Category Archives: Uncategorized
Thermodynamics of interaction between polyreactive immunoglobulins and immobilized antigen
S. A. Bobrovnik1*, O. V. Ogloblya2, M. O. Demchenko1, S. V. Komisarenko1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2ESC Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Ukraine;
*e-mail: s-bobrov@ukr.net
Received: 22 April 2021; Accepted: 22 September 2021
In order to determine thermodynamic parameters of the interaction between polyreactive immunoglobulins (PRIGs) and immobilized antigen, several of experimental kinetic curves of PRIGs binding to immobilized ovalbumin were obtained at different temperatures. This allowed determining the rate constants for every step of the binding process for each temperature. Then, using appropriate equations, thermodynamic parameters, such as activation energy, enthalpy, entropy, and standard free energy (Gibbs energy), were calculated. Thermodynamic values obtained show that the main energy consuming step in the study process of PRIGs bindingis the transformation of “inactive” PRIGs into “active” PRIGs, i.e. formation of hydrophobic patches on the surface of PRIGs molecules. In contrast, the following step of the binding of “active” PRIGs to an immobilized antigen is not an energy dependent process.
Semicarbazide diminishes the signs of bleomycin-induced pulmonary fibrosis in rats
O. O. Hudkova*, I. P. Krysiuk, T. O. Kishko,
N. M. Popova, L. B. Drobot, N. V. Latyshko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: ogudkova@biochem.kiev.ua
Received: 16 July 2021; Accepted: 22 September 2021
The pathogenesis of pulmonary fibrosis (PF) is accompanied by extracellular matrix (ECM) deposition, oxidative stress, and inflammation progression, as well as hyperactivation of amine oxidases (AOs), which contribute to disease manifestation. The present study aims to elucidate the effect of semicarbazide (SC), an inhibitor of Cu-containing AOs: lysyl oxidase (LOX), semicarbazide sensitive amine oxidase (SSAO), diamine oxidase (DAO), on PF induced in rats by bleomycin (BLM). Eighteen male Wistar rats were randomly divided into four groups: Control, rats of BLM group received BLM (5 mg/kg, intratracheally once), BLM+SC group obtained 0.005% solution of SC (about 50 µg per capita per day) for three weeks starting immediately after BLM injection, and the Control+SC group drank the same solution as BLM+SC group. The content of cross-linked collagen in total bronchi and free radicals in lung, activities of LOX, SSAO, DAO, polyamine oxidase (PAO), Cu, Zn-superoxide dismutase (SOD1), catalase (CAT) and glutathione peroxidase (GPx) in lung and blood were measured. BLM injection induced PF that was confirmed histologically and morphometrically as well as by the elevation of the content of cross-linked collagen and free radicals. The activities of LOX and SSAO involved in post-translational modification of ECM and inflammation were significantly increased (P < 0.05). The activities of DAO, and PAO that control polyamine metabolism were also essentially raised. Among antioxidant enzymes, only GPx was activated in the BLM group as compared to control. These changes were absent in the BLM+SC group. SC intake promoted the fact that the histology and morphometric parameters of lung tissue, the content of cross-linked collagen in the bronchi and free radicals in the lung, as well as the activity of the studied enzymes remained at the control level. Our data suggest that SC suppresses the development of BLM-induced PF by inhibiting AOs activities.
Determination the binding ability of N-acetyl cysteine and its derivatives with SARS-COV-2 main protease using molecular docking and molecular dynamics studies
A. H. Shntaif*, N. A. Alrazzak, A. Bader, A. M. Almarzoqi
University of Babylon, College of Science for Women, Iraq;
*e-mail: ahmed1979sh@gmail.com
Received: 25 May 2021; Accepted: 22 September 2021
N-acetyl cysteine (NAC) drug has been used as an antioxidant and anti-inflammatory agent in clinical practice and more recently in the treatment of COVID-19 patients. Using docking analysis and molecular dynamics studies we compare the interaction between of N-acetyl cysteine and its derivatives with SARS-COV-2 main protease (Mpro) which is essential for processing the proteins translated from the viral RNA. The results obtained from this study showed that NAC benzyl ester (NACBn), NAC ethyl ester (NACEt) and NAC amide (NACA) could bind with SARS-COV-2 protease better than NAC drug.
