[Nuclear spin catalysis in nanoreactors of living cells].

There is a great variety of chemical elements with magnetic and nonmagnetic isotopes in living cells. The question arises as to whether living cells can perceive the difference between magnetic and non-magnetic isotopes of chemical elements. It has been shown that bacteria Escherichia coli, which were previously enriched with the magnetic isotope of magnesium, 25Mg, essentially faster adapt to the new growth media in comparison with the cells, which were enriched with the nonmagnetic isotopes, 24Mg or 26Mg. In the experiments with another commonly accepted cell model, yeast Saccharomyces cerevisiae, it has been shown that the magnetic 25Mg, in comparison with the nonmagnetic 24Mg, essentially better stimulates recovery of the cells after short wave UV irradiation. Thus, for the first time, the magnetic isotope effects in vivo have been discovered. These findings reveal the novel, based on the stable magnetic isotopes, ways of control over efficiency and reliability of biological systems.

[Reliability of electron-transport membranes and the role of oxygen anion-radicals in aging: stochastic modulation of the genetic program].

All biomolecular constructions and nanorecators are designed to perform preset functions. All of them operate with limited reliability, namely, for each and every device or bionanoreactor normal operation alternates with accidental malfunctions (failures). Timely preventive maintenance replacement (prophylaxis) of functional elements in cells and tissues, the so-called turnover, is the main line of assuring high system reliability of organism as a whole. There is a finite number of special groups of genes (reliability assuring structures, RAS) that perform supervisory functions over the preventive maintenance. In a hierarchic pluricellular organism, RAS are genetic regulatory networks of a special group of cells, like hypothalamic neurons in the suprachiasmatic nucleus of mammals. Of the primary importance is limited reliability of mitochondrial nanoreactors, since the random malfunctions of electron transport chains produce reactive anion-radicals of oxygen (superoxide radical, O2*(-)). With time, O2*(-) radicals initiate accumulation of irreparable damages in RAS. When these damages accumulate up to preset threshold level, a fatal decrease in reliability of RAS occurs. Thus, aging is the stochastic consequence of programmed deficiency in reliability of biomolecular constructions and nanoreactors including the genetically preset limit of the system reliability. This reliability approach provides the realistic explanation of the data on prolongation of life of experimental animals with antioxidants as well as the explanation of similar "hormetic" effects of ionizing radiation in low doses.

[The radioecological problem of radon]. / Radioékologicheskaia problema radona.

Radon and its daughter decay products are the main part of natural radiation background. The review presents the information on indoor radon radiation level, radon sources, exposure doses and effects on human health. In addition to radioecological aspects, the radon effects should be considered as the important problem of low-dose radiation biology.

[The modelling of survival and mortality curves for human populations based on the theory of reliability]. / Modelirovanie krivykh vyzhivaniia i smertnosti populiatsii cheloveka na osnove teorii nadezhnosti.

The reliability theory model of aging (Kol'tover 1981, 1982) was used for analysis of life-tables of Swedish males and females for 1951-1955, 1962-1973 and 1971-1975 calendar years. In terms of the model it has been possible 1) to explain the Gompertz "law" of mortality; 2) to describe quantitatively statistical life-table data including Gompertz's and geriatric ages; 3) to predict the behavior of mortality rate function depending on the extent of population heterogeneity, among them the existence, at respective degrees of heterogeneity, of a maximum in geriatric age range and 4) to estimate the species-specific maximum life-span potential of animals.

[Interconnection between activity and conformational mobility of alpha-chymotrypsin in reverse micelle systems]. / Vzaimosviaz' aktivnosti i konformatsionnoi podvizhnosti alpha- khimotripsina v sistemakh obrashchennykh mitsell.

