Nocistatin and Products of Its Proteolysis Are Dual Modulators of Type 3 Acid-Sensing Ion Channels (ASIC3) with Algesic and Analgesic Properties
AbstractThe neuropeptide nocistatin (NS) is expressed by the nervous system cells and neutrophils as a part of a precursor protein and can undergo stepwise limited proteolysis. Previously, it was shown that rat NS (rNS) is able to activate acid-sensing ion channels (ASICs) and that this effect correlates with the acidic nature of NS. Here, we investigated changes in the properties of rNS in the course of its proteolytic degradation by comparing the effects of the full-size rNS and its two cleavage fragments on the rat isoform 3 ASICs (ASIC3) expressed inX. laevis oocytes and pain perception in mice. The rNS acted as bo...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Topology of Ubiquitin Chains in the Chromatosomal Environment of the E3 Ubiquitin Ligase RNF168
In this study, we unequivocally showed that RNF168 does not have the ability to directly distinguish architecture of polyubiquitin chains, except for the tropism of its two ubiquitin-binding domains UDM1/2 to K63 ubiquitin chains. Analysis of intracellular chromatosomal environment of the full-length RNF168 and its domains using the ligand-induced bioluminescence resonance energy transfer (BRET) revealed that the C-terminal part of UDM1 is associated with the K63 ubiquitin chains; RING and the N-terminal part of UDM2 are sterically close to the K63- and K48-ubiquitin chains, while the C-terminal part of UDM1 is co-localize...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
A New Mouse Strain with a Mutation in the NFE2L2 (NRF2) Gene
AbstractTranscription factor NRF2 is involved in inflammatory reactions, maintenance of redox balance, metabolism of xenobiotics, and is of particular interest for studying aging. In the present work, the CRISPR/Cas9 genome editing technology was used to generate the NRF2ΔNeh2 mice containing a substitution of eight amino acid residues at the N-terminus of the NRF2 protein, upstream of the functional Neh2 domain, which ensures binding of NRF2 to its inhibitor KEAP1. Heterozygote NRF2wt/ ΔNeh2 mice gave birth to homozygous mice with lower than expected frequency, accompanied by their increased embryonic lethality and visu...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
The Role of Ubiquitin –Proteasome System in the Biology of Stem Cells
AbstractSelective degradation of cellular proteins by the ubiquitin –proteasome system (UPS) is one of the key regulatory mechanisms in eukaryotic cells. A growing body of evidence indicates that UPS is involved in the regulation of fundamental processes in mammalian stem cells, including proliferation, differentiation, cell migration, aging, and programmed cell d eath, via proteolytic degradation of key transcription factors and cell signaling proteins and post-translational modification of target proteins with ubiquitin. Studying molecular mechanisms of proteostasis in stem cells is of great importance for the developm...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Effect of Dexamethasone on Adhesion of Human Neutrophils and Concomitant Secretion
AbstractNeutrophils play a dual role in protecting the body. They are able to penetrate infected tissues and destroy pathogens there by releasing aggressive bactericidal substances. While into the surrounding tissues, the aggressive products secreted by neutrophils initiate development of inflammatory processes. Invasion of neutrophils into tissues is observed during the development of pneumonia in the patients with lung diseases of various etiologies, including acute respiratory distress syndrome caused by coronavirus disease. Synthetic corticosteroid hormone dexamethasone has a therapeutic effect in treatment of lung dis...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Impact of Lipid Matrix Composition on Activity of Membranotropic Enzymes Galactonolactone Oxidase from Trypanosoma cruzi and L-Galactono-1,4-Lactone Dehydrogenase from Arabidopsis thaliana in the System of Reverse Micelles
AbstractThe study of many membrane enzymes in an aqueous medium is difficult due to the loss of their catalytic activity, which makes it necessary to use membrane-like systems, such as reverse micelles of surfactants in nonpolar organic solvents. However, it should be taken into account that the micelles are a simplified model of natural membranes, since membranes contain many different components, a significant part of which are phospholipids. In this work, we studied impact of the main phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), on activity of the membrane enzymes using galactonolactone ...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Dicarbonyl-Modified Low-Density Lipoproteins Are Key Inducers of LOX-1 and NOX1 Gene Expression in the Cultured Human Umbilical Vein Endotheliocytes
AbstractExpression ofLOX-1 andNOX1 genes in the human umbilical vein endotheliocytes (HUVECs) cultured in the presence of low-density lipoproteins (LDL) modified with various natural dicarbonyls was investigated for the first time. It was found that among the investigated dicarbonyl-modified LDLs (malondialdehyde (MDA)-modified LDLs, glyoxal-modified LDLs, and methylglyoxal-modified LDLs), the MDA-modified LDLs caused the greatest induction of theLOX-1 andNOX1 genes, as well as of the genes of antioxidant enzymes and genes of proapoptotic factors in HUVECs. Key role of the dicarbonyl-modified LDLs in the molecular mechan...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Changes in the Glutamate/GABA System in the Hippocampus of Rats with Age and during Alzheimer ’s Disease Signs Development
