EPIGENETIC MODIFICATION UNDER THE INFLUENCE OF PEPTIDE BIOREGULATORS ON THE "OLD" CHROMATIN.

In the present study, on the one hand, the epigenetic modification of condensed "old" chromatin was determined, and on the other hand, the influence of peptide bioregulators (Ala-Glu-Asp-Gly-Epitalon; Lys-Glu-Asp-Ala-Livagen; Ala-Glu-Asp-Pro - Cortagen and Lys-Glu - Vilon) on condensed chromatin in lymphocytes from old individuals. Were used molecular-cytogenetic methods: differential scanning calorimetry; activity of ribosomal genes of acrocentric chromosome satellite stalks-NORs; polymorphism of structural pericentromeric C-heterochromatin; variability of the facultative heterochromatin (sister chromatid exchanges - SCE) in the culture of lymphocytes from 75-88-year-old individuals. The analysis of results shows the chromosome progressive heterochromatinization (condensation of eu - and heterochromatin regions) occur in aging. Epigenetics process - heterochromatinization can deactivate many previously functioning active genes. It blocks certain stages of normal metabolic processes in the cell, which inhibits many specific enzymes and leads to aging pathologies. We show that peptide bioregulators induced unrolling deheterochromatinization (decondensation) of total heterochromatin, deheterochromatinization of satellite stalks of acrocentric chromosome, activating synthetic processes of ribosomal genes, does not cause deheterochromatinized of pericentromeric structural heterochromatin. This data also indicates that each of the studied peptide bioregulators (Ala-Glu-Asp-Gly; Lys-Glu-Asp-Ala; Ala-Glu-Asp-Pro and Lys-Glu) has a selective effect on definite regions of chromosomes. Thus, short peptide bioregulators induce selective heterochromatinization and deheterochromatinization of chromosome regions (remodeling of facultative heterochromatin) in individuals 75-88 years old that opens up new opportunities in the treatment of aging diseases.

[GENOMIC VARIABILITY DURING PREGNANCY TRIMESTERS].

The article presents data on the genome status of pregnant women in different trimesters of pregnancy, during the normal course of pregnancy. The variability of ribosomal cystone activation as well as the variability of genome stability (frequencies of chromosomal aberrations and fragile sites) in different trimesters of pregnancy have been studied to detect genome-specific functional variability for each trimester.It was found that the level of genome stability determined by the frequency of chromosomal structural disorders and fragile sites in all three trimesters of pregnancy did not differ significantly from similar rates for non-pregnant healthy women. The exception was the frequency of fragile sites in the first trimester of pregnancy, which was statistically significantly higher than the control rate, which may be a specific feature (characteristic) for this trimester of pregnancy.At the same time, specific variability in genomic parameters was identified. In particular, deheterochromatization of pericentromeric heterochromatin and heterochromatinization of the medial region and pretelomeric heterochromatin.Based on data on the activation of Nucleolar organizing regions of acrocentric chromosomes and changes in the frequency of acrocentric chromosome associations, which are statistically significantly higher than the control level, a conclusion is made about increased activity of protein-synthesizing apparatus of the cell in all three trimesters of pregnancy. A statistically significant increase in the associative activity of the 15 acrocentric chromosome in the third trimester of pregnancy has been identified, which may also indicate possible specific modification variability on this chromosome and be characteristic of a given trimester of pregnancy.

EPIGENETIC MODIFICATION UNDER THE INFLUENCE OF PEPTIDE BIOREGULATORS ON "AGED" HETEROCHROMATIN.

Following the completion of the Human Genome Project, the strategic direction of modern genetics has moved toward functional genomics, to explore the functions of non-coding regions of DNA. These non-coding regions are localized in heterochromatin. The functions of heterochromatin largely remain unclear. Facultative heterochromatin occurs in aging. The effect of synthetic peptide bioregulators (tetrapeptides: Ala-Glu-Asp-Gly; Lys-Glu-Asp-Ala; Ala-Glu-Asp-Pro and dipeptide - Lys-Glu) on total heterochromatin, constitutive (structural) and facultative heterochromatin in cultured lymphocytes of individuals aged 75-88 and 20 - 40 years have been studied. We used a molecular-cytogenetic methods: differential scanning calorimetry; activity of ribosomal genes of acrocentric chromosome satellite stalks - NORs; C-heterochromatin; sister chromatid exchanges (SCE). The results showed that peptide bioregulators: 1. induce unrolling - deheterochromatinization of total heterochromatin, constitutive (pericentromeric, telomeric, and nucleolar organizer regions (NOR)) and facultative heterochromatin; 2. induce higher level of SCEs (deheterochromatinization), were registered in telomeric heterochromatin and decreased (heterochromatinization) SCEs level in the medial regions of chromosome arms; 3. each peptide bioregulator selectively deheterochromatinizes a specific region of chromosomes releasing inactive (once active) genes, which, apparently, can contribute to the targeted treatment of aging diseases. The proposed genetic mechanism responsible for the remodeling of constitutive and facultative heterochromatin emphasizes the importance of external and internal factors in the development of diseases and may lead to the development of a strategy for the therapeutic treatment of senile pathology.