A comparative study of the catalytic activity of alpha-chymotrypsin and the spin label rotation frequency in the alpha-chymotrypsin active center of reverse micellar systems solvated by H2O-organic mixtures was carried out. It was found that the decrease in the label rotation frequency resulting from the substitution of water in the micellar inner cavity by glycerol, 2.3-butanediol and dimethylsulfoxide (up to 95%) caused a marked increase (20-fold in the case of 2.3-butanediol) of the enzyme catalytic activity. The experimental results are quantitatively interpreted in terms of a simple kinetic scheme postulating the existence of the enzyme in two interconvertible forms differing in the conformational (intramolecular) mobility, i.e., the resting one predominantly existing in aqueous solution, and the tense one whose proportion rises with an increase in the concentration of the water-miscible organic solvent in the reverse micellar system. The value of kcat (2.4 s-1) for the tense form of the enzyme exceeded by more than 25 times the catalytic activity of chymotrypsin in aqueous solution (0.09 s-1) for the resting form.

[Structural state of the cardiomyocyte sarcolemma in animals of different ages]. / Strukturnoe sostoianie sarkolemmy kardiomiotsitov u zhivotnykh raznogo vozrasta.

Cardiomyocyte plasmalemma membranes of adult (12 months) and old (24-26 months) rats have been studied. Ageing is accompanied with an essential decrease of the content of the membrane protein SH-groups. We have found an increase in the fraction of strongly immobilized spin-labeled SH-groups, a decrease in that of unsaturated lipids, as well as an increase in that of lysophosphatidylcholine in old rats membranes. The pattern of the response of beta-adrenergic receptors to isoproterenol is changed with age. The mobility of spin probe 5NS in the membranes of old rats is lowered at 22.5 degrees C. However there is no statistically significant age difference in the spin-probe mobility at 37 degrees C. Possible role of lysophosphatidylcholine in the stabilization of membrane lipid "fluidity" at physiological temperatures is suggested.

[Stimulation of transcription in mouse liver cells by nitrogen oxide free radicals]. / Usilenie transkriptsii v kletkakh pecheni myshei svobodnymi radikalami okisi azota.

The ESR signal of nitrosyl complexes appears in mouse liver after hydroxylamine injection in vivo. This ESR signal testifies to the appearance of NO free radicals. The concomitant accumulation of [3H]uridine in liver RNA evidences for stimulation of transcription. This stimulation is about the same order of magnitude as the stimulation of transcription after gamma-irradiation of mice with lethal doses. It is assumed that NO and, possibly, other oxygen free radicals can disorder the gene expression machinery in the cells.

[Effect of enterosorption on EPR signals in the liver of rats of different ages]. / Vliianie énterosorbtsii na signaly EPR pecheni krys raznogo vozrasta.

Liver EPR signals were studied in adult (8 months) and old (24 months) Wistar male rats after the 30 days course of enterosorption carried out daily. The signals were analyzed at the values of g = 1.94, 2.00, 2.25, 2.035, 2.16, 2.10 and 1.97. Age-dependent differences were found in liver EPR signals of intact animals, i. e. the intensity of signals of g = 1.97, 2.00, 1.97 and 2.25 was decreased in old animals. In adult animals enterosorption caused a decrease of signals of g = 2.25, 1.94, 2.00, 2.16 and 2.10. In old animals the treatment led to a dissimilar effect: the intensity of signals was decreased at the ranges of g = 2.25, distinctly increased at g = 1.97 and unaltered at the other EPR signal values studied. Geroprotective action of enterosorption is discussed considering the decrease in enzymatic activity of electron transport systems due to the treatment studied.

[Effect of the antioxidant dibunol on the electron paramagnetic resonance signals in the tissues of rats of different ages]. / Vliianie antioksidanta dibunola na signaly élektronnnogo paramagnitnogo rezonansa v tkaniakh krys raznogo vozrasta.

Changes in the intensity of EPR signals from the skeletal and heart muscles, liver, kidneys, thyroid, adrenal cortex, and blood were studied in relation to the animals age and the effect of the antioxidant dibunol. Essential changes were revealed in metabolic activity of the majority of the tissues under study as early as within the first 6 hours after antioxidant administration.

