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This review considers the recent progress on the role of heat shock proteins (HSPs), as well as transcription factors of heat shock proteins genes (HSFs) in protecting plants from oxidative stress induced by various types of abiotic and biotic stresses. HSPs are pleiotropic proteins involved in various intracellular processes and performing many important functions. In particular, HSPs increase plant resistance to stress by protecting the structure and activity of proteins of the antioxidant system. Overexpression of Hsp genes under stressful conditions, leading to an increased content of HSPs, can be used as a marker of oxidative stress. Plant HSFs are encoded by large gene families with variable sequences, expression and function. Plant HSFs regulate transcription of a wide range of stress-induced genes, including HSPs and other chaperones, reactive oxygen species scavengers, enzymes involved in protective metabolic reactions and osmolytic biosynthesis, or other transcriptional factors. Genome-wide analysis of Arabidopsis, rice, poplar, lettuce, and wheat revealed a complex network of interaction between the Hsps and Hsfs gene families that form plant protection against oxidative stress. Plant protection systems are discussed, with special emphasis on the role of HSPs and HSFs in plant responses to stress, which will be useful for the development of technologies to increase productivity and stress resistance of plant crops.

Endothelial cells (ECs), which form the inner surface of the blood vessels, contact the blood, withstand mechanical pressure, and demonstrate heterogeneous reactions to exogenous and endogenous stimuli. ECs have unique properties in accordance with their niches and play an important role in regulating vascular homeostasis. Endothelial cells may undergo a dynamic phenotypic switch in terms of its heterogeneity, which may lead to endothelial dysfunction and a number of associated pathologies. Endothelial-mesenchymal transition (EndMT) is one of the possible molecular and cellular mechanisms of this kind. EndMT is characterized by phenotypic changes in ECs through which endothelial cells acquire new properties, i.e., start producing mesenchymal markers such as alpha-SMA and vimentin, change morphology, and become able to migrate. EndMT is a complex biological process that can be induced by inflammation, hypoxia, or oxidative stress and be involved in pathogenesis of cardiovascular disease. This review describes the key markers, inhibitors, and inducers of endothelial-mesenchymal transition and overall state-of-the-art of EndMT in cardiovascular diseases.

This review provides up-to-date information on the molecular basis of the pathogenesis of male infertility at the cellular and subcellular levels. The emphasis is on the importance of new next-generation sequencing technologies as a high-performance tool for studying the genome and epigenomic mechanisms, transcriptome, proteome and metabolome of ejaculate, and organs of the reproductive system. This methodology made it possible to identify differentially expressed metabolic and signaling pathways in fertile and infertile men that combine the genotype and phenotype of a particular individual into a single whole. The current ideas about the relationship between oxidative stress and imbalance of redox systems with DNA damage in spermatozoa as the leading mechanism for the development of idiopathic infertility are summarized. The role of miRNAs, methyloma aberrations, deficiency of phospholipase C zeta in spermatozoa in the pathology of fertility is given. Deciphering the molecular profile and molecular phenotypes of infertility as a result of the interaction of genetic and environmental factors is a necessary condition for screening the most informative biomarkers, assessing their stratification potential, and validating new molecules as potential targets for targeted therapy.

The ubiquitin-proteasome system is involved in the control of all essential molecular processes under normal conditions and the response of cells to stress. Rpn4p serves as a key transcriptional regulator of the proteasome in Saccharomycetes yeast and is also involved in the cellular response to various stresses. In addition to proteasomal genes, Rpn4 affects the expression of several hundred other genes, including genes involved in DNA repair and oxidative stress response. At the same time, the molecular mechanisms used by Rpn4 in controlling target genes and its functioning as a regulator of the cellular response to stress remain largely unclear. The aim of this work was to determine the Rpn4 domains required to ensure cell resistance to stress. It was shown that the N-terminal and central regions of the protein contain sites required for resistance to all types of stresses. The putative nuclear localization signal does not affect the functioning of Rpn4. Unexpectedly, a protein with the deletion of both zinc finger motifs that form the DNA-binding domain provides yeast resistance to oxidative stress and cycloheximide. Moreover, we showed that Rpn4 can be recruited to the promoter regions of the regulated genes even if they do not contain its binding sites. Based on these data, it can be assumed that Rpn4 is involved in gene regulation and the cellular response to stress due to protein-protein interactions.