[EVALUATION OF GENOMIC PARAMETERS IN DUCTAL BREAST CANCER PATIENTS AND THE ABILITY OF IT'S CORRECTION].

The level of DNA single strand breaks, chromosomal abnormalities and sister chromatid exchanges and the possibility of its normalization with oligopeptide bioregulator Livagen and cobalt ions in the lymphocyte culture from patients with breast cancer have been studied. The results show that the genome of ductal breast cancer patients is characterized by the high density of DNA single strand breaks, high frequency of chromosomal abnormalities and increased levels of chromatin condensation. The usage of Livagen and cobalt in the form of modifying agents has a protective effect by all studied parameters. The obtained results allow us to conclude that research of lymphocytes of ductal breast cancer patients using the analysis conducted by us, can be useful in assessing the therapeutic effect in the treatment of breast cancer patients.

[GENOMIC VARIABILITY IN PATIENTS WITH DUCTAL FORM OF BREAST CANCER AND THE POSSIBILITY OF CORRECTION THE PEPTIDE BIOREGULATOR AND METAL IONS].

Level of genome stability (structural aberrations, aneuploidy and fragile sites) was studied in cells of the lymphocyte culture of ductal breast cancer patients (DBC). Was studied the correctional influence of separate and combinative action of peptide bioregulator (Ala-Glu-Asp-Gly) and heavy metal - nickel. It is shown that DBC patients are characterized by high level of genome instability, which is the result of the chromatin changing state. The used tests makes it possible to conclude that in the case of this form of cancer subordinates to specific epigenetic variation as a hetero- also euchromatic regions of genome. The agents - peptide bioregulator (Ala-Glu-Asp-Gly) and nickel ions, used in cell culture of ductal breast cancer patients, revealed the protective effect what indicates the prospects to further study for their involving purpose in combined therapy of this form of cancer.

[Genomic instability in atherosclerosis].

A comparative study of the level of genomic instability, parameters of quantitative and structural mutations of chromosomes (aberration, aneuploidy, polyploidy) in lymphocyte cultures from patients with atherosclerosis of age 80 years and older (control group - 30-35 years old) was conducted. The possibility of correction of disturbed genomic indicators by peptide bioregulators - Livagen (Lys-Glu-Asp-Ala) and cobalt ions with separate application or in combination was also studied. Control was lymphocyte culture of two healthy respective age groups. It was also shown that patients with atherosclerosis exhibit high level of genomic instability in all studied parameters, regardless of age, which may suggest that there is marked increase in chromatin condensation in atherosclerosis. It was also shown that Livagen (characterized by modifying influence on chromatin) separately and in combination with cobalt ions, promotes normalization of altered genomic indicators of atherosclerosis in both age groups. The results show that Livagen separately and in combination with cobalt ions has impact on chromatin of patients with atherosclerosis. The identified protective action of Livagen proves its efficacy in prevention of atherosclerosis.

[Functional regulation of genome with peptide bioregulators by hypertrophic cardiomyopathy (by patients and relatives)].

In this paper, a comparative study of the functional genome indicators using lymphocyte cultures of patients with hypertrophic cardiomyopathy (HCM) and their first relatives. Studies conducted both in intact cultures and cultures exposed to the influence of peptide - bioregulators Epithalon, Vilon and Livagen. Last (Livagen) tested at separate and joint application with cobalt chloride salt. As indicated according to the results of the analysis, the cells of the individuals with HCM and their first relatives were characterized by higher frequency of spontaneous quantitative - structural disorders in comparison with the cells of healthy individuals. The findings suggest a different effect of bioregulators. The most effective protective action in relation normalization of functional parameters of the genome shows Epithalon for lowering the level of chromosomal instability in patients with hypertrophic cardiomyopathy and relatives of patients with HCM. On the basis of identified protective action Epithalon concludes prospects of its application in the development of preventive measures for individuals at increased risk of morbidity HCM.