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.

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.

COMPARATIVE ANALYSIS OF WHOLE CARTILAGE TISSUE THERMOSTABILITY IN DISEASED PATIENTS VERSUS INJURED PATIENTS.

We conducted comparative thermodynamic analysis of femoral cartilages tissue of injured (healthy) patients and patients with congenital hip dislocation. It is shown, that temperature which corresponds to maximum of heat absorption peak of femoral cartilages tissue of diseased patient is on 6.4oC lower than heat absorption peak of femoral cartilages tissue of healthy patient.

[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.

Conformations of DNA in the presence of nanomole concentrations of Co+2 ions and mezo-tetra(4-N-oxyethylpiridil) porphyrin.

Conformation changes of calf thymus DNA induced by nanomole concentrations of Co(+2) and TOEPyP4 and influence of this ion on porphyrin binding mode with DNA duplex were studied at two NaCl concentrations (10 and 100 mM) using circular dichroism spectroscopy and absorption data. It was shown that addition of 85 nM Co(+2) into TOEPyP4/DNAb.p.

Influence of tetrapeptide on chromatin thermostability.

It is known that short peptides are capable to interact with DNA, as a result of changes in particular gene expression. In the given work, influence of Ala-Asp-Glu-Leu peptide on thermostability of white rat liver chromatin, in which H1 histone and non-histone proteins are depleted, have been studied. It was shown that in 10 nm chromatin filaments, in which nucleosomas do not interact, the tetrapeptide unfolds the nucleosomal nucleus (core) and this causes release of about 15% of core DNA that melts in the melting temperature range of internucleosomal linker DNA.

Effect of the peptide bronchogen (Ala-Asp-Glu-Leu) on DNA thermostability.

Thermodynamic parameters of DNA melting in the presence of a peptide bronchogen in various concentrations were estimated on a differential scanning microcalorimeter. Bronchogen was shown to serve as a DNA-stabilizing agent. Bronchogen increased the melting temperature of DNA from calf thymus and mouse liver by 3.

Remodeling of heterochromatin induced by heavy metals in extreme old age.

The levels of chromosome instability and heat absorption of chromatin have been studied in cultured lymphocytes derived from blood of 80-93- and 18-30-year-old individuals, under the effect of heavy metal Cu(II) and Cd(II) salts. The analysis of the results obtained indicates that 50 μM Cu(II) induced a significantly higher level of cells with chromosome aberrations in old donors (13.8 ± 1.

Gerontology research in Georgia.

Gerontology research carried out in different scientific centers of Georgia follows the basic directions of most work in this field: epidemiology, investigation of the mechanisms of aging, and finding ways to prevent senile pathologies and to prolong life. The genealogy and epidemiology of long-living peaple have been studied in areas with high occurrence of these people by considering the sex ratio and social status of the long-living, the influence of environmental factors, and the development of senile pathologies. According to the centrosome (centriole) model of aging, the centrosomes and the cytoskeleton, important structures in cellular differentiation and morphogenesis, may be involved in the initiation of the replication senescence mechanism.

Influence of anticarcinogenic metalloporphyrin Cu(II)TOEPyP(4) on DNA thermostability in vitro.

The influence of a new anticarcinogenic compound Cu(II)TOEPyP(4) (Cu(II)-Meso-tetra(4-N-oxyethylpyridyl) porphyrin) (the analogue of TMPy4[tetra(N-mrthyl-4-pyridyl)-porphyrin chloride] - an inhibitor of telomerase activity - on the thermostability of calf thymus DNA in vitro has been studied. It has been shown that Cu(II)TOEPyP(4) is a stronger stabilizing DNA agent, which is expressed with an increase of its thermostability by 20 degrees C. It was determined that complex formation does not disturb the DNA double-helix, and the melting enthalpy (DeltaHm) remains unchanged and it is equal to 11.

Microcalorimetric study of human blood lymphocytes culture at presence of copper, cadmium and prostamax.

Research goal was study of separate and joint influence of bioregulator prostamax and Cu(II) and Cd(II) ions on the chromatin structure in situ. The thermal characteristics of the denaturation process of blood lymphocytes culture of aging people in the presence of some microg quantities of Cu(II) and Cd(II) ions have been determined. It has been shown that Cu(II) and Cd(II) ions at these low concentrations don't influence on the temperature stability of membrane, nuclear and cytoplasm proteins.

Thermodynamic properties of blood plasma of patient suffering from atherosclerosis.