The GO system is part of the DNA base excision repair pathway and is required for the error-free repair of 8-oxoguanine (oxoG), one of the most common oxidative DNA lesions. Due to the ability of oxoG to form oxoG:A mispairs, this base is highly mutagenic. Its repair requires the action of two enzymes: 8-oxoguanine DNA glycosylase (Fpg or MutM in bacteria and OGG1 in eukaryotes), which removes oxoG from oxoG:C pairs, and adenine DNA glycosylase (MutY in bacteria and MUTYH in eukaryotes), which removes A from oxoG:A mispairs to prevent mutations. The third enzyme of the system (MutT in bacteria and MTH1 or NUDT1 in eukaryotes) hydrolyzes 8-oxo-2'-deoxyguanosine triphosphate, thus preventing its incorporation into DNA. Recent data point to the proteins of the GO system as promising targets for the therapy of cancer, autoimmune diseases, and bacterial infections. This review highlights the structure and specificity of the GO system in bacteria and eukaryotes and its unique role in mutation avoidance.

The base and nucleotide excision DNA repair (BER and NER) systems are aimed at removing specific types of damaged DNA, i.e., oxidized, alkylated, or deaminated bases in the case of BER and bulky damage caused by UV radiation or chemical carcinogens in the case of NER. In some cases, however, the repair process follows a more complex scenario, which implies that the repair pathways exchange proteins and interact with each other to form a common interactome. This review describes the BER and NER mechanisms and discusses the current data on the involvement of the NER proteins in the repair of DNA lesions caused by oxidative stress and the BER proteins in the removal of bulky DNA adducts. We also discuss the role of poly(ADP-ribose) polymerase 1 in the regulation of the BER and NER processes and their coordination in the repair of complex (cluster) lesions.

The purpose of our study was to identify the nature of the cause-effect relationship between the risks of developing of Chronic Obstructive Pulmonary Disease (COPD) and Cardio-vascular Disease (CVD) in patients residing in the villages of Chiatura district, characterized by varying degrees of environmental stress. The residents (n=400) of the Chiatura district living in the villages, Khreiti, Perevisa and Rgani were examined. The villages are characterized by different degrees of ecological tension (the villages differ both in their remoteness from sources of environmental pollution - manganese mining quarries and the scale of its extraction, which allows them to rank according to the degree of environmental tension: Khreiti - low, Perevis - medium, Rgani - high). In the patients the blood general redox balance and genetic parameters (the number of micronuclei in the scrapings of the oral mucosa) were studied. In the zone of moderate environmental stress (the village of Perevisa), a significant increase in the indicator of the total antiradical activity of blood plasma and an increase in the frequency of micronucleated buccal cells were revealed in comparison with the zone of low environmental stress (the village of Khreiti). In residents of the village of Rgani, characterized by the highest level of pollution, the indicator of the total antiradical activity of blood plasma decreases sharply, the number of micronuclei decreases, the presence of various types of damage to the nucleus is noted, which is characteristic of intensive apoptosis. Under the conditions of moderate air pollution, observed mobilization of protective anti-radical and replication mechanisms in the body are aimed at preserving the stability of the somatic cell genome. Identified oxidative stress can also act as mediators of secondary alteration and the development of the inflammatory process in the circulatory bed, resulting in an increased risk of arterial hypertension (AH) against the background of a relatively high risk of chronic nonspecific obstructive pulmonary diseases (COPD). High level of environmental pollution contributes to the development of permanent intense oxidative stress in the affected tissues of the respiratory tract. That contributes to the development of predominantly nonreparable changes in the cell genome, apoptosis and intensification of secondary oxidative stress, which, under conditions of depletion of antiradical protection, causes preferential defeat of the microenvironment of apoptotic cells, the development of local effects, reflected in a sharp increase in the risk of COPD.

The aim of the study was to assess the prooxidant-antioxidant balance depending on endothelial nitric oxide synthase G894T polymorphism. The frequency distribution of alleles and genotypes of G894T polymorphism, nitrite concentration, hydrogen sulphide, lipid peroxidation products (diene conjugates, malonic dialdehyde), antioxidants (reduced glutathione, catalase, ceruloplasmin, retinol) were determined in venous blood of healthy males. The incidence of the GG genotype was 49.1%, GT - 44.2%, TT - 6.7%. The level of malonic dialdehyde in erythrocytes with the GG genotype is 16.8% lower than in the genotype GT. The concentration of hydrogen sulphide in the blood with the GG genotype was 27.5 [18,2; 32,5] mM, GT - 28.6 [22.9; 33.8] mM, TT - 36.3 [33.8; 42.5] mM. The content of total nitrites in plasma with the GG genotype was 10.4 [9,0; 12,5] mM, GT - 10.4 [8.9; 11.8] mM, TT - 9.4 [8.8; 9.8] mM. The genotype GG causes a lower level of malonic dialdehyde in comparison with the heterozygous genotype. The G894T polymorphism allele T is associated with a low content of total nitrites in the plasma and a high concentration of hydrogen sulfide. The data obtained suggest that if the oxygen supply of the organism is impaired, the endothelial nitric oxide synthase G894T polymorphism may be important for the oxidative stress development.