Permeability of bilayer lipid membranes for superoxide (O2-.) radicals.

Egg yolk phosphatidylcholine monolamellar liposomes (1000 A in diameter) loaded with cytochrome c were placed into an external solution, in which superoxide radicals, O2-., were generated by a xanthine-xanthine oxidase system. The penetration of the superoxide radicals across the liposomal membrane was detected by cytochrome c reduction in the inner liposome compartment. The effects of modifiers and temperature on this process were studied. The permeability of liposomal membrane for O2-. (P'O-2 = (7.6 +/- 0.3) X 10(-8) cm/s), or HO.2 (P'HO.2 = 4.9 X 10(-4) cm/s) were determined. The effect of the transmembrane electric potential (K+ concentration gradient, valinomycin) on the permeability of liposomal membranes for O2-. were investigated. It was found that O2-. can penetrate across liposomal membrane in an uncharged form. The feasibility of penetration of superoxide radicals through liposomal membrane, predominantly via anionic channels, was demonstrated by the use of an intramolecular cholesterol-amphotericin B complex.

[Permeability of bilayer phospholipid membranes to superoxide oxygen radicals]. / Pronitsaemost' bisloinykh fosfolipidnykh membran dlia superoksidnykh radikalov kisloroda.

Lecithin monolayer liposomes (1000 A in diameter) loaded with cytochrome c were placed into the external solution, in which O2 superoxide radicals were regenerated by the xanthine-xanthine oxidase system. The penetration of superoxide radicals across the liposomal membranes was followed by cytochrome c reduction in the interval volume of the liposomes. The effects of lipid membrane modifiers and temperature on this process were investigated. The results obtained were used for calculation of the permeability coefficients of bilayer lipid membranes for O(2) (P'O(2) = (7.6 +/- 0.3) . 10(-8) cm . s-1) or HO . 2(P'HO(2) = 4.9 x 10(-4) cm . s-1). The effect of the transmembrane electric potential (concentration gradient of H+, valinomycin) on the permeability of liposomal membranes for the superoxide radical was studied. The superoxide radical was down to penetrate across the bilayer lipid membranes in an unloaded state. Using an intramolecular cholesterol-amphotericin B-complex, the superoxide radicals were shown to penetrate across the bilayer lipid membranes, predominantly via the anionic channels.

[Structural characteristics of paramagnetic analogs of enzyme-substrate complexes of phosphorylation coupling factors]. / Strukturno-dinamicheskie kharakteristiki paramagnitnykh analogov ferment-substratnykh kompleksov sopriagaiushchego faktora fotofosforilirovaniia.

Mn2+-ion is linked to isolated chloroplast coupling factor CF-1 via the ATP bridge in the catalytically competent ternary complex as deduced from water proton relaxation rate measurements. Two essential SH-groups in CF-1 protein were modified with nitroxyl mercuric derivative as spin label. The substrate complex Ca2+-ATP is shown to induce the structural transition near the active site to the state with a stronger immobilized spin label. The distances between the paramagnetic metal ions and nitroxyl bound to the protein SH-group were evaluated as being in the range of 5-8,5 A for Cu2+ and 14-22 A for Mn2+.

[Reliability of enzyme systems and molecular mechanisms of aging]. / Nadezhnost' fermentnykh sistem i molekuliarnye mekhanizmy stareniia.

A stochastic model of animal mortality and ageing is proposed. In a living being there is a "biological clock", constructed from Q kinds of functional elements (genes), The reliability of functioning of these genes determines the biological age of the being. Oxidative processes in the cells are accompanied by random failures of electron transfer enzyme systems, which result in appearance of free superoxide radicals. Failures of electron transfer enzymes and of defence enzymes lead to accumulation of functional damages in the genes of the "clock". In terms of the model experimental data of gerontology (Gompertz's law, Strehler-Mildvan's compensation effect, etc) are easily explained. The value of Q for the man is estimated to be of the order of 10. Some possible mechanisms of action of "geroprotectors" have been discussed.