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R I Zhdanov

Publications and source records attributed to R I Zhdanov.

At least 19 recordsLinked to original sources
PubMed2002

Specific natural DNA-bound lipids in post-genome era. The lipid conception of chromatin organization.

Two pools of DNA-bound lipids were isolated from DNA supramolecular complex (SC-DNA): loosely bound (extracted with 35% ethanol) and tightly bound lipids (extracted after additional treatment DNase I). The compositions of the two lipid pools from different sources (rat thymus, liver, loach sperm, pigeon erythrocytes, Zajdel ascites hepatoma, Ehrlich ascites carcinoma, sarcoma 37, Escherichia coli B and T2 phage) were studied. The possible functions of DNA-bound lipids, especially of cardiolipin and cholesterol, at the attachment of DNA loops to the nuclear matrix, in DNA replicon organization, replication and transcription are discussed.

Animals↗
PubMed2002

DNA-phospholipid recognition: modulation by metal ion and lipid nature. Complexes structure and stability calculated by molecular mechanics.

The structures and formation energies of nucleic acid-phospholipid complexes both in the absence and in the presence of Mg(2+) ions were calculated taking double-stranded trinucleoside diphosphates NpNpN or heptanucleotides ApAp(NpNpN)pApA, composed of 64 possible combinations of genetic code, and phosphatidylcholine (PC) and sphingomyelin (SM) as model compounds. The dependence of intramolecular interactions on the primary structure of nucleic acid molecules and on the presence of a cationic bridge was revealed. The formation energies and structure of oligonucleotides were found by molecular mechanics calculations with the AMBER force field. The structures of phospholipid and MgCl(2) molecules were calculated by the semiempirical PM3 method, while the energies of phospholipid-oligonucleotide complexes were calculated by the molecular mechanics method. Calculations of complexes were carried out with consideration of solvation effects. Considerable gain in the formation energy of triple complexes is achieved due to the presence of the electroneutral metal bridge. A tendency toward increasing the stability of "triple" PC complexes (but not SM ones), containing guanosine- and cytidine-enriched triplets was revealed. Depending on the structure of NpNpN trinucleotides, the formation energy values of NpNpN-MgCl(2)-PC and ApAp(NpNpN)pApA-MgCl(2)-PC complexes differ by 1.7-2.6 kcal mol(-1), which can be considered as the atomic-scale manifestation of the recognition phenomenon. Presence of metal (II) ion bridge results in a greater stabilization of the phospholipid-nucleic acid complexes for SM in comparison to PC (the total energy difference equals to 4-16 kcal mol(-1)). Depending on the structure of NpNpN trinucleotides, the formation energies of NpNpN-MgCl(2)-SM and ApAp(NpNpN)pApA-MgCl(2)-SM complexes differ by 1.7-2.1 kcal.mol(-1), which is essential at physiological conditions and can also be considered as the recognition effect.

Base Sequence↗
PubMed2002

DNA-bound lipids of normal and tumor cells: retrospective and outlooks for functional genomics.

By very soft phenol method, the high-molecular-mass natural DNA complexes (10(8)-10(9) Da), which contain 1-3% specific lipids, were isolated from different eukaryotic and prokaryotic cells. Two pools of DNA-bound lipids were isolated: loosely bound (extracted with 35% ethanol) and tightly bound lipids (extracted after additional treatment DNAse I). The composition of these two lipid pools of different sources (rat thymus, liver, regenerating liver, loach sperm, pigeon erythrocytes, Zajdel ascites hepatoma, Ehrlich ascites carcinoma, sarcoma 37, Escherichia coli B, T2 phage) was studied. The DNA-bound lipid pools consist of neutral lipids (NL) and phospholipids (PL), moreover NL is always in a few fold more than PL. The composition of these lipid pools of eukaryotes distinguishes between themselves, mainly, by free cholesterol (minor fraction), cardiolipin (major fraction), and by phosphatidylcholine. Only the tightly bound lipid pool was present in T2 phage DNA. The dramatic redistribution effect between all fractions of NL pools (free and ester cholesterol, free fatty acids, diglycerides) was observed in DNA synthesis phase of cell cycle on the background of the unchanged composition of PL pools. Comparative analysis of DNA-bound lipid pools of normal and cancer cells was carried out. The DNA-bound lipid pools of transformed cells significantly differ from the same normal cells both by PL composition (cardiolipin) and by the presence of additional fractions (mono- and triglycerides) as well. The possible functions of DNA-bound lipid pools, especially of cardiolipin and cholesterol at the attachment of DNA loops to the nuclear matrix, DNA replicon organization, replication, and transcription are discussed.

