The MEK/ERK pathway is essential for maintenance of cytoprotective autophagy in <Emphasis Type="Italic">E1A</Emphasis>+<Emphasis Type="Italic">cHA</Emphasis>-<Emphasis Type="Italic">RAS</Emphasis> transformants after exposure to radiation

Autophagy is a conserved process of protein and organelle degradation that serves to maintain cell viability. Autophagy is frequently induced in response to stress or to exposure to DNA-damaging agents or retinoids, as well as to starvation and deficiency of growth factors. In this work, autophagy induced in E1A+cHA-RAS transformed cells in response to X-ray radiation was studied, with a focus on the role of the MEK/ERK signaling pathway in the regulation of radiation-induced autophagy. It was found that inhibition of the MEK/ERK pathway diminished cell viability and altered the sequence of events in radiation-induced autophagy. In particular, it caused aberrations in its final stages, leading to cytoplasmic accumulation of the p62/SQSTM1 adaptor protein in autophagic cavities of unclear origin. Thus, the MEK/ERK pathway activity is essential for the induction and maintenance of autophagy, increasing the viability of exposed cells in response to radiation.     

Functional characteristics of the mature and developing brain following neuroimmunization: an analysis of the short-term plasticity of the rat hypothalamus

In experiments on mature and developing (3-4 weeks old) rats the influence was shown of neuroimmunization with summate antigens of hippocampal or neocortical tissue cytosolic fraction on short-term plasticity of hippocampal CA3 field potentials under dentate gyrus zone stimulation. An increase of paired facilitation and frequency potentiation was revealed in pyramidal layer responses of hippocampal tissue immunized animals. In case of immunization with neocortical antigens the changes were less expressed, had mainly the opposite direction and took place in the apical dendrites zone. In young animals besides antigen spectrum depending effects of neuroimmunization an earlier manifestation (in comparison with age norm) of some focal activity definitive properties was described. The suggestions are made about different localization of hippocampal or neocortical tissue immunization "targets" with possible preferential damage of intrahippocampal systems when using this structure antigens, and also about dependence of physiological consequences on the extent of target structure ontogenetic maturity.     

Induction of premature senescence program by an inhibitor of histone deacetylase sodium butyrate in normal and transformed rat fibroblasts

We investigated a possibility to induce the premature cell senescence in rat embryo fibroblasts and E1A + cHa-ras transformants. We found that after the treatment with sodium butyrate, an inhibitor of histone deacetylases, both normal and transformed cells completely stopped to proliferate and accumulated at G1/S and G2/M phases of the cell cycle. The cloning efficiency data show that the cell cycle arrest induced by sodium butyrate is irreversible and correlates with the accumulation of active phosphorylated form of stress kinase p38, and with the expression of marker of senescence--beta-galactosidase activity (SA beta-Gal). The program resembling the premature senescence after sodium butyrate treatment is supposed to develop both in normal and transformed cells. The irreversible block of proliferation in E1A + cHa-ras transformants may be regarded as an example of activation of anticancer program like that of premature senescence in the tumor rodent cells.     

Linear growth of sparsely rakered whitefish <Emphasis Type="Italic">Coregonus lavaretus</Emphasis> (Coregonidae) of the Imandra Lake (Murmansk oblast)

This paper studies the properties of linear growth in sparsely rakered whitefish Coregonus lavaretus in the stretches of the large subarctic Imandra Lake, which are characterized by the diversity of habitat conditions and anthropogenic stress levels. The groups of sparsely rakered whitefish that are confined to different areas of the lake are marked out based on the properties of growth, trophic status, and anthropogenic stress intensity. A direct relationship of the linear growth in whitefish with the age of sexual development and trophic level of its habitats is found.     

p21Waf1 is required for complete oncogenic transformation of mouse embryo fibroblasts by E1Aad5 and c-Ha-ras oncogenes

