Biological Clocks: Why We Need Them, Why We Cannot Trust Them, How They Might Be Improved
AbstractLate in life, the body is at war with itself. There is a program of self-destruction (phenoptosis) implemented via epigenetic and other changes. I refer to these as type (1) epigenetic changes. But the body retains a deep instinct for survival, and other epigenetic changes unfold in response to a perception of accumulated damage (type (2)). In the past decade, epigenetic clocks have promised to accelerate the search for anti-aging interventions by permitting prom pt, reliable, and convenient measurement of their effects on lifespan without having to wait for trial results on mortality and morbidity. However, ext...
Source: Biochemistry (Moscow) - February 1, 2024 Category: Biochemistry Source Type: research
Two Types of Survival Curves of Different Lines of Progeric Mice
AbstractFor most of their lifespan, the probability of death for many animal species increases with age. Gompertz law states that this increase is exponential. In this work, we have compared previously published data on the survival kinetics of different lines of progeric mice. Visual analysis showed that in six lines of these rapidly aging mutants, the probability of death did not strictly depend on age. In contrast, ten lines of progeric mice have survival curves similar to those of the control animals, that is, in agreement with Gompertz law, similar to the shape of an exponential curve upside down. Interestingly, these...
Source: Biochemistry (Moscow) - February 1, 2024 Category: Biochemistry Source Type: research
Free Radical Lipid Peroxidation Induced by Reactive Halogen Species
AbstractThe review is devoted to the mechanisms of free radical lipid peroxidation (LPO) initiated by reactive halogen species (RHS) produced in mammals, including humans, by heme peroxidase enzymes, primarily myeloperoxidase (MPO). It has been shown that RHS can participate in LPO both in the initiation and branching steps of the LPO chain reactions. The initiation step of R HS-induced LPO mainly involves formation of free radicals in the reactions of RHS with nitrite and/or with amino groups of phosphatidylethanolamine or Lys. The branching step of the oxidative chain is the reaction of RHS with lipid hydroperoxide...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
Electroanalysis in Pharmacogenomic Studies: Mechanisms of Drug Interaction with DNA
AbstractThe review discusses electrochemical methods for analysis of drug interactions with DNA. The electroanalysis method is based on the registration of interaction-induced changes in the electrochemical oxidation potential of heterocyclic nitrogenous bases in the DNA molecule and in the maximum oxidation current amplitude. The mechanisms of DNA –drug interactions can be identified based on the shift in the electrooxidation potential of heterocyclic nitrogenous bases toward more negative (cathodic) or positive (anodic) values. Drug intercalation into DNA shifts the electrochemical oxidation potential to positive value...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
Synthetic Biology Approaches to Posttranslational Regulation in Plants
AbstractTo date synthetic biology approaches involving creation of functional genetic modules are used in a wide range of organisms. In plants, such approaches are used both for research in the field of functional genomics and to increase the yield of agricultural crops. Of particular interest are methods that allow controlling genetic apparatus of the plants at post-translational level, which allow reducing non-targeted effects from interference with the plant genome. This review discusses recent advances in the plant synthetic biology for regulation of the plant metabolism at posttranslational level and highlights their ...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
The Role of Vitamin K in the Development of Neurodegenerative Diseases
AbstractNeurodegenerative diseases are a growing global health problem with enormous consequences for individuals and society. The most common neurodegenerative diseases, such as Alzheimer ’s and Parkinson’s diseases, can be caused by both genetic factors (mutations) and epigenetic changes caused by the environment, in particular, oxidative stress. One of the factors contributing to the development of oxidative stress that has an important effect on the nervous system is vitamin K, which is involved in redox processes. However, its role in cells is ambiguous: accumulation of high concentrations of vitamin K increas...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
Tumor Organoids: The Era of Personalized Medicine
AbstractThe strategies of future medicine are aimed to modernize and integrate quality approaches including early molecular-genetic profiling, identification of new therapeutic targets and adapting design for clinical trials, personalized drug screening (PDS) to help predict and individualize patient treatment regimens. In the past decade, organoid models have emerged as an innovativein vitro platform with the potential to realize the concept of patient-centered medicine. Organoids are spatially restricted three-dimensional clusters of cellsex vivo that self-organize into complex functional structures through genetical...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
Direct Determination of the Structure of Single Biopolymer Molecules Using Nanopore Sequencing
