Category Archives: Uncategorized
Citicoline affects serum angiostatin and neurospecific protein levels in patients with atrial fibrillation and ischemic stroke
A. A. Tykhomyrov1, Yu. S. Kushnir2, V. S. Nedzvetsky3,
T. V. Grinenko1, O. V. Kuryata2
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2State Establishment “Dnipropetrovsk Medical Academy of Health Ministry of Ukraine”, Dnipro;
3Bingöl University, Bingöl, Turkey;
e-mail: artem_tykhomyrov@ukr.net
Received: 22 May 2019; Accepted: 13 August 2019
Ischemic stroke is considered as one of the most frequent and severe complications of atrial fibrillation. The present study was undertaken to examine whether post-insult treatment with cytidine diphosphate-choline (CDP-choline, or citicoline) affects serum levels of the angiogenesis inhibitor angiostatin and neurospecific proteins as markers of brain damage in patients with cerebral ischemia associated with atrial fibrillation. Thirty-three patients with a diagnosis of acute ischemic stroke received citicoline sodium by intravenous infusions (1,000 mg daily for 14 days) in addition to the standard treatment (basic group). Twenty-five patients with the same pathologies, who received only standard therapy, were enrolled in the study as a control group. Serum content of angiostatin and neurospecific proteins, namely neurofilament heavy subunit (NF-H) and glial fibrillary acidic protein (GFAP), was measured by immunoblotting at the basal level and after the treatment. Citicoline treatment caused significant decreases in serum levels of angiostatin (by 40% vs. basal level, P < 0.05), GFAP (by 61%, P < 0.01), and the NF-H subunit (by 19%, P < 0.05) and had no effect on the serum albumin content. In contrast, there were no statistically significant differences between baseline levels of the studied protein markers and their content after the treatment period in the control group. These findings indicate for the first time that CDP-choline protects both astrocytes and neurons and improves angiogenic capacity through down-regulation of angiostatin in post-ischemic patients with atrial fibrillation after acute ischemic stroke. Further studies are needed to test associations between serum levels of these biomarkers, clinical outcomes, and treatment efficacy of stroke.
Influence of human HB-EGF secreted form on cells with different EGFR and ErbB4 quantity
O. I. Krynina, N. V. Korotkevych, A. J. Labyntsev,
S. I. Romaniuk, D. V. Kolybo, S. V. Komisarenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: olyakrynina@gmail.com
Received: 18 July 2019; Accepted: 13 August 2019
HB-EGF is one of the most potent ligands of EGFR and ErbB4 receptors. This growth factor plays a pivotal role in many cellular processes, but its effect differs from one cell type to another and remains not fully understood. The aim of this work was to investigate the dependence between the rate of HB-EGF mediated cell proliferation and activation of EGFR and ErbB4 receptors. Therefore, the effects of human recombinant sHB-EGF (rsHB-EGF) on the proliferation of cell lines with different EGFR and ErbB4 quantity and ratio, as well as activation of the MARK-cascade p38 and ERK1/2 (p42/44) kinases, were analyzed. For comparison, a similar study of the effect of native sHB-EGF secreted by human histiocytic lymphoma cells U937 during co-cultivation with different cell lines was performed.
It was proved that cell proliferation in response to sHB-EGF depends not only on the quantity but also on the ratio of EGFR and ErbB4. It was shown that signaling through ErbB4 is associated with activation of p38 kinase and signaling through EGFR associated with activation of ERK1/2 (p42/44) kinase. We assume the existence of two different mechanisms for sHB-EGF-mediated stimulation of cell proliferation, and the simultaneous launch of these mechanisms provides a maximal proliferative response. The results of this study support the feasibility of creating anti-proliferative drugs that target ErbB4.
Agonists of CB1 and NMDA receptors decrease the toxic effect of organophosphorus compound paraoxon on PC12 cells
F. Salem1, F. Bahrami1,2, Z. Bahari2, Z. Jangravi3, S. Najafizadeh-Sari4
1Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;
2Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran;
3Departmentof Biochemistry, Faculty of Medicine, Baqiyatallah University
of Medical Sciences, Tehran, Iran;
4Student’ Research Committee (SRC), Baqiyatallah University of Medical Sciences, Tehran, Iran;
e-mail: f.bahrami@bmsu.ac.ir or farideh_bahrami@yahoo.com
Received: 01 July 2019; Accepted: 13 August 2019
Pharmacological studies allow to suggest that activation of cannabinoid type 1 receptors (CB1) have a neuroprotective role against toxicity induced by organophosphate agents, but the exact mechanisms of this effect as well as interaction with receptors of other types are far from clear. Therefore, the aim of current study was to evaluate the effect of CB1 and NMDA receptors agonists on cell viability and biomarkers of oxidative stress and lipid peroxidation in PC12 cells exposed to paraoxon. PC12 cells were exposed to 100 µm paraoxon as organophosphate agent. Treatments with 1 µM arachidonyl-2′-chloroethylamide (ACEA) as specific agonist of CB1 receptors, 100 µM N-methyl-D-aspartate (NMDA) as agonist of NMDA receptors and 1 µM AM251 as antagonist of CB1 receptors were done. Cell viability and biomarkers of oxidative stress were evaluated after 48 h of incubation. The level of CB1 receptor protein was evaluated by Western blotting. It was demonstrated that PC12 cells treatment with paraoxon led to cell viability inhibition, glutathione level, superoxide dismutase and catalase activity reduction, lipid peroxidation intensification and CB1 receptor expression attenuation. Application of ACEA and NMDA was shown to be followed by normalization of these indices. The protective effect of ACEA was abolished when the CB1 receptors antagonist AM251 was applied. The study revealed that application of ACEA and NMDA can protect PC12 cells against paraoxon induced toxicity through antioxidant capacity increment, lipid peroxidation inhibition and enhanced expression of CB1 receptors.
