Том 109, № 1 (2023)

Solving the question of the origin of life on Earth is impossible without understanding how the chemical, functional, and regulatory principles that determine cellular metabolism arose, how cells acquired the properties that determine their evolution, and how biological systems function and develop. This review is devoted to the consideration of the versatility of the functions of glycolytic enzymes, the expression of which is significantly increased in some types of cells, for example, cells with stem properties or malignant tumor cells. Almost all glycolysis enzymes have been found to have non-catalytic functions that are necessary to maintain a high rate of cell proliferation, their a-ctive migration, and the formation of a stem-like phenotype. Glycolytic enzymes arose very early during the evolution. Since the genomes of ancient life forms had a limited number of genes to encode the entire set of necessary functions, glycolytic enzymes or the products of the reactions they catalyzed could be used as ancient regulators of intercellular and intracellular communication. Subsequently, the multifunctionality of the main metabolic enzymes began to be used by tumor cells to ensure their survival and growth. In this review, we discuss some of the noncatalytic functions of glycolytic enzymes, as well as the possible evolutionary significance of acquiring such multifunctionality.

The goal of the study was analysis of the role for dihydropyrimidinase-related protein 2 (DRP2) in regulation of anxiety in humans and animals. For this purpose, the levels of DRP2 in the platelets and saliva and the levels of natural autoantibodies to DRP2 in the blood serum of the patients, admitted for a surgical operation, were analyzed alongside with the effects of DRP2 on rat behavior using the model of elevated plus-maze. Blood samples were collected from the veins of the patients, feeling anxiety at the day of surgery, into test tubes containing 5% EDTA as an anticoagulant. Platelets and serum were purified and through indirect ELISA-test the levels of DRP2 were evaluated in the platelets, while the levels of natural anti-DRP2 autoantibodies were measured in the blood serum. Concomitantly, the levels of DRP2 were estimated in the patients’ saliva sampled on the same day. The results showed upregulation of DRP2 in the platelets (p < 0.05 on Student’s t-criterion) and natural anti-DRP2 autoantibodies in the serum of the patients (p < 0.001) relative to healthy persons. Evaluation of the level of the stress hormone cortisol in the patients’ serum revealed its upregulation (p < 0.01). At the same time downregulation of DRP2 in the patients’ saliva (p < 0.01) was noticed. Intra-cerebral administration of DRP2 to the rats resulted in an increase in the number of crossed squares in the open arms of the maze relative to the control rats injected with inactivated DRP2 (p < 0.01, Wilcoxon and Mann–Whitney U-criterion) which indicates their reduced anxiety. Based on the data obtained we conclude that evaluation of DRP2 in the platelets, natural anti-DRP2 autoantibodies in the blood serum and DRP2 in the saliva might serve as an indicator of anxiety levels in humans.

Higt fat diet can lead to the development of metabolic syndrome (MS). However, the question of the mechanisms of pathophysiological processes in MS has not been studied enough. The aim of the work was to study the effect of a high-fat diet (HFD) on the reactivity of the mesenteric arteries of Wistar rats in vivo, as well as to evaluate the change in the mechanisms of endothelium-dependent arterial dilatation in HFD. The HFD-group of rats (n = 25) received HFD containing 50% animal fat for 10 weeks, the control group (n = 25) received a standard diet. The effect of HFD on endothelium-dependent and endothelium-independent responses of the mesenteric arteries under the action of agonists in the absence and with the use of blockers of NO-synthase (L-NAME), cyclooxygenase (indomethacin), and K⁺-channels (tetraethylammonium) was assessed using photomicrography and video recording of mesenteric artery diameter in vivo. HFD in rats led to the development of MS, including dyslipidemia, hyperglycemia and insulin resistance, and an increase in blood pressure. MS was accompanied by impaired functional state of the mesenteric arteries. In rats of the HFD group, compared with the control group, there was an increase in the constrictor reaction to phenylephrine by 29%, as well as a decrease in the reactivity of vessels previously contracted by phenylephrine under the action of acetylcholine by 36%. Pre-incubation of vessels with blockers reduced the amplitude of relaxation under the action of acetylcholine, compared with the initial acetylcholine-induced vasorelaxation, in HFD-group rats: with L-NAME – by 47%, L-NAME and indomethacin – by 50%, L-NAME, indomethacin and tetraethylammonium – by 65%; in the control group – by 69, 72 and 83%, respectively. HFD had no significant effect on the amplitude of vasodilation under the action of sodium nitroprusside. Thus, endothelial dysfunction in HFD-treated rats was mediated both by impairment of NO-dependent mechanisms of vasodilation, in particular, by a decrease in NO production by the endothelium, and by a decrease in the effectiveness of ВК_Са. The decrease in NO bioavailability in HFD was partially compensated by the activation of endothelial hyperpolarization mechanisms (mediated by IK_Ca and SK_Ca activities) in acetylcholine-induced vasodilation.