The concentration of soluble epoxide hydrolase (sEH) protein was studied in renal medulla of adult rats from hypertensive ISIAH strain and normotensive WAG strain. The sEH is a key enzyme in metabolism of epoxyeicosatrienoic acids capable of activating endothelial NO-synthase and nitrogen oxide formation, and therefore being vasodilators. An increase in the sEH protein concentration (that we found) allows one to assume that the oxidative stress is increased in the renal medulla of hypertensive rats, and the bloodflow is decreased.

The purpose of study was to evaluate the system ofperoxidation of lipids as an antioxidant defense in women of peri-menopause period with sleep disorders. The sampling included 73 examined women of peri-menopause period of Russian (n=45) and Buryat (n=28) ethnic groups. All women were applied clinical anamnestic examination. The evaluation of sleep disorders was implemented using the Stanford Center for Sleep sciences and medicine questionnaire, the insomnia subjective severity evaluation test, questionnaires of quantitative estimate of risk of occurrence of syndrome of obstructive sleep apnea and the Epworth Sleepiness Scale. According the results of survey the ethnic groups were separated on main (with sleep disorders) and control (without sleep disorders) subgroups. The processes of lipoperoxidation and the system antioxidant defense are evaluated using spectrophotometric techniques. The survey established higher rate of occurrence of troubles with falling asleep and morning awakenings in female representatives of the Russian ethnic group. The total number on the Epworth Sleepiness Scale in the Russian group amounted to 12.2±0.42 and in the Buryat group - 10.01±1.29. The study of processes of lipoperoxidation in women of the Russian ethnic group established increasing of level of ketodienes and coupled trienes (p<0.05) in subgroup with sleep disorders as compared with control group. The sleep disorders in women of Buryat ethnic group are accompanied by higher levels of substrates of lipoperoxidation with coupled doubled bounds (p<0.05), diene conjugates (p<0.05), ketodienes and coupled trienes (p<0.05). The value of coefficient of oxidative stress in female patients of Russian ethnic group amounted to 2.2 and in women of Buryat ethnic group - 3.8. The study results both demonstrate development of oxidative stress in female patients with sleep disorders in peri-menopause period in Russian and Buryat ethnic groups and substantiate ethnic specificity ofprocesses of lipoperoxidation.

The paraoxonase (PON) gene family includes three members: PON1, PON2, and PON3 aligned in tandem on chromosome 7 in humans. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. Increased production of reactive oxygen species as a result of decreased activities of mitochondrial electron transport chain complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. PON1 and PON3 proteins can be detected in plasma and reside in the high-density lipoprotein fraction and protect against oxidative stress by hydrolyzing certain oxidized lipids in lipoproteins, macrophages, and atherosclerotic lesions. Paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells. In contrast to PON1 and PON3, PON2 is cell-associated and is not found in plasma. It is widely expressed in a variety of tissues, including the kidney, and protects against cellular oxidative stress. Overexpression of PON2 reduces oxidative status, prevents apoptosis in vascular endothelial cells, and inhibits cell-mediated low density lipoprotein oxidation. PON2 also inhibits the development of atherosclerosis, via mechanisms involving the reduction of oxidative stress. In this review we explore the physiological roles of PON in disease development and modulation of PONs by infective (bacterial, viral) agents.

Reactive oxygen species (ROS) are produced via catabolic and anabolic processes during normal embryonic development, and ROS content in the cell is maintained at a certain level. Peroxiredoxins are a family of selenium-independent peroxidases and play a key role in maintaining redox homeostasis of the cell. In addition to regulating the ROS level, peroxiredoxins are involved in intracellular and intercellular signaling, cell differentiation, and tissue development. The time course of peroxiredoxin gene (prx1-6) expression was studied in Xenopus laevis during early ontogeny (Nieuwkoop and Faber stages 10-63). The highest expression level was observed for prx1 at these developmental stages. The prx1, prx3, and prx4 expression level changed most dramatically in response to oxidative stress artificially induced in X. laevis embryos. In X. laevis adults, prx1-6 were all intensely expressed in all organs examined, the prx1 expression level being the highest. The X. laevis prx1-6 genes were cloned and expressed in Escherichia coli, and physico-chemical characteristics were compared for the recombinant enzymes. The highest peroxidase activity and thermal stability were observed for Prx1 and Prx2. It was assumed that Prx1 plays a leading role in X. laevis early development.

The purpose of the review is to analyze modern data on pathogenesis, principles of treatment and future prospects treat- ment of nonalcoholic fatty liver disease (NAFLD). Modern ideas about the role of insulin resistance, oxidative stress gene polymorphisms in the pathogenesis of disease progression. This has led in recent years to a new strategy of treatment of the disease. Examines the role of physical load, modified diet, the weight loss. Substantiates the primary role of the use of insulin sensitizers, and agents with cytoprotective and antioxidant effect. The lack of the only effective drug for the treat- ment of NAFLD justifies the appropriateness of the appointment of combination therapy with exposure to various aspects of the pathogenesis. Elaborates on new drugs under clinical study.