Effect of recombinant human interleukin-7 on Pseudomonas aeruginosa wound infection
S. M. Grigorieva1, D. B. Starosyla1, S. L. Rybalko1,
V. V. Motronenko2, T. M. Lutsenko2,3, O. Yu. Galkin2
1Gromashevsky Institute of Epidemiology and Infectious Diseases,
National Academy of Medical Sciences of Ukraine, Kyiv;
2National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”;
3UA Pro-Pharma LLC, Kyiv, Ukraine;
e-mail: alexfbt@gmail.com
Received: 01 July 2019; Accepted: 13 August 2019
A wide range of interleukin-7 (IL-7) biological effects suggests that application of appropriate preparations in clinical practice will stimulate immunity in patients with lymphocytic exhaustion or autoimmune diseases. Studies are being conducted for IL-7 based preparations aimed at restoration of the immune system of patients with immunodeficiency of different origins. Pseudomonas aeruginosa is an important pathogen, which causes nosocomial infections in hospitalized patients. Infection factors, affecting the immune status of the host, play a key role. A promising and relevant scientific endeavor is the study of the effect of recombinant IL-7 (rIL-7) as an adjunct therapy in wound infections caused by P. aeruginosa. The aim of this study was to evaluate the effectiveness of rIL-7 use in P. aeruginosa wound infection in mice. The experiments were conducted using a standardized rIL-7 preparation, P. aeruginosa strain and 20 white non-inbred mice. The preparation of rIL-7 after all stages of purification was characterized by the content of ballast proteins and impurities via electrophoresis in a polyacrylamide gel in reducing conditions, and its biological activity was evaluated in the MTT test by means of proliferation of peripheral blood mononuclear cells. In the mice, the fur was removed, the neck nape was intentionally injured and P. aeruginosa bacteria were injected into the wound of each animal (0.1 ml of suspension with a bacterial cell concentration of 0.08×109 cells/ml). Starting from the 2nd day, bacterial examination of the wound material was carried out daily. Starting from the 3rd day, the mice (experimental group, n = 10) were intraperitoneally administered 5 μg (0.1 ml) of the rIL-7 preparation. In the control group of animals (n = 10), the rIL-7 preparation was not administered. In 80% of experimental animals (administered the rIL-7 preparation), the healing of wounds and elimination of the pathogen of purulent inflammatory infection P. aeruginosa occurred on the 7th day. On the 9th day from the beginning of wound infection, wound healing and elimination of P. aeruginosa occurred in all experimental mice. In 60% of mice from the control group (did not receive treatment with rIL-7), wound healing and the elimination of P. aeruginosa occurred on the 9th day. Wound healing and elimination of P. aeruginosa in all mice of the control group occurred on the 14th day. Thus, in mice treated with rIL-7, wound healing and elimination of the pathogen occurred 5 days earlier than in mice from the control group (without rIL-7 treatment). Subsequent studies may be aimed at developing protocols for the treatment of wound infections using an rIL-7 preparation in patients with a compromised immune system Therefore, rIL-7 is a promising preparation for the treatment of complex wound infections.
Joining the global scientific community – UBJ on its way
M. Grigorieva, V. Chernyshenko, S. Komisarenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: mayagrigorieva@gmail.com
Over the last decade, The Ukrainian Biochemical Journal (UBJ) has taken a number of measures that have allowed it to leave its narrowly domestic past behind and come a step closer to the international community of scientific publications. In the first phase of the UBJ transformation the journal was made English-lingual only, its manuscript handling process was somewhat streamlined, and a brand-new website for the journal was developed. The range of international databases, in which the UBJ was listed, was also significantly extended. The second phase of the UBJ upgrade began in October 2018, when the journal received a grant from the Regional Cooperation for Health, Science and Technology (RECOOP) to implement the project “Scientific communication of RECOOP partners using the UBJ platform”. The project’s objectives include raising the journal’s quality level to international standards, globalizing it, and making it a reliable platform for the RECOOP publishing activity in Eastern Europe by promoting articles within the scope of RECOOP research strategy.