Animals↗
PubMed2002

Cationic lipid-DNA complexes-lipoplexes-for gene transfer and therapy.

Cationic lipid-mediated gene transfer and delivery still attract great attention of many gene therapy laboratories. From the point of view of the most important characteristics of lipoplex particles, e.g. its charge and size, we reviewed recent studies available. In general, the paper deals with non-viral systems of gene transfer into eukaryotic cell based on various lipids. Having usually less efficiency in gene transfer, lipid-based gene transfer vehicles (lipoplexes/genosomes) are characterized with certain advantages even over viral ones: they are less toxic and immunogenic, could be targetable and are easy for large-scale production, a size of transferred DNA being quite high. Conditions of DNA condensation during interactions with lipids are described. Results of the studies of mechanism of DNA-lipid complex interactions with the cell membrane and their transport into the nucleus are summarized. Dependence of efficiency of gene transfer on lipoplex structure and physical-chemical properties is reviewed. Advantages and disadvantages of different macromolecule complexes from the point of view of transfection efficiency, possibility of use in vivo, cytotoxicity and targeted gene transfer in certain organs and tissues are also discussed. Results of transfection of different cells using neutral, anion and cation liposomes are reviewed. The conclusion reached was that efficiency and specificity of gene transfer may grow considerably when mixed macromolecule lipid systems including polycations and glycolipids are used.

Animals↗
PubMed2002

Role of lipid membrane-nucleic acid interactions, DNA-membrane contacts and metal (II) cations in origination of initial cells and in evolution of prokaryotes to eukaryotes.

The problems of the origin of primary cells and eukaryotic cells are discussed in terms of possible role of interactions between nucleic acids with lipid membrane according to corresponding original hypothesis. We propose that there are two main hypotheses of the origin of primary cells: (a). RNA appeared before proteins and DNA [Nature 213 (1967) 119]; (b). it is needed for the appearance of a primary cell, the volume closed by the lipid membrane. There was no information about the ways on how RNA appeared inside that volume for saving the reaction products around. Our hypothesis suggests that one of the starting points in the origination of primary cells was the interaction of nucleic acid and lipid membrane bubbles in the presence of metal (II) ions (which existed in high concentrations in prebiotic conditions), and this resulted in the enclosing of the pro-RNAs inside the lipid membrane. This hypothesis is formulated by us on the basis of experimental biochemical and biophysical studies of the DNA/RNA-phospholipid vesicles interactions in the presence of metal ions (II) fulfilled in the Institute of Biomedical Chemistry, RAMS, Moscow and Institute of Biophysics, RAS, Pushchino. Our belief is that DNA-membrane contacts (DNA-MCs) played an important role in the prokaryotes-to-eukaryotes transition. The model of the confluence of four prokaryotic cells may explain the prokaryotes-to-eukaryotes transition by the way of eukaryotic nuclear pore formation from prokaryotic Bayer' contacts. The main requirement for the following fusion of prokaryotic cells must be their mutual orientation. After possible association, the division of the formed cell is begun. The great advantage of the model of four prokaryotic cells is the profit in the metabolism and the possibility of the intensive growth of intercellular membrane structures.

Animals↗
PubMed2002

A spectroscopic and surface plasmon resonance study of oleic acid/DNA complexes.