The aim of this work was a comparative study of the effects of spring diseases cytogenetic years of tick-borne encephalitis in elderly and young age due to differences in genes of glutathione-S-transferase. Surveyed by routine cytogenetics 120 patients with tick-borne encephalitis residents North of Tomsk region. We have taken in the study persons aged 20-35 years (Group 1) and 65-85 years old (Group 2). Material for study (buccal epithelium) was taken from each subject 3-5 times: 1st-2nd day after hospitalization, in 1 week, 1, 3 and 6 months. Tick-borne encephalitis infection causes a significantly large changes in cytogenetic regimens using buccal epithelium in the elderly than in younger patients. Restoring cytogenetic norms observed in a group of young in 3 months after hospitalization, in the elderly - in 6 months. When comparing cytogenetic effects of encephalitis shows: the young patients tick-borne encephalitis level by routine cytogenetics abnormal cells was significantly higher in carriers of inactive forms of gene GSTM1 (0)/GSTT1 (0) than containing active homozygous variants of these genes. Such patterns have not been noted in a group of elderly patients.

Aim: To study the rs1001179 polymorphism of the catalase (CAT) gene and to estimate the serum levels of the enzymes catalase and glutathione peroxidase (GP) in patients with chronic hepatitis C (CHC) and in those with ulcerative colitis (UC) in the Perm Territory., Subjects and Methods: Ninety patients with reactivation-phase CHC and 50 patients with exacerbation-phase UC were examined. The serum levels of catalase and GP were determined and the polymorphic variants of the marker of CAT gene rs1001179 in the DNA isolated from whole blood were found in all the patients., Results: In the CHC and UC groups, the levels of catalase and GP were found to be lower than that in apparently healthy individuals. Furthermore, both groups showed a direct correlation between the activities of the enzymes. In the patients with CHC and in those with UC, the spread of genotypes and alleles generally failed to virtually differ from that in the control group. The G/G genotype was prevalent in all the groups. In the patients with CHC, the minor A allele demonstrated a significant inverse correlation with the enzyme catalase (r = -0.16; p = 0.02) and GP (r = -0.13; p = 0.047)., Conclusion: The lower serum levels of catalase and GP are indicative of oxidative stress in the patients with CHC or UC. In the patients with CHC, the significant correlation of the pathological rs1701179 A allele marker with the processes of synthesis of antioxidant enzymes may suggest that CAT gene polymorphism in the A/A homozygotes might affect the regulation mechanism involved in the antioxidant system in the liver.

Dabetic retinopatny Is the most common microvascular complication of diabetes and a leading cause of blindness in industrialized countries. Oxidative stress plays an important role in the development of microangiopathic complications in diabetes. Manganese superoxide dismutase (MnSOD) is a key mitochondrial antioxidant enzyme in the cellular defense against agents that induce oxidative stress. The aim of the present study was to assess whether the MnSODA16V (C47T) polymorphism is associated with Diabetic retinopathy in northern Iran. 140 patients with Diabetic retinopathy and 140 healthy individuals, aged 30 to 75 years old, participated in this study. For genotyping of the MnSOD A16V polymorphism, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used. The prevalence of genotype frequencies of AA, AV, VW in Diabetic retinopathy subject were 5.71, 71.43 and 22.86%, respectively while in controls were 21.43, 38.57 and 40%, respectively. Significantly increased frequency of AV genotype was observed in patients compared with controls (OR = 6.94, 95% CI = 2.98-16.20, P< 0.0001). In conclusion, it is suggested that the MnSOD A16V polymorphism may be associated with the risk of Diabetic retinopathy in northern Iran. However, larger population-based studies are needed for clarifying the relation between Diabetic retinopathy and MnSOD A16V polymorphism.

The article presents results of individual evaluation of coefficient of oxidative stress as an integral indicator of balance of the system "lipids peroxidation-antioxidant defense" in women with sleep disturbances in post menopause conditions. The condition of the system "lipids peroxidation-antioxidant defense" was evaluated using analysis of content of substrates of oxidation of processes of lipid peroxidation with conjugated double bonds, diene conjugates, ketodienes and conjugated trienes, TBC-active products of retinol α-tokoferol, reduced and oxidized glutathione, activity of superoxiddismutase in blood. The application of coefficient of oxidative stress permitted to demonstrate differences in processes of lipids peroxidation in women with the same diagnosis and use it as a justification of individual approach under prescription of antioxidant therapy.

