Effect of Polypeptides on Cell Proliferation and Apoptosis during Aging.

Polypeptide complexes derived from the bronchi, blood vessels, muscles, kidneys, ovaries, testes, and retina stimulated the processes of cell renewal in organotypic cultures of the corresponding organs of young and old animals. A correlation between the intensity of regeneration and animal' age was revealed. The polypeptide complexes reduced the expression of apoptotic factors p53 and caspase 3 and increased the expression of proliferation protein Ki-67.

Peptide Regulation of Cells Renewal Processes in Kidney Tissue Cultures from Young and Old Animals.

Polypeptide complex isolated from calf kidneys stimulates the processes of cell renewal in organotypic kidney tissue cultures from young and old rats. The polypeptide complex enhances expression of proliferation marker Ki-67 and reduces expression of proapoptotic peptide p53 in kidney explants obtained from young and old animals. Short peptides T-31 (AED) and T-35 (EDL) also stimulate proliferation and reduce apoptosis of the kidney cells, but to a lesser degree than the polypeptide complex.

[Molecular aspects of renal desease].

The review considers molecular mechanisms of chronic renal failure and cancer kidney disease. The most important molecules inducing inflammation are cytokines (MCP-1, TNFalpha, IFN-gamma, IL-1,6,8,18), matrix metalloproteinases MMP-2,3,9,14, tissue inhibitors of metalloproteinases (TIMPs) and grow factors (VEGF PDGE FGF). This signal molecules regulate the activity of immune cells and remodeling extracellular matrix (ECM) components taken place in inflammatory reactions, proliferation, apoptosis and also in the differentiation of kidney cells.

Effect of amino acids on expression of signal molecules in organotypic culture of the spleen.

Opposite effects of amino acids on proliferation and differentiation of immune cells in organotypic culture of the spleen were demonstrated. It was found that methionine stimulates differentiation of CD5(+) lymphocyte precursors into T-helpers, cytotoxic T lymphocytes, and B cells and induces proliferation of CD68(+)-macrophages. Glutamic acid and arginine induce proliferation of B cells, while histidine and leucine promote differentiation of precursors towards cytotoxic T cells.

Effect of tripeptide Lys-Glu-Asp on physiological activity of neuroimmunoendocrine system cells.

Tripeptide Lys-Glu-Asp stimulates proliferation and inhibits apoptosis in organotypic cultures of neuroimmunoendocrine system cells. Lys-Glu-Asp accelerates cell renewal processes (decrease of apoptosis marker p53 and increase of proliferation marker Ki-67) in the pineal gland; this effect is more pronounced in cultures derived from old animals than in young cultures. The tripeptide induces the expression of low-differentiated lymphocyte marker CD5 and macrophage marker CD68, but in "old" cultures this effect is less pronounced than in "young" ones.

Peptidergic regulation of expression of genes encoding antioxidant and anti-inflammatory proteins.

Geroprotective peptide T-34 regulates the expression of mRNA for various genes. The development of gastric ulcer is associated with morphological and molecular changes resulting from modulation of the synthesis of antioxidant and anti-inflammatory proteins. Peptide T-34 normalizes the synthesis of these proteins by regulating the expression of the corresponding genes.

Effect of short peptides on expression of signaling molecules in organotypic pineal cell culture.

We demonstrated the influence of short peptides on the expression of signaling molecules in organotypic culture of the pineal gland from 3-month-old rats. Peptides Ala-Glu-Asp-Gly and Lys-Glu-Asp stimulate the expression of proliferative protein Ki-67 in pineal gland culture. These peptides as well as Glu-Asp-Arg and Lys-Glu do not affect the expression of apoptosis marker AIF.

Peptides from the pituitary gland and cortex stimulate differentiation of polypotent embryonic tissue.

We studied the effects of synthetic peptides from the pituitary gland and brain cortex on differentiation of polypotent ectodermal tissue of the early gastrula of Xenopus laevis. It was shown that the pituitary gland peptide stimulates differentiation of polypotent tissue into epidermis and nerve tissue, while brain cortex peptide induces the development of mesenchyma and epidermis. Differentiation of polypotent tissue under the effect of the peptide is a mechanism of their geroprotective effect and suggests that they are promising as preparations for the treatment of neurodegenerative diseases.

Peptides regulate cortical thymocytes differentiation, proliferation, and apoptosis.

The processes of differentiation, proliferation, and apoptosis were studied in a cell culture of human cortical thymocytes under the influence of short peptides T-32 (Glu-Asp-Ala) and T-38 (Lys-Glu-Asp). Peptides T-32 and T-38 amplified cortical thymocytes differentiation towards regulatory T cells, increased their proliferative activity, and decreased the level of apoptosis. Moreover, peptides under study stimulated proliferative and antiapoptotic activity of the mature regulatory T cells.

[Tetrapeptide stimulates functional activity of the pancreatic cells in aging].

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.

[Application of peptide bioregulators by elderly people suffering from psycho-emotional disorders].

The material presented contributes to the study of such a priority research issue in gerontology and geriatrics as the effectiveness and mechanisms of influence of peptide bioregulators on psycho-emotional state of older patients. Most important clinical and physiological signs of psychosomatic disorders have been identified therefore and the evaluation of peptide bioregulators impact on the indices of psycho-emotional status in the elderly have been conducted. This has been achieved by monitoring psycho-emotional status of patient employing an equipment and software for psychophysiological assessment "Expert" including module "Reflex".