The interaction of synthetic polynucleotide double strands with a natural lipid, oleic acid, was examined in diluted aqueous solutions by circular dichroism spectra, UV-absorption measurements, and surface plasmon resonance biosensor investigations. The investigations were performed with defined double and triple stranded oligo- and polydeoxyribonucleotides. Whereas duplexes are influenced by oleic acid ligandation, which could not be removed by ethanol dialysis procedure, no binding occurs to triple stranded DNA. The spectroscopic results indicate that oleic acid shows molecular recognition to AT b.p. motifs by groove binding. GC tracts - in particular alternating d[G-C] motifs - are strongly influenced by ligand interaction up to a ratio of one molecule per two base pairs. Likewise, the spectroscopic and morphologic changes in the supramolecular association of the complexes after treatment occur even after dialysis procedure. This was monitored with scanning force microscopy (SFM) as well. Additionally, monolayers of biotinylated DNA duplexes were immobilized on a streptavidin sensor-layer for surface plasmon resonance (SPR) observations. Small portions of the ligand were injected in continuous flow. Loosely bound molecules were removed by washing procedure. Injections of sodium hydroxide denature the DNA, releasing the tightly bound effectors. The amount of tightly bound oleic acid molecules was determined at one molecule per 2-3 base pairs. As consequence, a new mechanism of regulation of gene expression at nuclear membrane or by lipids inside DNA double helix has to be discussed.

Base Pairing↗
PubMed2001

Chromatin-bound cardiolipin: the phospholipid of proliferation.

Chromatin-bound lipids, cardiolipin (CL), diglycerides, cholesterol, and cholesterol esters, together with nonhistone proteins, play a key role in structural and functional organization of the chromatin genome during various stages of evolution. There are two pools of chromatin lipids, namely loosely- and tightly-bound lipids. The entire chromatin cardiolipin is bound to DNA. The CL molecule has a common 'interphosphate' structural motive with DNA, i.e. DNA and CL phosphate moieties separated from each other with six chemical bonds and equidistant, which is important for CL functional role, the regulation of gene expression. The CL dominates in the DNA of the active genome but not in the DNA of the repressed genome. The amount of CL in the DNA from the repressed genome of pigeon erythrocytes (one CL molecule per 20 nucleosomes) is 20 times less than in the DNA from the active genome of rat thymus and liver and in the DNA of transformed cells. Cardiolipin provides A-form DNA in the complex with RNA-polymerase, which is necessary for transcription. The biological and structural function of cardiolipin can be realised only when unsaturated fatty acyl residues are present in its structure.

Animals↗
PubMed2001

Action of nonviral gene delivery vectors on human complement system: low anticomplementary activity of lipoplexes based on lacZ plasmid and phospholipid/oligocation liposomes.

A simple test-system has been developed for the first time in order to detect the ability of effectors (lipoplexes) to activate the complement system in an antibody-independent manner to serve as acceptors of nascent C4b and to inhibit formation of the key enzyme of complement, C3-convertase. The effect of plasmid DNA (pCMV-SPORT-LacZ), negatively charged cardiolipin (CL), neutral phosphatidylcholine (PC) vesicles and their lipoplexes, on the complement system was studied using the method developed. It was revealed that PC vesicles did not affect the complement system, while CL vesicles manifested low activation. The influence of plasmid DNA and its lipoplex based on PC liposomes as well on the complement system was very low. PC/LacZ lipoplex (143 microg/ml) acted on the complement system like 5.36 microg/ml heat aggregated IgG (agg) (the level of no pathological ruptures), whereas CL/LacZ lipoplex (143 microg/ml) acted similar to 10.7 microg/ml IgG (agg). Thus, weak activation of the complement system with CL lipoplex, and even weaker for the PC lipoplex testified to the use of neutral and positively charged lipoplexes preferably in gene therapy protocols. The technique can also be used for testing the influence of injectable gene therapy vectors on the complement system.

Animals↗
PubMed2001

The lacZ gene transfer into L929 cells and [14C]-DNA tissue distribution following intraperitoneal administration of new pH-sensitive lipoplexes in mice.

