Molekulyarnaya Biologiya最新文献

Experimental data were summarized to assume that dinitrosyl iron complexes (DNICs) with thiol-containing ligands are an endogenous "working form" of the nitric oxide (NO) system in living organisms. DNICs can function as donors of both neutral NO molecules, which are responsible for positive regulatory effects of the NO system on various physiological and biochemical processes in humans and animals, and nitrosonium cations (NO^(+)), which are responsible mostly for negative cytotoxic activity of the system. Special attention is paid to the finding that DNICs, especially in combination with dithiocarbamate derivatives, suppress SARS-CoV-2 infection in Syrian hamsters.

Metabolic stress caused by a lack of glucose significantly affects the state of red blood cells, where glycolysis is the main pathway for the production of ATP. Hypoglycemia can be both physiological (occurring during fasting and heavy physical exertion) and pathological (accompanying a number of diseases, such as diabetes mellitus). In this study, we have characterized the state of isolated erythrocytes under metabolic stress caused by the absence of glucose. It was established that 24 h of incubation of the erythrocytes in a glucose-free medium to simulate blood plasma led to a two-fold decrease in the ATP level into them. The cell size, as well as intracellular sodium concentration increased. These findings could be the result of a disruption in ion transporter functioning because of a decrease in the ATP level. The calcium level remained unchanged. With a lack of glucose in the medium of isolated erythrocytes, there was no increase in ROS and a significant change in the level of nitric oxide, while the level of the main low-molecular weight thiol of cells, glutathione (GSH) decreased by almost 2 times. It was found that the metabolic stress of isolated red blood cells induced hemoglobin glutathionylation despite the absence of ROS growth. The cause was the lack of ATP, which led to a decrease in the level of GSH because of the inhibition of its synthesis and, probably, due to a decrease in the NADPH level required for glutathione (GSSG) reduction and protein deglutathionylation. Thus, erythrocyte metabolic stress induced hemoglobin glutathionylation, which is not associated with an increase in ROS. This may have an important physiological significance, since glutathionylation of hemoglobin changes its affinity for oxygen.

The aim of this work was to study the effects of thymosin-1 alpha (Tα1) on the anti-inflammatory response of RAW 264.7 macrophages cultured in the presence of lipopolysaccharide (LPS) from the walls of gram-negative bacteria. As well, we evaluated production of pro-inflammatory cytokines and the activity of the NF-κB and SAPK/JNK signaling pathways. In addition, the level of expression of a number of genes that regulate cell apoptosis, as well as the activity of receptors involved in the pro-inflammatory response, was determined. First, the addition of Tα1 normalized the level of cytokine production to varying degrees, with a particularly noticeable effect on IL-1β and IL-6. Second, the addition of Tα1 normalized the activity of the NF-κB and SAPK/JNK signaling cascades and the expression of the Tlr4 gene. Third, Tα1 significantly reduced p53 and the activity of the P53 gene, which is a marker of cell apoptosis. Fourth, it was shown that the increase in Ar-1 gene expression under the influence of LPS was significantly reduced using Tα1. Thus, it was found that the presence of Tα1 in the RAW 264.7 cell culture medium significantly reduced the level of the pro-inflammatory response of cells.

Plant polyphenols are characterized by a wide range of biological activities, including antioxidant properties, and have a high geroprotective potential. The purpose of this work was to investigate the effect of the extract of rowan berries (Sorbus aucuparia L.) on the lifespan and stress resistance of Drosophila melanogaster with the identification of possible mechanisms of its biological activity. It has been established that an ethanol extract of S. aucuparia berries, the main components of which are rutin and cyanidin-3-rutinoside, has a pronounced antioxidant activity in vitro. At the same time, treatment with rowan berry extract increased the resistance of D. melanogaster males to starvation, but reduced resistance to hyperthermia. In females, the extract reduced resistance to oxidative stress but increased resistance to hyperthermia. The effects of rowan berry extract on longevity depended both on its concentration and on the sex of fruit flies. In response to treatment with rowan berry extract, D. melanogaster males and females showed slight differences in the background level of expression of cellular stress response genes, including heat shock genes (hsp27, hsp68, and hsp83), oxidative stress resistance genes (hif1, nrf2, and sod1), circadian rhythm genes (clk and per), and the longevity gene sirt1, which may explain the differences in the observed effects.

Ischemia-reperfusion is a cascade of complex and interrelated pathological processes underlying many human diseases, including such socially significant diseases as stroke, myocardial infarction, acute renal failure, etc. The present review considers modern ideas about the main biochemical and signal-regulatory processes in the cell under conditions of ischemia-reperfusion. Both generally accepted and newly developed ways of ischemia-reperfusion lesion correction aimed at different chains of this pathological process are considered.