Aim: To assess the association of the CYBA, NOS3, and MTHFR gene polymorphisms and a rate of fibrosis progression in chronic hepatitis C (CHC)., Subjects and Methods: One hundred and nine CHC patients with the verified stage of liver fibrosis and cirrhosis at its onset were examined. The disease duration was determined in all the patients and additional risk factors of liver lesion were absent. A group of rapidly progressive fibrosis comprised 55 patients with a calculated fibrosis progression rate of 0.130 fibrosis units/year or higher and 54 patients with a progression rate of less than 0.130 fibrosis units/year were assigned to a slow fibrosis group. A compression group consisted of 299 healthy blood donors. The polymorphism of the genes under study was determined by polymerase chain reaction-restriction fragment length polymorphism analysis., Results: The mutant TT genotype of the CYBA gene was significantly more common in the CHC patients with rapidly progressive fibrosis than in those with slowly progressive fibrosis (odds ratio for TT 9.09 at 95% confidence interval, 1.09 to 74.83; p = 0.0161). No significant differences were found in the distribution of the alleles and genotypes of the NOS3 and MTHFR genes between the groups of patients with slowly and rapidly progressive fibrosis., Conclusion: The findings make it possible to regard the TT genotype of the CYBA gene from the C242T locus as profibrogenic and as one of the markers of the poor course of CHC.

Objective: Telomeres which are formed by double-strand breaks and DNA under replication, cause cell cycle arrest resulting in cellular senescence and apoptosis. The erosion of telomeres is an important mechanism for regulating the aging process by limiting cell proliferation. Over the last decade, many investigations in the field of telomeric biology showed that telomeric DNA and telomeric proteins are involved in the pathogenesis of some human diseases. The aim of the study was to compare telomere length in patients with Parkinson's disease (PD)., Material and Methods: Telomere length was measured in buccal epithelial cells and leukocytes in PD patients and controls., Results and Conclusion: The length of telomeres in cells of buccal epithelium was shorter in patients with PD than in the control group. In blood cells, telomere length did not differ. It is suggested that shortening of telomeres in buccal epithelial cells may be due to oxidative stress and, hence, it can be used as a marker for the early stages of disease.

It is now becoming increasingly clear that the course and outcome of craniocerebral injury (CCI) are determined not only by its biomechanism, severity, patient's age, presence of premorbid factors, etc., but also by individual features of the genome of each patient, which puts traumatic brain injury among multifactorial diseases. The genome determines the presence or absence of«genetic predilection to the development of various complications and sequelae of CCI, which generally determines the progression of traumatic brain injury disease. The first part of the review by Potapov et al. (201 0) [2] was devoted to the role of apolipoprotein E (apoE) gene polymorphism in CCI, the second one [3]- to the role of inflammation and immune response genes in the course and outcome of CCI. The present (third) part will provide a review of modern data on the effect of genes underlying intracellular processes of oxidative stress, apoptosis, regeneration, and synthesis of neurotransmitters and their receptors.

Ribosomal genes (RG), or genes for rRNA, are represented by multiple tandem repeats in eukaryotic genomes, and just a part of them is transcriptionally active. The quantity of active copies is a stable genome feature which determines the cell's capability for rapid synthesis of proteins, necessary to cope with stress conditions. Low number of active RG copies leads to reduced stress resistance and elevated risk of multifactorial disorders (MFD). Oxidative stress (OS) in the brain cells is believed to be involved in the pathogenesis of infantile autism (IA) and schizophrenia, i.e., MFDs with a manifested genetic predisposition. With autism, OS markers are found almost in every research, whilst with schizophrenia, the OS data are contradictory. Earlier, in a sample of patients with schizophrenia, we have found significantly higher quantity of active RG copies than at the average in healthy population. Here we have estimated the number of active RG copies in a sample of patients with IA (n = 51) and revealed significantly lower mean value than in healthy population. A novel mathematical model of the dynamic pattern of OS has been proposed. The model is realized as an ordinary differential equation system, supposing induction of antioxidant protection enzymes being mediated by reactive oxygen species (ROS), with the subsequent decrease of ROS content in a cell. The rate of synthesis of antioxidant protection enzymes is limited by the ribosome synthesis rate which depends on the number of active RG copies. Analysis of the model showed that the system always approaches a single stable equilibrium point along a damped oscillation trajectory, which in some degree resembles the dynamics of 'predator-prey' interaction in Lotka-Volterra model. The stationary ROS level inversely depends on the number of active RG copies. Our study explains the inconsistency of clinical data of OS in schizophrenia and suggests a novel criterion for discriminative cytogenetic diagnostics of schizophrenia and IA, as well as allows to assume that antioxidant therapy should be effective only for children with low number of active RG copies.