The efficacy of lacZ gene transfer into the L929 cell line and a local [l4C]-DNA delivery in male NMRI mice (10-12 weeks old), were studied using new pH-sensitive liposomes, containing phosphatidylcholine/glycyrrhizin (PC/GL) or alpha-tocopherol ester of succinic acid (PC/TSA). The reporter gene (pQE-LacZ plasmid) was transferred into L929 cells using corresponding lipoplexes, 0.5% of cells being transfected. Tissue distribution of Gasserian ganglion neurinoma cell [14C]-DNA fragments and corresponding PC/GL and PC/TSA lipoplexes, were examined following intraperitoneal administration of a 24 h postdose. The [14C]-DNA itself was not detected in any organs at a 1.5 h postdose. The use of PC/GL or PC/TSA lipoplexes considerably changed the biodistribution of [14C]-DNA in mice tissues. The maximal content of [14C]-DNA for both types of lipoplexes was observed in the intestine (50% dose equiv./g) and the spleen (30% dose equiv./g). The content of [14C]-DNA in liver and kidneys was equal to 4 and 10% for liver and kidneys in the case of PC/GL-lipoplexes, and 15 and 6%, for PC/TSA, respectively. Thus, the tropicity for PC/GL-lipoplexes to liver was not detected under i.p. administration.

Animals↗
PubMed1998

Role of DNA-membrane interactions in prokaryote-to-eukaryote transition: an hypothesis.

A model system of experiments to consider the problem of the origin of eukaryotic cells as well as the prokaryote-to-eukaryote transition was investigated, in terms of the role of nucleic acid-membrane interactions. It was thought worthwhile to consider the importance of DNA-membrane contacts for the organization of the prokaryotic nucleoid. The model for the fusion of four proto-eukaryotic cells was proposed to clarify the prokaryote-to-eukaryote transition as well as the formation of the nuclear pores of eukaryotes from the Bayer's junctions of proto-eukaryotes. The basic requirements following from the cell fusion model suggest such orientation of the cells involved. The obstacles for division of the ancestor cell were excluded by merging. Enormous advantages to the cell metabolism due to the fusion of four proto-eukaryotic cells and an intensive growth of the inner membranous structures resulted.

Cell Fusion↗
PubMed1993

Use of nitroxides as MRI contrast agents to study in vivo carbon tetrachloride induced hepatotoxicity in rats.

CCl4 and related compounds, such as halothane, are metabolized by the liver to form free radical intermediates, which are thought to be implicated in the hepatotoxic response. Two to three hours following CCl4 exposure (i.p.) there is a localized edematous region surrounding the portal vein which is observable by proton MRI in vivo. Enhancement of the CCl4-induced edematous region was possible using Gd-DTPA, a paramagnetic contrast agent. However, with the use of a nitroxide contrast agent (3-PCA) there was no enhancement, but rather a significant diminution of the CCl4-induced edematous response. These results suggest that the nitroxide contrast agents, which are themselves free radicals, act as free radical scavengers and therefore reduce the formation of the CCl4-induced hepatic 'damage' observed in proton MR images.

Animals↗
PubMed1993

[Thermo-induced structural reorganizations of platelet membranes as affected by aggregation inducers and inhibitors].

Thermo-induced structural reorganizations in thrombocytes' membranes in the presence of aggregation inductor ADP and aggregation inhibitors--aspirin or alpha-tocopherol at the temperature range of 0-40 degrees C above zero, have been studied by mean of spin probe. It has been shown that in this temperature range alpha-tocopherol decrease structural flexibility of phospholipid fatty acid residua and increase the parameter of order S of 5-doxilstearin probe. ADP and aspirin increase structural flexibility of fatty acid residua of this cells. The temperature plots' study of 2A'11 parameter in EPR, proportional to parameter of order S made possible to find out essential difference between influences of these substances to thrombocyte membrane. The aggregation inductor ADP results in removal of the curve bent-point in Arrhenius coordinates to the lower temperature region (17-13 degrees C) when aspirin and alpha-tocopherol induce either low temperature removal of the bent-point and formation of the supplementary bent in higher temperature region (28 degrees C for alpha-tocopherol, 20 degrees C for aspirin). Such differently directed changes of parameter of order under the aggregation inhibitors' influence is probably connected with different mechanisms of their antiaggregation activity.

Adenosine Diphosphate↗