The pathogenesis of a number of diseases is characterized by a violation of the regulation of bone homeostasis, with the progressive development of osteodestruction. At the same time, an active study of the mechanisms leading to a shift in the balance of osteoreparative and osteoresorption directions of osteogenesis is underway. The determination of molecular and cellular patterns affecting the dynamics of changes in bone metabolism is a significant task among a wide range of specialists. Such research works allow us to propose algorithms for targeted therapeutic effects on various key links in the pathogenesis of osteodestruction. The study analyzed the expression of genes involved in maintaining bone homeostasis, changes in the histological picture under experimental conditions, depending on the time elapsed since the induction of aseptic necrosis. The result of the work showed the heterogeneity of the development of osteodestruction in an experiment on Wistar rats, with a surgically created focus of hypoperfusion of the femoral head against the background of increased intra-articular pressure. In the first two weeks of the development of aseptic necrosis, the expression of the hif1a gene was most actively determined, which can be considered from the position of a trigger for further disruption of bone metabolism. At the same time, the concentration of m-RNA of osteogenesis and osteoresorption genes was reduced. The most active osteolytic processes according to electron microscopy data, increases in the expression of osteoclastogenesis induction genes were observed at 6 weeks of the experiment. The osteoreporative orientation of bone metabolism gradually increased from the beginning of the study and 2 months after the manifestation of avascular necrosis of the femoral head, active osteoblasts, increased expression of bone matrix genes, osteoblastogenesis were determined. Thus, the development of osteodestruction is an extremely heterogeneous process, with dynamically changing molecular patterns depending on time, determining the activity of signaling pathways of bone metabolism.

Acute stress exposure causes a cascade of neurochemical reactions, leading, in particular, to a change in behavior and increased tolerance to pain in humans and animals. ACTH/MSH-like peptides play an important role in regulating the body’s response to stressful exposures. The aim of the present study was to assess the effects of the ACTH_4–10 analogue heptapeptide Semax in various models of acute stress. The effect of intraperitoneal Semax administration at doses of 0.05 and 0.5 mg/kg on changes in behavior and pain sensitivity of Wistar rats in models of inescapable intermittent foot shock stress and forced cold-water swim stress was investigated. To assess the involvement of the endogenous opioid system in the effects of stress, an impact of pretreatment with opioid receptor antagonist naloxone (1 mg/kg) was studied. The stressors used led to an increase in the pain threshold in the paw-pressure test, which indicates the development of stress-induced analgesia (SIA). In addition, rats exposed to stress had an decrease in exploratory behavior and an increase in the anxiety-like behavior in the hole board test. Both Semax and naloxone attenuated SIA in the model of inescapable foot shock stress, but did not affect the value of the pain threshold in the model of forced cold swim stress. Both studied drugs did not affect the behavior of rats in the models of acute stress used. It can be concluded that Semax blocks the opioid form of stress-induced analgesia, but does not affect the behavioral alterations in rats exposed to acute stress.