The localization of signaling molecules close to their targets is the central principle of cell signaling. The colocalization of multicomponent signaling complexes is realized through protein scaffolds that provide better specificity than undirected diffusion ofthe same components. ROS-generating complexes have been suggested to follow this principle by specific intracellular localization of ROS production and the limitation of ROS diffusion distances. However, the lack of adequate methods did not allow direct detection of local ROS production to confirm the model ofredox signaling compartmentalization. Nevertheless, evidences of local ROS production and restriction of diffusion were provided by kinetic modeling and data on the subcellular localization of NADPH-oxidase isoforms, their adapter proteins and local restriction of ROS diffusion. Here we shall discuss the properties of antioxidant system which prevents uncontrolled ROS diffusion from the sites of generation to the adjacent subcellular compartments; the current data of the specific localization NADPH-oxidases activity and its influence on intracellular processes; the recent evidences of the ROS diffusion restriction.

Glutathione S-transferases (GSTs) are ubiquitous enzymes in animals and plants, and they are multifunctional proteins encoded by a large gene family. GSTs are involved in response to the oxidative stress including drought, salt, heavy metals, and so on. Under oxidative stress, the excessive reactive oxygen species (ROS) induce an increase in GST levels, and then the GSTs metabolize the toxic products of lipid peroxidation, damaged DNA and other molecules. Previously, a full-length cDNA of a novel zeta GST gene, PpGST, was characterized from fruit of Pyrus pyrifolia Nakai cv Huobali. In the present study, a constitutive plant expression vector of PpGSTwas constructed and transferred into tobacco (Nicotiana tabacum L. cv Xanthi) to verify the function of PpGST. As a result, the PpGSTgene was successfully integrated into the genome of the transgenic tobacco lines and expressed as expected in the transformants through Southern blotting and quantitative reverse transcription-polymerase chain reaction analysis. Growth of T1 generation plants of PpGST transgenic lines and WT under non-stressful conditions was similar, however, the transgenic tobacco lines showed relatively normal growth under drought, NaCl, and cadmium (Cd) stresses. Furthermore, the T1 transgenic tobacco lines showed significantly slower superoxide anion production rate than the WT under abiotic stress. Simultaneously, the MDA content of each T1 transgenic tobacco plant was only slightly increased and significantly lower than that of the WT under drought, salt and Cd stress. Together with the GST activity of the transgenic tobacco lines, which was significantly increased under stressful conditions, as compared with that in WT, overexpression of PpGSTin tobacco enhanced the tolerance of transgenic tobacco lines to oxidative damage caused by drought, NaCl, and Cd stresses.

We studied association between the frequencies of gamma-induced (1 Gy in vitro) chromosome aberrations in blood lymphocytes and polymorphism of 45 repair candidate genes, detoxification and oxidative stress genes (53 sites) for 99 healthy volunteers. The levels of chromosome-type aberrations correlated with carriage of the minor alleles of the genes OGG1 Ser326Cys, ABCB1 Ile1145 = and NQO1 Pro187Ser (p = 0.0002). We have shown that all the revealed genetic associations were less effective in predicting chromosomal radiosensitivity as compared to the correlations between spontaneous and gamma-induced aberrations (p = 1.0 x 10(-6)). The addition of genetic markers to cytogenetic predictors improved the predictive accuracy for chromosomal radiosensitivity with the multiple correlation coefficient reaching R = 0.58 (p = 3.1 x 10(-8)). Thereby we were able to explain more than 30% of the population variability in chromosomal radiosensitivity.

Oxidative stress plays an important role in the pathogenesis the most of diseases. Important components of protecting cells from oxidative stress are antioxidant enzymes. Antioxidant enzymes are characterized by population differences in enzyme activity. The purpose of the study to summarize and discuss information on genetic polymorphisms of antioxidant enzymes in the most pathology. The development plays of the role of oxidative stress.

The paper presents the results of investigating the phenotypic polymorphism of a number of biochemical and immunological parameters (the values of oxidative stress, the activity of catalase and glutathione-S-transferase in red blood cells, the serum levels of catecholamines, tumor-necrosis factor-?, and IgG antibody subclasses) in the authors' hygienic studies of genotypic and nongenotypic population samples.

The association between polymorphisms in genes COMT, HFE that takes part in oxidative stress regulation, and chromosome aberration frequency in lymphocytes was assessed in 278 female residents of radiation polluted regions of Central Russia: Bryansk (322 kBk/m2) and Tula Districts (137Cs - 171 kBk/m2). The C187G, G845A genotyping of HFE and G1947A (H/L) of COMT was done by means of polymerase chain reaction-restriction fragment length polymorphism. Studied population was divided into 3 subgroups by level of chromosome aberrations per cell (0-2, 3-4, >5). There was shown statistically significant difference in distribution of COMTand HFE genotypes between the groups. The high frequency of chromosome aberrations (> or = 5%) was associated with homozygotes of the high activity COMT G/G and HFE CC. Heterozygotes for G1947A COMT and C187G HFE reveal negative association with the high frequency of chromosome aberrations and correspond to "resistance factors".