AbstractGABA and glutamate are the most abundant neurotransmitters in the CNS and play a pivotal part in synaptic stability/plasticity. Glutamate and GABA homeostasis is important for healthy aging and reducing the risk of various neurological diseases, while long-term imbalance can contribute to the development of neurodegenerative disorders, including Alzheimer ’s disease (AD). Normalization of the homeostasis has been discussed as a promising strategy for prevention and/or treatment of AD, however, data on the changes in the GABAergic and glutamatergic systems with age, as well as on the dynamics of AD development, a...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Serotonin Receptors as a Potential Target in the Treatment of Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD) is the most common cause of dementia worldwide that has an increasing impact on aging societies. Besides its critical role in the control of various physiological functions and behavior, brain serotonin (5-HT) system is involved in the regulation of migration, proliferation, diffe rentiation, maturation, and programmed death of neurons. At the same time, a growing body of evidence indicates the involvement of 5-HT neurotransmission in the formation of insoluble aggregates of β-amyloid and tau protein, the main histopathological signs of AD. The review describes the role of v arious 5-H...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Opposite Effects of CRABP1 and CRABP2 Homologs on Proliferation of Breast Cancer Cells and Their Sensitivity to Retinoic Acid
AbstractResistance of tumor cells to retinoic acid (RA), a promising therapeutic agent, is the major factor limiting the use of RA in clinical practice. The mechanisms of resistance to RA are still poorly understood. Cellular Retinoic Acid Binding Proteins, CRABP1 and CRABP2, are essential mediators of RA signaling, but role of the two CRABP homol ogs in regulating cellular sensitivity to RA has not been well studied. In addition, the effects of CRABP1 and CRABP2 on cell proliferation have not been compared. Here, using a broad panel of breast cancer cell lines with different levels of RA sensitivity/resistance, we show ...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Phenoptosis and the Various Types of Natural Selection
AbstractIn the first description of evolution, the fundamental mechanism is the natural selection favoring the individuals best suited for survival and reproduction (selection at the individual level or classical Darwinian selection). However, this is a very reductive description of natural selection that does not consider or explain a long series of known phenomena, including those in which an individual sacrifices or jeopardizes his life on the basis of genetically determined mechanisms (i.e., phenoptosis). In fact, in addition to (i) selection at the individual level, it is essential to consider other types of natural...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Phenoptosis. Preface to the Special Issue
(Source: Biochemistry (Moscow))
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Viral Vectors in Gene Replacement Therapy
AbstractThroughout the years, several hundred million people with rare genetic disorders have been receiving only symptom management therapy. However, research and development efforts worldwide have led to the development of long-lasting, highly efficient, and safe gene therapy for a wide range of hereditary diseases. Improved viral vectors are now able to evade the preexisting immunity and more efficiently target and transduce therapeutically relevant cells, ensuring genome maintenance and expression of transgenes at the relevant levels. Hematological, ophthalmological, neurodegenerative, and metabolic therapeutic areas h...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Role of Mitochondrial DNA in Yeast Replicative Aging
AbstractDespite the diverse manifestations of aging across different species, some common aging features and underlying mechanisms are shared. In particular, mitochondria appear to be among the most vulnerable systems in both metazoa and fungi. In this review, we discuss how mitochondrial dysfunction is related to replicative aging in the simplest eukaryotic model, the baker ’s yeastSaccharomyces cerevisiae. We discuss a chain of events that starts from asymmetric distribution of mitochondria between mother and daughter cells. With age, yeast mother cells start to experience a decrease in mitochondrial transmembrane pote...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
Changes in the Structure of Potato Virus A Virions after Limited in situ Proteolysis According to Tritium Labeling Data and Computer Simulation
AbstractCoat proteins (CP) of the potato virus A virions (PVA) contain partially disordered N-terminal domains, which are necessary for performing vital functions of the virus. Comparative analysis of the structures of coat proteins (CPs) in the intact PVA virions and in the virus particles lacking N-terminal 32 amino acids (PVA Δ32) was carried out in this work based on the tritium planigraphy data. Using atomic-resolution structure of the potato virus Y potyvirus (PVY) protein, which is a homolog of the CP PVA, the available CP surfaces in the PVY virion were calculated and the areas of intersubunit/interhelix contacts ...
Source: Biochemistry (Moscow) - December 1, 2023 Category: Biochemistry Source Type: research