AbstractThis review highlights operational principles, features, and modern aspects of the development of third-generation sequencing technology of biopolymers focusing on the nucleic acids analysis, namely the nanopore sequencing system. Basics of the method and technical solutions used for its realization are considered, from the first works showing the possibility of creation of these systems to the easy-to-handle procedure developed by Oxford Nanopore Technologies company. Moreover, this review focuses on applications, which were developed and realized using equipment developed by the Oxford Nanopore Technologies, incl...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
Biomolecular Condensates: Structure, Functions, Methods of Research
AbstractThe term “biomolecular condensates” is used to describe membraneless compartments in eukaryotic cells, accumulating proteins and nucleic acids. Biomolecular condensates are formed as a result of liquid–liquid phase separation (LLPS). Often, they demonstrate properties of liquid-like droplets or gel-lik e aggregates; however, some of them may appear to have a more complex structure and high-order organization. Membraneless microcompartments are involved in diverse processes both in cytoplasm and in nucleus, among them ribosome biogenesis, regulation of gene expression, cell signaling, and stress re sponse. Con...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
G-Quadruplexes as Sensors of Intracellular Na+/K+ Ratio: Potential Role in Regulation of Transcription and Translation
AbstractData on the structure of G-quadruplexes, noncanonical nucleic acid forms, supporting an idea of their potential participation in regulation of gene expression in response to the change in intracellular Na+i/K+i ratio are considered in the review. Structural variety of G-quadruplexes, role of monovalent cations in formation of this structure, and thermodynamic stability of G-quadruplexes are described. Data on the methods of their identification in the cells and biological functions of these structures are presented. Analysis of information about specific interactions of G-quadruplexes with some proteins was conduct...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
Animal Models of FUS-Proteinopathy: A Systematic Review
AbstractMutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the key features in ALS pathogenesis is the formation of insoluble protein aggregates containing aberrant isoforms of the FUS protein in the cytoplasm of upper and lower motor neurons. Reproduction of human pathology in animal models is the main tool for studying FUS-associated pathology and searching for potential therapeutic agents for ALS treatment. In this review, we provide a systematic analysis of the role of FUS protein in ALS pathogenesis and ...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
Fenton Reaction in vivo and in vitro. Possibilities and Limitations
AbstractThe review considers the problem of hydrogen peroxide decomposition and hydroxyl radical formation in the presence of ironin vivo andin vitro. Analysis of the literature data allows us to conclude that, under physiological conditions, transport of iron, carried out with the help of carrier proteins, minimizes the possibility of appearance of free iron ions in cytoplasm of the cell. Under pathological conditions, when the process of transferring an iron ion from a donor protein to an acceptor protein can be disrupted due to modifications of the carrier proteins, iron ions can enter cytosol. However, at pH values...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
Formation of Supplementary Metal-Binding Centers in Proteins under Stress Conditions
AbstractIn many proteins, supplementary metal-binding centers appear under stress conditions. They are known as aberrant or atypical sites. Physico-chemical properties of proteins are significantly changed after such metal binding, and very stable protein aggregates are formed, in which metals act as “cross-linking” agents. Supplementary metal-binding centers in proteins often arise as a result of posttranslational modifications caused by reactive oxygen and nitrogen species and reactive carbonyl compounds. New chemical groups formed as a result of these modifications can act as ligands for binding metal ions. Special ...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
Multicomponent DNAzyme Nanomachines: Structure, Applications, and Prospects
AbstractNucleic acids (NAs) are important components of living organisms responsible for the storage and transmission of hereditary information. They form complex structures that can self-assemble and bind to various biological molecules. DNAzymes are NAs capable of performing simple chemical reactions, which makes them potentially useful elements for creating DNA nanomachines with required functions. This review focuses on multicomponent DNA-based nanomachines, in particular on DNAzymes as their main functional elements, as well as on the structure of DNAzyme nanomachines and their application in the diagnostics and treat...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
Post-Translational Oxidative Modifications of Hemostasis Proteins: Structure, Function, and Regulation
AbstractReactive oxygen species (ROS) are constantly generated in a living organism. An imbalance between the amount of generated reactive species in the body and their destruction leads to the development of oxidative stress. Proteins are extremely vulnerable targets for ROS molecules, which can cause oxidative modifications of amino acid residues, thus altering structure and function of intra- and extracellular proteins. The current review considers the effect of oxidation on the structural rearrangements and functional activity of hemostasis proteins: coagulation system proteins such as fibrinogen, prothrombin/thrombin,...
Source: Biochemistry (Moscow) - January 1, 2024 Category: Biochemistry Source Type: research