The goal of the work is to find out the changes in the heat parameters of blood plasma denaturation of a son and a granddaughter, in comparison with the same parameters of a 91 years old grandfather with atherosclerosis. The significant changes in heat (Q(d)) and denaturation temperature (T(d)) of albumin, globulins and fibrinogen of 91-year-old patient suffering from atherosclerosis relative to the norm (88-year-old man) are found out. In particular, Q(d) increase by 60% of albumin fat fraction and fibrinogen of F domain and the increase of their T(d) by 2.

The microcalorimetric investigation of cellular suspensions of blood lymphocytes from healthily and suffering from atherosclerosis individuals.

The denaturation thermodynamic parameters--enthalpy (DeltaH) and temperature of hetero-and active chromatin of lymphocytes and metabolic heat of these cells were determined for healthy and suffering from atherosclerosis individuals. It is supposed that atherosclerosis disease leads to chromatin rebuilding in the interphase state and decrease of cell survival. The chromatin rebuilding may be imagined as partially unfolding of 30 nm chromatin fiber into 10 nm one due to loss of some part of H1 histone.

Microcalorimetric investigation of DNA, poly(dA)poly(dT) and poly[d(A-C)]poly[d(G-T)] melting in the presence of water soluble (meso tetra (4 N oxyethylpyridyl) porphyrin) and its Zn complex.

Thermodynamic parameters of melting process (DeltaHm, Tm, DeltaTm) of calf thymus DNA, poly(dA)poly(dT) and poly(d(A-C)).poly(d(G-T)) were determined in the presence of various concentrations of TOEPyP(4) and its Zn complex. The investigated porphyrins caused serious stabilization of calf thymus DNA and poly poly(dA)poly(dT), but not poly(d(A-C))poly(d(G-T)).

Anti-aging peptide bioregulators induce reactivation of chromatin.

The effect of synthetic peptide bioregulators (Epitalon, Livagen and Vilon) on structural and facultative heterochromatin of cultivated lymphocytes have been studied among old (75-88yr.) people. The data obtained indicate that epitalon, livagen and vilon: 1) activate synthetic processes, caused by reactivation of ribosomal genes as a result of deheterochromatinization (decondensation) of nucleolus organizer regions; 2) induce unrolling (deheterochromatinization) of total heterochromatin; 3) release genes repressed by heterochromatinization (condensation) of euchromatic regions forming facultative heterochromatin; 4) epitalon and livagen induce deheterochromatinization (decondensation) of pericentromeric structural heterochromatin of the chromosomes1 and 9.

Bioregulator Vilon-induced reactivation of chromatin in cultured lymphocytes from old people.

The effect of the synthetic peptide bioregulator Vilon on structural and facultative heterochromatin of cultured lymphocytes from old people has been studied. The data obtained indicate that Vilon (a) induces unrolling (deheterochromatinization) of total heterochromatin; (b) activates synthetic processes caused by the reactivation of ribosomal genes as a result of deheterochromatinization of nucleolus organizer regions; (c) releases the genes repressed due to the condensation of euchromatic regions forming facultative heterochromatin; (d) does not induce decondensation of pericentromeric structural heterochromatin. Our results indicate that Vilon causes progressive activation (deheterochromatinization) of the facultative heterochromatin with increased aging.

Effects of Livagen peptide on chromatin activation in lymphocytes from old people.

We studied the effects of the synthetic peptide Livagen on activity of ribosomal genes, denaturation parameters of heterochromatin, polymorphism of structural C-heterochromatin, and variability of facultative heterochromatin in lymphocytes from old people. Livagen induced activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin, and release of genes repressed due to age-related condensation of euchromatic regions in chromosomes. Our results indicate that Livagen causes de-heterochromatinization (activation) of chromatin, which is realized via modification of heterochromatin and heterochromatinized regions in chromosomes from old people.

Thermal characteristics of Spirulina platensis cells under nongrowing conditions at various values of pH medium.

The total value of heat (-Q) evolved by green-blue microalgae Spirulina platensis cells in a dark and stationary regime in the range of pH values 8.0-11.6 was determined.

Microcalorimetric study of iodized and noniodized cells and C-phycocyanin of Spirulina platensis.

It was shown that eight stages of transition are observed in the heating process of Spirulina platensis cells in temperature range 5-140 degrees C. The first stage covers the temperature range 5-53 degrees C with maximum approximately 45 degrees C. The heat evolved in this temperature range is equal to 380 +/- 20 J/g of dry biomass, it does not change at scanning rate lower than 0.