cell senescence. On the basis of experimental data models of interaction of peptides with various sites of DNA were constructed. Both peptides form most energetically favorable complexes with d(ATATATATAT)2 sequences in minor groove of DNA. It is shown that interaction of peptides AED and EDL with DNA is the cause of gene expression, encoded marker of ageing in renal cells.
Assuntos
Senescência Celular/efeitos dos fármacos , Rim/efeitos dos fármacos , Oligopeptídeos/farmacologia , Animais , Sítios de Ligação , Biomarcadores/metabolismo , Contagem de Células , Células Cultivadas , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , DNA/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/citologia , Rim/metabolismo , Simulação de Acoplamento Molecular , Cultura Primária de Células , Ratos Wistar , Sirtuínas/genética , Fatores de Tempo , Proteína Supressora de Tumor p53/genéticaRESUMO
Cytokines CCL11 (eotaxin) and HMGB1 (alarmin1) are molecular markers of ageing and neurological, cardiovascular and immune diseases. Created in St. Petersburg Institute of Bioregulation and Gerontology short peptides are known to regulate gene expression and protein synthesis. They promote the mortality decrease and slowdown the development of pathology in the elderly. The article presents the proposed role of dipeptide vilon (Lys-Glu) and tetrapeptide epitalon (Ala-Glu-Asp-Gly) in CCL11 and HMGB1 genes regulation as activators of their expression. Geroprotective action of vilon and epitalon probably realizes in suppression of these genes.
Assuntos
Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Quimiocina CCL11/metabolismo , Dipeptídeos/uso terapêutico , Proteína HMGB1/metabolismo , Oligopeptídeos/uso terapêutico , Envelhecimento/genética , Animais , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Sequência de Bases , Sítios de Ligação , Biomarcadores/metabolismo , Quimiocina CCL11/genética , Dipeptídeos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/genética , Humanos , Dados de Sequência Molecular , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/prevenção & controle , Oligopeptídeos/administração & dosagemRESUMO
The review contains different aspects indicating the participation of cytokines in aging-associated diseases. Authors reveal the role of short peptides in molecular mechanisms of homeostatic regulation in immune, cardiovascular, haemostatic systems which is based on the literature data and own experimental data. It is established that short peptides realize their geroprotective effect by changing gene expression of immune and proinflammatory cytokines and g-interferon.
Assuntos
Envelhecimento/genética , Aterosclerose/genética , Citocinas/genética , Regulação da Expressão Gênica no Desenvolvimento , Sistema Imunitário/fisiologia , Peptídeos/genética , Trombose/genética , Envelhecimento/metabolismo , Aterosclerose/metabolismo , Citocinas/biossíntese , Hemostasia/genética , Homeostase/genética , Humanos , Peptídeos/metabolismo , Trombose/metabolismoRESUMO
In this study the molecular mechanisms of pancreoprotective action of researched tetrapeptide H-Lys-Glu-Asp-Trp-NH2 in aging pancreatic cells of a human were investigated. It is established that the studied tetrapeptide increases the expression of matrix metalloproteinase MMP2, MMP9, serotonin, glycoprotein CD79alpha, antiapoptotic protein Mcl1, proliferation markers PCNA and Ki67 and decreases the expression of proapoptotic protein p53 in aged pancreatic cell cultures. Thus, the capability to activate the expression of signaling molecules--markers of functional activity of pancreatic cells lies behind the clinical effect of studied tetrapeptide observing in elderly patients with type 2 diabetes mellitus.