Drosophila is used as a model organism to review the mechanisms of neuroendocrine system involvement in lifespan control. The role of neuron specific expression of genes participating in antioxidative system in lifespan control is described. Data on endocrine function of the nervous system in lifespan control are discussed. The participation of genes involved in the regulation of nervous system development and function in lifespan control is contemplated. Based on the data available, hypotheses considering assembly of neurons as the lifespan limiting tissue and (or) the tissue providing regulation of lifespan via systemic effects on other cell types are evaluated.

New molecular-genetic methods stimulate substantial advances in complex diseases studies, speed up identification of new candidate genes participating in functional genetic modules (gene nets) associated with many common diseases. Decisive impact of predictive genetic studies in efficient implementation of genomic technology advances into presymptomatic identification of the subjects of high risk groups prone to various common complex diseases is reviewed. Substantial progress of genomic studies in genetic of aging processes, including complex metabolic processes and gene regulation is outlined. Advances of predictive medicine in pharmacogenomic, nutrigenomic, sport genomic as well as in genomic of aging substantiate real and soon progress in promotion active healthy longevity.

An antioxidant activity of the water-alcohol extracts of leaves of ten herbs from Western Siberia was studied. In vivo the capability of extracts to protect cells of Escherichia coli against the bacteriostatic action of H2O2 and the influence of the extracts on the expression of the antioxidant gene katG coding catalase-hydroperoxidase I were investigated. In vitro the radical-binding activity with DPhPG (1,1-diphenyl-2-picrylhydrazyl radical), the chelating capability with ferrozine, and total composition of flavonoids and tannins were determined. The extracts of Filipendula stepposa and Limonium gmelinii were characterized by the highest antioxidant activity. According to data, the test extracts could have an antioxidant effect on bacteria in different ways at once including the direct inhibition of ROS (reactive oxygen species), iron ion chelation and antioxidant gene induction.

Mitochondrial transhydrogenase catalyzes the reaction H(+)(out) + NADP(+) + NADH = NAD(+) + NADPH + H(+)(in). The maintenance of the NADPH pool increases the mitochondrial antioxidant potential. Therefore, according to the commonly adopted free radical theory of aging, ablation of the transhydrogenase gene should reduce the life span. However, contrary to this reasoning, the life span of Caenorhabditis elegans nematodes with null mutations in the gene does not differ from that in wild-type worms. This fact indicates that free radical damage of mitochondria is not associated with aging. Meta analysis of data on the life span in mice possessing a spontaneous mutation in the transhydrogenase gene shows that a lack of this enzyme does not accelerate aging in mammals either. The heart is the tissue with the highest transhydrogenase production rate, and it is likely that this enzyme contributes to the protection of cardiac myocytes from oxidative stress.

It was proved that hypoxia tolerance often goes together with forming of oxidative stress tolerance and has genetic predetermination on hypoxic influence. Interline difference ofhypoxia sensitivity is mainly defined by difference of oxygen-transport systems state. Genetically predetermined differences between investigated lines give the August rats the ability to use mechanisms of resistant strategy more effectively, and the Wistar rats--to use tolerant strategy more effectively.

The paper deals with the impact of infrared low-intensity laser radiation (IRLILR) on a mutation process and the proliferative activity of the animal cornea during stimulation of circulatory brain hypoxia. During an experiment on laboratory albino rats, IRLILR was studied for its impact on the level of chromosomal rearrangements and the mitotic index in the corneal cells was calculated in circulatory brain hypoxia. Laser exposure during stimulation of circulatory brain hypoxia favors normalization of the level of chromosomal aberrations and a mitotic cycle in the rat corneal epithelial cells. The experimental findings suggest that IRLILR may be used in ophthalmological care for antihypoxic purposes.

It is reviewed the achievements in the field of radiation-genetics investigations of low doze radiation influence on life span. It is suggested that life span decreasing after irradiation is due to stress-induced premature cell senescence. Life span increasing after irradiation, possibly, is connected with stress-induced activation of FOXO transcription factors, which induce on the basis of stress depth: 1) genes of stress tolerance (MnSOD, catalase, GADD45, p27), 2) apoptosis genes (Bim, FasL). Stress-resistance as well as apoptosis of damaged cells can attenuate aging. In generations of chronic irradiation life span increasing may be due to inbreeding depression removal in populations of laboratory animals.

Used in this work are PC12 cells transfected with human gene expressing amyloid precursor protein of beta-peptide and carrying the so-called "Swedish mutation" leading to the appearance of one Alzheimer's disease family forms. It has been shown that the PC12 cells transfected with this mutant gene, at action of various hydrogen peroxide concentrations, die to the significant greater degree than the used for comparison PC12 cells transfected with analogous human gene of the wild type or than vector-transfected cells. It has been found that ganglioside GM1 at micro- or nanomolar concentrations is able to increase viability of the PC12 cells transfected with the mutant gene causing a significant accumulation of endogenous amyloid beta-peptide. The obtained data confirm an important role of oxidative stress in injury and death of brain nerve cells in Alzheimer's disease.