Intracellular calcium signaling is involved in regulating the key functional mechanisms of the nervous system. The control of neuronal excitability and plasticity by calcium ions underlies the mechanisms of higher nervous activity, and the mechanisms of this control are of particular interest to researchers. A family of highly specialized neuronal proteins described in recent decades can translate the information contained in calcium signals into the regulation of channels, enzymes, receptors, and transcription factors. Neuronal calcium sensor-1 (NCS-1) is the most common member of the family, which is intensely expressed in central nervous system (CNS) cells; and controls several vital processes, such as neuronal growth and survival, reception, neurotransmission, and synaptic plasticity. In addition to calcium ions, NCS-1 can bind the so-called mobile, or signaling intracellular zinc, an increased concentration of which is a characteristic feature of cells in oxidative stress. Zinc coordination under these conditions stimulates NCS-1 oxidation to form a disulfide dimer (dNCS-1) with altered functional properties. A combined effect of mobile zinc and an increased redox potential of the medium can thus induce aberrant NCS-1 activity, including signals that promote survival of neuronal cells or induce their apoptosis and, consequently, the development of neurodegenerative processes. The review details the localization, expression regulation, structure, and molecular properties of NCS-1 and considers the current data on its signaling activity in health and disease, including zinc-dependent redox regulation cascades.

One of the key regulators of hematopoietic stem cell (HSC) maintenance is cellular metabolism. Resting HSCs use anaerobic glycolysis as the main source of energy. During expansion and differentiation under conditions of steady state hematopoiesis, the energy needs of activated HSCs increase by many fold. To meet the increased demands, cells switch to mitochondrial oxidative phosphorylation, which is accompanied by an increase in reactive oxygen species (ROS) production. Here, the molecular mechanisms maintaining glycolysis in HSCs, as well as the factors determining the increase in metabolic activity and the transition to mitochondrial biogenesis during HSC activation are discussed. We focus on the role of HIF (hypoxia-inducible factor) proteins as key mediators of the cellular response to hypoxia, and also consider the phenomenon of extraphysiological oxygen shock (EPHOSS), leading to the forced differentiation of HSCs as well as methods of overcoming it. Finally, the role of fatty acid oxidation (FAO) in hematopoiesis is discussed. Understanding the metabolic needs of normal HSCs and precursors is crucial for the development of new treatments for diseases related to the hematopoietic and immune systems.

Inflammatory bowel disease (IBD) is widespread in industrial countries with every 20th citizen being affected. Dysregulation of the epithelial barrier function is considered to play a key role in IBD. Permeability of the intestinal epithelium depends mostly on its self-renewal potential and the condition of intercellular junctions. Mitochondria are involved in regulating various intracellular processes in addition to their energy function. Recent data implicate mitochondria in intestinal epithelial barrier regulation and IBD. Mitochondrial dysfunction is possibly one of the factors that underlie the structural abnormalities of tight junctions and the cytoskeleton in intestinal epithelial cells and decrease the self-renewal capacity of the epithelium. The barrier function of the intestinal epithelium is consequently distorted, and IBD develops. The mechanisms of these processes are still unclear and require further research.

Cancer cells are characterized by an increased level of metabolism and are highly dependent on the correct functioning of the processes that ensure homeostasis. Reactive sulfur species (RSS) are important molecular modulators of metabolic processes in both healthy and tumor cells. The effect of RSS and, in particular, H2S, on key cellular systems, including the ubiquitin-proteasome system (UPS), which provides the destruction of most intracellular proteins, has been shown. The main components of the UPS are proteasomes, multisubunit protein complexes, within which proteolysis occurs. At the same time, data on the effect of H2S directly on the pool of proteasomes in tumor cells are insufficient. Here, we studied the effect of incubation of SW620B8-mCherry colorectal adenocarcinoma cells expressing a fluorescently labeled proteasome subunit with 50, 100, and 200 μM of the hydrogen sulfide donor GYY4137. The effect of the substance on the proteasome pool was assessed 6, 24, 48, and 72 h after administration. It was shown that the chymotrypsin-like and caspase-like proteasome activity decreases in cells incubated with 200 μM of the GYY4137 for 24 h. This coincided with an increase in the expression of proteasome subunit genes. In lysates of cells incubated with 200 μM GYY4137 for 48 h an increase in the content of the constitutive β5 subunit was observed and the activity of proteasomes leveled off. Following prolonged incubation with GYY4137 (72h), an increase in the expression levels of some proteasome genes was also observed, although this did not have a significant effect on the activity and subunit composition of proteasomes. Thus, the obtained data indicate the modulation of proteasome activity by the hydrogen sulfide donor and the effect of GYY4137 on transcription and translation of proteasome genes.

δ-Aminolevulinic acid dehydratase (ALAD) is a key enzyme of the cytoplasmic heme biosynthesis pathway. The primary structure of the ALAD gene, the multimeric structure of the ALAD/hemB protein, and ALAD expression during the annual reproductive cycle were studied in the cold-water marine sponge Halisarca dujardinii. The results implicated the GATA-1 transcription factor and DNA methylation in regulating ALAD expression. Re-aggregation of sponge cells was accompanied by a decrease in ALAD expression and a change in the cell content of an active ALAD/hemB form. Further study of heme biosynthesis and the role of ALAD/hemB in morphogenesis of basal animals may provide new opportunities for treating pathologies in higher animals.