Cyclin-dependent kinase inhibitor p21^Waf1 is known to have alternative functions associated with positive regulation of proliferation, actin cytoskeleton remodeling and suppression of apoptosis. The goal of the present study was to assess the role of p21^Waf1 in the establishment of the transformed phenotype of mouse embryo fibroblasts with stable expression of E1Aad5 and c-Ha-ras complementary oncogenes. Herein, we demonstrate that E1A/c-Ha-Ras-transformed p21^Waf1-null fibroblasts possess some characteristic features of transformed cells, such as loss of contact inhibition, high saturation density, shortened cell cycle, inability to undergo cell-cycle arrest after DNA damage and serum deprivation, but, at the same time, they are not completely transformed in that they are unable to proliferate at clonal density, are anchorage-dependent, retain a fibroblast-like morphology with pronounced actin cytoskeleton and show reduced migration and invasion. Our data support the concept of p21^Waf1 “tumor suppressor” having alternative oncogenic functions in the cytoplasm and for the first time indicate that p21^Waf1 can be indispensable for complete oncogenic transformation.     

Analysis of Serum Insulin,Cortisol, and Glucose Levels in the Settlement Inhabitants of the Yamalo-Nenets Autonomous Okrug

We studied the concentrations of insulin, cortisol and glucose in blood serum of two groups of inhabitants of the Yamalo-Nenets Autonomous okrug (YaNAO) settlements (indigenous population and those who arrived from Central Russia). The insulin level in all groups (in indigenous and non-native population, men and women) was above 9.0 μIU/mL. The insulin level in non-native women and men was higher than that in the indigenous people by 19% and 26%, respectively. The tendency of increasing insulin level with age was revealed in both the indigenous and non-native inhabitants. The highest level of insulin and glucose was observed in Samburg and Kharampur settlements; the lowest, in Gyda settlement. The cortisol level was higher in men than in women. The reduced cortisol/insulin index was observed in both groups of men. A most significant decrease in the cortisol/insulin index and an increase in HOMA–IR index were observed in nonnative men and women as compared with indigenous population. These data confirm the likelihood of the metabolic syndrome and type 2 diabetes mellitus in the YaNAO population, especially among non-native inhabitants.     

Program of premature senescence is not induced by sodium butyrate in transformants with JNK1,2 knockout

The role of JNK1,2 stress kinases in the regulation of premature senescence stimulated by sodium butyrate (NaB), a histone deacetylase inhibitor, has been studied. It was found that NaB did not block the cell cycle in E1A+cHa-ras transformants selected from embryonic mouse fibroblasts with jnk1,2 stress-kinase gene knockout (mERasJNK^?/? cells). Even long-term (five days) NaB treatment did not block cell cycle distribution or cell proliferation, nor did it induce cellular hypertrophy or activate SA-β-galactosidase activity, a senescence marker. The data show that JNK stress kinases are involved in senescence induced in E1A+cHa-ras mouse transformants by NaB. It is possible to suggest that JNK1,2 have tumor suppressor properties because the process of senescence, which prevents tumor cell proliferation, does not occur if they are absent.     

Phase state of aqueous gelatin-polysaccharide (1)-polysaccharide (2) systems

Optical microscopy, ultracentrifugation, phase analysis and turbidimetric titration methods were used to study phase state and phase equilibria of quaternary water-gelatin-pectin-dextran system in the absence of salts and at pH higher than the isoionic point. It was found that these systems are two-phase ones, contrary to the single-phase behaviour of the ternary water-gelatin-pectin and water-gelatin-dextran systems under the same conditions. The observed phase separation is the result of incompatibility of gelatin with pectin, dextran molecules being distributed practically uniformly between coexisting phases. This phenomenon is rather typical for many water-gelatin-polysaccharide-1-polysaccharide-2 systems under the conditions when all the pairs of biopolymers are compatible. The high compatibility of gelatin with pectin or dextran in the ternary systems under given conditions is due to the formation of weakly bonded interpolymer complexes. The incompatibility of gelatin with pectin in the presence of dextran can be explained by the blockage of the reactive gelatin groups due to their competitive interactions with dextran.