The genotoxicity of doxorubicin was assessed by the induction of ribonucleotide reductase gene expression and by the oxidative stress induction in Saccharomyces cerevisiae as a eukaryote cell model. Doxorubicin induced dose-dependent inhibition of cell proliferation, increased the intracell concentration of GSH and GSSG, and did not significantly influence the malonic dialdehyde concentration. Doxorubicin activated (independently of the concentration) ribonucleotide reductase gene expression, thus increasing GSH concentration. The increase in GSSG concentration is probably indicative of the development of oxidative stress in Saccharomyces cerevisiae cells, although this is not accompanied by an increase the MDA concentration in the cells.

This review demonstrates the theory of presumably main role of microorganisms as a trigger of well-known mechanisms of ageing. It is shown that latent and chronic infections may initiate and support processes of senescence, stimulating signs of ageing and age-related diseases.

A comparative study of the changes in the components of the antioxidant defense system (ADS), the activity of superoxide dismutase (SOD) and catalase and the level of extractable SH-groups, during the growth of wild-type and mutant (white collar-1 and white colar-2) Neurospora crassa strains was performed. Oxidative stress developing during spore germination and upon the transition to a stationary growth phase was accompanied in all strains by an increase in the level of extractable SH-groups and SOD activity, whereas the total catalase activity decreased during growth. However, in contrast to the wild-type strain, the activity of the catalase in the mutant strains wc-1 and wc-2 slightly increased upon the transition to the stationary phase. In the wc-2 mutant, SOD activity and the level of extractable SH-groups in the exponential growth phase were always lower than in the wild-type and wc-2 strains. The role of wc-1 and wc-2 genes in the level regulation of reactive oxygen species is discussed.

We analyzed distribution of heavy neurofilament (NF-H) gene S/L-polymorphic variants in 51 patients with idiopathic motor neuron disease (MND) vs control group and in relation to superoxide dismutases (SODs) activity and thiobarbituric acid reactive substances (TBARS) level in cerebrospinal fluid (CSF), erythrocytes and blood serum. We found that individuals with homozygosity for NF-H gene short allele (S/S-genotype carriers) in MND group predominate significantly over those in control one (p < 0.001). We revealed significant increase of oxidative markers in CSF and blood serum in MDN patients vs controls (p < 0.05), but not in patients with spondylogenic myelopathy, conforming non-specific role of oxidative stress in MND pathogenesis. There were no differences between TBARS level in CSF and serum in relation to the rate of MND progression, suggesting that oxidative stress does not influence the MND course. We showed normal SOD-1 activity in erythrocytes and CSF of MND patients that argued for the absence of these antioxidant enzymes deficiency in MND without SOD-1 gene mutations. We found significant association between homozygosity for short allele (S) and increased TBARS level in CSF (p < 0.02). These findings specify the role of NF-H with lower molecular weight in MND pathogenesis and make expedient antioxidants administration to MND patients homozygous for S-allele of NF-H gene.

Selective systems for screening Arabidopsis thaliana (L.) Heynh. mutants with altered sensitivity to the oxidative stress (OS) inductors norflurazon (NF), acifluorfen (AF), and plumbagin (PB) were developed and a collection of 28 mutants was obtained. Dwarf and necrotic forms predominated among the NF-tolerant mutants, while pigment mutants and those with changed root morphology prevailed among the AF-tolerant and PB-sensitive mutants, respectively. Genetic and biochemical analysis of certain mutants was performed; quantitative and qualitative changes in the content of superoxide dismutase and peroxidase isoforms have been revealed. These data, complemented by the data on the cross-tolerance (sensitivity) of the mutants to paraquat, indicate a correlation between tolerance to the OS inductors and the functions of antioxidant systems.

The role of putrescine in the adaptive response of Escherichia coli grown aerobically in synthetic M9 medium with glucose to the H2O2-induced oxidative stress was studied. Under oxidative stress, the expression of the single-copy reporter gene fusions oxyR::lacZ and katG::lacZ was found to undergo biphasic changes, which were most pronounced in glucose-starved E. coli cells. The concentration-dependent activating effect of putrescine on the expression of the oxyR regulon genes was maximum when the oxyR gene was inhibited by high concentrations of hydrogen peroxide.

It is shown that in vitro infection of human peripheral blood lymphocytes by mycoplasmas (Acholeplasma laid-lawii PG8 and Mycoplasma hominis PG21) leads to multiple chromosome aberrations, predominantly to chromatid gaps and breaks. Oxidative stress in the infected cells is regarded as one of the factors causing chromosome damage.