Overall hemostasis potential of blood plasma and its connection to molecular markers of the hemostasis system in patients with stenosis of coronary artery
N. V. Storozhuk1, L. V. Pyrogova2, Т. М. Chernyshenko2,
O. P. Kostyuchenko2, T. M. Platonova2, O. B. Storozhuk1,
B. G. Storozhuk1, R. Yu. Marunich2,
G. K. Bereznytsky2, E. M. Makogonenko2*
1MI Pirogov Vinnytsia National Medical University, Vinnytsia, Ukraine;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: ymakogonenko@gmail.com
Received: 01 April 2021; Accepted: 22 September 2021
The correlation relationships between hemostatic potential parameters and concentrations of molecular markers of the hemostasis system: soluble fibrin (sf), D-dimer (DD), fibrinogen (Fg) and protein C (PC) in patients with stenosis of coronary artery 6 months after coronary angioplasty have been investigated. It was found three directions of changes in the state of the patients hemostasis system: an increasing in fibrinolytic activity (C) ~18% of patients; an increasing in coagulative activity (B) ~31% of patients; and maintaining of the balance between coagulation and fibrinolysis (A) ~51% of patients. In patients with signs of stenosis without angina pectoris, a strong Pearson correlation was shown between the half-life of the clot and the overall hemostatic potential (OHP) (r = 0.75, P << 0.05), a moderate relationship between concentrations of sf and D-dimer (r = 0.67, P <0.05), almost complete connection between coagulation potential (CP) and OHP (r = 0.975, P << 0,05) and strong connection between CP and fibrinolytic potential (FP) (r = 0.80, P << 0.05). In patients with signs of stable angina pectoris, almost complete connection was found between the concentration of sf and D-dimer (r = 0.981, P << 0.05), CP and OHP (r = 0.979, P << 0.05) and a strong connection between CP and FP (r = 0.846, P << 0.05). Possible functional mechanisms of connection between these parameters are discussed.
Oxidative stress in rat heart mitochondria under a rotenone model of Parkinson’ disease: a corrective effect of capicor treatment
O. O. Gonchar*, O. O. Klymenko, T. I. Drevytska,
L. V. Bratus, I. M. Mankovska
Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: olga.gonchar@i.ua
Received: 22 March 2021; Accepted: 22 September 2021
Biochemical and genetic mechanisms of oxidative stress (OS) developing in rat heart mitochondria were studied in a rotenone model of Parkinson’s disease (PD), and the effect of Capicor (combination of meldonium dihydrate and gamma-butyrobetain dihydrate) on these mechanisms was evaluated. Experiments were carried out on adult male Wistar rats: I – intact rats (control); II –with rotenone administration subcutaneously at dose 3 mg/kg per day along 2 weeks; III – with rotenone/Capicor administration: after rotenone intoxication, capicor was injected intraperitoneally at dose 50 mg/kg per day along following 2 weeks. As OS biomarkers, lipid peroxidation, protein oxidative modification, H2O2 production, the activity of MnSOD, GPx and glutathione pool indexes were measured. The PD-related genes Parkin (PARK2) and DJ-1 (PARK7) as well as MnSOD and DJ-1 protein expressions were detected. Rotenone intoxication increased the intensity of lipid peroxidation, protein oxidative modification, and H2O2 production. These events were accompanied by decreased in GSH content, GSH/GSSG ratio, and GPx activity. Increased ROS production and impaired antioxidant defenses could result from the established DJ-1 gene and DJ-1 protein deficiency. Capicor administration increased the endogenous antioxidant defense, weakening the lipid peroxidation and oxidative modification of mitochondrial proteins. Capicor treatment led to an increase in GSH content and GSH/GSSG ratio in heart mitochondria that may serve as additional indicators of the OS intensity reducing. Capicor promoted overexpression of DJ-1 and PARK2 genes in the heart that may indicate a rise in mitophagy and a decrease in OS.
Short peptide sequences: current knowledge and future prospects
C. M. Nasadyuk
Danylo Halytsky Lviv National Medical University,
Department of Biochemistry, Lviv, Ukraine;
e-mail: nasadyukch@gmail.com
Received: 09 March 2021; Accepted: 22 September 2021
According to modern knowledge, the biological effect of many peptides is mediated by their short-chain fragments – oligopeptides – ranging from 2 to 20 amino acids and the activity of short peptides often significantly exceeds the activity of the peptide precursor. Aim of the review was to summarize the uptodate data on the stability of short peptide sequences, mechanisms of cell penetration, interaction with cell receptors, biological effects and approaches to clinical application. Stability of short peptides is mediated by their structure and molecular weight. Some di-/tripeptides were reported to be able to permeate through intestinal membranes in their intact forms via peptide transporter systems, while others are vulnerable to protease degradation. Although pinocytosis is presumed to be the main mechanism how short peptide sequences enter the cell, some lipophilic oligopeptides were shown to penetrate the cell membrane by the same mechanism as steroid or thyroid hormones and specific extracellular receptors were also described. Low-weighing oligopeptides realize their effect on the cell, chromosomal, genome and molecular levels. The advantages of oligopeptides include oral availability (for low weight compounds), low immunogenicity, high tissue specificity, faster biological effect, better cost efficiency and environmental friendliness of their synthesis. Hence, short peptide sequences are regarded as promising candidates for pharmacotherapy, cell cultures and drug delivery purposes.