The contribution of the Nobel prize laureates to the development of knowledge of vitamin biochemistry: Ch. Eijkman, F. G. Hopkins, A. Szent-Györgyi, W. Haworth, P. Karrer, R. Kuhn, H. Dam, E. A. Doisy, G. Minot, W. Murphy, G. Whipple, D. Hodgkin, R. Woodward
V. M. Danilova, R. P. Vynogradova, S. V. Komisarenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: valdan@biochem.kiev.ua
In the first half of the 20th century, the experimental research of chemists, biochemists and physiologists in collaboration with doctors led to the discovery of a new class of biologically active compounds – vitamins. Many of these scientists were awarded the Nobel Prizes. Thanks to their efforts, almost all currently known vitamins (B1, B2, B6, B9, B12, C, A, E, K) were identified, their structure and the mechanism of biological action were characterized. Many vitamins were found to serve as coenzymes in important biochemical conversions. This article talks about the history of the discovery of the most familiar vitamins and scientists involved in their research. The contribution made by these distinguished scientists to the development of modern biochemical science, in particular, vitaminology, cannot be overestimated.
Kinetics of interaction between polyreactive immunoglobulins and antigen. The theory
S. A. Bobrovnik, M. O. Demchenko, S. V. Komisarenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: s-bobrov@ukr.net
Received: 14 February 2019; Accepted: 17 May 2019
Dynamics of association between polyreactive immunoglobulins (PRIGs) and immobilized antigens is considered on the base of our model of PRIGs-antigen interaction, which was suggested by us earlier. This process of PRIGs binding to an immobilized antigen was described with a system of differential equations. The solution of this system of differential equations gives mathematical expressions that relate the dynamics of the reactant concentrations and time of the reaction. Using Microsoft Excel program the theoretical curves were calculated and plotted that described the dynamics of “active”, “nonactive” PRIGs in solution as well as PRIGs that were bound to an immobilized antigen. Conclusions drawn by us earlier about very high dependence of reaction PRIGs with an antigen from temperature were confirmed.
Consideration of the contribution of chemical (non-enzymatic) conversion of substrate in the general mechanism of enzyme reaction
S. O. Kosterin, S. O. Karakhim, P. F. Zhuk
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: kinet@biochem.kiev.ua; laserlab@biochem.kiev.ua
Received: 13 September 2018; Accepted: 13 December 2018
When enzyme-catalyzed reactions are studied, it is necessary to take into account the contribution of the chemical (non-enzymatic) conversion of the substrate to the product, which is carried out together with the enzyme-catalyzed conversion of the substrate. It is generally believed that the difference of the product concentration that was formed in the presence of the enzyme and in its absence (during the same time interval) is the concentration of the product that was formed directly in the enzyme-catalyzed reaction, i.e. that there is additivity of the product concentrations at each time point. In this paper, we have analyzed when there is additivity and how to correctly take into account the contribution of chemical (non-catalytic) substrate conversion when the enzyme-catalyzed reactions are investigated. We have shown that the additivity of product concentrations and initial rates is observed only for a period when the product concentration increases linearly with time. The longer the reaction proceeds the more the deviation from the additivity. Under equilibrium condition, there is no additivity of equilibrium product concentrations but under conditions of detailed balance the equilibrium product concentration of the overall reaction, including the enzyme-catalyzed and chemical (non-enzymatic) conversion of the substrate, is also at the same time the equilibrium concentration of the product of the enzyme-catalyzed conversion of the substrate.
Calculations of supramolecular structures of peptidylboronic acid (bortezomib) with ABO blood system antigen
A. D. Kustovska1, S. V. Prymachenko1, Zh. M. Minchenko2,
T. F. Liubarets2, O. O. Dmytrenko2
1National Aviation University, Kyiv, Ukraine;
e-mail: akust@bigmir.net;
2SI “National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
Received: 08 April 2019; Accepted: 17 May 2019
Peptidylboronic acids have recently become widespread as effective drugs for cancer treatment. However, the use of these drugs is often accompanied by negative side effects associated with the phenotypic affiliation to the ABO system. Therefore, it is important to determine the role of pharmaco-chemical characteristics of antigens of ABO system and therapeutic agents (for example, bortezomib) in the selection of individualized therapies for patients with chronic lymphoproliferative neoplasms. The expediency and efficiency of bortezomib use for patients with plasma cell myeloma depending on the phenotype affiliation to the ABO system were evaluated. Efficiency of plasma cell myeloma therapy was analyzed in 104 patients who received treatment according to clinical protocols. Dependence of the duration of remission in performance of standard polychemotherapy was researched. Calculation of energy parameters and geometry of probable supramolecular structures of peptidylboronic (bortezomib) and boric acids with antigens of the ABO blood system was performed in the HyperChem 8.07 software package. It was demonstrated that the ability of antigens to form supramolecular complexes with bortezomib varies in the series: B1 >> 01 > A1, which is in line with the results of clinical researches. It was assumed that in case of patients with В blood group secondary process (interaction of bortezomib with carbohydrate antigen) is energetically more beneficial than the main process (inhibition of proteasome), while for patients with O and A groups, equilibrium is shifted toward the main reaction, which results in the therapeutic effect of the drug.